WorldWideScience

Sample records for primary cilia rely

  1. Unique properties of Drosophila spermatocyte primary cilia

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Riparbelli

    2013-09-01

    The primary cilium is an essential organelle required for animal development and adult homeostasis that is found on most animal cells. The primary cilium contains a microtubule-based axoneme cytoskeleton that typically grows from the mother centriole in G0/G1 phase of the cell cycle as a membrane-bound compartment that protrudes from the cell surface. A unique system of bidirectional transport, intraflagellar transport (IFT, maintains the structure and function of cilia. While the axoneme is dynamic, growing and shrinking at its tip, at the same time it is very stable to the effects of microtubule-targeting drugs. The primary cilia found on Drosophila spermatocytes diverge from the general rules of primary cilium biology in several respects. Among these unique attributes, spermatocyte cilia assemble from all four centrioles in an IFT-independent manner in G2 phase, and persist continuously through two cell divisions. Here, we show that Drosophila spermatocyte primary cilia are extremely sensitive to microtubule-targeting drugs, unlike their mammalian counterparts. Spermatocyte cilia and their axonemes fail to assemble or be maintained upon nocodazole treatment, while centriole replication appears unperturbed. On the other hand, paclitaxel (Taxol, a microtubule-stabilizing drug, disrupted transition zone assembly and anchoring to the plasma membrane while causing spermatocyte primary cilia to grow extensively long during the assembly/elongation phase, but did not overtly affect the centrioles. However, once assembled to their mature length, spermatocyte cilia appeared unaffected by Taxol. The effects of these drugs on axoneme dynamics further demonstrate that spermatocyte primary cilia are endowed with unique assembly properties.

  2. 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

  3. 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...

  4. Imaging intraflagellar transport in mammalian primary cilia.

    Science.gov (United States)

    Besschetnova, Tatiana Y; Roy, Barnali; Shah, Jagesh V

    2009-01-01

    The primary cilium is a specialized organelle that projects from the surface of many cell types. Unlike its motile counterpart it cannot beat but does transduce extracellular stimuli into intracellular signals and acts as a specialized subcellular compartment. The cilium is built and maintained by the transport of proteins and other biomolecules into and out of this compartment. The trafficking machinery for the cilium is referred to as IFT or intraflagellar transport. It was originally identified in the green algae Chlamydomonas and has been discovered throughout the evolutionary tree. The IFT machinery is widely conserved and acts to establish, maintain, and disassemble cilia and flagella. Understanding the role of IFT in cilium signaling and regulation requires a methodology for observing it directly. Here we describe current methods for observing the IFT process in mammalian primary cilia through the generation of fluorescent protein fusions and their expression in ciliated cell lines. The observation protocol uses high-resolution time-lapse microscopy to provide detailed quantitative measurements of IFT particle velocities in wild-type cells or in the context of genetic or other perturbations. Direct observation of IFT trafficking will provide a unique tool to dissect the processes that govern cilium regulation and signaling. 2009 Elsevier Inc. All rights reserved.

  5. Adenylate cyclase regulates elongation of mammalian primary cilia

    International Nuclear Information System (INIS)

    Ou, Young; Ruan, Yibing; Cheng, Min; Moser, Joanna J.; Rattner, Jerome B.; Hoorn, Frans A. van der

    2009-01-01

    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-3β 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.

  6. 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.

  7. Sensing a Sensor: Identifying the Mechanosensory Function of Primary Cilia

    Science.gov (United States)

    Prasad, Rahul M.; Jin, Xingjian; Nauli, Surya M.

    2014-01-01

    Over the past decade, primary cilia have emerged as the premier means by which cells sense and transduce mechanical stimuli. Primary cilia are sensory organelles that have been shown to be vitally involved in the mechanosensation of urine in the renal nephron, bile in the hepatic biliary system, digestive fluid in the pancreatic duct, dentin in dental pulp, lacunocanalicular fluid in bone and cartilage, and blood in vasculature. The prevalence of primary cilia among mammalian cell types is matched by the tremendously varied disease states caused by both structural and functional defects in cilia. In the process of delineating the mechanisms behind these disease states, calcium fluorimetry has been widely utilized as a means of quantifying ciliary function to both fluid flow and pharmacological agents. In this review, we will discuss the approaches used in associating calcium levels to cilia function. PMID:24839551

  8. Sensing a Sensor: Identifying the Mechanosensory Function of Primary Cilia

    Directory of Open Access Journals (Sweden)

    Rahul M. Prasad

    2014-03-01

    Full Text Available Over the past decade, primary cilia have emerged as the premier means by which cells sense and transduce mechanical stimuli. Primary cilia are sensory organelles that have been shown to be vitally involved in the mechanosensation of urine in the renal nephron, bile in the hepatic biliary system, digestive fluid in the pancreatic duct, dentin in dental pulp, lacunocanalicular fluid in bone and cartilage, and blood in vasculature. The prevalence of primary cilia among mammalian cell types is matched by the tremendously varied disease states caused by both structural and functional defects in cilia. In the process of delineating the mechanisms behind these disease states, calcium fluorimetry has been widely utilized as a means of quantifying ciliary function to both fluid flow and pharmacological agents. In this review, we will discuss the approaches used in associating calcium levels to cilia function.

  9. Lack of centrioles and primary cilia in STIL(-/-) mouse embryos.

    Science.gov (United States)

    David, Ahuvit; Liu, Fengying; Tibelius, Alexandra; Vulprecht, Julia; Wald, Diana; Rothermel, Ulrike; Ohana, Reut; Seitel, Alexander; Metzger, Jasmin; Ashery-Padan, Ruth; Meinzer, Hans-Peter; Gröne, Hermann-Josef; Izraeli, Shai; Krämer, Alwin

    2014-01-01

    Although most animal cells contain centrosomes, consisting of a pair of centrioles, their precise contribution to cell division and embryonic development is unclear. Genetic ablation of STIL, an essential component of the centriole replication machinery in mammalian cells, causes embryonic lethality in mice around mid gestation associated with defective Hedgehog signaling. Here, we describe, by focused ion beam scanning electron microscopy, that STIL(-/-) mouse embryos do not contain centrioles or primary cilia, suggesting that these organelles are not essential for mammalian development until mid gestation. We further show that the lack of primary cilia explains the absence of Hedgehog signaling in STIL(-/-) cells. Exogenous re-expression of STIL or STIL microcephaly mutants compatible with human survival, induced non-templated, de novo generation of centrioles in STIL(-/-) cells. Thus, while the abscence of centrioles is compatible with mammalian gastrulation, lack of centrioles and primary cilia impairs Hedgehog signaling and further embryonic development.

  10. 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. Copyright © 2014 Wiley Periodicals, Inc.

  11. 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...... that localization of EB1 at the centriole/basal body is required for primary cilia assembly in fibroblasts....

  12. The Roles of Primary Cilia in Cardiovascular System

    Science.gov (United States)

    2016-10-01

    stages of heart development. An example is the Hedgehog (Hh) signaling pathway which regulates the L-R asymmetry in vertebrates and promotes the...Seol AD, So PL, et al. Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis. Nat Med 2009; 15(9): 1055-61. [29...Pauerstein CJ. Anatomy and physiology of the fallopian tube. Clin Obstet Gynecol 1980; 23(4): 1177-93. [38] Lyons RA, Saridogan E, Djahanbakhch O

  13. Distinct patterns of primary and motile cilia in Rathke's cleft cysts and craniopharyngioma subtypes.

    Science.gov (United States)

    Coy, Shannon; Du, Ziming; Sheu, Shu-Hsien; Woo, Terri; Rodriguez, Fausto J; Kieran, Mark W; Santagata, Sandro

    2016-12-01

    Cilia are highly conserved organelles, which serve critical roles in development and physiology. Motile cilia are expressed in a limited range of tissues, where they principally regulate local extracellular fluid dynamics. In contrast, primary cilia are expressed by many vertebrate cell types during interphase, and are intimately involved in the cell cycle and signal transduction. Notably, primary cilia are essential for vertebrate hedgehog pathway activity. Improved detection of motile cilia may assist in the diagnosis of some pathologic entities such as Rathke's cleft cysts, whereas characterizing primary cilia in neoplastic tissues may implicate cilia-dependent signaling pathways as critical for tumorigenesis. We show that immunohistochemistry for the nuclear transcription factor FOXJ1, a master regulator of motile ciliogenesis, robustly labels the motile ciliated epithelium of Rathke's cleft cysts. FOXJ1 expression discriminates Rathke's cleft cysts from entities in the sellar/suprasellar region with overlapping histologic features such as craniopharyngiomas. Co-immunohistochemistry for FOXJ1 and markers that highlight motile cilia such as acetylated tubulin (TUBA4A) and the small GTPase ARL13B further enhance the ability to identify diagnostic epithelial cells. In addition to highlighting motile cilia, ARL13B immunohistochemistry also robustly highlights primary cilia in formalin-fixed paraffin-embedded sections. Primary cilia are present throughout the neoplastic epithelium of adamantinomatous craniopharyngioma, but are limited to basally oriented cells near the fibrovascular stroma in papillary craniopharyngioma. Consistent with this differing pattern of primary ciliation, adamantinomatous craniopharyngiomas express significantly higher levels of SHH, and downstream targets such as PTCH1 and GLI2, compared with papillary craniopharyngiomas. In conclusion, motile ciliated epithelium can be readily identified using immunohistochemistry for FOXJ1, TUBA4A, and

  14. Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells

    Science.gov (United States)

    McMurray, R. J.; Wann, A. K. T.; Thompson, C. L.; Connelly, J. T.; Knight, M. M.

    2013-01-01

    The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation. PMID:24346024

  15. HDAC6 inhibition suppresses chondrosarcoma by restoring the expression of primary cilia.

    Science.gov (United States)

    Xiang, Wei; Guo, Fengjing; Cheng, Weiting; Zhang, Jiaming; Huang, Junming; Wang, Rui; Ma, Zhongxi; Xu, Kai

    2017-07-01

    Chondrosarcoma is a bone tumor characterized by the secretion of a cartilage-like extracellular matrix. It has been proved to lack extracellular sensor primary cilia. This study aimed to illustrate a feasible therapeutic method for chondrosarcoma by regulating primary cilia assembly through inhibiting histone deacetylases 6 (HDAC6) activation. In order to detect the interaction between primary cilia and HDAC6 in human chondrosarcoma, Tubastatin A and small interfering RNA (siRNA) were used to inhibit the endogenous expression of HDAC6. Cell viability test and Transwell assay were applied to evaluate the effects of malignant biological properties. Primary cilia staining and related proteins were detected. The abnormal expression of HDAC6 and cilia intraflagellar transport protein 88 (IFT88) was found in chondrosarcoma tissues. The inhibition of HDAC6 could downregulate the proliferation of chondrosarcoma cells in a concentration- and time-dependent manner and suppress the invasion capacity of tumor cells. Besides, the downregulation of HDAC6 exhibited a negative effect on the proliferation of relevant proteins but a positive effect on the primary cilia-related expression of IFT88 and acetylated α-tubulin. Primary cilia restoration could be observed after HDAC6 siRNA transfection. The Aurora A-HDAC6 cascade was involved in regulating primary cilia resorption by affecting α-tubulin deacetylation and Tubastatin A could inhibit chondrosarcoma cell growth in vivo. These results indicate that restricting HDAC6 can restore primary cilia assembly accompanied with suppressed chondrosarcoma cell proliferation and invasion capacities. Thus, promoting primary cilia restoration by targeting HDAC6 may be a feasible potential therapeutic method for chondro-sarcoma treatment.

  16. Distinct Patterns of Primary and Motile Cilia in Rathke’s Cleft Cysts and Craniopharyngioma Subtypes

    Science.gov (United States)

    Coy, Shannon; Du, Ziming; Sheu, Shu-Hsien; Woo, Terri; Rodriguez, Fausto J.; Kieran, Mark W.; Santagata, Sandro

    2017-01-01

    Cilia are highly conserved organelles which serve critical roles in development and physiology. Motile cilia are expressed in a limited range of tissues, where they principally regulate local extracellular fluid dynamics. In contrast, primary cilia are expressed by many vertebrate cell types during interphase, and are intimately involved in the cell cycle and signal transduction. Notably, primary cilia are essential for vertebrate hedgehog pathway activity. Improved detection of motile cilia may assist in the diagnosis of some pathologic entities such as Rathke’s cleft cysts while characterizing primary cilia in neoplastic tissues may implicate cilia-dependent signaling pathways as critical for tumorigenesis. We show that immunohistochemistry for the nuclear transcription factor FOXJ1, a master regulator of motile ciliogenesis, robustly labels the motile ciliated epithelium of Rathke’s cleft cysts. FOXJ1 expression discriminates Rathke’s cleft cysts from entities in the sellar/suprasellar region with overlapping histologic features such as craniopharyngiomas. Co-immunohistochemistry for FOXJ1 and markers that highlight motile cilia such as acetylated tubulin (TUBA4A) and the small GTPase ARL13B further enhance the ability to identify diagnostic epithelial cells. In addition to highlighting motile cilia, ARL13B immunohistochemistry also robustly highlights primary cilia in formalin-fixed paraffin-embedded sections. Primary cilia are present throughout the neoplastic epithelium of adamantinomatous craniopharyngioma, but are limited to basally oriented cells near the fibrovascular stroma in papillary craniopharyngioma. Consistent with this differing pattern of primary ciliation, adamantinomatous craniopharyngiomas express significantly higher levels of SHH, and downstream targets such as PTCH1 and GLI2, compared to papillary craniopharyngiomas. In conclusion, motile ciliated epithelium can be readily identified using immunohistochemistry for FOXJ1, TUBA4A and

  17. Primary cilia modulate Ihh signal transduction in response to hydrostatic loading of growth plate chondrocytes.

    Science.gov (United States)

    Shao, Yvonne Y; Wang, Lai; Welter, Jean F; Ballock, R Tracy

    2012-01-01

    Indian hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Primary Cilia Modulate IHH Signal Transduction in Response to Hydrostatic Loading of Growth Plate Chondrocytes

    Science.gov (United States)

    Shao, Y, Yvonne Y.; Wang, Lai; Welter, J, Jean F.; Ballock, R. Tracy

    2011-01-01

    Indian Hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. PMID:21930256

  19. 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.

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

    International Nuclear Information System (INIS)

    Miyoshi, Ko; Kasahara, Kyosuke; Miyazaki, Ikuko; Asanuma, Masato

    2009-01-01

    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 2 CO 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. Primary Cilia in the Murine Cerebellum and in Mutant Models of Medulloblastoma.

    Science.gov (United States)

    Di Pietro, Chiara; Marazziti, Daniela; La Sala, Gina; Abbaszadeh, Zeinab; Golini, Elisabetta; Matteoni, Rafaele; Tocchini-Valentini, Glauco P

    2017-01-01

    Cellular primary cilia crucially sense and transduce extracellular physicochemical stimuli. Cilium-mediated developmental signaling is tissue and cell type specific. Primary cilia are required for cerebellar differentiation and sonic hedgehog (Shh)-dependent proliferation of neuronal granule precursors. The mammalian G-protein-coupled receptor 37-like 1 is specifically expressed in cerebellar Bergmann glia astrocytes and participates in regulating postnatal cerebellar granule neuron proliferation/differentiation and Bergmann glia and Purkinje neuron maturation. The mouse receptor protein interacts with the patched 1 component of the cilium-associated Shh receptor complex. Mice heterozygous for patched homolog 1 mutations, like heterozygous patched 1 humans, have a higher incidence of Shh subgroup medulloblastoma (MB) and other tumors. Cerebellar cells bearing primary cilia were identified during postnatal development and in adulthood in two mouse strains with altered Shh signaling: a G-protein-coupled receptor 37-like 1 null mutant and an MB-susceptible, heterozygous patched homolog 1 mutant. In addition to granule and Purkinje neurons, primary cilia were also expressed by Bergmann glia astrocytes in both wild-type and mutant animals, from birth to adulthood. Variations in ciliary number and length were related to the different levels of neuronal and glial cell proliferation and maturation, during postnatal cerebellar development. Primary cilia were also detected in pre-neoplastic MB lesions in heterozygous patched homolog 1 mutant mice and they could represent specific markers for the development and analysis of novel cerebellar oncogenic models.

  2. Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis.

    Science.gov (United States)

    Zhang, Jingwei; Dalbay, Melis T; Luo, Xiaoman; Vrij, Erik; Barbieri, Davide; Moroni, Lorenzo; de Bruijn, Joost D; van Blitterswijk, Clemens A; Chapple, J Paul; Knight, Martin M; Yuan, Huipin

    2017-07-15

    The surface topography of synthetic biomaterials is known to play a role in material-driven osteogenesis. Recent studies show that TGFβ signalling also initiates osteogenic differentiation. TGFβ signalling requires the recruitment of TGFβ receptors (TGFβR) to the primary cilia. In this study, we hypothesize that the surface topography of calcium phosphate ceramics regulates stem cell morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation. We developed a 2D system using two types of tricalcium phosphate (TCP) ceramic discs with identical chemistry. One sample had a surface topography at micron-scale (TCP-B, with a bigger surface structure dimension) whilst the other had a surface topography at submicron scale (TCP-S, with a smaller surface structure dimension). In the absence of osteogenic differentiation factors, human bone marrow stromal cells (hBMSCs) were more spread on TCP-S than on TCP-B with alterations in actin organization and increased primary cilia prevalence and length. The cilia elongation on TCP-S was similar to that observed on glass in the presence of osteogenic media and was followed by recruitment of transforming growth factor-β RII (p-TGFβ RII) to the cilia axoneme. This was associated with enhanced osteogenic differentiation of hBMSCs on TCP-S, as shown by alkaline phosphatase activity and gene expression for key osteogenic markers in the absence of additional osteogenic growth factors. Similarly, in vivo after a 12-week intramuscular implantation in dogs, TCP-S induced bone formation while TCP-B did not. It is most likely that the surface topography of calcium phosphate ceramics regulates primary cilia length and ciliary recruitment of p-TGFβ RII associated with osteogenesis and bone formation. This bioengineering control of osteogenesis via primary cilia modulation may represent a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery

  3. 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...... that the primary cilium continues to coordinate Hh signaling in cells derived from the mature pancreas. The fact that the Hh signaling pathway is active in the CFPAC-1 and PANC-1 cell lines without Hh stimulation suggests that ciliary Hh signaling plays a potential role in tumorigenesis. In conclusion, this thesis...

  4. Lack of centrioles and primary cilia in STIL−/− mouse embryos

    Science.gov (United States)

    David, Ahuvit; Liu, Fengying; Tibelius, Alexandra; Vulprecht, Julia; Wald, Diana; Rothermel, Ulrike; Ohana, Reut; Seitel, Alexander; Metzger, Jasmin; Ashery-Padan, Ruth; Meinzer, Hans-Peter; Gröne, Hermann-Josef; Izraeli, Shai; Krämer, Alwin

    2014-01-01

    Although most animal cells contain centrosomes, consisting of a pair of centrioles, their precise contribution to cell division and embryonic development is unclear. Genetic ablation of STIL, an essential component of the centriole replication machinery in mammalian cells, causes embryonic lethality in mice around mid gestation associated with defective Hedgehog signaling. Here, we describe, by focused ion beam scanning electron microscopy, that STIL−/− mouse embryos do not contain centrioles or primary cilia, suggesting that these organelles are not essential for mammalian development until mid gestation. We further show that the lack of primary cilia explains the absence of Hedgehog signaling in STIL−/− cells. Exogenous re-expression of STIL or STIL microcephaly mutants compatible with human survival, induced non-templated, de novo generation of centrioles in STIL−/− cells. Thus, while the abscence of centrioles is compatible with mammalian gastrulation, lack of centrioles and primary cilia impairs Hedgehog signaling and further embryonic development. PMID:25486474

  5. Ultrastructural characterization of primary cilia in pathologically characterized human glioblastoma multiforme (GBM) tumors.

    Science.gov (United States)

    Moser, Joanna J; Fritzler, Marvin J; Rattner, Jerome B

    2014-01-01

    Primary cilia are non-motile sensory cytoplasmic organelles that are involved in cell cycle progression. Ultrastructurally, the primary cilium region is complex, with normal ciliogenesis progressing through five distinct morphological stages in human astrocytes. Defects in early stages of ciliogenesis are key features of astrocytoma/glioblastoma cell lines and provided the impetus for the current study which describes the morphology of primary cilia in molecularly characterized human glioblastoma multiforme (GBM) tumors. Seven surgically resected human GBM tissue samples were molecularly characterized according to IDH1/2 mutation status, EGFR amplification status and MGMT promoter methylation status and were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. We report for the first time that primary cilia are disrupted in the early stages of ciliogenesis in human GBM tumors. We confirm that immature primary cilia and basal bodies/centrioles have aberrant ciliogenesis characteristics including absent paired vesicles, misshaped/swollen vesicular hats, abnormal configuration of distal appendages, and discontinuity of centriole microtubular blades. Additionally, the transition zone plate is able to form in the absence of paired vesicles on the distal end of the basal body and when a cilium progresses beyond the early stages of ciliogenesis, it has electron dense material clumped along the transition zone and a darkening of the microtubules at the proximal end of the cilium. Primary cilia play a role in a variety of human cancers. Previously primary cilia structure was perturbed in cultured cell lines derived from astrocytomas/glioblastomas; however there was always some question as to whether these findings were a cell culture phenomena. In this study we confirm that disruptions in ciliogenesis at early stages do occur in GBM tumors and that these ultrastructural findings bear resemblance to those previously

  6. Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules.

    Science.gov (United States)

    Armour, Eric A; Carson, Robert P; Ess, Kevin C

    2012-08-15

    Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia.

  7. Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules

    Science.gov (United States)

    Armour, Eric A.; Carson, Robert P.

    2012-01-01

    Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia. PMID:22674026

  8. 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 hESC d...

  9. 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 asse...

  10. Ionizing radiation increases primary cilia incidence and induces multiciliation in C2C12 myoblasts

    Czech Academy of Sciences Publication Activity Database

    Filipová, A.; Diaz-Garcia, D.; Bezrouk, A.; Čížková, D.; Havelek, R.; Vávrová, J.; Dayanithi, Govindan; Řezáčová, M.

    2015-01-01

    Roč. 39, č. 8 (2015), s. 943-953 ISSN 1065-6995 Institutional support: RVO:68378041 Keywords : cell line * ionizing radiation * multiple cilia * myoblast * primary cilium * serum starvation stress Subject RIV: FP - Other Medical Disciplines Impact factor: 1.663, year: 2015

  11. 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.

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

    Science.gov (United States)

    Omori, Yoshihiro; Chaya, Taro; Yoshida, Satoyo; Irie, Shoichi; Tsujii, Toshinori; Furukawa, Takahisa

    2015-01-01

    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.

  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. 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...... of follicular granulosa cells. We show that the Ca2+ permeable cation channel, polycystin-2, as well as polycystin-1, a receptor that forms a functional protein complex with polycystin 2, distinctively localize to primary cilia emerging from granulosa cells of antral follicles in vivo and in vitro. Both...... polycystins are localized to motile oviduct cilia and this localization is greatly increased upon ovulatory gonadotropic stimulation. Further, the Ca2+ permeable cation channel, TRP vaniloid 4 (TRPV4), localizes to a sub-population of motile cilia on the epithelial cells of the ampulla and isthmus with high...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    summarize selected methods in analyzing ciliary function in directional cell migration, including immunofluorescence microscopy, scratch assay, and chemotaxis assay by micropipette addition of PDGFRα ligands to cultures of fibroblasts. These methods should be useful not only in studying cell migration....... In particular, platelet-derived growth factor receptor alpha (PDGFRα) is compartmentalized to the primary cilium to activate signaling pathways that regulate reorganization of the cytoskeleton required for lamellipodium formation and directional migration in the presence of a specific ligand gradient. We...

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

    Science.gov (United States)

    Choi, Hyunjung; Shin, Ji Hyun; 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.

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

    Directory of Open Access Journals (Sweden)

    Hyunjung Choi

    Full Text Available 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.

  18. Reduced primary cilia length and altered Arl13b expression are associated with deregulated chondrocyte Hedgehog signaling in alkaptonuria.

    Science.gov (United States)

    Thorpe, Stephen D; Gambassi, Silvia; Thompson, Clare L; Chandrakumar, Charmilie; Santucci, Annalisa; Knight, Martin M

    2017-09-01

    Alkaptonuria (AKU) is a rare inherited disease resulting from a deficiency of the enzyme homogentisate 1,2-dioxygenase which leads to the accumulation of homogentisic acid (HGA). AKU is characterized by severe cartilage degeneration, similar to that observed in osteoarthritis. Previous studies suggest that AKU is associated with alterations in cytoskeletal organization which could modulate primary cilia structure/function. This study investigated whether AKU is associated with changes in chondrocyte primary cilia and associated Hedgehog signaling which mediates cartilage degradation in osteoarthritis. Human articular chondrocytes were obtained from healthy and AKU donors. Additionally, healthy chondrocytes were treated with HGA to replicate AKU pathology (+HGA). Diseased cells exhibited shorter cilia with length reductions of 36% and 16% in AKU and +HGA chondrocytes respectively, when compared to healthy controls. Both AKU and +HGA chondrocytes demonstrated disruption of the usual cilia length regulation by actin contractility. Furthermore, the proportion of cilia with axoneme breaks and bulbous tips was increased in AKU chondrocytes consistent with defective regulation of ciliary trafficking. Distribution of the Hedgehog-related protein Arl13b along the ciliary axoneme was altered such that its localization was increased at the distal tip in AKU and +HGA chondrocytes. These changes in cilia structure/trafficking in AKU and +HGA chondrocytes were associated with a complete inability to activate Hedgehog signaling in response to exogenous ligand. Thus, we suggest that altered responsiveness to Hedgehog, as a consequence of cilia dysfunction, may be a contributing factor in the development of arthropathy highlighting the cilium as a novel target in AKU. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals Inc.

  19. 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.

  20. 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

    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...

  1. Revealing the Molecular Structure and the Transport Mechanism at the Base of Primary Cilia Using Superresolution STED Microscopy

    Science.gov (United States)

    Yang, Tung-Lin

    The primary cilium is an organelle that serves as a signaling center of the cell and is involved in the hedgehog signaling, cAMP pathway, Wnt pathways, etc. Ciliary function relies on the transportation of molecules between the primary cilium and the cell, which is facilitated by intraflagellar transport (IFT). IFT88, one of the important IFT proteins in complex B, is known to play a role in the formation and maintenance of cilia in various types of organisms. The ciliary transition zone (TZ), which is part of the gating apparatus at the ciliary base, is home to a large number of ciliopathy molecules. Recent studies have identified important regulating elements for TZ gating in cilia. However, the architecture of the TZ region and its arrangement relative to intraflagellar transport (IFT) proteins remain largely unknown, hindering the mechanistic understanding of the regulation processes. One of the major challenges comes from the tiny volume at the ciliary base packed with numerous proteins, with the diameter of the TZ close to the diffraction limit of conventional microscopes. Using a series of stimulated emission depletion (STED) superresolution images mapped to electron microscopy images, we analyzed the structural organization of the ciliary base. Subdiffraction imaging of TZ components defines novel geometric distributions of RPGRIP1L, MKS1, CEP290, TCTN2 and TMEM67, shedding light on their roles in TZ structure, assembly, and function. We found TCTN2 at the outmost periphery of the TZ close to the ciliary membrane, with a 227+/-18 nm diameter. TMEM67 was adjacent to TCTN2, with a 205+/-20 nm diameter. RPGRIP1L was localized toward the axoneme at the same axial level as TCTN2 and TMEM67, with a 165+/-8 nm diameter. MKS1 was situated between TMEM67 and RPGRIP1L, with an 186+/-21 nm diameter. Surprisingly, CEP290 was localized at the proximal side of the TZ close to the distal end of the centrin-labeled basal body. The lateral width was unexpectedly close to

  2. Neuropeptide Y family receptors traffic via the Bardet-Biedl syndrome pathway to signal in neuronal primary cilia.

    Science.gov (United States)

    Loktev, Alexander V; Jackson, Peter K

    2013-12-12

    Human monogenic obesity syndromes, including Bardet-Biedl syndrome (BBS), implicate neuronal primary cilia in regulation of energy homeostasis. Cilia in hypothalamic neurons have been hypothesized to sense and regulate systemic energy status, but the molecular mechanism of this signaling remains unknown. Here, we report a comprehensive localization screen of 42 G-protein-coupled receptors (GPCR) revealing seven ciliary GPCRs, including the neuropeptide Y (NPY) receptors NPY2R and NPY5R. We show that mice modeling BBS disease or obese tubby mice fail to localize NPY2R to cilia in the hypothalamus and that BBS mutant mice fail to activate c-fos or decrease food intake in response to the NPY2R ligand PYY3-36. We find that cells with ciliary NPY2R show augmented PYY3-36-dependent cAMP signaling. Our data demonstrate that ciliary targeting of NPY receptors is important for controlling energy balance in mammals, revealing a physiologically defined ligand-receptor pathway signaling within neuronal cilia. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  3. 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...... 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...

  4. Biological and Chemical Removal of Primary Cilia Affects Mechanical Activation of Chondrogenesis Markers in Chondroprogenitors and Hypertrophic Chondrocytes.

    Science.gov (United States)

    Deren, Matthew E; Yang, Xu; Guan, Yingjie; Chen, Qian

    2016-02-04

    Chondroprogenitors and hypertrophic chondrocytes, which are the first and last stages of the chondrocyte differentiation process, respectively, are sensitive to mechanical signals. We hypothesize that the mechanical sensitivity of these cells depends on the cell surface primary cilia. To test this hypothesis, we removed the primary cilia by biological means with transfection with intraflagellar transport protein 88 (IFT88) siRNA or by chemical means with chloral hydrate treatment. Transfection of IFT88 siRNA significantly reduced the percentage of ciliated cells in both chondroprogenitor ATDC5 cells as well as primary hypertrophic chondrocytes. Cyclic loading (1 Hz, 10% matrix deformation) of ATDC5 cells in three-dimensional (3D) culture stimulates the mRNA levels of chondrogenesis marker Type II collagen (Col II), hypertrophic chondrocyte marker Type X collagen (Col X), and a molecular regulator of chondrogenesis and chondrocyte hypertrophy bone morphogenetic protein 2 (BMP-2). The reduction of ciliated chondroprogenitors abolishes mechanical stimulation of Col II, Col X, and BMP-2. In contrast, cyclic loading stimulates Col X mRNA levels in hypertrophic chondrocytes, but not those of Col II and BMP-2. Both biological and chemical reduction of ciliated hypertrophic chondrocytes reduced but failed to abolish mechanical stimulation of Col X mRNA levels. Thus, primary cilia play a major role in mechanical stimulation of chondrogenesis and chondrocyte hypertrophy in chondroprogenitor cells and at least a partial role in hypertrophic chondrocytes.

  5. Biological and Chemical Removal of Primary Cilia Affects Mechanical Activation of Chondrogenesis Markers in Chondroprogenitors and Hypertrophic Chondrocytes

    Directory of Open Access Journals (Sweden)

    Matthew E. Deren

    2016-02-01

    Full Text Available Chondroprogenitors and hypertrophic chondrocytes, which are the first and last stages of the chondrocyte differentiation process, respectively, are sensitive to mechanical signals. We hypothesize that the mechanical sensitivity of these cells depends on the cell surface primary cilia. To test this hypothesis, we removed the primary cilia by biological means with transfection with intraflagellar transport protein 88 (IFT88 siRNA or by chemical means with chloral hydrate treatment. Transfection of IFT88 siRNA significantly reduced the percentage of ciliated cells in both chondroprogenitor ATDC5 cells as well as primary hypertrophic chondrocytes. Cyclic loading (1 Hz, 10% matrix deformation of ATDC5 cells in three-dimensional (3D culture stimulates the mRNA levels of chondrogenesis marker Type II collagen (Col II, hypertrophic chondrocyte marker Type X collagen (Col X, and a molecular regulator of chondrogenesis and chondrocyte hypertrophy bone morphogenetic protein 2 (BMP-2. The reduction of ciliated chondroprogenitors abolishes mechanical stimulation of Col II, Col X, and BMP-2. In contrast, cyclic loading stimulates Col X mRNA levels in hypertrophic chondrocytes, but not those of Col II and BMP-2. Both biological and chemical reduction of ciliated hypertrophic chondrocytes reduced but failed to abolish mechanical stimulation of Col X mRNA levels. Thus, primary cilia play a major role in mechanical stimulation of chondrogenesis and chondrocyte hypertrophy in chondroprogenitor cells and at least a partial role in hypertrophic chondrocytes.

  6. 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...... adenocarcinoma cell lines, PANC-1 and CFPAC-1. We show that the onset of Hh signaling from human embryogenesis to fetal development is associated with accumulation of Hh signaling components Smo and Gli2 in duct primary cilia and a reduction of Gli3 in the duct epithelium. Smo, Ptc, and Gli2 localized to primary...... cilia of PANC-1 and CFPAC-1 cells, which may maintain high levels of nonstimulated Hh pathway activity. These findings indicate that primary cilia are involved in pancreatic development and postnatal tissue homeostasis....

  7. Odf2-deficient mother centrioles lack distal/subdistal appendages and the ability to generate primary cilia.

    Science.gov (United States)

    Ishikawa, Hiroaki; Kubo, Akiharu; Tsukita, Shoichiro; Tsukita, Sachiko

    2005-05-01

    Outer dense fibre 2 (Odf2; also known as cenexin) was initially identified as a main component of the sperm tail cytoskeleton, but was later shown to be a general scaffold protein that is specifically localized at the distal/subdistal appendages of mother centrioles. Here we show that Odf2 expression is suppressed in mouse F9 cells when both alleles of Odf2 genes are deleted. Unexpectedly, the cell cycle of Odf2(-/-) cells does not seem to be affected. Immunofluorescence and ultrathin-section electron microscopy reveals that in Odf2(-/-) cells, distal/subdistal appendages disappear from mother centrioles, making it difficult to distinguish mother from daughter centrioles. In Odf2(-/-) cells, however, the formation of primary cilia is completely suppressed, although approximately 25% of wild-type F9 cells are ciliated under the steady-state cell cycle. The loss of primary cilia in Odf2(-/-) F9 cells can be rescued by exogenous Odf2 expression. These findings indicate that Odf2 is indispensable for the formation of distal/subdistal appendages and the generation of primary cilia, but not for other cell-cycle-related centriolar functions.

  8. 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...

  9. 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

  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, prima...

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  12. 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.

  13. Reduction of the immunostainable length of the hippocampal dentate granule cells’ primary cilia in 3xAD-transgenic mice producing human Aβ1-42 and tau

    International Nuclear Information System (INIS)

    Chakravarthy, Balu; Gaudet, Chantal; Ménard, Michel; Brown, Leslie; Atkinson, Trevor; LaFerla, Frank M.; Ito, Shingo; Armato, Ubaldo; Dal Prà, Ilaria; Whitfield, James

    2012-01-01

    Highlights: ► Aβ and tau-induced neurofibrillary tangles play a key role in Alzheimer’s disease. ► Aβ 1-42 and mutant tau protein together reduce the primary cilium length. ► This shortening likely reduces cilium-dependent neurogenesis and memory function. ► This provides a model of an Aβ/tau targeting of a neuronal signaling organelle. -- Abstract: The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis in adult rodents and humans. Virtually all dentate granule cells have a single immobile cilium with a microtubule spine or axoneme covered with a specialized cell membrane loaded with receptors such as the somatostatin receptor 3 (SSTR3), and the p75 neurotrophin receptor (p75 NTR ). The signals from these receptors have been reported to stimulate neuroprogenitor proliferation and the post-mitotic maturation of newborn granule cells into functioning granule cells. We have found that in 6–24-months-old triple transgenic Alzheimer’s disease model mice (3xTg-AD) producing both Aβ 1-42 and the mutant human tau protein tau P301L, the dentate granule cells still had immunostainable SSTR3- and p75 NTR -bearing cilia but they were only half the length of the immunostained cilia in the corresponding wild-type mice. However, the immunostainable length of the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large amounts of Aβ 1-42 or in mice accumulating only a mutant human tau protein. Thus it appears that a combination of Aβ 1-42 and tau protein accumulation affects the levels of functionally important receptors in 3xTg-AD mice. These observations raise the important possibility that structural and functional changes in granule cell cilia might have a role in AD.

  14. Maintaining protein composition in cilia.

    Science.gov (United States)

    Stephen, Louise A; Elmaghloob, Yasmin; Ismail, Shehab

    2017-12-20

    The primary cilium is a sensory organelle that is vital in regulating several signalling pathways. Unlike most organelles cilia are open to the rest of the cell, not enclosed by membranes. The distinct protein composition is crucial to the function of cilia and many signalling proteins and receptors are specifically concentrated within distinct compartments. To maintain this composition, a mechanism is required to deliver proteins to the cilium whilst another must counter the entropic tendency of proteins to distribute throughout the cell. The combination of the two mechanisms should result in the concentration of ciliary proteins to the cilium. In this review we will look at different cellular mechanisms that play a role in maintaining the distinct composition of cilia, including regulation of ciliary access and trafficking of ciliary proteins to, from and within the cilium.

  15. A Wnt/beta-catenin pathway antagonist Chibby binds Cenexin at the distal end of mother centrioles and functions in primary cilia formation.

    Directory of Open Access Journals (Sweden)

    Nathan Steere

    Full Text Available The mother centriole of the centrosome is distinguished from immature daughter centrioles by the presence of accessory structures (distal and subdistal appendages, which play an important role in the organization of the primary cilium in quiescent cells. Primary cilia serve as sensory organelles, thus have been implicated in mediating intracellular signal transduction pathways. Here we report that Chibby (Cby, a highly conserved antagonist of the Wnt/β-catenin pathway, is a centriolar component specifically located at the distal end of the mother centriole and essential for assembly of the primary cilium. Cby appeared as a discrete dot in the middle of a ring-like structure revealed by staining with a distal appendage component of Cep164. Cby interacted with one of the appendage components, Cenexin (Cnx, which thereby abrogated the inhibitory effect of Cby on β-catenin-mediated transcriptional activation in a dose-dependent manner. Cby and Cnx did not precisely align, as Cby was detected at a more distal position than Cnx. Cnx emerged earlier than Cby during the cell cycle and was required for recruitment of Cby to the mother centriole. However, Cby was dispensable for Cnx localization to the centriole. During massive centriogenesis in in vitro cultured mouse tracheal epithelial cells, Cby and Cnx were expressed in a similar pattern, which was coincident with the expression of Foxj1. Our results suggest that Cby plays an important role in organization of both primary and motile cilia in collaboration with Cnx.

  16. A Wnt/beta-catenin pathway antagonist Chibby binds Cenexin at the distal end of mother centrioles and functions in primary cilia formation.

    Science.gov (United States)

    Steere, Nathan; Chae, Vanessa; Burke, Michael; Li, Feng-Qian; Takemaru, Ken-ichi; Kuriyama, Ryoko

    2012-01-01

    The mother centriole of the centrosome is distinguished from immature daughter centrioles by the presence of accessory structures (distal and subdistal appendages), which play an important role in the organization of the primary cilium in quiescent cells. Primary cilia serve as sensory organelles, thus have been implicated in mediating intracellular signal transduction pathways. Here we report that Chibby (Cby), a highly conserved antagonist of the Wnt/β-catenin pathway, is a centriolar component specifically located at the distal end of the mother centriole and essential for assembly of the primary cilium. Cby appeared as a discrete dot in the middle of a ring-like structure revealed by staining with a distal appendage component of Cep164. Cby interacted with one of the appendage components, Cenexin (Cnx), which thereby abrogated the inhibitory effect of Cby on β-catenin-mediated transcriptional activation in a dose-dependent manner. Cby and Cnx did not precisely align, as Cby was detected at a more distal position than Cnx. Cnx emerged earlier than Cby during the cell cycle and was required for recruitment of Cby to the mother centriole. However, Cby was dispensable for Cnx localization to the centriole. During massive centriogenesis in in vitro cultured mouse tracheal epithelial cells, Cby and Cnx were expressed in a similar pattern, which was coincident with the expression of Foxj1. Our results suggest that Cby plays an important role in organization of both primary and motile cilia in collaboration with Cnx.

  17. 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......This chapter describes the procedures for immunofluorescence microscopy (IFM) and quantitative PCR (qPCR) analyses of human embryonic stem cells (hESCs) grown specifically under feeder-free conditions. A detailed protocol is provided outlining the steps from initially growing the cells, passaging...

  18. Assembly of primary cilia

    DEFF Research Database (Denmark)

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

    2008-01-01

    knowledge about IFT is based on studies performed in Chlamydomonas and Caenorhabditis elegans. Therefore, our review of the IFT literature includes studies performed in these two model organisms. The role of several non-IFT proteins (e.g., centrosomal proteins) in the ciliary assembly process is also...... discussed. Developmental Dynamics, 2008. (c) 2008 Wiley-Liss, Inc....

  19. Myosin VIIa as a common component of cilia and microvilli.

    Science.gov (United States)

    Wolfrum, U; Liu, X; Schmitt, A; Udovichenko, I P; Williams, D S

    1998-01-01

    The distribution of myosin VIIa, which is defective or absent in Usher syndrome 1B, was studied in a variety of tissues by immunomicroscopy. The primary aim was to determine whether this putative actin-based mechanoenzyme is a common component of cilia. Previously, it has been proposed that defective ciliary function might be the basis of some forms of Usher syndrome. Myosin VIIa was detected in cilia from cochlear hair cells, olfactory neurons, kidney distal tubules, and lung bronchi. It was also found to cofractionate with the axonemal fraction of retinal photoreceptor cells. Immunolabeling appeared most concentrated in the periphery of the transition zone of the cilia. This general presence of a myosin in cilia is surprising, given that cilia are dominated by microtubules, and not actin filaments. In addition to cilia, myosin VIIa was also found in actin-rich microvilli of different types of cell. We conclude that myosin VIIa is a common component of cilia and microvilli.

  20. Overview of structure and function of mammalian cilia

    DEFF Research Database (Denmark)

    Satir, Peter; Christensen, Søren Tvorup

    2007-01-01

    nonmotile 9 + 0 primary cilia are found on epithelial cells, such as those of the kidney tubule, but also on nonepithelial cells, such as chondrocytes, fibroblasts, and neurons. The ciliary membranes of all cilia contain specific receptors and ion channel proteins that initiate signaling pathways...

  1. Simulation of actuated synthetic cilia expelling microorganisms from a surface

    Science.gov (United States)

    Shum, Henry; Tripathi, Anurag; Yeomans, Julia; Balazs, Anna

    2013-11-01

    The continual motion of cilia provides a defense against biofouling for a variety of marine organisms. Inspired by this natural solution, we perform numerical simulations to study the interactions between actuated, biomimetic cilia and model microswimmers that are hydrodynamically attracted to bare surfaces and therefore behave similarly to fouling organisms. The 3-dimensional fluid flow is coupled to the motion of the cilia and swimmers using an integrated lattice Boltzmann and immersed boundary method. We show that a sparse array of actuated cilia, through which the organisms are able to swim, is able to robustly expel swimmers. The average residence time of the swimmers in the ciliary layer is reduced if the motion of the cilia generates a net fluid flow, but for relatively fast swimmers, the steric interaction with the moving cilia alone is sufficient to ``knock'' the organisms away from the surface. As the demonstrated mechanisms for antifouling do not rely on specific chemical or physical properties of the surface or swimmer, actuated cilia can potentially protect microfluidic devices, filtration membranes or ship hulls from a wide range of fouling species.

  2. 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.

  3. High expression of the taurine transporter TauT in primary cilia of NIH3T3 fibroblasts

    DEFF Research Database (Denmark)

    Christensen, Søren Tvorup; Voss, Jesper W.; Teilmann, Stefan C.

    2005-01-01

    Taurine, present in high concentrations in various mammalian cells, is essential for regulation of cell volume, cellular oxidative status as well as the cellular Ca2+ homeostasis. Cellular taurine content is a balance between active uptake through the saturable, Na+-dependent taurine transporter...... TauT expression and (iii) long-term exposure to hypertonic taurine medium, i.e., growth medium supplemented with 100 mM taurine, reduces ciliary TauT expression. These results point to an important role of taurine in the regulation of physiological processes located to the primary cilium....

  4. Gli2a protein localization reveals a role for Iguana/DZIP1 in primary ciliogenesis and a dependence of Hedgehog signal transduction on primary cilia in the zebrafish

    Directory of Open Access Journals (Sweden)

    van Eeden Freek

    2010-04-01

    Full Text Available Abstract Background In mammalian cells, the integrity of the primary cilium is critical for proper regulation of the Hedgehog (Hh signal transduction pathway. Whether or not this dependence on the primary cilium is a universal feature of vertebrate Hedgehog signalling has remained contentious due, in part, to the apparent divergence of the intracellular transduction pathway between mammals and teleost fish. Results Here, using a functional Gli2-GFP fusion protein, we show that, as in mammals, the Gli2 transcription factor localizes to the primary cilia of cells in the zebrafish embryo and that this localization is modulated by the activity of the Hh pathway. Moreover, we show that the Igu/DZIP1protein, previously implicated in the modulation of Gli activity in zebrafish, also localizes to the primary cilium and is required for its proper formation. Conclusion Our findings demonstrate a conserved role of the primary cilium in mediating Hedgehog signalling activity across the vertebrate phylum and validate the use of the zebrafish as a representative model for the in vivo analysis of vertebrate Hedgehog signalling.

  5. Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

    Science.gov (United States)

    Nikopoulos, Konstantinos; Farinelli, Pietro; Giangreco, Basilio; Tsika, Chrysanthi; Royer-Bertrand, Beryl; Mbefo, Martial K; Bedoni, Nicola; Kjellström, Ulrika; El Zaoui, Ikram; Di Gioia, Silvio Alessandro; Balzano, Sara; Cisarova, Katarina; Messina, Andrea; Decembrini, Sarah; Plainis, Sotiris; Blazaki, Styliani V; Khan, Muhammad Imran; Micheal, Shazia; Boldt, Karsten; Ueffing, Marius; Moulin, Alexandre P; Cremers, Frans P M; Roepman, Ronald; Arsenijevic, Yvan; Tsilimbaris, Miltiadis K; Andréasson, Sten; Rivolta, Carlo

    2016-09-01

    Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  6. 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

  7. Motile cilia of human airway epithelia contain hedgehog signaling components that mediate noncanonical hedgehog signaling.

    Science.gov (United States)

    Mao, Suifang; Shah, Alok S; Moninger, Thomas O; Ostedgaard, Lynda S; Lu, Lin; Tang, Xiao Xiao; Thornell, Ian M; Reznikov, Leah R; Ernst, Sarah E; Karp, Philip H; Tan, Ping; Keshavjee, Shaf; Abou Alaiwa, Mahmoud H; Welsh, Michael J

    2018-02-06

    Differentiated airway epithelia produce sonic hedgehog (SHH), which is found in the thin layer of liquid covering the airway surface. Although previous studies showed that vertebrate HH signaling requires primary cilia, as airway epithelia mature, the cells lose primary cilia and produce hundreds of motile cilia. Thus, whether airway epithelia have apical receptors for SHH has remained unknown. We discovered that motile cilia on airway epithelial cells have HH signaling proteins, including patched and smoothened. These cilia also have proteins affecting cAMP-dependent signaling, including Gα i and adenylyl cyclase 5/6. Apical SHH decreases intracellular levels of cAMP, which reduces ciliary beat frequency and pH in airway surface liquid. These results suggest that apical SHH may mediate noncanonical HH signaling through motile cilia to dampen respiratory defenses at the contact point between the environment and the lung, perhaps counterbalancing processes that stimulate airway defenses. Copyright © 2018 the Author(s). Published by PNAS.

  8. TSC1 and TSC2 regulate cilia length and canonical Hedgehog signaling via different mechanisms

    DEFF Research Database (Denmark)

    Rosengren, Thomas; Larsen, Lasse Jonsgaard; Pedersen, Lotte Bang

    2018-01-01

    Primary cilia are sensory organelles that coordinate multiple cellular signaling pathways, including Hedgehog (HH), Wingless/Int (WNT) and Transforming Growth Factor-β (TGF-β) signaling. Similarly, primary cilia have been implicated in regulation of mTOR signaling, in which Tuberous Sclerosis Com...

  9. Reduction of the immunostainable length of the hippocampal dentate granule cells' primary cilia in 3xAD-transgenic mice producing human A{beta}{sub 1-42} and tau

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarthy, Balu, E-mail: Balu.Chakravarthy@nrc-cnrc.gc.ca [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); Gaudet, Chantal; Menard, Michel; Brown, Leslie; Atkinson, Trevor [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); LaFerla, Frank M. [Department of Neurobiology and Behavior, University of California, Irvine, CA (United States); Ito, Shingo [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); Armato, Ubaldo; Dal Pra, Ilaria [Department of Life and Reproduction Sciences, University of Verona Medical School, Verona (Italy); Whitfield, James [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A{beta} and tau-induced neurofibrillary tangles play a key role in Alzheimer's disease. Black-Right-Pointing-Pointer A{beta}{sub 1-42} and mutant tau protein together reduce the primary cilium length. Black-Right-Pointing-Pointer This shortening likely reduces cilium-dependent neurogenesis and memory function. Black-Right-Pointing-Pointer This provides a model of an A{beta}/tau targeting of a neuronal signaling organelle. -- Abstract: The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis in adult rodents and humans. Virtually all dentate granule cells have a single immobile cilium with a microtubule spine or axoneme covered with a specialized cell membrane loaded with receptors such as the somatostatin receptor 3 (SSTR3), and the p75 neurotrophin receptor (p75{sup NTR}). The signals from these receptors have been reported to stimulate neuroprogenitor proliferation and the post-mitotic maturation of newborn granule cells into functioning granule cells. We have found that in 6-24-months-old triple transgenic Alzheimer's disease model mice (3xTg-AD) producing both A{beta}{sub 1-42} and the mutant human tau protein tau{sub P301L,} the dentate granule cells still had immunostainable SSTR3- and p75{sup NTR}-bearing cilia but they were only half the length of the immunostained cilia in the corresponding wild-type mice. However, the immunostainable length of the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large amounts of A{beta}{sub 1-42} or in mice accumulating only a mutant human tau protein. Thus it appears that a combination of A{beta}{sub 1-42} and tau protein accumulation affects the levels of functionally important receptors in 3xTg-AD mice. These observations raise the important possibility that structural and functional changes in granule cell cilia might have a role in AD.

  10. 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.

  11. Magnetic artificial cilia for microfluidic propulsion

    NARCIS (Netherlands)

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

    2015-01-01

    Cilia are tiny hair-like structures that cover the surfaces of biological cells. One of their functions is to generate flow. Artificial cilia are mechanical actuators that are designed to mimic the motion of natural cilia in order to create fluid transport in microchannels. These fluid propulsion

  12. Magnetic Artificial Cilia for Microfluidic Propulsion

    NARCIS (Netherlands)

    Khaderi, Syed N.; den Toonder, Jaap M. J.; Onck, Patrick R.; Bordas, Stéphane P.A.; Balint, Daniel S.

    2015-01-01

    Cilia are tiny hair-like structures that cover the surfaces of biological cells. One of their functions is to generate flow. Artificial cilia are mechanical actuators that are designed to mimic the motion of natural cilia in order to create fluid transport in microchannels. These fluid propulsion

  13. Metachronal Motion of Artificial Magnetic Cilia

    Science.gov (United States)

    Hanasoge, Srinivas; Hesketh, Peter; Alexeev, Alexander

    2017-11-01

    Most microorganisms use asymmetrically oscillating hair like cilia on their surface to achieve fluid transport. These cilia are often seen to beat in a metachronal fashion with a constant phase difference with the neighbors which generates a travelling wave. Although the origin of metachronal waves in such cilia is not well understood, mimicking such behavior in synthetic systems could prove useful in achieving similar advantages. In this work, we demonstrate metachronal waves in synthetic magnetic ciliary systems. The soft magnetic cilia are forced by a uniform rotating magnetic field. The cilia bend as the field rotates and tend to align along the direction of field to minimize the potential energy. Longer cilia bend to a larger degree, while the shorter cilia show less bending. This difference in the bending of cilia based on their length leads to a phase difference in their oscillation cycle. We exploit this phase differences to metachronally oscillate the synthetic cilia. We fabricate an array consisting of cilia with increasing lengths, in which the cilia beat with a constant phase difference with the neighboring cilia, producing a travelling wave. Such behavior could potentially be useful in enhanced fluid and particle transport as seen in natural systems. USDA.

  14. Emerging ciliopathies: are respiratory cilia compromised in Usher syndrome?

    Science.gov (United States)

    Piatti, G; De Santi, M M; Brogi, M; Castorina, P; Ambrosetti, U

    2014-01-01

    Usher syndrome is a ciliopathy involving photoreceptors and cochlear hair cells (sensory cilia): since sensory and motor ciliopathies can overlap, we analysed the respiratory cilia (motile) in 17 patients affected by Usher syndrome and 18 healthy control subject. We studied the mucociliary transport time with the saccharine test, ciliary motility and ultrastructure of respiratory cilia obtained by nasal brushing; we also recorded the classical respiratory function values by spirometry. All enrolled subjects showed normal respiratory function values. The mean mucociliary transport time with saccharine was 22.33 ± 17.96 min, which is in the range of normal values. The mean ciliary beat frequency of all subjects was 8.81 ± 2.18 Hz, which is a value approaching the lower physiological limit. None of the classical ciliary alterations characterizing the "ciliary primary dyskinesia" was detected, although two patients showed alterations in number and arrangement of peripheral microtubules and one patient had abnormal ciliary roots. Respiratory cilia in Usher patients don't seem to have evident ultrastructural alterations, as expected, but the fact that the ciliary motility appeared slightly reduced could emphasize that a rigid distinction between sensory and motor ciliopathies may not reflect what really occurs. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Lewis, Wesley R; Malarkey, Erik B; Tritschler, Douglas; Bower, Raqual; Pasek, Raymond C; Porath, Jonathan D; Birket, Susan E; Saunier, Sophie; Antignac, Corinne; Knowles, Michael R; Leigh, Margaret W; Zariwala, Maimoona A; Challa, Anil K; Kesterson, Robert A; Rowe, Steven M; Drummond, Iain A; Parant, John M; Hildebrandt, Friedhelm; Porter, Mary E; Yoder, Bradley K; Berbari, Nicolas F

    2016-07-01

    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 variants in

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

    Directory of Open Access Journals (Sweden)

    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

  17. Life without centrioles: cilia in the spotlight.

    Science.gov (United States)

    Badano, Jose L; Katsanis, Nicholas

    2006-06-30

    Centrioles are critical cellular components that form the architectural core of both centrosomes and basal bodies, the nucleating structures of cilia. New work, including a study in this issue (), highlights the unexpected finding that lack of centrioles does not impede development in the fruit fly. Rather, flies reach maturity but then die because their sensory neurons lack cilia.

  18. 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

  19. Presence of Ca2+-dependent K+ channels in chemosensory cilia support a role in odor transduction.

    Science.gov (United States)

    Delgado, Ricardo; Saavedra, M Veronica; Schmachtenberg, Oliver; Sierralta, Jimena; Bacigalupo, Juan

    2003-09-01

    Olfactory receptor neurons (ORNs) respond to odorants with changes in the action potential firing rate. Excitatory responses, consisting of firing increases, are mediated by a cyclic AMP cascade that leads to the activation of cationic nonselective cyclic nucleotide-gated (CNG) channels and Ca2+-dependent Cl- (ClCa) channels. This process takes place in the olfactory cilia, where all protein components of this cascade are confined. ORNs from various vertebrate species have also been shown to generate inhibitory odor responses, expressed as decreases in action potential discharges. Odor inhibition appears to rely on Ca2+-dependent K+ (KCa) channels, but the underlying transduction mechanism remains unknown. If these channels are involved in odor transduction, they are expected to be present in the olfactory cilia. We found that a specific antibody against a large conductance KCa recognized a protein of approximately 116 kDa in Western blots of purified rat olfactory ciliary membranes. Moreover, the antibody labeled ORN cilia in isolated ORNs from rat and toad (Caudiverbera caudiverbera). In addition, single-channel recordings from inside-out membrane patches excised from toad chemosensory cilia showed the presence of 4 different types of KCa channels, with unitary conductances of 210, 60, 12, and 29 and 60 pS, high K+-selectivity, and Ca2+ sensitivities in the low micromolar range. Our work demonstrates the presence of K+ channels in the ORN cilia and supports their participation in odor transduction.

  20. Role of Primary Cilia in Odontogenesis

    Czech Academy of Sciences Publication Activity Database

    Hampl, Marek; Celá, Petra; Szabo-Rogers, H. L.; Kunová Bosáková, M.; Dosedělová, Hana; Krejčí, P.; Buchtová, Marcela

    2017-01-01

    Roč. 96, č. 9 (2017), s. 965-974 ISSN 0022-0345 R&D Projects: GA MŠk EF15_003/0000460; GA ČR(CZ) GA17-14886S Institutional support: RVO:67985904 Keywords : craniofacial anomalies * growth/development * mineralized tissue/development Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Developmental biology Impact factor: 4.755, year: 2016

  1. Specialized Cilia in Mammalian Sensory Systems

    Directory of Open Access Journals (Sweden)

    Nathalie Falk

    2015-09-01

    Full Text Available Cilia and flagella are highly conserved and important microtubule-based organelles that project from the surface of eukaryotic cells and act as antennae to sense extracellular signals. Moreover, cilia have emerged as key players in numerous physiological, developmental, and sensory processes such as hearing, olfaction, and photoreception. Genetic defects in ciliary proteins responsible for cilia formation, maintenance, or function underlie a wide array of human diseases like deafness, anosmia, and retinal degeneration in sensory systems. Impairment of more than one sensory organ results in numerous syndromic ciliary disorders like the autosomal recessive genetic diseases Bardet-Biedl and Usher syndrome. Here we describe the structure and distinct functional roles of cilia in sensory organs like the inner ear, the olfactory epithelium, and the retina of the mouse. The spectrum of ciliary function in fundamental cellular processes highlights the importance of elucidating ciliopathy-related proteins in order to find novel potential therapies.

  2. Relying on the Information

    Directory of Open Access Journals (Sweden)

    TK YAYIN KURULU

    2013-11-01

    Full Text Available The editorial discusses internet filtering in the light of the optional internet packages for users, namely Family, Standard, Kids and Domestic, to be offered by the Information Technologies Board with the "Secure Internet Law" to take effect on August 22, 2011. Also sharing the hesitations about the objectivity of the application with the reader, editorial emphasizes an education system focused on breeding citizens who are not scared of relying on the information and who can, by themselves, decide whether information is harmful or not. References are made to the results of similar applications abroad while the press statement made by Turkish NGOs on the issue are included.

  3. Lack of cilia and differentiation defects in the liver of human foetuses with the Meckel syndrome.

    Science.gov (United States)

    Clotman, Frédéric; Libbrecht, Louis; Killingsworth, Murray C; Loo, Christine C K; Roskams, Tania; Lemaigre, Frédéric P

    2008-03-01

    Meckel syndrome is an autosomal-recessive disease characterized by a combination of renal cysts, anomalies of the central nervous system, polydactyly and ductal plate malformations (DPM), which are hepatic anomalies consisting of excessive and abnormal foetal biliary structures. Among the genomic loci associated with Meckel syndrome, mutations in four genes were recently identified. These genes code for proteins associated with primary cilia and are possibly involved in cell differentiation. The aim of the present work was to investigate the formation of the primary cilia and the differentiation of the hepatic cells in foetuses with Meckel syndrome. Sections of livers from human foetuses with Meckel syndrome were analysed by immunofluorescence, immunohistochemistry and electron microscopy. The primary cilia of the biliary cells were absent in some Meckel foetuses, but were present in others. In addition, defects in hepatic differentiation were observed in Meckel livers, as evidenced by the presence of hybrid cells co-expressing hepatocytic and biliary markers. Defects in cilia formation occur in some Meckel livers, and most cases show DPM associated with abnormal hepatic cell differentiation. Because differentiation precedes the formation of the cilia during liver development, we propose that defective differentiation may constitute the initial defect in the liver of Meckel syndrome foetuses.

  4. Particle sorting by Paramecium cilia arrays.

    Science.gov (United States)

    Mayne, Richard; Whiting, James G H; Wheway, Gabrielle; Melhuish, Chris; Adamatzky, Andrew

    Motile cilia are cell-surface organelles whose purposes, in ciliated protists and certain ciliated metazoan epithelia, include generating fluid flow, sensing and substance uptake. Certain properties of cilia arrays, such as beating synchronisation and manipulation of external proximate particulate matter, are considered emergent, but remain incompletely characterised despite these phenomena having being the subject of extensive modelling. This study constitutes a laboratory experimental characterisation of one of the emergent properties of motile cilia: manipulation of adjacent particulates. The work demonstrates through automated videomicrographic particle tracking that interactions between microparticles and somatic cilia arrays of the ciliated model organism Paramecium caudatum constitute a form of rudimentary 'sorting'. Small particles are drawn into the organism's proximity by cilia-induced fluid currents at all times, whereas larger particles may be held immobile at a distance from the cell margin when the cell generates characteristic feeding currents in the surrounding media. These findings can contribute to the design and fabrication of biomimetic cilia, with potential applications to the study of ciliopathies. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A Parallel Modular Biomimetic Cilia Sorting Platform

    Directory of Open Access Journals (Sweden)

    James G. H. Whiting

    2018-03-01

    Full Text Available The aquatic unicellular organism Paramecium caudatum uses cilia to swim around its environment and to graze on food particles and bacteria. Paramecia use waves of ciliary beating for locomotion, intake of food particles and sensing. There is some evidence that Paramecia pre-sort food particles by discarding larger particles, but intake the particles matching their mouth cavity. Most prior attempts to mimic cilia-based manipulation merely mimicked the overall action rather than the beating of cilia. The majority of massive-parallel actuators are controlled by a central computer; however, a distributed control would be far more true-to-life. We propose and test a distributed parallel cilia platform where each actuating unit is autonomous, yet exchanging information with its closest neighboring units. The units are arranged in a hexagonal array. Each unit is a tileable circuit board, with a microprocessor, color-based object sensor and servo-actuated biomimetic cilia actuator. Localized synchronous communication between cilia allowed for the emergence of coordinated action, moving different colored objects together. The coordinated beating action was capable of moving objects up to 4 cm/s at its highest beating frequency; however, objects were moved at a speed proportional to the beat frequency. Using the local communication, we were able to detect the shape of objects and rotating an object using edge detection was performed; however, lateral manipulation using shape information was unsuccessful.

  6. 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.

  7. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu–Gli protein complexes

    OpenAIRE

    Tukachinsky, Hanna; Lopez, Lyle V.; Salic, Adrian

    2010-01-01

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu–Gli complexes to cilia, suggesting a model in wh...

  8. Reptin/Ruvbl2 is a Lrrc6/Seahorse interactor essential for cilia motility.

    Science.gov (United States)

    Zhao, Lu; Yuan, Shiaulou; Cao, Ying; Kallakuri, Sowjanya; Li, Yuanyuan; Kishimoto, Norihito; DiBella, Linda; Sun, Zhaoxia

    2013-07-30

    Primary ciliary dyskinesia (PCD) is an autosomal recessive disease caused by defective cilia motility. The identified PCD genes account for about half of PCD incidences and the underlying mechanisms remain poorly understood. We demonstrate that Reptin/Ruvbl2, a protein known to be involved in epigenetic and transcriptional regulation, is essential for cilia motility in zebrafish. We further show that Reptin directly interacts with the PCD protein Lrrc6/Seahorse and this interaction is critical for the in vivo function of Lrrc6/Seahorse in zebrafish. Moreover, whereas the expression levels of multiple dynein arm components remain unchanged or become elevated, the density of axonemal dynein arms is reduced in reptin(hi2394) mutants. Furthermore, Reptin is highly enriched in the cytosol and colocalizes with Lrrc6/Seahorse. Combined, these results suggest that the Reptin-Lrrc6/Seahorse complex is involved in dynein arm formation. We also show that although the DNA damage response is induced in reptin(hi2394) mutants, it remains unchanged in cilia biogenesis mutants and lrrc6/seahorse mutants, suggesting that increased DNA damage response is not intrinsic to ciliary defects and that in vertebrate development, Reptin functions in multiple processes, both cilia specific and cilia independent.

  9. 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...

  10. Regeneration of cilia in heavily irradiated sea urchin embryos

    International Nuclear Information System (INIS)

    Rustad, R.C.

    1981-01-01

    Cilia were removed from blastulae, gastrulae, and plutei of the sea urchins Arbacia punctulata and Lytechinus variegatus by shaking the embryos in hypertonic media. Exposure to 50 krad (and in some experiments 100 krad) of γ radiation either before or after deciliation had no effect on the time of appearance of regenerating cilia. There were no visually obvious differences in the rate of growth of the cilia in control and irradiated embryos. The cilia commenced beating at the same time, but the initial beating sometimes seemed less vigorous following irradiation. The data support the hypothesis that radiation has no major effect on the assembly from mature basal bodies of the microtubules of cilia

  11. Transport and mixing by artificial cilia

    NARCIS (Netherlands)

    Baltussen, M.G.H.M.

    2012-01-01

    Microfluidic analysis devices are becoming more common as a tool for clinical analysis. In these devices fluid transport and mixing of multiple components are common tasks. A possible way of achieving these tasks can be found in nature, where small hairs, named cilia, are found on micro-organisms

  12. Neuronal NOS localises to human airway cilia.

    Science.gov (United States)

    Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M

    2015-01-30

    Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. IFT46 plays an essential role in cilia development

    Science.gov (United States)

    Lee, Mi-Sun; Hwang, Kyu-Seok; Oh, Hyun-Woo; Ji-Ae, Kim; Kim, Hyun-Taek; Cho, Hyun-Soo; Lee, Jeong-Ju; Ko, Je Yeong; Choi, Jung-Hwa; Jeong, Yun-Mi; You, Kwan-Hee; Kim, Joon; Park, Doo-Sang; Nam, Ki-Hoan; Aizawa, Shinichi; Kiyonari, Hiroshi; Shioi, Go; Park, Jong-Hoon; Zhou, Weibin; Kim, Nam-Soon; Kim, Cheol-Hee

    2015-01-01

    Cilia are microtubule-based structures that project into the extracellular space. Ciliary defects are associated with several human diseases, including polycystic kidney disease, primary ciliary dyskinesia, left-right axis patterning, hydrocephalus and retinal degeneration. However, the genetic and cellular biological control of ciliogenesis remains poorly understood. The IFT46 is one of the highly conserved intraflagellar transport complex B proteins. In zebrafish, ift46 is expressed in various ciliated tissues such as Kupffer’s vesicle, pronephric ducts, ears and spinal cord. We show that ift46 is localized to the basal body. Knockdown of ift46 gene results in multiple phenotypes associated with various ciliopathies including kidney cysts, pericardial edema and ventral axis curvature. In ift46 morphants, cilia in kidney and spinal canal are shortened and abnormal. Similar ciliary defects are observed in otic vesicles, lateral line hair cells, olfactory pits, but not in Kupffer’s vesicle. To explore the functions of Ift46 during mouse development, we have generated Ift46 knock-out mice. The Ift46 mutants have developmental defects in brain, neural tube and heart. In particular Ift46(−/−) homozygotes displays randomization of the embryo heart looping, which is a hallmark of defective left-right (L/R) axis patterning. Taken together, our results demonstrated that IFT46 has an essential role in vertebrate ciliary development. PMID:25722189

  14. Directed Fluid Transport and Mixing with Biomimetic Cilia Arrays

    Science.gov (United States)

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

    2009-03-01

    We present results on the long-range, directed fluid transport and fluidic mixing produced by the collective beating of arrays of biomimetic cilia. These artificial cilia are arrays of free-standing nanorods roughly the size of biological cilia, which we fabricate from a polymer-magnetic nanoparticle composite material and actuate with permanent magnets to mimic biological cilia. Biological cilia have evolved to produce microscale fluid transport and are increasingly being recognized as critical components in a wide range of biological systems. However, despite much effort cilia generated fluid flows remain an area of active study. In the last decade, cilia-driven fluid flow in the embryonic node of vertebrates has been implicated as the initial left-right symmetry breaking event in these embryos. With silia we generate directional fluid transport by mimicking the tilted conical beating of these nodal cilia. By seeding fluorescent microparticles into the fluid we have noted the existence of two distinct flow regimes. The fluid flow is directional and coherent above the cilia tips, while between the cilia tips and the floor particle motion is complicated and suggestive of chaotic advection.

  15. Magnetically-actuated artificial cilia for microfluidic propulsion

    NARCIS (Netherlands)

    Khaderi, S.N.; Craus, C.B.; Hussong, J.; Schorr, N.; Belardi, J.; Westerweel, J.; Prucker, O.; Ruehe, J.; Toonder, den J.M.J.; Onck, P.R.

    2011-01-01

    In this paper we quantitatively analyse the performance of magnetically-driven artificial cilia for labon-a-chip applications. The artificial cilia are fabricated using thin polymer films with embeddedmagnetic nano-particles and their deformation is studied under different external magnetic fields

  16. Magnetically-actuated artificial cilia for microfluidic propulsion

    NARCIS (Netherlands)

    Khaderi, S. N.; Craus, C. B.; Hussong, J.; Schorr, N.; Belardi, J.; Westerweel, J.; Prucker, O.; Ruehe, J.; den Toonder, J.M.J.; Onck, P. R.

    2011-01-01

    In this paper we quantitatively analyse the performance of magnetically-driven artificial cilia for lab-on-a-chip applications. The artificial cilia are fabricated using thin polymer films with embedded magnetic nano-particles and their deformation is studied under different external magnetic fields

  17. Artificial cilia for microparticle manipulation and anti-fouling

    NARCIS (Netherlands)

    Zhang, S.; Wang, Y.; den Toonder, J.M.J.

    2016-01-01

    The (bio-)fouling of surfaces submerged in liquid forms serious a problem for many applications. One inspiration to address this issue is the use of cilia which, in nature, are found very effective in particle manipulation. We have fabricated magnetically actuated artificial cilia (MAAC) using a

  18. 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.

  19. 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.

  20. 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.

  1. Evolution: Tracing the origins of centrioles, cilia, and flagella.

    Science.gov (United States)

    Carvalho-Santos, Zita; Azimzadeh, Juliette; Pereira-Leal, José B; Bettencourt-Dias, Mónica

    2011-07-25

    Centrioles/basal bodies (CBBs) are microtubule-based cylindrical organelles that nucleate the formation of centrosomes, cilia, and flagella. CBBs, cilia, and flagella are ancestral structures; they are present in all major eukaryotic groups. Despite the conservation of their core structure, there is variability in their architecture, function, and biogenesis. Recent genomic and functional studies have provided insight into the evolution of the structure and function of these organelles.

  2. The primary cilium as a multiple cellular signaling scaffold in development and disease

    Directory of Open Access Journals (Sweden)

    Hyuk Wan Ko*

    2012-08-01

    Full Text Available Primary cilia, single hair-like appendage on the surface of themost mammalian cells, were once considered to be vestigialcellular organelles for a past century because of their tinystructure and unknown function. Although they lack ancestralmotility function of cilia or flagella, they share common groundwith multiciliated motile cilia and flagella on internal structuresuch as microtubule based nine outer doublets nucleated from thebase of mother centrioles called basal body. Making cilia,ciliogenesis, in cells depends on the cell cycle stage due to reuseof centrioles for cell division forming mitotic spindle pole (Mphase and assembling cilia from basal body (starting G1 phaseand maintaining most of interphase. Ciliary assembly requiredtwo conflicting processes such as assembly and disassembly andbalance between these two processes determines the length ofcilia. Both process required highly conserved transport system tosupply needed substance to grow tip of cilia and bring ciliaryturnover product back to the base of cilia using motor protein,kinesin and dynein, and transport protein complex, IFT particles.Disruption of ciliary structure or function causes multiple humandisorder called ciliopathies affecting disease of diverse ciliatedtissues ranging from eye, kidney, respiratory tract and brain.Recent explosion of research on the primary cilia and theirinvolvement on animal development and disease attracts scientificinterest on how extensively the function of cilia related to specificcell physiology and signaling pathway. In this review, I introducegeneral features of primary cilia and recent progress inunderstanding of the ciliary length control and signaling pathwaystransduced through primary cilia in vertebrates.

  3. 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

  4. Asynchronous beating of cilia enhances particle capture rate

    Science.gov (United States)

    Ding, Yang; Kanso, Eva

    2014-11-01

    Many aquatic micro-organisms use beating cilia to generate feeding currents and capture particles in surrounding fluids. One of the capture strategies is to ``catch up'' with particles when a cilium is beating towards the overall flow direction (effective stroke) and intercept particles on the downstream side of the cilium. Here, we developed a 3D computational model of a cilia band with prescribed motion in a viscous fluid and calculated the trajectories of the particles with different sizes in the fluid. We found an optimal particle diameter that maximizes the capture rate. The flow field and particle motion indicate that the low capture rate of smaller particles is due to the laminar flow in the neighbor of the cilia, whereas larger particles have to move above the cilia tips to get advected downstream which decreases their capture rate. We then analyzed the effect of beating coordination between neighboring cilia on the capture rate. Interestingly, we found that asynchrony of the beating of the cilia can enhance the relative motion between a cilium and the particles near it and hence increase the capture rate.

  5. 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.

  6. A single magnetic nanocomposite cilia force sensor

    KAUST Repository

    Alfadhel, Ahmed; Khan, Mohammed Asadullah; Cardoso, Susana; Kosel, Jü rgen

    2016-01-01

    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.

  7. Genetics Home Reference: primary ciliary dyskinesia

    Science.gov (United States)

    ... primary ciliary dyskinesia also have year-round nasal congestion and a chronic cough. Chronic respiratory tract infections ... likely due to abnormal cilia in the fallopian tubes. Another feature of primary ciliary dyskinesia is recurrent ...

  8. The spatiotemporal organization of cilia activity drives multiscale circular flows of mucus in reconstituted human bronchial epithelium

    Science.gov (United States)

    Loiseau, Etienne; Gras, Delphine; Chanez, Pascal; Viallat, Annie

    2017-11-01

    Chronic respiratory diseases affect hundreds of millions of people worldwide. The bronchial epithelium is the first barrier to protect the respiratory tract via an innate mechanism called mucociliary clearance. It consists in the active transport of a sticky fluid, the mucus, via a myriad of cilia at the epithelial surface of the airways. The mucus traps inhaled pathogens and the protective role of the mucociliary clearance relies on the ability of the cilia to self-organize and coordinate their beating to transport the mucus over the full bronchial tree till its elimination through swallowing or expectoration. Despite a rich corpus of clinical studies, chronic respiratory diseases remain poorly understood and quantitative biophysical studies are still missing. Here we will present the physical mechanisms underlying the mucociliary transport. We will show how the cilia self-organize during the ciliogenesis and how the coordination of their beating direction leads to the formation of fluid flow patterns at the macroscopic scale. Finally, we will discuss the role of long range hydrodynamics interactions in this intricate coupled system. ANR MUCOCIL project, Grant ANR-13-BSV5-0015 and European Union's Seventh Framework Programme (FP7/2007-2013) under REA Grant agreement n. PCOFUND-GA-2013-609102.

  9. Variations in the ultrastructure of human nasal cilia including abnormalities found in retinitis pigmentosa.

    OpenAIRE

    Fox, B; Bull, T B; Arden, G B

    1980-01-01

    The electron microscopic structure of cilia from the inferior turbinate of the nose was studied in 12 adults, four with chronic sinusitis, one with allergic rhinitis, two with bronchiectasis, three with deviated nasal septum, and two normals. The changes are compared with those found in nasal cilia in 14 patients with retinitis pigmentosa. There were compound cilia in the seven cases with chronic sinusitis, allergic rhinitis, and bronchiectasis but, apart from this, the structure of the cilia...

  10. Centrioles, centrosomes, and cilia in health and disease.

    Science.gov (United States)

    Nigg, Erich A; Raff, Jordan W

    2009-11-13

    Centrioles are barrel-shaped structures that are essential for the formation of centrosomes, cilia, and flagella. Here we review recent advances in our understanding of the function and biogenesis of these organelles, and we emphasize their connection to human disease. Deregulation of centrosome numbers has long been proposed to contribute to genome instability and tumor formation, whereas mutations in centrosomal proteins have recently been genetically linked to microcephaly and dwarfism. Finally, structural or functional centriole aberrations contribute to ciliopathies, a variety of complex diseases that stem from the absence or dysfunction of cilia.

  11. 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.

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

    Science.gov (United States)

    Yano, Junji; Valentine, Megan S.; Van Houten, Judith L.

    2015-01-01

    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. PMID:26230712

  13. The Roles of Primary Cilia in Cardiovascular System

    Science.gov (United States)

    2015-10-01

    vascular hypertension. Int J Vasc Med 2011; 2011: 376281. Received: December 10, 2014 Revised: June 09, 2015 Accepted: June 09, 2015 Graphical Abstract Current...Hypertension Reviews, 2015, Vol. 11, No. 1 i Graphical Abstract Current Hypertension Reviews, 2015, Vol. 11, No. 1 00 Vascular

  14. 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.

  15. Centrioles want to move out and make cilia.

    Science.gov (United States)

    Pearson, Chad G; Culver, Brady P; Winey, Mark

    2007-09-01

    Cilia formation in mammalian cells requires basal bodies that are either derived from centrioles that transition from their cytoplasmic role in centrosome organization or that form en masse in multiciliated cells. Several recent studies have begun to uncover the links between centriole duplication and their transformation to basal bodies.

  16. Simulation of Micro-fluidic Mixing Using Artificial Cilia

    NARCIS (Netherlands)

    Baltussen, M.G.H.M.; Toonder, den J.M.J.; Bos, F.M.; Anderson, P.D.

    2008-01-01

    Our recently developed micro-mixer based on artificial cilia shows good mixing over relatively short lengthscales[1], which was unexpected. In this paper we present a numerical tool and use it to simulate the micromixerto explain the observed effects. The tool consists of a fully coupled fluid-solid

  17. Microtubules Enable the Planar Cell Polarity of Airway Cilia

    Science.gov (United States)

    Vladar, Eszter K.; Bayly, Roy D.; Sangoram, Ashvin; Scott, Matthew P.; Axelrod, Jeffrey D.

    2012-01-01

    Summary Background Airway cilia must be physically oriented along the longitudinal tissue axis for concerted, directional motility that is essential for proper mucociliary clearance. Results We show that Planar Cell Polarity (PCP) signaling specifies directionality and orients respiratory cilia. Within all airway epithelial cells a conserved set of PCP proteins shows interdependent, asymmetric junctional localization; non-autonomous signaling coordinates polarization between cells; and a polarized microtubule (MT) network is likely required for asymmetric PCP protein localization. We find that basal bodies dock after polarity of PCP proteins is established, are polarized nearly simultaneously, and refinement of basal body/cilium orientation continues during airway epithelial development. Unique to mature multiciliated cells, we identify PCP-regulated, planar polarized MTs that originate from basal bodies and interact, via their plus ends, with membrane domains associated with the PCP proteins Frizzled and Dishevelled. Disruption of MTs leads to misoriented cilia. Conclusions A conserved PCP pathway orients airway cilia by communicating polarity information from asymmetric membrane domains at the apical junctions, through MTs, to orient the MT and actin based network of ciliary basal bodies below the apical surface. PMID:23122850

  18. Centrioles initiate cilia assembly but are dispensable for maturation and maintenance in C. elegans.

    Science.gov (United States)

    Serwas, Daniel; Su, Tiffany Y; Roessler, Max; Wang, Shaohe; Dammermann, Alexander

    2017-06-05

    Cilia are cellular projections that assemble on centriole-derived basal bodies. While cilia assembly is absolutely dependent on centrioles, it is not known to what extent they contribute to downstream events. The nematode C. elegans provides a unique opportunity to address this question, as centrioles do not persist at the base of mature cilia. Using fluorescence microscopy and electron tomography, we find that centrioles degenerate early during ciliogenesis. The transition zone and axoneme are not completely formed at this time, indicating that cilia maturation does not depend on intact centrioles. The hydrolethalus syndrome protein HYLS-1 is the only centriolar protein known to remain at the base of mature cilia and is required for intraflagellar transport trafficking. Surprisingly, targeted degradation of HYLS-1 after initiation of ciliogenesis does not affect ciliary structures. Taken together, our results indicate that while centrioles are essential to initiate cilia formation, they are dispensable for cilia maturation and maintenance. © 2017 Serwas et al.

  19. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes.

    Science.gov (United States)

    Tukachinsky, Hanna; Lopez, Lyle V; Salic, Adrian

    2010-10-18

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu-Gli complexes to cilia, suggesting a model in which Smo activates Gli by relieving inhibition by SuFu. In support of this model, we find that Hh causes rapid dissociation of the SuFu-Gli complex, thus allowing Gli to enter the nucleus and activate transcription. Activation of protein kinase A (PKA), an inhibitor of Hh signaling, blocks ciliary localization of SuFu-Gli complexes, which in turn prevents their dissociation by signaling. Our results support a simple mechanism in which Hh signals at vertebrate cilia cause dissociation of inactive SuFu-Gli complexes, a process inhibited by PKA.

  20. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu–Gli protein complexes

    Science.gov (United States)

    Tukachinsky, Hanna; Lopez, Lyle V.

    2010-01-01

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu–Gli complexes to cilia, suggesting a model in which Smo activates Gli by relieving inhibition by SuFu. In support of this model, we find that Hh causes rapid dissociation of the SuFu–Gli complex, thus allowing Gli to enter the nucleus and activate transcription. Activation of protein kinase A (PKA), an inhibitor of Hh signaling, blocks ciliary localization of SuFu–Gli complexes, which in turn prevents their dissociation by signaling. Our results support a simple mechanism in which Hh signals at vertebrate cilia cause dissociation of inactive SuFu–Gli complexes, a process inhibited by PKA. PMID:20956384

  1. Functional aspects of cilia and tumor suppressors

    NARCIS (Netherlands)

    Basten, S.G.

    2013-01-01

    Sensing the cellular environment and responding accordingly is pivotal for tissue development and homeostasis. One cellular structure that functions almost exclusively as a sensory organelle is the nearly ubiquitously present primary cilium, that has been implicated in orchestrating cellular

  2. Voltage-gated calcium channels of Paramecium cilia.

    Science.gov (United States)

    Lodh, Sukanya; Yano, Junji; Valentine, Megan S; Van Houten, Judith L

    2016-10-01

    Paramecium cells swim by beating their cilia, and make turns by transiently reversing their power stroke. Reversal is caused by Ca 2+ entering the cilium through voltage-gated Ca 2+ (Ca V ) channels that are found exclusively in the cilia. As ciliary Ca 2+ levels return to normal, the cell pivots and swims forward in a new direction. Thus, the activation of the Ca V channels causes cells to make a turn in their swimming paths. For 45 years, the physiological characteristics of the Paramecium ciliary Ca V channels have been known, but the proteins were not identified until recently, when the P. tetraurelia ciliary membrane proteome was determined. Three Ca V α1 subunits that were identified among the proteins were cloned and confirmed to be expressed in the cilia. We demonstrate using RNA interference that these channels function as the ciliary Ca V channels that are responsible for the reversal of ciliary beating. Furthermore, we show that Pawn (pw) mutants of Paramecium that cannot swim backward for lack of Ca V channel activity do not express any of the three Ca V 1 channels in their ciliary membrane, until they are rescued from the mutant phenotype by expression of the wild-type PW gene. These results reinforce the correlation of the three Ca V channels with backward swimming through ciliary reversal. The PwB protein, found in endoplasmic reticulum fractions, co-immunoprecipitates with the Ca V 1c channel and perhaps functions in trafficking. The PwA protein does not appear to have an interaction with the channel proteins but affects their appearance in the cilia. © 2016. Published by The Company of Biologists Ltd.

  3. 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.

  4. Effect of Cilia Beat Frequency on Mucociliary Clearance

    Directory of Open Access Journals (Sweden)

    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.

  5. Betal-integrins in the primary cilium of MDCK cells potentiate fibronectin-induced Ca2+ signalling

    DEFF Research Database (Denmark)

    Prætorius, Helle; Prætorius, Jeppe; Nielsen, Søren

    2004-01-01

    observed that β1-integrin, α3-integrin, and perhaps α5-integrin were localized to the primary cilium of MDCK cells by combining lectin and immunofluorescence confocal microscopy. β1-Integrin was also colocalized with tubulin to the primary cilia of the rat renal collecting ducts, as well as to the cilia...

  6. Cilia are required for asymmetric nodal induction in the sea urchin embryo.

    Science.gov (United States)

    Tisler, Matthias; Wetzel, Franziska; Mantino, Sabrina; Kremnyov, Stanislav; Thumberger, Thomas; Schweickert, Axel; Blum, Martin; Vick, Philipp

    2016-08-23

    Left-right (LR) organ asymmetries are a common feature of metazoan animals. In many cases, laterality is established by a conserved asymmetric Nodal signaling cascade during embryogenesis. In most vertebrates, asymmetric nodal induction results from a cilia-driven leftward fluid flow at the left-right organizer (LRO), a ciliated epithelium present during gastrula/neurula stages. Conservation of LRO and flow beyond the vertebrates has not been reported yet. Here we study sea urchin embryos, which use nodal to establish larval LR asymmetry as well. Cilia were found in the archenteron of embryos undergoing gastrulation. Expression of foxj1 and dnah9 suggested that archenteron cilia were motile. Cilia were polarized to the posterior pole of cells, a prerequisite of directed flow. High-speed videography revealed rotating cilia in the archenteron slightly before asymmetric nodal induction. Removal of cilia through brief high salt treatments resulted in aberrant patterns of nodal expression. Our data demonstrate that cilia - like in vertebrates - are required for asymmetric nodal induction in sea urchin embryos. Based on these results we argue that the anterior archenteron represents a bona fide LRO and propose that cilia-based symmetry breakage is a synapomorphy of the deuterostomes.

  7. Fluid propulsion using magnetically-actuated artificial cilia : Experiments and simulations

    NARCIS (Netherlands)

    Khaderi, Syed; Hussong, Jeanette; Westerweel, Jerry; den Toonder, Jaap; Onck, Patrick

    2013-01-01

    We conducted a combined modelling and experimental approach to explore the underlying physical mechanisms responsible for fluid flow caused by magnetically-actuated plate-like artificial cilia. After independently calibrating the elastic and magnetic properties of the cilia, the model predictions

  8. Fluid propulsion using magnetically-actuated artificial cilia : experiments and simulations

    NARCIS (Netherlands)

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

    2013-01-01

    We conducted a combined modelling and experimental approach to explore the underlying physical mechanisms responsible for fluid flow caused by magnetically-actuated plate-like artificial cilia. After independently calibrating the elastic and magnetic properties of the cilia, the model predictions

  9. Cilia in the head of hornets: form and function.

    Science.gov (United States)

    Ishay, Jacob S; Plotkin, Marian; Ermakov, Natalya; Jongebloed, Willem L; Kalicharan, Dharamdajal; Bergman, David J

    2005-06-01

    In the head of the Oriental hornet, beneath the cuticle, there are plaques of hair cells. These are distributed throughout the upper front part of the head; to wit: in the region of the vertex (i.e., around and behind the ocelli), in the genae around and behind the compound eyes (the ommatidia), and in the region of the forehead or frons. These hair cells are arranged with their thin whip-like part (i.e., cilia) directed outward and morphologically fall into three distinct groups: type (a) thin elongated cilia connected to each other alongside by side-links; type (b) thin elongated cilia of which two or more interconnect at their distal ends via a delicate nerve fiber bearing a knob at its center; and type (c) shorter and thicker cilia that roughly resemble a triangular thorn and are also interconnected by a thin thread, which, however, bears a ball rather then a knob at its center. The knob in the one case and the ball in the other vary in their diameter, but in both instances the interconnecting elements, be they nerve fibers or threads, are seemingly multidirectional. Beneath the frons, in the region of the coronal suture, the hair cells (cilial plaques) are inwardly directed and bear a large trachea at their center. Presumably, the "weighted" cilial cells that are directed toward the exterior of the body aid the hornet in navigation and gravity determination whereas the inwardly directed ciliary cells may possibly serve in acoustic communication. Another element worthy of mention within the hair cells are yellow granules (yg). These yg's originate from the whip-like portion of the ciliary cells that are distributed beneath the frons plate, and also in the yellow stripes of the gastral cuticle. Conceivably, these yellow granules, in both cases, may play a role in the absorption and storage of solar energy. In summary, ciliary structures are involved in the hornet in gravity sensing, in acoustical communication and in light sensing, i.e., with some similarity

  10. Artificial cilia of magnetically tagged polymer nanowires for biomimetic mechanosensing

    International Nuclear Information System (INIS)

    Schroeder, P; Schotter, J; Shoshi, A; Eggeling, M; Brückl, H; Bethge, O; Hütten, A

    2011-01-01

    Polymeric nanowires of polypyrrole have been implemented as artificial cilia on giant-magneto-resistive multilayer sensors for a biomimetic sensing approach. The arrays were tagged with a magnetic material, the stray field of which changes relative to the underlying sensor as a consequence of mechanical stimuli which are delivered by a piezoactuator. The principle resembles balance sensing in mammals. Measurements of the sensor output voltage suggest a proof of concept at frequencies of around 190 kHz and a tag thickness of ∼300 nm. Characterization was performed by scanning electron microscopy and magnetic force microscopy. Micromagnetic and finite-element simulations were conducted to assess basic sensing aspects.

  11. 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.

  12. Centrioles are freed from cilia by severing prior to mitosis.

    Science.gov (United States)

    Parker, Jeremy D K; Hilton, Laura K; Diener, Dennis R; Rasi, M Qasim; Mahjoub, Moe R; Rosenbaum, Joel L; Quarmby, Lynne M

    2010-07-01

    Cilia are necessary for normal tissue development and homeostasis and are generally present during interphase, but not in mitosis. The precise mechanism of premitotic ciliary loss has been controversial, with data supporting either sequential disassembly through the transition zone or, alternatively, a severing event at the base of the cilia. Here we show by live cell imaging and immunofluorescence microscopy that resorbing flagella of Chlamydomonas leave remnants associated with the mother cell wall. We postulated that the remnants are the product of severing of doublet microtubules between the basal bodies and the flagellar transition zone, thereby freeing the centrioles to participate in spindle organization. We show via TEM that flagellar remnants are indeed flagellar transition zones encased in vesicles derived from the flagellar membrane. This transition zone vesicle can be lodged within the cell wall or it can be expelled into the environment. This process is observable in Chlamydomonas, first because the released flagellar remnants can remain associated with the cell by virtue of attachments to the cell wall, and second because the Chlamydomonas transition zone is particularly rich with electron-dense structure. However, release of basal bodies for spindle-associated function is likely to be conserved among the eukaryotes. 2010 Wiley-Liss, Inc.

  13. 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.

  14. Juxtaposed Color Halftoning Relying on Discrete Lines

    OpenAIRE

    Babaei, Vahid; Hersch, Roger

    2013-01-01

    Most halftoning techniques allow screen dots to overlap. They rely on the assumption that the inks are transparent, i.e. the inks do not scatter a significant portion of the light back to the air. However, many special effect inks such as metallic inks, iridescent inks or pigmented inks are not transparent. In order to create halftone images, halftone dots formed by such inks should be juxtaposed, i.e. printed side by side. We propose an efficient juxtaposed color halftoning technique for pla...

  15. An atom trap relying on optical pumping

    International Nuclear Information System (INIS)

    Bouyer, P.; Lemonde, P.; Ben Dahan, M.; Michaud, A.; Salomon, C.; Dalibard, J.

    1994-01-01

    We have investigated a new radiation pressure trap which relies on optical pumping and does not require any magnetic field. It employs six circularly polarized divergent beams and works on the red of a J g →J e = J g + 1 atomic transition with J g ≥1/2. We have demonstrated this trap with cesium atoms from a vapour cell using the 852 nm J g = 4→J e = 5 resonance transition. The trap contained up to 3.10 7 atoms in a cloud of 1/√e radius of 330 μm. (orig.)

  16. Bacteriology and treatment of infections in the upper and lower airways in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Alanin, Mikkel Christian

    2017-01-01

    The respiratory tract is lined with motile cilia that transport respiratory mucus. Primary ciliary dyskinesia (PCD) is a chronic genetic disease caused by mutations in genes responsible for ciliary structure and function. Non-functional airway cilia impair the mucociliary clearance (MCC), causing...

  17. Juxtaposed color halftoning relying on discrete lines.

    Science.gov (United States)

    Babaei, Vahid; Hersch, Roger D

    2013-02-01

    Most halftoning techniques allow screen dots to overlap. They rely on the assumption that the inks are transparent, i.e., the inks do not scatter a significant portion of the light back to the air. However, many special effect inks, such as metallic inks, iridescent inks, or pigmented inks, are not transparent. In order to create halftone images, halftone dots formed by such inks should be juxtaposed, i.e., printed side by side. We propose an efficient juxtaposed color halftoning technique for placing any desired number of colorant layers side by side without overlapping. The method uses a monochrome library of screen elements made of discrete lines with rational thicknesses. Discrete line juxtaposed color halftoning is performed efficiently by multiple accesses to the screen element library.

  18. Synchronization and Collective Dynamics of Flagella and Cilia as Hydrodynamically Coupled Oscillators

    Science.gov (United States)

    Uchida, Nariya; Golestanian, Ramin; Bennett, Rachel R.

    2017-10-01

    Cooperative motion of flagella and cilia faciliates swimming of microorganisms and material transport in the body of multicellular organisms. Using minimal models, we address the roles of hydrodynamic interaction in synchronization and collective dynamics of flagella and cilia. Collective synchronization of bacterial flagella is studied with a model of bacterial carpets. Cilia and eukaryotic flagella are characterized by periodic modulation of their driving forces, which produces various patterns of two-body synchronization and metachronal waves. Long-range nature of the interaction introduces novel features in the dynamics of these model systems. The flagella of a swimmer synchronize also by a viscous drag force mediated through the swimmer's body. Recent advance in experimental studies of the collective dynamics of flagella, cilia and related artificial systems are summarized.

  19. 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

    to such determination. We previously identified GALNT11 as a candidate disease gene in a patient with heterotaxy, and now demonstrate, in Xenopus tropicalis, that galnt11 activates Notch signalling. GALNT11 O-glycosylates human NOTCH1 peptides in vitro, thereby supporting a mechanism of Notch activation either...... by increasing ADAM17-mediated ectodomain shedding of the Notch receptor or by modification of specific EGF repeats. We further developed a quantitative live imaging technique for Xenopus left-right organizer cilia and show that Galnt11-mediated Notch1 signalling modulates the spatial distribution and ratio...... 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...

  20. Caenorhabditis elegans as a model to study renal development and disease: sexy cilia.

    Science.gov (United States)

    Barr, Maureen M

    2005-02-01

    The nematode Caenorhabditis elegans has no kidney per se, yet "the worm" has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases.

  1. Variations in the ultrastructure of human nasal cilia including abnormalities found in retinitis pigmentosa.

    Science.gov (United States)

    Fox, B; Bull, T B; Arden, G B

    1980-01-01

    The electron microscopic structure of cilia from the inferior turbinate of the nose was studied in 12 adults, four with chronic sinusitis, one with allergic rhinitis, two with bronchiectasis, three with deviated nasal septum, and two normals. The changes are compared with those found in nasal cilia in 14 patients with retinitis pigmentosa. There were compound cilia in the seven cases with chronic sinusitis, allergic rhinitis, and bronchiectasis but, apart from this, the structure of the cilia was similar in all 12 cases. There were variations in the microtubular pattern in about 4% of cilia, dynein arms were not seen in 4%, and in the rest an average of 5-6 dynein arms were seen in each cilium. The orientation of the cilia was 0 to 90 degrees. In the retinitis pigmentosa patients there was a highly significant increase in cilial abnormalities. The establishment on a quantitative basis of the variations in normal structure of nasal cilila facilitated the recognition of an association between cilial abnormalities and retinitis pigmentosa and should help in the identification of associations that may exist between cilial abnormalities and other diseases. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 7 Fig. 8 PMID:7400333

  2. Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic Fibrosis.

    Science.gov (United States)

    Blue, Elizabeth; Louie, Tin L; Chong, Jessica X; Hebbring, Scott J; Barnes, Kathleen C; Rafaels, Nicholas M; Knowles, Michael R; Gibson, Ronald L; Bamshad, Michael J; Emond, Mary J

    2018-04-01

    Cystic fibrosis, like primary ciliary dyskinesia, is an autosomal recessive disorder characterized by abnormal mucociliary clearance and obstructive lung disease. We hypothesized that genes underlying the development or function of cilia may modify lung disease severity in persons with cystic fibrosis. To test this hypothesis, we compared variants in 93 candidate genes in both upper and lower tertiles of lung function in a large cohort of children and adults with cystic fibrosis with those of a population control dataset. Variants within candidate genes were tested for association using the SKAT-O test, comparing cystic fibrosis cases defined by poor (n = 127) or preserved (n = 127) lung function with population controls (n = 3,269 or 3,148, respectively). Associated variants were then tested for association with related phenotypes in independent datasets. Variants in DNAH14 and DNAAF3 were associated with poor lung function in cystic fibrosis, whereas variants in DNAH14 and DNAH6 were associated with preserved lung function in cystic fibrosis. Associations between DNAH14 and lung function were replicated in disease-related phenotypes characterized by obstructive lung disease in adults. Genetic variants within DNAH6, DNAH14, and DNAAF3 are associated with variation in lung function among persons with cystic fibrosis.

  3. Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport

    OpenAIRE

    Blacque, Oliver E.; Reardon, Michael J.; Li, Chunmei; McCarthy, Jonathan; Mahjoub, Moe R.; Ansley, Stephen J.; Badano, Jose L.; Mah, Allan K.; Beales, Philip L.; Davidson, William S.; Johnsen, Robert C.; Audeh, Mark; Plasterk, Ronald H.A.; Baillie, David L.; Katsanis, Nicholas

    2004-01-01

    Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Impor...

  4. The Centrioles, Centrosomes, Basal Bodies, and Cilia of Drosophila melanogaster.

    Science.gov (United States)

    Lattao, Ramona; Kovács, Levente; Glover, David M

    2017-05-01

    Centrioles play a key role in the development of the fly. They are needed for the correct formation of centrosomes, the organelles at the poles of the spindle that can persist as microtubule organizing centers (MTOCs) into interphase. The ability to nucleate cytoplasmic microtubules (MTs) is a property of the surrounding pericentriolar material (PCM). The centriole has a dual life, existing not only as the core of the centrosome but also as the basal body, the structure that templates the formation of cilia and flagellae. Thus the structure and functions of the centriole, the centrosome, and the basal body have an impact upon many aspects of development and physiology that can readily be modeled in Drosophila Centrosomes are essential to give organization to the rapidly increasing numbers of nuclei in the syncytial embryo and for the spatially precise execution of cell division in numerous tissues, particularly during male meiosis. Although mitotic cell cycles can take place in the absence of centrosomes, this is an error-prone process that opens up the fly to developmental defects and the potential of tumor formation. Here, we review the structure and functions of the centriole, the centrosome, and the basal body in different tissues and cultured cells of Drosophila melanogaster , highlighting their contributions to different aspects of development and cell division. Copyright © 2017 Lattao et al.

  5. Discrete cilia modelling with singularity distributions: application to the embryonic node and the airway surface liquid.

    Science.gov (United States)

    Smith, D J; Gaffney, E A; Blake, J R

    2007-07-01

    We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous 'singularity models' is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a 'posterior tilt,' and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 mum/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this

  6. 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

    Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with the abnormal function of motile cilia. Approximately half of individuals with PCD also have alterations in the left-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...

  7. 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.

  8. From single cilia to collective waves in human airway ciliated tissues

    Science.gov (United States)

    Cicuta, Pietro; Chioccioli, Maurizio; Feriani, Luigi; Pellicciotta, Nicola; Kotar, Jurij

    I will present experimental results on activity of motile cilia on various scales: from waveforms on individual cilia to the synchronised motion in cilia carpets of airway cells. Model synthetic experiments have given us an understanding of how cilia could couple with each other through forces transmitted by the fluid, and thus coordinate to beat into well organized waves (previous work is reviewed in Annu. Rev. Condens. Matter Phys. 7, 1-26 (2016)). Working with live imaging of airway human cells at the different scales, we can now test whether the biological system satisfies the ``simple'' behavior expected of the fluid flow coupling, or if other factors of mechanical forces transmission need to be accounted for. In general being able to link from the scale of molecular biological activity up to the phenomenology of collective dynamics requires to understand the relevant physical mechanism. This understanding then allows informed diagnostics (and perhaps therapeutic) approaches to a variety of diseases where mucociliary clearance in the airways is compromised. We have started exploring particularly cystic fibrosis, where the rheological properties of the mucus are affected and prevent efficient cilia synchronization. ERC Grant HydroSync.

  9. Cilia-driven fluid flow as an epigenetic cue for otolith biomineralization on sensory hair cells of the inner ear.

    Science.gov (United States)

    Yu, Xianwen; Lau, Doreen; Ng, Chee Peng; Roy, Sudipto

    2011-02-01

    Ciliary motility is necessary for many developmental and physiological processes in animals. In zebrafish, motile cilia are thought to be required for the deposition of otoliths, which comprise crystals of protein and calcium carbonate, on hair cells of the inner ear. The identity of the motile cilia and their role in otolith biogenesis, however, remain controversial. Here, we show that the ear vesicle differentiates numerous motile cilia, the spatial distribution of which changes as a function of the expression pattern of the ciliogenic gene foxj1b. By contrast, the hair cells develop immotile kinocilia that serve as static tethers for otolith crystallization. In ears devoid of all cilia, otoliths can form but they are of irregular shapes and sizes and appear to attach instead to the hair cell apical membranes. Moreover, overproduction of motile cilia also disrupts otolith deposition through sustained agitation of the precursor particles. Therefore, the correct spatial and temporal distribution of the motile cilia is crucial for proper otolith formation. Our findings support the view that the hair cells express a binding factor for the otolith precursors, while the motile cilia ensure that the precursors do not sediment prematurely and are efficiently directed towards the hair cells. We also provide evidence that the kinocilia are modified motile cilia that depend on Foxj1b for their differentiation. We propose that in hair cells, a Foxj1b-dependent motile ciliogenic program is altered by the proneural Atoh proteins to promote the differentiation of immotile kinocilia.

  10. 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

    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

  11. 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.

  12. 3D structure of eukaryotic flagella/cilia by cryo-electron tomography.

    Science.gov (United States)

    Ishikawa, Takashi

    2013-01-01

    Flagella/cilia are motile organelles with more than 400 proteins. To understand the mechanism of such complex systems, we need methods to describe molecular arrange-ments and conformations three-dimensionally in vivo. Cryo-electron tomography enabled us such a 3D structural analysis. Our group has been working on 3D structure of flagella/cilia using this method and revealed highly ordered and beautifully organized molecular arrangement. 3D structure gave us insights into the mechanism to gener-ate bending motion with well defined waveforms. In this review, I summarize our recent structural studies on fla-gella/cilia by cryo-electron tomography, mainly focusing on dynein microtubule-based ATPase motor proteins and the radial spoke, a regulatory protein complex.

  13. Immotile cilia syndrome: A recombinant family at HLA-linked gene locus

    Energy Technology Data Exchange (ETDEWEB)

    Gasparini, P.; Grifa, A.; Oggiano, N.; Fabbrizzi, E.; Giorgi, P.L. [Univsita di Ancona (Israel)

    1994-02-15

    The immotile-cilia syndrome (ICS) is an autosomal recessive trait of congenital dismobility or even complete immobility of cilia in the ciliated epithelia (MIM 244400). Recurrent upper respiratory infections in early childhood are the most common clinical findings. Recently a disease locus was mapped by sib pair analysis in two unrelated families on 6p tightly linked to HLA class II loci, such as DR and DQ. In order to confirm this assignment and to test the presence of possible heterogeneity, the authors analyzed several ICS families utilizing DNA makers of HLA class II region. Here they report the identification of a recombinant family at this locus. 3 refs., 1 fig.

  14. Alternative Fuels Data Center: Colorado Airport Relies on Natural Gas

    Science.gov (United States)

    Fueling Stations Colorado Airport Relies on Natural Gas Fueling Stations to someone by E-mail Share Alternative Fuels Data Center: Colorado Airport Relies on Natural Gas Fueling Stations on Facebook Tweet about Alternative Fuels Data Center: Colorado Airport Relies on Natural Gas Fueling Stations on

  15. The role of hair cells, cilia and ciliary motility in otolith formation in the zebrafish otic vesicle.

    Science.gov (United States)

    Stooke-Vaughan, Georgina A; Huang, Peng; Hammond, Katherine L; Schier, Alexander F; Whitfield, Tanya T

    2012-05-01

    Otoliths are biomineralised structures required for the sensation of gravity, linear acceleration and sound in the zebrafish ear. Otolith precursor particles, initially distributed throughout the otic vesicle lumen, become tethered to the tips of hair cell kinocilia (tether cilia) at the otic vesicle poles, forming two otoliths. We have used high-speed video microscopy to investigate the role of cilia and ciliary motility in otolith formation. In wild-type ears, groups of motile cilia are present at the otic vesicle poles, surrounding the immotile tether cilia. A few motile cilia are also found on the medial wall, but most cilia (92-98%) in the otic vesicle are immotile. In mutants with defective cilia (iguana) or ciliary motility (lrrc50), otoliths are frequently ectopic, untethered or fused. Nevertheless, neither cilia nor ciliary motility are absolutely required for otolith tethering: a mutant that lacks cilia completely (MZovl) is still capable of tethering otoliths at the otic vesicle poles. In embryos with attenuated Notch signalling [mindbomb mutant or Su(H) morphant], supernumerary hair cells develop and otolith precursor particles bind to the tips of all kinocilia, or bind directly to the hair cells' apical surface if cilia are absent [MZovl injected with a Su(H)1+2 morpholino]. However, if the first hair cells are missing (atoh1b morphant), otolith formation is severely disrupted and delayed. Our data support a model in which hair cells produce an otolith precursor-binding factor, normally localised to tether cell kinocilia. We also show that embryonic movement plays a minor role in the formation of normal otoliths.

  16. Intestinal cell kinase, a protein associated with endocrine-cerebro-osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog signaling.

    Science.gov (United States)

    Moon, Heejung; Song, Jieun; Shin, Jeong-Oh; Lee, Hankyu; Kim, Hong-Kyung; Eggenschwiller, Jonathan T; Bok, Jinwoong; Ko, Hyuk Wan

    2014-06-10

    Endocrine-cerebro-osteodysplasia (ECO) syndrome is a recessive genetic disorder associated with multiple congenital defects in endocrine, cerebral, and skeletal systems that is caused by a missense mutation in the mitogen-activated protein kinase-like intestinal cell kinase (ICK) gene. In algae and invertebrates, ICK homologs are involved in flagellar formation and ciliogenesis, respectively. However, it is not clear whether this role of ICK is conserved in mammals and how a lack of functional ICK results in the characteristic phenotypes of human ECO syndrome. Here, we generated Ick knockout mice to elucidate the precise role of ICK in mammalian development and to examine the pathological mechanisms of ECO syndrome. Ick null mouse embryos displayed cleft palate, hydrocephalus, polydactyly, and delayed skeletal development, closely resembling ECO syndrome phenotypes. In cultured cells, down-regulation of Ick or overexpression of kinase-dead or ECO syndrome mutant ICK resulted in an elongation of primary cilia and abnormal Sonic hedgehog (Shh) signaling. Wild-type ICK proteins were generally localized in the proximal region of cilia near the basal bodies, whereas kinase-dead ICK mutant proteins accumulated in the distal part of bulged ciliary tips. Consistent with these observations in cultured cells, Ick knockout mouse embryos displayed elongated cilia and reduced Shh signaling during limb digit patterning. Taken together, these results indicate that ICK plays a crucial role in controlling ciliary length and that ciliary defects caused by a lack of functional ICK leads to abnormal Shh signaling, resulting in congenital disorders such as ECO syndrome.

  17. The retrograde IFT machinery of C. elegans cilia: two IFT dynein complexes?

    Directory of Open Access Journals (Sweden)

    Limin Hao

    Full Text Available We analyzed the relatively poorly understood IFT-dynein (class DYNC2-driven retrograde IFT pathway in C. elegans cilia, which yielded results that are surprising in the context of current models of IFT. Assays of C. elegans dynein gene expression and intraflagellar transport (IFT suggest that conventional IFT-dynein contains essential heavy (CHE-3, light-intermediate (XBX-1, plus three light polypeptide chains that participate in IFT, but no "essential" intermediate chain. IFT assays of XBX-1::YFP suggest that IFT-dynein is transported as cargo to the distal tip of the cilium by kinesin-2 motors, but independent of the IFT-particle/BBSome complexes. Finally, we were surprised to find that the subset of cilia present on the OLQ (outer labial quadrant neurons assemble independently of conventional "CHE-3" IFT-dynein, implying that there is a second IFT-dynein acting in these cilia. We have found a novel gene encoding a dynein heavy chain, DHC-3, and two light chains, in OLQ neurons, which could constitute an IFT-dynein complex in OLQ neuronal cilia. Our results underscore several surprising features of retrograde IFT that require clarification.

  18. Metachronal waves in epithelium cilia to transport bronchial mucus in airways

    Science.gov (United States)

    Favier, Julien; Sylvain, Chateau; D'Ortona, Umberto; Poncet, Sébastien

    2017-11-01

    Metachronal waves of beating cilia are an efficient mechanism to transport mucus in human airways. The numerical results we will present will shed new light on the understanding of chronic respiratory diseases, such as Asthma of COPD. A coupled lattice Boltzmann - Immersed Boundary is used to simulate the multiphase environment in which the cilia are immersed: a periciliary layer and the mucus layer. A purely hydrodynamical feedback of the fluids is taken into account, and a coupling parameter α is introduced, allowing the tuning of both the direction of the wave propagation, and the strength of the fluid feedback. The cilia, initially set in a random state, quickly synchronize with their immediate neighbors giving birth to metachronal waves. A comparative study of both antipleptic and sympleptic waves is performed by imposing the metachrony. Antiplectic waves are found to be the most efficient to transport and mix fluids compared to other random or synchronised cilia motions. The numerical results will be discussed and compared to experimental and clinical results obtained by collaborators, to progress on the understanding of the inner mechanisms of chronic respiratory diseases.

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

    NARCIS (Netherlands)

    Khaderi, S.N.; Toonder, den 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

  20. 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

  1. Spatial distribution of calcium-gated chloride channels in olfactory cilia.

    Science.gov (United States)

    French, Donald A; Badamdorj, Dorjsuren; Kleene, Steven J

    2010-12-30

    In vertebrate olfactory receptor neurons, sensory cilia transduce odor stimuli into changes in neuronal membrane potential. The voltage changes are primarily caused by the sequential openings of two types of channel: a cyclic-nucleotide-gated (CNG) cationic channel and a calcium-gated chloride channel. In frog, the cilia are 25 to 200 µm in length, so the spatial distributions of the channels may be an important determinant of odor sensitivity. To determine the spatial distribution of the chloride channels, we recorded from single cilia as calcium was allowed to diffuse down the length of the cilium and activate the channels. A computational model of this experiment allowed an estimate of the spatial distribution of the chloride channels. On average, the channels were concentrated in a narrow band centered at a distance of 29% of the ciliary length, measured from the base of the cilium. This matches the location of the CNG channels determined previously. This non-uniform distribution of transduction proteins is consistent with similar findings in other cilia. On average, the two types of olfactory transduction channel are concentrated in the same region of the cilium. This may contribute to the efficient detection of weak stimuli.

  2. Loss of Dishevelleds disrupts planar polarity in ependymal motile cilia and results in hydrocephalus

    Science.gov (United States)

    Ohata, Shinya; Nakatani, Jin; Herranz-Pérez, Vicente; Cheng, JrGang; Belinson, Haim; Inubushi, Toshiro; Snider, William D.; García-Verdugo, Jose Manuel; Wynshaw-Boris, Anthony; Álvarez-Buylla, Arturo

    2014-01-01

    SUMMARY Defects in ependymal (E) cells, which line the ventricle and generate cerebrospinal fluid flow through ciliary beating, can cause hydrocephalus. Dishevelled genes (Dvls) are essential for Wnt signaling and Dvl2 has been shown to localize to the rootlet of motile cilia. Using the hGFAP-Cre;Dvl1−/−;2flox/flox;3+/− mouse, we show that compound genetic ablation of Dvls causes hydrocephalus. In hGFAP-Cre;Dvl1−/−;2flox/flox;3+/− mutants, E cells differentiated normally, but the intracellular and intercellular rotational alignments of ependymal motile cilia were disrupted. As a consequence, the fluid flow generated by the hGFAP-Cre;Dvl1−/−;2flox/flox;3+/− E cells was significantly slower than that observed in control mice. Dvls were also required for the proper positioning of motile cilia on the apical surface. Tamoxifen-induced conditional removal of Dvls in adult mice also resulted in defects in intracellular rotational alignment and positioning of ependymal motile cilia. These results suggest that Dvls are continuously required for E cell planar polarity and may prevent hydrocephalus. PMID:25043421

  3. 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...

  4. Cilia induced cerebrospinal fluid flow in the third ventricle of brain

    Science.gov (United States)

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

    2016-11-01

    Cerebrospinal fluid (CSF) conveys many physiologically important signaling factors through the ventricles of the mammalian brain. The walls of the ventricles are covered with motile cilia that were thought to generate a laminar flow purely following the curvature of walls. However, we recently discovered that cilia of the ventral third ventricle (v3V) generate a complex flow network along the wall, leading to subdivision of the v3V. The contribution of such cilia induced flow to the overall three dimensional volume flow remains to be investigated by using numerical simulation, arguably the best approach for such investigations. The lattice Boltzmann method is used to study the CFS flow in a reconstructed geometry of the v3V. Simulation of CSF flow neglecting cilia in this geometry confirmed that the previous idea about pure confined flow does not reflect the reality observed in experiment. The experimentally recorded ciliary flow network along the wall was refined with the smoothed particle hydrodynamics and then adapted as boundary condition in simulation. We study the contribution of the ciliary network to overall CSF flow and identify site-specific delivery of CSF constituents with respect to the temporal changes.

  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. Role of spatial heterogeneity in the collective dynamics of cilia beating in a minimal one-dimensional model

    Science.gov (United States)

    Dey, Supravat; Massiera, Gladys; Pitard, Estelle

    2018-01-01

    Cilia are elastic hairlike protuberances of the cell membrane found in various unicellular organisms and in several tissues of most living organisms. In some tissues such as the airway tissues of the lung, the coordinated beating of cilia induces a fluid flow of crucial importance as it allows the continuous cleaning of our bronchia, known as mucociliary clearance. While most of the models addressing the question of collective dynamics and metachronal wave consider homogeneous carpets of cilia, experimental observations rather show that cilia clusters are heterogeneously distributed over the tissue surface. The purpose of this paper is to investigate the role of spatial heterogeneity on the coherent beating of cilia using a very simple one-dimensional model for cilia known as the rower model. We systematically study systems consisting of a few rowers to hundreds of rowers and we investigate the conditions for the emergence of collective beating. When considering a small number of rowers, a phase drift occurs, hence, a bifurcation in beating frequency is observed as the distance between rower clusters is changed. In the case of many rowers, a distribution of frequencies is observed. We found in particular the pattern of the patchy structure that shows the best robustness in collective beating behavior, as the density of cilia is varied over a wide range.

  7. Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells

    Directory of Open Access Journals (Sweden)

    Rattner Jerome B

    2009-12-01

    Full Text Available Abstract Background Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines. Methods Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis. Results We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis. Conclusions The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first

  8. [Scope of the latest RE-LY substudies: clinical implications].

    Science.gov (United States)

    Ruiz-Giménez Arrieta, N

    2012-03-01

    The approval of the use of dabiatran in stroke prevention in patients with nonvalvular atrial fibrilation (NVAF) is based on the results of the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, one of the largest studies to date in this entity. In this trial, dabigatran showed similar safety and efficacy to warfarin in primary and secondary prevention of stroke in patients with AF. At a dose of 150 mg twice daily, dabigatran was superior to warfarin in the prevention of stroke or systemic embolism and the 110 mg dose twice daily showed similar efficacy and greater safety, given the lower incidence of hemorrhage. These results were consistently found in the various subanalyses, with some slight differences of interest for clinical practice. The ideal candidates for dabiatran are patients with NVAF suitable for cardioversion, who require short periods of anticoagulation, patients in remote geographical areas with difficulty in achieving good anticoagulation control or good control with anti-vitamin K treatment due to IRN fluctuations, and patients with a low risk of hemorrhage and a CHADS score ≥ 3 and/or with prior stroke, whenever there are no contraindications. The choice of dabigatran dose should be evaluated according to the patient's individual characteristics (caution must be exercised when prescribing this drug in the elderly and in renal insufficiency) and embolic and/or hemorrhagic risk. Studies of the long-term safety of this drug, pharmacoeconomic analyses in Spain and post-commercialization pharmacovigilance data are required before the definitive uses of this drug can be established. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  9. Effect of Xiaoqinglong decoction on mucus hypersecretion in the airways and cilia function in a murine model of asthma

    Directory of Open Access Journals (Sweden)

    Mingyue Qi

    2017-07-01

    Conclusion: XQL can attenuate cilia shortening, aid the clearance function of ciliated epithelial cells, and reduce mucus production in an OVA-induced asthma model in mice. XQL can inhibit mucus hypersecretion and could be a new type of pharmacotherapy.

  10. Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport

    Science.gov (United States)

    Blacque, Oliver E.; Reardon, Michael J.; Li, Chunmei; McCarthy, Jonathan; Mahjoub, Moe R.; Ansley, Stephen J.; Badano, Jose L.; Mah, Allan K.; Beales, Philip L.; Davidson, William S.; Johnsen, Robert C.; Audeh, Mark; Plasterk, Ronald H.A.; Baillie, David L.; Katsanis, Nicholas; Quarmby, Lynne M.; Wicks, Stephen R.; Leroux, Michel R.

    2004-01-01

    Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Importantly, we demonstrate that BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11, and to a notably lesser extent, CHE-2. We propose that BBS proteins play important, selective roles in the assembly and/or function of IFT particle components. Our findings also suggest that some of the cardinal and secondary symptoms of BBS, such as obesity, diabetes, cardiomyopathy, and learning defects may result from cilia dysfunction. PMID:15231740

  11. 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

  12. Microfluidic active mixers employing ultra-high aspect-ratio rare-earth magnetic nano-composite polymer artificial cilia

    International Nuclear Information System (INIS)

    Rahbar, Mona; Gray, Bonnie L; Shannon, Lesley

    2014-01-01

    We present a new micromixer based on highly magnetic, flexible, high aspect-ratio, artificial cilia that are fabricated as individual micromixer elements or in arrays for improved mixing performance. These new cilia enable high efficiency, fast mixing in a microchamber, and are controlled by small electromagnetic fields. The artificial cilia are fabricated using a new micromolding process for nano-composite polymers. Cilia fibers with aspect-ratios as high as 8:0.13 demonstrate the fabrication technique's capability in creating ultra-high aspect-ratio microstructures. Cilia, which are realized in polydimethylsiloxane doped with rare-earth magnetic powder, are magnetized to produce permanent magnetic structures with bidirectional deflection capabilities, making them highly suitable as mixers controlled by electromagnetic fields. Due to the high magnetization level of the polarized nano-composite polymer, we are able to use miniature electromagnets providing relatively small magnetic fields of 1.1 to 7 mT to actuate the cilia microstructures over a very wide motion range. Mixing performances of a single cilium, as well as different arrays of multiple cilia ranging from 2 to 8 per reaction chamber, are characterized and compared with passive diffusion mixing performance. The mixer cilia are actuated at different amplitudes and frequencies to optimize mixing performance. We demonstrate that more than 85% of the total volume of the reaction chamber is fully mixed after 3.5 min using a single cilium mixer at 7 mT compared with only 20% of the total volume mixed with passive diffusion. The time to achieve over 85% mixing is further reduced to 70 s using an array of eight cilia microstructures. The novel microfabrication technique and use of rare-earth permanently-magnetizable nano-composite polymers in mixer applications has not been reported elsewhere by other researchers. We further demonstrate improved mixing over other cilia micromixers as enabled by the high

  13. Discrete multi-physics simulations of diffusive and convective mass transfer in boundary layers containing motile cilia in lungs.

    Science.gov (United States)

    Ariane, Mostapha; Kassinos, Stavros; Velaga, Sitaram; Alexiadis, Alessio

    2018-04-01

    In this paper, the mass transfer coefficient (permeability) of boundary layers containing motile cilia is investigated by means of discrete multi-physics. The idea is to understand the main mechanisms of mass transport occurring in a ciliated-layer; one specific application being inhaled drugs in the respiratory epithelium. The effect of drug diffusivity, cilia beat frequency and cilia flexibility is studied. Our results show the existence of three mass transfer regimes. A low frequency regime, which we called shielding regime, where the presence of the cilia hinders mass transport; an intermediate frequency regime, which we have called diffusive regime, where diffusion is the controlling mechanism; and a high frequency regime, which we have called convective regime, where the degree of bending of the cilia seems to be the most important factor controlling mass transfer in the ciliated-layer. Since the flexibility of the cilia and the frequency of the beat changes with age and health conditions, the knowledge of these three regimes allows prediction of how mass transfer varies with these factors. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation

    DEFF Research Database (Denmark)

    Clement, Christian A; Kristensen, Stine G; Møllgård, Kjeld

    2009-01-01

    Defects in the assembly or function of primary cilia, which are sensory organelles, are tightly coupled to developmental defects and diseases in mammals. Here, we investigated the function of the primary cilium in regulating hedgehog signaling and early cardiogenesis. We report that the pluripotent...... P19.CL6 mouse stem cell line, which can differentiate into beating cardiomyocytes, forms primary cilia that contain essential components of the hedgehog pathway, including Smoothened, Patched-1 and Gli2. Knockdown of the primary cilium by Ift88 and Ift20 siRNA or treatment with cyclopamine...... development. These data support the conclusion that cardiac primary cilia are crucial in early heart development, where they partly coordinate hedgehog signaling....

  15. Three types of ependymal cells with intracellular calcium oscillation are characterized by distinct cilia beating properties.

    Science.gov (United States)

    Liu, Tongyu; Jin, Xingjian; Prasad, Rahul M; Sari, Youssef; Nauli, Surya M

    2014-09-01

    Ependymal cells are multiciliated epithelial cells that line the ventricles in the adult brain. Abnormal function or structure of ependymal cilia has been associated with various neurological deficits. For the first time, we report three distinct ependymal cell types, I, II, and III, based on their unique ciliary beating frequency and beating angle. These ependymal cells have specific localizations within the third ventricle of the mouse brain. Furthermore, neither ependymal cell types nor their localizations are altered by aging. Our high-speed fluorescence imaging analysis reveals that these ependymal cells have an intracellular pacing calcium oscillation property. Our study further shows that alcohol can significantly repress the amplitude of calcium oscillation and the frequency of ciliary beating, resulting in an overall decrease in volume replacement by the cilia. Furthermore, the pharmacological agent cilostazol could differentially increase cilia beating frequency in type II, but not in type I or type III, ependymal cells. In summary, we provide the first evidence of three distinct types of ependymal cells with calcium oscillation properties. © 2014 Wiley Periodicals, Inc.

  16. A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

    Science.gov (United States)

    Abdelhamed, Zakia; Vuong, Shawn M; Hill, Lauren; Shula, Crystal; Timms, Andrew; Beier, David; Campbell, Kenneth; Mangano, Francesco T; Stottmann, Rolf W; Goto, June

    2018-01-09

    Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 ( Ccdc39 ) is responsible for early postnatal hydrocephalus in the progressive hydrocephal us ( prh ) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39 prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development. © 2018. Published by The Company of Biologists Ltd.

  17. 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

  18. Cilia-like structures anchor the amphioxus notochord to its sheath.

    Science.gov (United States)

    Bočina, Ivana; Ljubešić, Nikola; Saraga-Babić, Mirna

    2011-01-01

    Body stiffness is important during undulatory locomotion in fish. In amphioxus, the myosepta play an important role in transmission of muscular forces to the notochord. In order to define the specific supporting role of the notochord in amphioxus during locomotion, the ultrastructure of 10 adult amphioxus specimens was analyzed using transmission electron microscopy. Numerous cilia-like structures were found on the surface of each notochordal cell at the sites of their attachment to the notochordal sheath. Ultrastructurally, these structures consisted of the characteristic arrangement of peripheral and central microtubular doublets and were anchored to the inner layer of the notochordal sheath. Immunohistochemically, a positive reaction to applied dynein and β-tubulin antibodies characterized the area of the cilia-like structures. We propose that reduced back-and-forth movements of the cilia-like structures might contribute to the flow of the fluid content inside the notochord, thus modulating the stiffness of the amphioxus body during its undulatory locomotion. Copyright © 2009 Elsevier GmbH. All rights reserved.

  19. RTTN mutations link primary cilia function to organization of the human cerebral cortex

    NARCIS (Netherlands)

    S.K. Kia; E. Verbeek (Elly); M.P. Engelen (Erik); R. Schot (Rachel); R.A. Poot (Raymond); I.F.M. de Coo (René); M. Leguin (Maarten); C.J. Poulton (Cathryn); F. Pourfarzad, F. (Farzin); F.G. Grosveld (Frank); A. Brehm (António); M.C.Y. de Wit (Marie Claire); R. Oegema (Renske); W.B. Dobyns (William); F.W. Verheijen (Frans); G.M.S. Mancini (Grazia)

    2012-01-01

    textabstractPolymicrogyria is a malformation of the developing cerebral cortex caused by abnormal organization and characterized by many small gyri and fusion of the outer molecular layer. We have identified autosomal-recessive mutations in RTTN, encoding Rotatin, in individuals with bilateral

  20. Truncated SALL1 Impedes Primary Cilia Function in Townes-Brocks Syndrome

    DEFF Research Database (Denmark)

    Bozal-Basterra, Laura; Martín-Ruíz, Itziar; Pirone, Lucia

    2018-01-01

    by mutations in the gene encoding the transcriptional repressor SALL1 and is associated with the presence of a truncated protein that localizes to the cytoplasm. Here, we provide evidence that SALL1 mutations might cause TBS by means beyond its transcriptional capacity. By using proximity proteomics, we show...

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

    Czech Academy of Sciences Publication Activity Database

    Ohazama, A.; Haycraft, C. J.; Seppala, M.; Ghafoor, S.; Cobourne, M.; Martinelli, D. C.; Fan, CH. M.; Peterková, Renata; Lesot, H.; Yoder, B. K.; Sharpe, P. T.

    2009-01-01

    Roč. 136, č. 6 (2009), s. 897-903 ISSN 0950-1991 R&D Projects: GA ČR GA304/07/0223; GA MŠk OC B23.002 Institutional research plan: CEZ:AV0Z50390512 Keywords : intraflagellar transport * supernumerary tooth * tooth development Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.194, year: 2009

  2. ETHANOL EXPOSURE DISRUPTS CRANIAL NEURAL CREST MIGRATION AND PRIMARY CILIA IN DEVELOPING ZEBRAFISH EMBRYOS

    OpenAIRE

    BORIC BRENET, KATICA ANDREA; BORIC BRENET, KATICA ANDREA

    2012-01-01

    Durante el desarrollo temprano la exposición a etanol (EtOH) puede causar el Síndrome de Alcohol Fetal (SAF), el cual afecta estructuras craneofaciales (CF) y partes del sistema nervioso (SN), ambos derivados de las células de la cresta neural craneal (CCNC). Por lo tanto, proponemos que la migración de las CCNC se ve afectada por la exposición a EtOH. Para determinar si la exposición a EtOH altera la migración celular, incubamos embriones de pez cebra durante 20 horas usando conc...

  3. Msd1/SSX2IP-dependent microtubule anchorage ensures spindle orientation and primary cilia formation

    OpenAIRE

    Hori, Akiko; Ikebe, Chiho; Tada, Masazumi; Toda, Takashi

    2014-01-01

    Anchoring microtubules to the centrosome is critical for cell geometry and polarity, yet the molecular mechanism remains unknown. Here we show that the conserved human Msd1/SSX2IP is required for microtubule anchoring. hMsd1/SSX2IP is delivered to the centrosome in a centriolar satellite-dependent manner and binds the microtubule-nucleator ?-tubulin complex. hMsd1/SSX2IP depletion leads to disorganised interphase microtubules and misoriented mitotic spindles with reduced length and intensity....

  4. Reliģijas makdonaldizācija

    OpenAIRE

    Siliņš, Toms

    2012-01-01

    Bakalaura darbā apskatītas makdonaldizācijas procesa izpausmes Latvijas reliģisko organizāciju darbībā. Pētījuma mērķis ir noskaidrot makdonaldizācijas izpausmes Latvijas reliģiskajās organizācijās, tādēļ izvirzīti pētījuma jautājumi – kādas ir liecības par makdonaldizācijas procesa ietekmi uz reliģiskajām organizācijām Latvijā un kā vērtējama makdonaldizācijas procesa ietekme uz reliģiskajām organizācijām Latvijā. Pētījuma ietvaros veiktas divas ekspertu intervijas, kuru analīzes rezultātā i...

  5. 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.

  6. Localization of a guanylyl cyclase to chemosensory cilia requires the novel ciliary MYND domain protein DAF-25.

    Directory of Open Access Journals (Sweden)

    Victor L Jensen

    2010-11-01

    Full Text Available In harsh conditions, Caenorhabditis elegans arrests development to enter a non-aging, resistant diapause state called the dauer larva. Olfactory sensation modulates the TGF-β and insulin signaling pathways to control this developmental decision. Four mutant alleles of daf-25 (abnormal DAuer Formation were isolated from screens for mutants exhibiting constitutive dauer formation and found to be defective in olfaction. The daf-25 dauer phenotype is suppressed by daf-10/IFT122 mutations (which disrupt ciliogenesis, but not by daf-6/PTCHD3 mutations (which prevent environmental exposure of sensory cilia, implying that DAF-25 functions in the cilia themselves. daf-25 encodes the C. elegans ortholog of mammalian Ankmy2, a MYND domain protein of unknown function. Disruption of DAF-25, which localizes to sensory cilia, produces no apparent cilia structure anomalies, as determined by light and electron microscopy. Hinting at its potential function, the dauer phenotype, epistatic order, and expression profile of daf-25 are similar to daf-11, which encodes a cilium-localized guanylyl cyclase. Indeed, we demonstrate that DAF-25 is required for proper DAF-11 ciliary localization. Furthermore, the functional interaction is evolutionarily conserved, as mouse Ankmy2 interacts with guanylyl cyclase GC1 from ciliary photoreceptors. The interaction may be specific because daf-25 mutants have normally-localized OSM-9/TRPV4, TAX-4/CNGA1, CHE-2/IFT80, CHE-11/IFT140, CHE-13/IFT57, BBS-8, OSM-5/IFT88, and XBX-1/D2LIC in the cilia. Intraflagellar transport (IFT (required to build cilia is not defective in daf-25 mutants, although the ciliary localization of DAF-25 itself is influenced in che-11 mutants, which are defective in retrograde IFT. In summary, we have discovered a novel ciliary protein that plays an important role in cGMP signaling by localizing a guanylyl cyclase to the sensory organelle.

  7. Chapter 10 the primary cilium coordinates signaling pathways in cell cycle control and migration during development and tissue repair

    DEFF Research Database (Denmark)

    Christensen, Søren T; Pedersen, Stine F; Satir, Peter

    2008-01-01

    Cell cycle control and migration are critical processes during development and maintenance of tissue functions. Recently, primary cilia were shown to take part in coordination of the signaling pathways that control these cellular processes in human health and disease. In this review, we present...... an overview of the function of primary cilia and the centrosome in the signaling pathways that regulate cell cycle control and migration with focus on ciliary signaling via platelet-derived growth factor receptor alpha (PDGFRalpha). We also consider how the primary cilium and the centrosome interact...... with the extracellular matrix, coordinate Wnt signaling, and modulate cytoskeletal changes that impinge on both cell cycle control and cell migration....

  8. Loss of Centrobin Enables Daughter Centrioles to Form Sensory Cilia in Drosophila.

    Science.gov (United States)

    Gottardo, Marco; Pollarolo, Giulia; Llamazares, Salud; Reina, Jose; Riparbelli, Maria G; Callaini, Giuliano; Gonzalez, Cayetano

    2015-08-31

    Sensory cilia are organelles that convey information to the cell from the extracellular environment. In vertebrates, ciliary dysfunction results in ciliopathies that in humans comprise a wide spectrum of developmental disorders. In Drosophila, sensory cilia are found only in the neurons of type I sensory organs, but ciliary dysfunction also has dramatic consequences in this organism because it impairs the mechanosensory properties of bristles and chaetae and leads to uncoordination, a crippling condition that causes lethality shortly after eclosion. The cilium is defined by the ciliary membrane, a protrusion of the cell membrane that envelops the core structure known as the axoneme, a microtubule array that extends along the cilium from the basal body. In vertebrates, basal body function requires centriolar distal and subdistal appendages and satellites. Because these structures are acquired through centriole maturation, only mother centrioles can serve as basal bodies. Here, we show that although centriole maturity traits are lacking in Drosophila, basal body fate is reserved to mother centrioles in Drosophila type I neurons. Moreover, we show that depletion of the daughter-centriole-specific protein Centrobin (CNB) enables daughter centrioles to dock on the cell membrane and to template an ectopic axoneme that, although structurally defective, protrudes out of the cell and is enveloped by a ciliary membrane. Conversely, basal body capability is inhibited in mother centrioles modified to carry CNB. These results reveal the crucial role of CNB in regulating basal body function in Drosophila ciliated sensory organs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. 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.

  10. Flow pattern in the ventricle of brain with cilia beating and CSF circulation

    Science.gov (United States)

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

    We recently discovered that cilia of the ventral third ventricle (v3V) of mammalian brain generate a complex flow network close to the wall. However, the flow pattern in the overall three dimensional v3V, especially under physiological condition, remains to be investigated. Computational fluid dynamics is arguably the best approach for such investigations. Several v3V geometries are reconstructed from different data for comparison study. The lattice Boltzmann method and immersed boundary method are used to reproduce the experimental set-up for an opened v3V firstly. The experimentally recorded cilia induced flow network is projected on the curved v3V wall. The flow maps obtained numerically at different heights from the v3V wall agree with the experimental data qualitatively. We then consider the entire v3V with ciliary flow network along the wall for boundary condition. Moreover, we add a time dependent flow rate to represent the CSF circulation, and study flow pattern in the ventricle. We thank the Max Planck Society (MPG) for financial support. This work is conducted within the Physics and Medicine Initiative at Goettingen Campus between MPG and University Medical Center.

  11. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms

    Science.gov (United States)

    Panizzi, Jennifer R.; Becker-Heck, Anita; Castleman, Victoria H.; Al-Mutairi, Dalal; Liu, Yan; Loges, Niki T.; Pathak, Narendra; Austin-Tse, Christina; Sheridan, Eamonn; Schmidts, Miriam; Olbrich, Heike; Werner, Claudius; Häffner, Karsten; Hellman, Nathan; Chodhari, Rahul; Gupta, Amar; Kramer-Zucker, Albrecht; Olale, Felix; Burdine, Rebecca D.; Schier, Alexander F.; O’Callaghan, Christopher; Chung, Eddie MK; Reinhardt, Richard; Mitchison, Hannah M.; King, Stephen M.; Omran, Heymut; Drummond, Iain A.

    2012-01-01

    Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation, and to establish laterality1. Cilia motility defects cause Primary Ciliary Dyskinesia (PCD, MIM 242650), a disorder affecting 1:15-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive cilia bending2. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD linked loci3. Here we show that the zebrafish cilia paralysis mutant schmalhanstn222 (smh) mutant encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a regulated gene. Screening 146 unrelated PCD families identified patients in six families with reduced outer dynein arms, carrying mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103 functions as a tightly bound, axoneme-associated protein. The results identify Ccdc103 as a novel dynein arm attachment factor that when mutated causes Primary Ciliary Dyskinesia. PMID:22581229

  12. Chemical-Free Technique to Study the Ultrastructure of Primary Cilium.

    Science.gov (United States)

    Mohieldin, Ashraf M; AbouAlaiwi, Wissam A; Gao, Min; Nauli, Surya M

    2015-11-02

    A primary cilium is a hair-like structure with a width of approximately 200 nm. Over the past few decades, the main challenge in the study of the ultrastructure of cilia has been the high sensitivity of cilia to chemical fixation, which is required for many imaging techniques. In this report, we demonstrate a combined high-pressure freezing (HPF) and freeze-fracture transmission electron microscopy (FFTEM) technique to examine the ultrastructure of a cilium. Our objective is to develop an optimal high-resolution imaging approach that preserves cilia structures in their best natural form without alteration of cilia morphology by chemical fixation interference. Our results showed that a cilium has a swelling-like structure (termed bulb), which was previously considered a fixation artifact. The intramembrane particles observed via HPF/FFTEM indicated the presence of integral membrane proteins and soluble matrix proteins along the ciliary bulb, which is part of an integral structure within the ciliary membrane. We propose that HPF/FFTEM is an important and more suitable chemical-free method to study the ultrastructure of primary cilia.

  13. Primary Cilium-Regulated EG-VEGF Signaling Facilitates Trophoblast Invasion.

    Science.gov (United States)

    Wang, Chia-Yih; Tsai, Hui-Ling; Syu, Jhih-Siang; Chen, Ting-Yu; Su, Mei-Tsz

    2017-06-01

    Trophoblast invasion is an important event in embryo implantation and placental development. During these processes, endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is the key regulator mediating the crosstalk at the feto-maternal interface. The primary cilium is a cellular antenna receiving environmental signals and is crucial for proper development. However, little is known regarding the role of the primary cilium in early human pregnancy. Here, we demonstrate that EG-VEGF regulates trophoblast cell invasion via primary cilia. We found that EG-VEGF activated ERK1/2 signaling and subsequent upregulation of MMP2 and MMP9, thereby facilitating cell invasion in human trophoblast HTR-8/SVneo cells. Inhibition of ERK1/2 alleviated the expression of MMPs and trophoblast cell invasion after EG-VEGF treatment. In addition, primary cilia were observed in all the trophoblast cell lines tested and, more importantly, in human first-trimester placental tissue. The receptor of EG-VEGF, PROKR1, was detected in primary cilia. Depletion of IFT88, the intraflagellar transporter required for ciliogenesis, inhibited primary cilium growth, thereby ameliorating ERK1/2 activation, MMP upregulation, and trophoblast cell invasion promoted by EG-VEGF. These findings demonstrate a novel function of primary cilia in controlling EG-VEGF-regulated trophoblast invasion and reveal the underlying molecular mechanism. J. Cell. Physiol. 232: 1467-1477, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Intuitive Face Judgments Rely on Holistic Eye Movement Pattern

    Directory of Open Access Journals (Sweden)

    Laura F. Mega

    2017-06-01

    Full Text Available Non-verbal signals such as facial expressions are of paramount importance for social encounters. Their perception predominantly occurs without conscious awareness and is effortlessly integrated into social interactions. In other words, face perception is intuitive. Contrary to classical intuition tasks, this work investigates intuitive processes in the realm of every-day type social judgments. Two differently instructed groups of participants judged the authenticity of emotional facial expressions, while their eye movements were recorded: an ‘intuitive group,’ instructed to rely on their “gut feeling” for the authenticity judgments, and a ‘deliberative group,’ instructed to make their judgments after careful analysis of the face. Pixel-wise statistical maps of the resulting eye movements revealed a differential viewing pattern, wherein the intuitive judgments relied on fewer, longer and more centrally located fixations. These markers have been associated with a global/holistic viewing strategy. The holistic pattern of intuitive face judgments is in line with evidence showing that intuition is related to processing the “gestalt” of an object, rather than focusing on details. Our work thereby provides further evidence that intuitive processes are characterized by holistic perception, in an understudied and real world domain of intuition research.

  15. Intuitive Face Judgments Rely on Holistic Eye Movement Pattern.

    Science.gov (United States)

    Mega, Laura F; Volz, Kirsten G

    2017-01-01

    Non-verbal signals such as facial expressions are of paramount importance for social encounters. Their perception predominantly occurs without conscious awareness and is effortlessly integrated into social interactions. In other words, face perception is intuitive. Contrary to classical intuition tasks, this work investigates intuitive processes in the realm of every-day type social judgments. Two differently instructed groups of participants judged the authenticity of emotional facial expressions, while their eye movements were recorded: an 'intuitive group,' instructed to rely on their "gut feeling" for the authenticity judgments, and a 'deliberative group,' instructed to make their judgments after careful analysis of the face. Pixel-wise statistical maps of the resulting eye movements revealed a differential viewing pattern, wherein the intuitive judgments relied on fewer, longer and more centrally located fixations. These markers have been associated with a global/holistic viewing strategy. The holistic pattern of intuitive face judgments is in line with evidence showing that intuition is related to processing the "gestalt" of an object, rather than focusing on details. Our work thereby provides further evidence that intuitive processes are characterized by holistic perception, in an understudied and real world domain of intuition research.

  16. Enteric neurons show a primary cilium.

    Science.gov (United States)

    Luesma, Ma José; Cantarero, Irene; Castiella, Tomás; Soriano, Mario; Garcia-Verdugo, José Manuel; Junquera, Concepción

    2013-01-01

    The primary cilium is a non-motile cilium whose structure is 9+0. It is involved in co-ordinating cellular signal transduction pathways, developmental processes and tissue homeostasis. Defects in the structure or function of the primary cilium underlie numerous human diseases, collectively termed ciliopathies. The presence of single cilia in the central nervous system (CNS) is well documented, including some choroid plexus cells, neural stem cells, neurons and astrocytes, but the presence of primary cilia in differentiated neurons of the enteric nervous system (ENS) has not yet been described in mammals to the best of our knowledge. The enteric nervous system closely resembles the central nervous system. In fact, the ultrastructure of the ENS is more similar to the CNS ultrastructure than to the rest of the peripheral nervous system. This research work describes for the first time the ultrastructural characteristics of the single cilium in neurons of rat duodenum myenteric plexus, and reviews the cilium function in the CNS to propose the possible role of cilia in the ENS cells. © 2012 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  17. Maladies reliées aux loisirs aquatiques

    Science.gov (United States)

    Sanborn, Margaret; Takaro, Tim

    2013-01-01

    Résumé Objectif Passer en revue les facteurs de risque, la prise en charge et la prévention des maladies reliées aux loisirs aquatiques en pratique familiale. Sources des données Des articles originaux et de synthèse entre janvier 1998 et février 2012 ont été identifiés à l’aide de PubMed et des expressions de recherche en anglais water-related illness, recreational water illness et swimmer illness. Message principal Il y a un risque de 3 % à 8 % de maladies gastrointestinales (MGI) après la baignade. Les groupes à risque élevé de MGI sont les enfants de moins de 5 ans, surtout s’ils n’ont pas été vaccinés contre le rotavirus, les personnes âgées et les patients immunodéficients. Les enfants sont à plus grand risque parce qu’ils avalent plus d’eau quand ils nagent, restent dans l’eau plus longtemps et jouent dans l’eau peu profonde et le sable qui sont plus contaminés. Les adeptes des sports dans lesquels le contact avec l’eau est abondant comme le triathlon et le surf cerf-volant sont aussi à risque élevé et même ceux qui s’adonnent à des activités impliquant un contact partiel avec l’eau comme la navigation de plaisance et la pêche ont un risque de 40 % à 50 % fois plus grand de MGI par rapport à ceux qui ne pratiquent pas de sports aquatiques. Il y a lieu de faire une culture des selles quand on soupçonne une maladie reliée aux loisirs aquatiques et l’échelle clinique de la déshydratation est utile pour l’évaluation des besoins de traitement chez les enfants affectés. Conclusion Les maladies reliées aux loisirs aquatiques est la principale cause de MGI durant la saison des baignades. La reconnaissance que la baignade est une source importante de maladies peut aider à prévenir les cas récurrents et secondaires. On recommande fortement le vaccin contre le rotavirus chez les enfants qui se baignent souvent.

  18. 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

  19. Robust Sensing of Approaching Vehicles Relying on Acoustic Cues

    Directory of Open Access Journals (Sweden)

    Mitsunori Mizumachi

    2014-05-01

    Full Text Available The latest developments in automobile design have allowed them to be equipped with various sensing devices. Multiple sensors such as cameras and radar systems can be simultaneously used for active safety systems in order to overcome blind spots of individual sensors. This paper proposes a novel sensing technique for catching up and tracking an approaching vehicle relying on an acoustic cue. First, it is necessary to extract a robust spatial feature from noisy acoustical observations. In this paper, the spatio-temporal gradient method is employed for the feature extraction. Then, the spatial feature is filtered out through sequential state estimation. A particle filter is employed to cope with a highly non-linear problem. Feasibility of the proposed method has been confirmed with real acoustical observations, which are obtained by microphones outside a cruising vehicle.

  20. Targeting of beta-arrestin2 to the centrosome and primary cilium: role in cell proliferation control.

    Directory of Open Access Journals (Sweden)

    Anahi Molla-Herman

    Full Text Available The primary cilium is a sensory organelle generated from the centrosome in quiescent cells and found at the surface of most cell types, from where it controls important physiological processes. Specific sets of membrane proteins involved in sensing the extracellular milieu are concentrated within cilia, including G protein coupled receptors (GPCRs. Most GPCRs are regulated by beta-arrestins, betaarr1 and betaarr2, which control both their signalling and endocytosis, suggesting that betaarrs may also function at primary cilium.In cycling cells, betaarr2 was observed at the centrosome, at the proximal region of the centrioles, in a microtubule independent manner. However, betaarr2 did not appear to be involved in classical centrosome-associated functions. In quiescent cells, both in vitro and in vivo, betaarr2 was found at the basal body and axoneme of primary cilia. Interestingly, betaarr2 was found to interact and colocalize with 14-3-3 proteins and Kif3A, two proteins known to be involved in ciliogenesis and intraciliary transport. In addition, as suggested for other centrosome or cilia-associated proteins, betaarrs appear to control cell cycle progression. Indeed, cells lacking betaarr2 were unable to properly respond to serum starvation and formed less primary cilia in these conditions.Our results show that betaarr2 is localized to the centrosome in cycling cells and to the primary cilium in quiescent cells, a feature shared with other proteins known to be involved in ciliogenesis or primary cilium function. Within cilia, betaarr2 may participate in the signaling of cilia-associated GPCRs and, therefore, in the sensory functions of this cell "antenna".

  1. da Vinci decoded: does da Vinci stereopsis rely on disparity?

    Science.gov (United States)

    Tsirlin, Inna; Wilcox, Laurie M; Allison, Robert S

    2012-11-01

    In conventional stereopsis, the depth between two objects is computed based on the retinal disparity in the position of matching points in the two eyes. When an object is occluded by another object in the scene, so that it is visible only in one eye, its retinal disparity cannot be computed. Nakayama and Shimojo (1990) found that a precept of quantitative depth between the two objects could still be established for such stimuli and proposed that this precept is based on the constraints imposed by occlusion geometry. They named this and other occlusion-based depth phenomena "da Vinci stereopsis." Subsequent research found quantitative depth based on occlusion geometry in several other classes of stimuli grouped under the term da Vinci stereopsis. However, Nakayama and Shimojo's findings were later brought into question by Gillam, Cook, and Blackburn (2003), who suggested that quantitative depth in their stimuli was perceived based on conventional disparity. In order to understand whether da Vinci stereopsis relies on one type of mechanism or whether its function is stimulus dependent we examine the nature and source of depth in the class of stimuli used by Nakayama and Shimojo (1990). We use three different psychophysical and computational methods to show that the most likely source for depth in these stimuli is occlusion geometry. Based on these experiments and previous data we discuss the potential mechanisms responsible for processing depth from monocular features in da Vinci stereopsis.

  2. Human children rely more on social information than chimpanzees do.

    Science.gov (United States)

    van Leeuwen, Edwin J C; Call, Josep; Haun, Daniel B M

    2014-11-01

    Human societies are characterized by more cultural diversity than chimpanzee communities. However, it is currently unclear what mechanism might be driving this difference. Because reliance on social information is a pivotal characteristic of culture, we investigated individual and social information reliance in children and chimpanzees. We repeatedly presented subjects with a reward-retrieval task on which they had collected conflicting individual and social information of equal accuracy in counterbalanced order. While both species relied mostly on their individual information, children but not chimpanzees searched for the reward at the socially demonstrated location more than at a random location. Moreover, only children used social information adaptively when individual knowledge on the location of the reward had not yet been obtained. Social information usage determines information transmission and in conjunction with mechanisms that create cultural variants, such as innovation, it facilitates diversity. Our results may help explain why humans are more culturally diversified than chimpanzees. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  3. Three-dimensional structural analysis of eukaryotic flagella/cilia by electron cryo-tomography

    International Nuclear Information System (INIS)

    Bui, Khanh Huy; Pigino, Gaia; Ishikawa, Takashi

    2011-01-01

    Based on the molecular architecture revealed by electron cryo-tomography, the mechanism of the bending motion of eukaryotic flagella/cilia is discussed. Electron cryo-tomography is a potential approach to analyzing the three-dimensional conformation of frozen hydrated biological macromolecules using electron microscopy. Since projections of each individual object illuminated from different orientations are merged, electron tomography is capable of structural analysis of such heterogeneous environments as in vivo or with polymorphism, although radiation damage and the missing wedge are severe problems. Here, recent results on the structure of eukaryotic flagella, which is an ATP-driven bending organelle, from green algae Chlamydomonas are presented. Tomographic analysis reveals asymmetric molecular arrangements, especially that of the dynein motor proteins, in flagella, giving insight into the mechanism of planar asymmetric bending motion. Methodological challenges to obtaining higher-resolution structures from this technique are also discussed

  4. The pressure is all in your head: A cilia-driven high-pressure pump in the head of a deep-sea animal

    Science.gov (United States)

    Nawroth, Janna; Katija, Kakani; Shelley, Michael; Kanso, Eva

    2017-11-01

    Motile cilia are microscopic, hair-like structures on the cell surface that can sense and propel the extracellular fluid environment. In many ciliated systems found in nature, such as the mammalian airways and marine sponges, the organization and collective behavior of the cilia favors the pumping of fluids at low pressures and high volumes. We recently discovered an alternate design located in the head of a deep-sea animal called Larvacean. Here, cilia morphology, kinematics and flow indicate a role in maintaining the hydrostatic skeleton of the animal by generating a high-pressure flow. We describe our empirical and computational approaches toward understanding the design principles and dynamic range of this newly discovered pumping mechanism. In ongoing work, we further explore the fluid dynamic constraints on the morphological diversity of cilia and the resulting categories of fluid transport functions.

  5. ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6

    DEFF Research Database (Denmark)

    Zariwala, Maimoona A; Gee, Heon Yung; Kurkowiak, Małgorzata

    2013-01-01

    Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the ...

  6. 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

    2013-01-01

    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.

  7. 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.

  8. Mathematical modelling of pressure-driven micropolar biological flow due to metachronal wave propulsion of beating cilia.

    Science.gov (United States)

    Akbar, N S; Tripathi, D; Khan, Z H; Bég, O Anwar

    2018-04-06

    In this paper, we present an analytical study of pressure-driven flow of micropolar non-Newtonian physiological fluids through a channel comprising two parallel oscillating walls. The cilia are arranged at equal intervals and protrude normally from both walls of the infinitely long channel. A metachronal wave is generated due to natural beating of cilia and the direction of wave propagation is parallel to the direction of fluid flow. Appropriate expressions are presented for deformation via longitudinal and transverse velocity components induced by the ciliary beating phenomenon with cilia assumed to follow elliptic trajectories. The conservation equations for mass, longitudinal and transverse (linear) momentum and angular momentum are reduced in accordance with the long wavelength and creeping Stokesian flow approximations and then normalized with appropriate transformations. The resulting non-linear moving boundary value problem is solved analytically for constant micro-inertia density, subject to physically realistic boundary conditions. Closed-form expressions are derived for axial velocity, angular velocity, volumetric flow rate and pressure rise. The transport phenomena are shown to be dictated by several non-Newtonian parameters, including micropolar material parameter and Eringen coupling parameter, and also several geometric parameters, viz eccentricity parameter, wave number and cilia length. The influence of these parameters on streamline profiles (with a view to addressing trapping features via bolus formation and evolution), pressure gradient and other characteristics are evaluated graphically. Both axial and angular velocities are observed to be substantially modified with both micropolar rheological parameters and furthermore are significantly altered with increasing volumetric flow rate. Free pumping is also examined. An inverse relationship between pressure rise and flow rate is computed which is similar to that observed in Newtonian fluids. The

  9. 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.

  10. Culture of primary ciliary dyskinesia epithelial cells at air-liquid interface can alter ciliary phenotype but remains a robust and informative diagnostic aid.

    Directory of Open Access Journals (Sweden)

    Robert A Hirst

    Full Text Available The diagnosis of primary ciliary dyskinesia (PCD requires the analysis of ciliary function and ultrastructure. Diagnosis can be complicated by secondary effects on cilia such as damage during sampling, local inflammation or recent infection. To differentiate primary from secondary abnormalities, re-analysis of cilia following culture and re-differentiation of epithelial cells at an air-liquid interface (ALI aids the diagnosis of PCD. However changes in ciliary beat pattern of cilia following epithelial cell culture has previously been described, which has brought the robustness of this method into question. This is the first systematic study to evaluate ALI culture as an aid to diagnosis of PCD in the light of these concerns.We retrospectively studied changes associated with ALI-culture in 158 subjects referred for diagnostic testing at two PCD centres. Ciliated nasal epithelium (PCD n = 54; non-PCD n  111 was analysed by high-speed digital video microscopy and transmission electron microscopy before and after culture.Ciliary function was abnormal before and after culture in all subjects with PCD; 21 PCD subjects had a combination of static and uncoordinated twitching cilia, which became completely static following culture, a further 9 demonstrated a decreased ciliary beat frequency after culture. In subjects without PCD, secondary ciliary dyskinesia was reduced.The change to ciliary phenotype in PCD samples following cell culture does not affect the diagnosis, and in certain cases can assist the ability to identify PCD cilia.

  11. X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3.

    NARCIS (Netherlands)

    Olcese, C.; Patel, M.P.; Shoemark, A.; Kiviluoto, S.; Legendre, M.; Williams, H.J.; Vaughan, C.K.; Hayward, J.; Goldenberg, A.; Emes, R.D.; Munye, M.M.; Dyer, L.; Cahill, T.; Bevillard, J.; Gehrig, C.; Guipponi, M.; Chantot, S.; Duquesnoy, P.; Thomas, L.; Jeanson, L.; Copin, B.; Tamalet, A.; Thauvin-Robinet, C.; Papon, J.F.; Garin, A.; Pin, I.; Vera, G.; Aurora, P.; Fassad, M.R.; Jenkins, L.; Boustred, C.; Cullup, T.; Dixon, M.; Onoufriadis, A.; Bush, A.; Chung, E.M.; Antonarakis, S.E.; Loebinger, M.R.; Wilson, R.; Armengot, M.; Escudier, E.; Hogg, C.; Amselem, S.; Sun, Z.; Bartoloni, L.; Blouin, J.L.; Mitchison, H.M.; Schmidts, M.; et al.,

    2017-01-01

    By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of

  12. Alternative Fuels Data Center: St. Louis Airport Relies on Biodiesel and

    Science.gov (United States)

    Natural Gas Vehicles St. Louis Airport Relies on Biodiesel and Natural Gas Vehicles to someone by E-mail Share Alternative Fuels Data Center: St. Louis Airport Relies on Biodiesel and Natural Gas Vehicles on Facebook Tweet about Alternative Fuels Data Center: St. Louis Airport Relies on Biodiesel and

  13. 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

    2009-09-01

    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.

  14. 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

  15. 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

    2010-02-01

    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.

  16. New Roles of the Primary Cilium in Autophagy.

    Science.gov (United States)

    Ávalos, Yenniffer; Peña-Oyarzun, Daniel; Budini, Mauricio; Morselli, Eugenia; Criollo, Alfredo

    2017-01-01

    The primary cilium is a nonmotile organelle that emanates from the surface of multiple cell types and receives signals from the environment to regulate intracellular signaling pathways. The presence of cilia, as well as their length, is important for proper cell function; shortened, elongated, or absent cilia are associated with pathological conditions. Interestingly, it has recently been shown that the molecular machinery involved in autophagy, the process of recycling of intracellular material to maintain cellular and tissue homeostasis, participates in ciliogenesis. Cilium-dependent signaling is necessary for autophagosome formation and, conversely, autophagy regulates both ciliogenesis and cilium length by degrading specific ciliary proteins. Here, we will discuss the relationship that exists between the two processes at the cellular and molecular level, highlighting what is known about the effects of ciliary dysfunction in the control of energy homeostasis in some ciliopathies.

  17. 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...... 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.......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...

  18. Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects

    NARCIS (Netherlands)

    Nikopoulos, K.; Farinelli, P.; Giangreco, B.; Tsika, C.; Royer-Bertrand, B.; Mbefo, M.K.; Bedoni, N.; Kjellstrom, U.; El Zaoui, I.; Di Gioia, S.A.; Balzano, S.; Cisarova, K.; Messina, A.; Decembrini, S.; Plainis, S.; Blazaki, S.V.; Khan, M.I.; Micheal, S.; Boldt, K.; Ueffing, M.; Moulin, A.P.; Cremers, F.P.; Roepman, R.; Arsenijevic, Y.; Tsilimbaris, M.K.; Andreasson, S.; Rivolta, C.

    2016-01-01

    Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis

  19. 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.

  20. Mouse V1 population correlates of visual detection rely on heterogeneity within neuronal response patterns

    Science.gov (United States)

    Montijn, Jorrit S; Goltstein, Pieter M; Pennartz, Cyriel MA

    2015-01-01

    Previous studies have demonstrated the importance of the primary sensory cortex for the detection, discrimination, and awareness of visual stimuli, but it is unknown how neuronal populations in this area process detected and undetected stimuli differently. Critical differences may reside in the mean strength of responses to visual stimuli, as reflected in bulk signals detectable in functional magnetic resonance imaging, electro-encephalogram, or magnetoencephalography studies, or may be more subtly composed of differentiated activity of individual sensory neurons. Quantifying single-cell Ca2+ responses to visual stimuli recorded with in vivo two-photon imaging, we found that visual detection correlates more strongly with population response heterogeneity rather than overall response strength. Moreover, neuronal populations showed consistencies in activation patterns across temporally spaced trials in association with hit responses, but not during nondetections. Contrary to models relying on temporally stable networks or bulk signaling, these results suggest that detection depends on transient differentiation in neuronal activity within cortical populations. DOI: http://dx.doi.org/10.7554/eLife.10163.001 PMID:26646184

  1. Learning Similar Actions by Reinforcement or Sensory-Prediction Errors Rely on Distinct Physiological Mechanisms.

    Science.gov (United States)

    Uehara, Shintaro; Mawase, Firas; Celnik, Pablo

    2017-09-14

    Humans can acquire knowledge of new motor behavior via different forms of learning. The two forms most commonly studied have been the development of internal models based on sensory-prediction errors (error-based learning) and success-based feedback (reinforcement learning). Human behavioral studies suggest these are distinct learning processes, though the neurophysiological mechanisms that are involved have not been characterized. Here, we evaluated physiological markers from the cerebellum and the primary motor cortex (M1) using noninvasive brain stimulations while healthy participants trained finger-reaching tasks. We manipulated the extent to which subjects rely on error-based or reinforcement by providing either vector or binary feedback about task performance. Our results demonstrated a double dissociation where learning the task mainly via error-based mechanisms leads to cerebellar plasticity modifications but not long-term potentiation (LTP)-like plasticity changes in M1; while learning a similar action via reinforcement mechanisms elicited M1 LTP-like plasticity but not cerebellar plasticity changes. Our findings indicate that learning complex motor behavior is mediated by the interplay of different forms of learning, weighing distinct neural mechanisms in M1 and the cerebellum. Our study provides insights for designing effective interventions to enhance human motor learning. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Mutations in ZMYND10, a gene essential for proper axonemal assembly of inner and outer dynein arms in humans and flies, cause primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Moore, Daniel J; Onoufriadis, Alexandros; Shoemark, Amelia

    2013-01-01

    Primary ciliary dyskinesia (PCD) is a ciliopathy characterized by airway disease, infertility, and laterality defects, often caused by dual loss of the inner dynein arms (IDAs) and outer dynein arms (ODAs), which power cilia and flagella beating. Using whole-exome and candidate-gene Sanger resequ...

  3. 47 CFR 15.717 - TVBDs that rely on spectrum sensing.

    Science.gov (United States)

    2010-10-01

    ... Television Band Devices § 15.717 TVBDs that rely on spectrum sensing. (a) Parties may submit applications for... that are identical in electrical characteristics and antenna systems may be certified under the...

  4. Increasing Uncertainty: The Dangers of Relying on Conventional Forces for Nuclear Deterrence

    Science.gov (United States)

    2016-03-14

    72 | Air & Space Power Journal Increasing Uncertainty The Dangers of Relying on Conventional Forces for Nuclear Deterrence Jennifer Bradley To put...relationships and should serve as the cornerstone of US nuclear deterrence policy. Although Russia and China are not identified as adversaries of...exactly what has happened over the past year. The US decision to meet the needs of deterrence by relying less on nuclear weapons and instead devel- oping

  5. Energetic solutions of Rock Sandpipers to harsh winter conditions rely on prey quality

    Science.gov (United States)

    Ruthrauff, Daniel R.; Dekinga, Anne; Gill, Robert E.; Piersma, Theunis

    2018-01-01

    Rock Sandpipers Calidris ptilocnemis have the most northerly non-breeding distribution of any shorebird in the Pacific Basin (upper Cook Inlet, Alaska; 61°N, 151°W). In terms of freezing temperatures, persistent winds and pervasive ice, this site is the harshest used by shorebirds during winter. We integrated physiological, metabolic, behavioural and environmental aspects of the non-breeding ecology of Rock Sandpipers at the northern extent of their range to determine the relative importance of these factors in facilitating their unique non-breeding ecology. Not surprisingly, estimated daily energetic demands were greatest during January, the coldest period of winter. These estimates were greatest for foraging birds, and exceeded basal metabolic rates by a factor of 6.5, a scope of increase that approaches the maximum sustained rate of energetic output by shorebirds during periods of migration, but far exceeds these periods in duration. We assessed the quality of their primary prey, the bivalve Macoma balthica, to determine the daily foraging duration required by Rock Sandpipers to satisfy such energetic demands. Based on size-specific estimates of M. balthica quality, Rock Sandpipers require over 13 h/day of foraging time in upper Cook Inlet in January, even when feeding on the highest quality prey. This range approaches the average daily duration of mudflat availability in this region (c. 18 h), a maximum value that annually decreases due to the accumulation of shore-fast ice. Rock Sandpipers are likely to maximize access to foraging sites by following the exposure of ice-free mudflats across the upper Cook Inlet region and by selecting smaller, higher quality M. balthica to minimize foraging times. Ultimately, this unusual non-breeding ecology relies on the high quality of their prey resources. Compared with other sites across their range, M. balthica from upper Cook Inlet have relatively light shells, potentially the result of the region

  6. 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.)

  7. Non-essential role for cilia in coordinating precise alignment of lens fibres

    Czech Academy of Sciences Publication Activity Database

    Sugiyama, Y.; Shelley, E.J.; Yoder, B.K.; Kozmik, Zbyněk; May-Simera, H.L.; Beales, P.L.; Lovicu, F.J.; McAvoy, J.W.

    2016-01-01

    Roč. 139, FEB 2016 (2016), s. 10-17 ISSN 0925-4773 R&D Projects: GA ČR GA15-23675S Institutional support: RVO:68378050 Keywords : Lens * Primary cilium * ift88 * Bardet-Biedl Syndrome (BBS) * Planar cell polarity (PCP) Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.333, year: 2016

  8. 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 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 the ...

  9. Usher syndrome type I associated with bronchiectasis and immotile nasal cilia in two brothers.

    OpenAIRE

    Bonneau, D; Raymond, F; Kremer, C; Klossek, J M; Kaplan, J; Patte, F

    1993-01-01

    Usher syndrome type I is an autosomal recessive disease characterised by congenital sensorineural deafness, involvement of the vestibular system, and progressive visual loss owing to retinitis pigmentosa. Here we report the association of this disease with bronchiectasis, chronic sinusitis, and reduced nasal mucociliary clearance in two sibs and we suggest Usher syndrome type I could be a primary ciliary disorder.

  10. 76 FR 69545 - Conditions and Requirements for Relying on Component Part Testing or Certification, or Another...

    Science.gov (United States)

    2011-11-08

    ... the final rule to incorporate the concept that a finished product certifier may rely upon finished... revised, on our own initiative, the final rule to incorporate the concept that a finished product... Vol. 76 Tuesday, No. 216 November 8, 2011 Part IV Consumer Product Safety Commission 16 CFR Parts...

  11. Cortical control of object-specific grasp relies on adjustments of both activity and effective connectivity

    DEFF Research Database (Denmark)

    Tia, Banty; Takemi, Mitsuaki; Kosugi, Akito

    2017-01-01

    The cortical mechanisms of grasping have been extensively studied in macaques and humans. Here, we investigated whether common marmosets could rely on similar mechanisms despite striking differences in manual dexterity. Two common marmosets were trained to grasp-and-pull three objects eliciting d...

  12. 77 FR 70117 - Purchase of Certain Debt Securities by Business and Industrial Development Companies Relying on...

    Science.gov (United States)

    2012-11-23

    ... 3235-AL02 Purchase of Certain Debt Securities by Business and Industrial Development Companies Relying... securities; (B) is engaged or proposes to engage in the business of issuing face-amount certificates of the... business of issuing redeemable securities, the operations of which are subject to regulation by the State...

  13. Inactivation of Ca2+-induced ciliary reversal by high-salt extraction in the cilia of Paramecium.

    Science.gov (United States)

    Kutomi, Osamu; Seki, Makoto; Nakamura, Shogo; Kamachi, Hiroyuki; Noguchi, Munenori

    2013-10-01

    Intracellular Ca(2+) induces ciliary reversal and backward swimming in Paramecium. However, it is not known how the Ca(2+) signal controls the motor machinery to induce ciliary reversal. We found that demembranated cilia on the ciliated cortical sheets from Paramecium caudatum lost the ability to undergo ciliary reversal after brief extraction with a solution containing 0.5 M KCl. KNO(3), which is similar to KCl with respect to chaotropic effect; it had the same effect as that of KCl on ciliary response. Cyclic AMP antagonizes Ca(2+)-induced ciliary reversal. Limited trypsin digestion prevents endogenous A-kinase and cAMP-dependent phosphorylation of an outer arm dynein light chain and induces ciliary reversal. However, the trypsin digestion prior to the high-salt extraction did not affect the inhibition of Ca(2+)-induced ciliary reversal caused by the high-salt extraction. Furthermore, during the course of the high-salt extraction, some axonemal proteins were extracted from ciliary axonemes, suggesting that they may be responsible for Ca(2+)-induced ciliary reversal.

  14. Smoothened-antagonists reverse homogentisic acid-induced alterations of Hedgehog signaling and primary cilium length in alkaptonuria.

    Science.gov (United States)

    Gambassi, Silvia; Geminiani, Michela; Thorpe, Stephen D; Bernardini, Giulia; Millucci, Lia; Braconi, Daniela; Orlandini, Maurizio; Thompson, Clare L; Petricci, Elena; Manetti, Fabrizio; Taddei, Maurizio; Knight, Martin M; Santucci, Annalisa

    2017-11-01

    Alkaptonuria (AKU) is an ultra-rare genetic disease, in which the accumulation of a toxic metabolite, homogentisic acid (HGA) leads to the systemic development of ochronotic aggregates. These aggregates cause severe complications mainly at the level of joints with extensive degradation of the articular cartilage. Primary cilia have been demonstrated to play an essential role in development and the maintenance of articular cartilage homeostasis, through their involvement in mechanosignaling and Hedgehog signaling pathways. Hedgehog signaling has been demonstrated to be activated in osteoarthritis (OA) and to drive cartilage degeneration in vivo. The numerous similarities between OA and AKU suggest that primary cilia Hedgehog signaling may also be altered in AKU. Thus, we characterized an AKU cellular model in which healthy chondrocytes were treated with HGA (66 µM) to replicate AKU cartilage pathology. We investigated the degree of activation of the Hedgehog signaling pathway and how treatment with inhibitors of the receptor Smoothened (Smo) influenced Hedgehog activation and primary cilia structure. The results obtained in this work provide a further step in the comprehension of the pathophysiological features of AKU, suggesting a potential therapeutic approach to modulate AKU cartilage degradation processes through manipulation of the Hedgehog pathway. © 2016 Wiley Periodicals, Inc.

  15. Un premier service mobile en Égypte qui relie les petits exploitants ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Un premier service mobile en Égypte qui relie les petits exploitants aux acheteurs. Un homme qui parle sur un téléphone mobile. Les petits exploitants agricoles dominent l'agriculture égyptienne, mais leur manque de connaissances en matière de commercialisation et de compétences techniques, ainsi qu'une mauvaise ...

  16. Can we rely on the antiretroviral treatment as the only means for human immunodeficiency virusprevention? A Public Health perspective.

    Science.gov (United States)

    Mozalevskis, Antons; Manzanares-Laya, Sandra; García de Olalla, Patricia; Moreno, Antonio; Jacques-Aviñó, Constanza; Caylà, Joan A

    2015-11-01

    The evidence that supports the preventive effect of combination antiretroviral treatment (cART) in HIV sexual transmission suggested the so-called 'treatment as prevention' (TAP) strategy as a promising tool for slowing down HIV transmission. As the messages and attitudes towards condom use in the context of TAP appear to be somehow confusing, the aim here is to assess whether relying on cART alone to prevent HIV transmission can currently be recommended from the Public Health perspective. A review is made of the literature on the effects of TAP strategy on HIV transmission and the epidemiology of other sexual transmitted infections (STIs) in the cART era, and recommendations from Public Health institutions on the TAP as of February 2014. The evolution of HIV and other STIs in Barcelona from 2007 to 2012 has also been analysed. Given that the widespread use of cART has coincided with an increasing incidence of HIV and other STIs, mainly amongst men who have sex with men, a combination and diversified prevention methods should always be considered and recommended in counselling. An informed decision on whether to stop using condoms should only be made by partners within stable couples, and after receiving all the up-to-date information regarding TAP. From the public health perspective, primary prevention should be a priority; therefore relying on cART alone is not a sufficient strategy to prevent new HIV and other STIs. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  17. Logical Characterisation of Concept Transformations from Human into Machine relying on Predicate Logic

    DEFF Research Database (Denmark)

    Badie, Farshad

    2016-01-01

    Providing more human-like concept learning in machines has always been one of the most significant goals of machine learning paradigms and of human-machine interaction techniques. This article attempts to provide a logical specification of conceptual mappings from humans’ minds into machines......’ knowledge bases. I will focus on the representation of the mappings (transformations) relying on First-Order Predicate Logic. Additionally, the structure of concepts in the common ground between humans and machines will be analysed. It seems quite necessary to pay attention to the philosophy...

  18. Regulated Medicare Advantage And Marketplace Individual Health Insurance Markets Rely On Insurer Competition.

    Science.gov (United States)

    Frank, Richard G; McGuire, Thomas G

    2017-09-01

    Two important individual health insurance markets-Medicare Advantage and the Marketplaces-are tightly regulated but rely on competition among insurers to supply and price health insurance products. Many local health insurance markets have little competition, which increases prices to consumers. Furthermore, both markets are highly subsidized in ways that can exacerbate the impact of market power-that is, the ability to set price above cost-on health insurance prices. Policy makers need to foster robust competition in both sectors and avoid designing subsidies that make the market-power problem worse. Project HOPE—The People-to-People Health Foundation, Inc.

  19. Anemonefishes rely on visual and chemical cues to correctly identify conspecifics

    Science.gov (United States)

    Johnston, Nicole K.; Dixson, Danielle L.

    2017-09-01

    Organisms rely on sensory cues to interpret their environment and make important life-history decisions. Accurate recognition is of particular importance in diverse reef environments. Most evidence on the use of sensory cues focuses on those used in predator avoidance or habitat recognition, with little information on their role in conspecific recognition. Yet conspecific recognition is essential for life-history decisions including settlement, mate choice, and dominance interactions. Using a sensory manipulated tank and a two-chamber choice flume, anemonefish conspecific response was measured in the presence and absence of chemical and/or visual cues. Experiments were then repeated in the presence or absence of two heterospecific species to evaluate whether a heterospecific fish altered the conspecific response. Anemonefishes responded to both the visual and chemical cues of conspecifics, but relied on the combination of the two cues to recognize conspecifics inside the sensory manipulated tank. These results contrast previous studies focusing on predator detection where anemonefishes were found to compensate for the loss of one sensory cue (chemical) by utilizing a second cue (visual). This lack of sensory compensation may impact the ability of anemonefishes to acclimate to changing reef environments in the future.

  20. Primary cilium depletion typifies cutaneous melanoma in situ and malignant melanoma.

    Directory of Open Access Journals (Sweden)

    Jinah Kim

    Full Text Available Cutaneous melanoma is a lethal malignancy that arises spontaneously or via in situ precursor neoplasms. While melanoma in situ and locally invasive malignant melanoma can be cured surgically, these lesions can sometimes be difficult to distinguish from melanocytic nevi. Thus, the identification of histolopathologic or molecular features that distinguish these biologically distinct lesions would represent an important advance. To this end, we determined the abundance of melanocytic primary cilia in a series of 62 cases composed of typical cutaneous melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma. Primary cilia are sensory organelles that modulate developmental and adaptive signaling and notably, are substantially depleted from the neoplastic epithelium of pancreatic carcinoma at a stage equivalent to melanoma in situ. In this series, we find that while nearly all melanocytes in 22 melanocytic nevi possessed a primary cilium, a near-complete loss of this organelle was observed in 16 cases of melanoma in situ, in 16 unequivocal primary invasive melanomas, and in 8 metastatic tumors, each associated with a cutaneous primary lesion. These findings suggest that the primary cilium may be used to segregate cutaneous invasive melanoma and melanoma in situ from melanocytic nevi. Moreover, they place the loss of an organelle known to regulate oncogenic signaling at an early stage of melanoma development.

  1. Hummingbirds rely on both paracellular and carrier-mediated intestinal glucose absorption to fuel high metabolism

    Science.gov (United States)

    McWhorter, Todd J; Bakken, Bradley Hartman; Karasov, William H; del Rio, Carlos Martínez

    2005-01-01

    Twenty years ago, the highest active glucose transport rate and lowest passive glucose permeability in vertebrates were reported in Rufous and Anna's hummingbirds (Selasphorus rufus, Calypte anna). These first measurements of intestinal nutrient absorption in nectarivores provided an unprecedented physiological foundation for understanding their foraging ecology. They showed that physiological processes are determinants of feeding behaviour. The conclusion that active, mediated transport accounts for essentially all glucose absorption in hummingbirds influenced two decades of subsequent research on the digestive physiology and nutritional ecology of nectarivores. Here, we report new findings demonstrating that the passive permeability of hummingbird intestines to glucose is much higher than previously reported, suggesting that not all sugar uptake is mediated. Even while possessing the highest active glucose transport rates measured in vertebrates, hummingbirds must rely partially on passive non-mediated intestinal nutrient absorption to meet their high mass-specific metabolic demands. PMID:17148346

  2. Episodic Memory Retrieval Functionally Relies on Very Rapid Reactivation of Sensory Information.

    Science.gov (United States)

    Waldhauser, Gerd T; Braun, Verena; Hanslmayr, Simon

    2016-01-06

    Episodic memory retrieval is assumed to rely on the rapid reactivation of sensory information that was present during encoding, a process termed "ecphory." We investigated the functional relevance of this scarcely understood process in two experiments in human participants. We presented stimuli to the left or right of fixation at encoding, followed by an episodic memory test with centrally presented retrieval cues. This allowed us to track the reactivation of lateralized sensory memory traces during retrieval. Successful episodic retrieval led to a very early (∼100-200 ms) reactivation of lateralized alpha/beta (10-25 Hz) electroencephalographic (EEG) power decreases in the visual cortex contralateral to the visual field at encoding. Applying rhythmic transcranial magnetic stimulation to interfere with early retrieval processing in the visual cortex led to decreased episodic memory performance specifically for items encoded in the visual field contralateral to the site of stimulation. These results demonstrate, for the first time, that episodic memory functionally relies on very rapid reactivation of sensory information. Remembering personal experiences requires a "mental time travel" to revisit sensory information perceived in the past. This process is typically described as a controlled, relatively slow process. However, by using electroencephalography to measure neural activity with a high time resolution, we show that such episodic retrieval entails a very rapid reactivation of sensory brain areas. Using transcranial magnetic stimulation to alter brain function during retrieval revealed that this early sensory reactivation is causally relevant for conscious remembering. These results give first neural evidence for a functional, preconscious component of episodic remembering. This provides new insight into the nature of human memory and may help in the understanding of psychiatric conditions that involve the automatic intrusion of unwanted memories. Copyright

  3. Cochlear implant users rely on tempo rather than on pitch information during perception of musical emotion.

    Science.gov (United States)

    Caldwell, Meredith; Rankin, Summer K; Jiradejvong, Patpong; Carver, Courtney; Limb, Charles J

    2015-09-01

    The purpose of this study was to investigate the extent to which cochlear implant (CI) users rely on tempo and mode in perception of musical emotion when compared with normal hearing (NH) individuals. A test battery of novel four-bar melodies was created and adapted to four permutations with alterations of tonality (major vs. minor) and tempo (presto vs. largo), resulting in non-ambiguous (major key/fast tempo and minor key/slow tempo) and ambiguous (major key/slow tempo, and minor key/fast tempo) musical stimuli. Both CI and NH participants listened to each clip and provided emotional ratings on a Likert scale of +5 (happy) to -5 (sad). A three-way ANOVA demonstrated an overall effect for tempo in both groups, and an overall effect for mode in the NH group. The CI group rated stimuli of the same tempo similarly, regardless of changes in mode, whereas the NH group did not. A subgroup analysis indicated the same effects in both musician and non-musician CI users and NH listeners. The results suggest that the CI group relied more heavily on tempo than mode in making musical emotion decisions. The subgroup analysis further suggests that level of musical training did not significantly impact this finding. CI users weigh temporal cues more heavily than pitch cues in inferring musical emotion. These findings highlight the significant disadvantage of CI users in comparison with NH listeners for music perception, particularly during recognition of musical emotion, a critically important feature of music.

  4. SEE ME ROAR: Self-determination Enhanced Engagement for Math Education Relying On Augmented Reality

    NARCIS (Netherlands)

    Li, J.; van der Spek, E.D.; Hu, J.; Feijs, L.M.G.

    2017-01-01

    Contemporary primary school students generally spend a lot of time playing digital games, but may be less interested in their schoolwork, such as learning mathematics. Mathematics includes many abstract concepts that can be difficult to grasp for some students. Augmented reality as a technology

  5. Defining the buffering process by a triprotic acid without relying on Stewart-electroneutrality considerations.

    Science.gov (United States)

    Nguyen, Minhtri K; Kao, Liyo; Kurtz, Ira

    2011-08-17

    Upon the addition of protons to an aqueous solution, a component of the H+ load will be bound i.e. buffered. In an aqueous solution containing a triprotic acid, H+ can be bound to three different states of the acid as well as to OH- ions that are derived from the auto-ionization of H2O. In quantifying the buffering process of a triprotic acid, one must define the partitioning of H+ among the three states of the acid and also the OH- ions in solution in order to predict the equilibrium pH value. However, previous quantitative approaches that model triprotic acid titration behaviour and used to predict the equilibrium pH rely on the mathematical convenience of electroneutrality/charge balance considerations. This fact has caused confusion in the literature, and has led to the assumption that charge balance/electroneutrality is a causal factor in modulating proton buffering (Stewart formulation). However, as we have previously shown, although charge balance can be used mathematically as a convenient tool in deriving various formulae, electroneutrality per se is not a fundamental physicochemical parameter that is mechanistically involved in the underlying buffering and proton transfer reactions. The lack of distinction between a mathematical tool, and a fundamental physicochemical parameter is in part a reason for the current debate regarding the Stewart formulation of acid-base analysis. We therefore posed the following question: Is it possible to generate an equation that defines and predicts the buffering of a triprotic acid that is based only on H+ partitioning without incorporating electroneutrality in the derivation? Towards this goal, we derived our new equation utilizing: 1) partitioning of H+ buffering; 2) conservation of mass; and 3) acid-base equilibria. In validating this model, we compared the predicted equilibrium pH with the measured pH of an aqueous solution consisting of Na2HPO4 to which HCl was added. The measured pH values were in excellent agreement

  6. Defining the buffering process by a triprotic acid without relying on stewart-electroneutrality considerations

    Directory of Open Access Journals (Sweden)

    Kao Liyo

    2011-08-01

    Full Text Available Abstract Upon the addition of protons to an aqueous solution, a component of the H+ load will be bound i.e. buffered. In an aqueous solution containing a triprotic acid, H+ can be bound to three different states of the acid as well as to OH- ions that are derived from the auto-ionization of H2O. In quantifying the buffering process of a triprotic acid, one must define the partitioning of H+ among the three states of the acid and also the OH- ions in solution in order to predict the equilibrium pH value. However, previous quantitative approaches that model triprotic acid titration behaviour and used to predict the equilibrium pH rely on the mathematical convenience of electroneutrality/charge balance considerations. This fact has caused confusion in the literature, and has led to the assumption that charge balance/electroneutrality is a causal factor in modulating proton buffering (Stewart formulation. However, as we have previously shown, although charge balance can be used mathematically as a convenient tool in deriving various formulae, electroneutrality per se is not a fundamental physicochemical parameter that is mechanistically involved in the underlying buffering and proton transfer reactions. The lack of distinction between a mathematical tool, and a fundamental physicochemical parameter is in part a reason for the current debate regarding the Stewart formulation of acid-base analysis. We therefore posed the following question: Is it possible to generate an equation that defines and predicts the buffering of a triprotic acid that is based only on H+ partitioning without incorporating electroneutrality in the derivation? Towards this goal, we derived our new equation utilizing: 1 partitioning of H+ buffering; 2 conservation of mass; and 3 acid-base equilibria. In validating this model, we compared the predicted equilibrium pH with the measured pH of an aqueous solution consisting of Na2HPO4 to which HCl was added. The measured pH values

  7. Defining the buffering process by a triprotic acid without relying on stewart-electroneutrality considerations

    Science.gov (United States)

    2011-01-01

    Upon the addition of protons to an aqueous solution, a component of the H+ load will be bound i.e. buffered. In an aqueous solution containing a triprotic acid, H+ can be bound to three different states of the acid as well as to OH- ions that are derived from the auto-ionization of H2O. In quantifying the buffering process of a triprotic acid, one must define the partitioning of H+ among the three states of the acid and also the OH- ions in solution in order to predict the equilibrium pH value. However, previous quantitative approaches that model triprotic acid titration behaviour and used to predict the equilibrium pH rely on the mathematical convenience of electroneutrality/charge balance considerations. This fact has caused confusion in the literature, and has led to the assumption that charge balance/electroneutrality is a causal factor in modulating proton buffering (Stewart formulation). However, as we have previously shown, although charge balance can be used mathematically as a convenient tool in deriving various formulae, electroneutrality per se is not a fundamental physicochemical parameter that is mechanistically involved in the underlying buffering and proton transfer reactions. The lack of distinction between a mathematical tool, and a fundamental physicochemical parameter is in part a reason for the current debate regarding the Stewart formulation of acid-base analysis. We therefore posed the following question: Is it possible to generate an equation that defines and predicts the buffering of a triprotic acid that is based only on H+ partitioning without incorporating electroneutrality in the derivation? Towards this goal, we derived our new equation utilizing: 1) partitioning of H+ buffering; 2) conservation of mass; and 3) acid-base equilibria. In validating this model, we compared the predicted equilibrium pH with the measured pH of an aqueous solution consisting of Na2HPO4 to which HCl was added. The measured pH values were in excellent agreement

  8. 12 CFR 221.117 - When bank in “good faith” has not relied on stock as collateral.

    Science.gov (United States)

    2010-01-01

    ... bank in “good faith” has not relied on stock as collateral. (a) The Board has received questions... “indirectly secured” by stock as indicated by the phrase, “if the lender, in good faith, has not relied upon...

  9. The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study

    DEFF Research Database (Denmark)

    Connolly, S. J.; Wallentin, L.; Ezekowitz, M. D.

    2013-01-01

    . There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY...

  10. Frugivorous bats maintain functional habitat connectivity in agricultural landscapes but rely strongly on natural forest fragments.

    Science.gov (United States)

    Ripperger, Simon P; Kalko, Elisabeth K V; Rodríguez-Herrera, Bernal; Mayer, Frieder; Tschapka, Marco

    2015-01-01

    Anthropogenic changes in land use threaten biodiversity and ecosystem functioning by the conversion of natural habitat into agricultural mosaic landscapes, often with drastic consequences for the associated fauna. The first step in the development of efficient conservation plans is to understand movement of animals through complex habitat mosaics. Therefore, we studied ranging behavior and habitat use in Dermanura watsoni (Phyllostomidae), a frugivorous bat species that is a valuable seed disperser in degraded ecosystems. Radio-tracking of sixteen bats showed that the animals strongly rely on natural forest. Day roosts were exclusively located within mature forest fragments. Selection ratios showed that the bats foraged selectively within the available habitat and positively selected natural forest. However, larger daily ranges were associated with higher use of degraded habitats. Home range geometry and composition of focal foraging areas indicated that wider ranging bats performed directional foraging bouts from natural to degraded forest sites traversing the matrix over distances of up to three hundred meters. This behavior demonstrates the potential of frugivorous bats to functionally connect fragmented areas by providing ecosystem services between natural and degraded sites, and highlights the need for conservation of natural habitat patches within agricultural landscapes that meet the roosting requirements of bats.

  11. Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation

    Science.gov (United States)

    Lakkaraju, Asvin K. K.; Thankappan, Ratheeshkumar; Mary, Camille; Garrison, Jennifer L.; Taunton, Jack; Strub, Katharina

    2012-01-01

    Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ≤100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway. PMID:22648169

  12. Regulatory theory: commercially sustainable markets rely upon satisfying the public interest in obtaining credible goods.

    Science.gov (United States)

    Warren-Jones, Amanda

    2017-10-01

    Regulatory theory is premised on the failure of markets, prompting a focus on regulators and industry from economic perspectives. This article argues that overlooking the public interest in the sustainability of commercial markets risks markets failing completely. This point is exemplified through health care markets - meeting an essential need - and focuses upon innovative medicines as the most desired products in that market. If this seemingly invulnerable market risks failure, there is a pressing need to consider the public interest in sustainable markets within regulatory literature and practice. Innovative medicines are credence goods, meaning that the sustainability of the market fundamentally relies upon the public trusting regulators to vouch for product quality. Yet, quality is being eroded by patent bodies focused on economic benefits from market growth, rather than ensuring innovatory value. Remunerative bodies are not funding medicines relative to market value, and market authorisation bodies are not vouching for robust safety standards or confining market entry to products for 'unmet medical need'. Arguably, this failure to assure quality heightens the risk of the market failing where it cannot be substituted by the reputation or credibility of providers of goods and/or information such as health care professionals/institutions, patient groups or industry.

  13. Quality of record linkage in a highly automated cancer registry that relies on encrypted identity data

    Directory of Open Access Journals (Sweden)

    Schmidtmann, Irene

    2016-06-01

    Full Text Available Objectives: In the absence of unique ID numbers, cancer and other registries in Germany and elsewhere rely on identity data to link records pertaining to the same patient. These data are often encrypted to ensure privacy. Some record linkage errors unavoidably occur. These errors were quantified for the cancer registry of North Rhine Westphalia which uses encrypted identity data. Methods: A sample of records was drawn from the registry, record linkage information was included. In parallel, plain text data for these records were retrieved to generate a gold standard. Record linkage error frequencies in the cancer registry were determined by comparison of the results of the routine linkage with the gold standard. Error rates were projected to larger registries.Results: In the sample studied, the homonym error rate was 0.015%; the synonym error rate was 0.2%. The F-measure was 0.9921. Projection to larger databases indicated that for a realistic development the homonym error rate will be around 1%, the synonym error rate around 2%.Conclusion: Observed error rates are low. This shows that effective methods to standardize and improve the quality of the input data have been implemented. This is crucial to keep error rates low when the registry’s database grows. The planned inclusion of unique health insurance numbers is likely to further improve record linkage quality. Cancer registration entirely based on electronic notification of records can process large amounts of data with high quality of record linkage.

  14. Pneumococcal Competence Coordination Relies on a Cell-Contact Sensing Mechanism.

    Directory of Open Access Journals (Sweden)

    Marc Prudhomme

    2016-06-01

    Full Text Available Bacteria have evolved various inducible genetic programs to face many types of stress that challenge their growth and survival. Competence is one such program. It enables genetic transformation, a major horizontal gene transfer process. Competence development in liquid cultures of Streptococcus pneumoniae is synchronized within the whole cell population. This collective behavior is known to depend on an exported signaling Competence Stimulating Peptide (CSP, whose action generates a positive feedback loop. However, it is unclear how this CSP-dependent population switch is coordinated. By monitoring spontaneous competence development in real time during growth of four distinct pneumococcal lineages, we have found that competence shift in the population relies on a self-activated cell fraction that arises via a growth time-dependent mechanism. We demonstrate that CSP remains bound to cells during this event, and conclude that the rate of competence development corresponds to the propagation of competence by contact between activated and quiescent cells. We validated this two-step cell-contact sensing mechanism by measuring competence development during co-cultivation of strains with altered capacity to produce or respond to CSP. Finally, we found that the membrane protein ComD retains the CSP, limiting its free diffusion in the medium. We propose that competence initiator cells originate stochastically in response to stress, to form a distinct subpopulation that then transmits the CSP by cell-cell contact.

  15. Frugivorous bats maintain functional habitat connectivity in agricultural landscapes but rely strongly on natural forest fragments.

    Directory of Open Access Journals (Sweden)

    Simon P Ripperger

    Full Text Available Anthropogenic changes in land use threaten biodiversity and ecosystem functioning by the conversion of natural habitat into agricultural mosaic landscapes, often with drastic consequences for the associated fauna. The first step in the development of efficient conservation plans is to understand movement of animals through complex habitat mosaics. Therefore, we studied ranging behavior and habitat use in Dermanura watsoni (Phyllostomidae, a frugivorous bat species that is a valuable seed disperser in degraded ecosystems. Radio-tracking of sixteen bats showed that the animals strongly rely on natural forest. Day roosts were exclusively located within mature forest fragments. Selection ratios showed that the bats foraged selectively within the available habitat and positively selected natural forest. However, larger daily ranges were associated with higher use of degraded habitats. Home range geometry and composition of focal foraging areas indicated that wider ranging bats performed directional foraging bouts from natural to degraded forest sites traversing the matrix over distances of up to three hundred meters. This behavior demonstrates the potential of frugivorous bats to functionally connect fragmented areas by providing ecosystem services between natural and degraded sites, and highlights the need for conservation of natural habitat patches within agricultural landscapes that meet the roosting requirements of bats.

  16. Toward a Better Nutritional Aiding in Disasters: Relying on Lessons Learned during the Bam Earthquake.

    Science.gov (United States)

    Nekouie Moghadam, Mahmoud; Amiresmaieli, Mohammadreza; Hassibi, Mohammad; Doostan, Farideh; Khosravi, Sajad

    2017-08-01

    Introduction Examining various problems in the aftermath of disasters is very important to the disaster victims. Managing and coordinating food supply and its distribution among the victims is one of the most important problems after an earthquake. Therefore, the purpose of this study was to recognize problems and experiences in the field of nutritional aiding during an earthquake. This qualitative study was of phenomenological type. Using the purposive sampling method, 10 people who had experienced nutritional aiding during the Bam Earthquake (Iran; 2003) were interviewed. Colaizzi's method of analysis was used to analyze interview data. The findings of this study identified four main categories and 19 sub-categories concerning challenges in the nutritional aiding during the Bam Earthquake. The main topics included managerial, aiding, infrastructural, and administrative problems. The major problems in nutritional aiding include lack of prediction and development of a specific program of suitable nutritional pattern and nutritional assessment of the victims in critical conditions. Forming specialized teams, educating team members about nutrition, and making use of experts' knowledge are the most important steps to resolve these problems in the critical conditions; these measures are the duties of the relevant authorities. Nekouie Moghadam M , Amiresmaieli M , Hassibi M , Doostan F , Khosravi S . Toward a better nutritional aiding in disasters: relying on lessons learned during the Bam Earthquake. Prehosp Disaster Med. 2017;32(4):382-386.

  17. The Low Pitch of High-Frequency Complex Tones Relies on Temporal Fine Structure Information

    DEFF Research Database (Denmark)

    Santurette, Sébastien; Dau, Torsten

    2010-01-01

    High-frequency complex tones containing only unresolved harmonic components with a frequency spacing Δf usually evoke a low pitch equal to Δf. However, for inharmonic components, the low pitch is often found to deviate slightly from Δf. Whether this pitch shift relies exclusively on temporal fine...... structure (TFS) cues has been a matter of debate. It is also controversial up to which frequency TFS information remains available, and to what extent envelope cues become dominant as frequency increases. Using a pitch-matching paradigm, this study investigated whether the pitch of transposed tones.......5]. All stimuli were presented at 50 dB SPL in broadband pink-noise (13.5 dB/Hz at 1 kHz), and 40 matches per condition were obtained. For fenv = fc/11.5, the results favored hypothesis A for all values of fc, indicating that TFS cues are available and used for pitch extraction, up to at least 7 k...

  18. Unparalleled sample treatment throughput for proteomics workflows relying on ultrasonic energy.

    Science.gov (United States)

    Jorge, Susana; Araújo, J E; Pimentel-Santos, F M; Branco, Jaime C; Santos, Hugo M; Lodeiro, Carlos; Capelo, J L

    2018-02-01

    We report on the new microplate horn ultrasonic device as a powerful tool to speed proteomics workflows with unparalleled throughput. 96 complex proteomes were digested at the same time in 4min. Variables such as ultrasonication time, ultrasonication amplitude, and protein to enzyme ratio were optimized. The "classic" method relying on overnight protein digestion (12h) and the sonoreactor-based method were also employed for comparative purposes. We found the protein digestion efficiency homogeneously distributed in the entire microplate horn surface using the following conditions: 4min sonication time and 25% amplitude. Using this approach, patients with lymphoma and myeloma were classified using principal component analysis and a 2D gel-mass spectrometry based approach. Furthermore, we demonstrate the excellent performance by using MALDI-mass spectrometry based profiling as a fast way to classify patients with rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis. Finally, the speed and simplicity of this method were demonstrated by clustering 90 patients with knee osteoarthritis disease (30), with a prosthesis (30, control group) and healthy individuals (30) with no history of joint disease. Overall, the new approach allows profiling a disease in just one week while allows to match the minimalism rules as outlined by Halls. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Laser-induced breakdown spectroscopy and chemometrics for classification of toys relying on toxic elements

    International Nuclear Information System (INIS)

    Godoi, Quienly; Leme, Flavio O.; Trevizan, Lilian C.; Pereira Filho, Edenir R.; Rufini, Iolanda A.; Santos, Dario; Krug, Francisco J.

    2011-01-01

    Quality control of toys for avoiding children exposure to potentially toxic elements is of utmost relevance and it is a common requirement in national and/or international norms for health and safety reasons. Laser-induced breakdown spectroscopy (LIBS) was recently evaluated at authors' laboratory for direct analysis of plastic toys and one of the main difficulties for the determination of Cd, Cr and Pb was the variety of mixtures and types of polymers. As most norms rely on migration (lixiviation) protocols, chemometric classification models from LIBS spectra were tested for sampling toys that present potential risk of Cd, Cr and Pb contamination. The classification models were generated from the emission spectra of 51 polymeric toys and by using Partial Least Squares - Discriminant Analysis (PLS-DA), Soft Independent Modeling of Class Analogy (SIMCA) and K-Nearest Neighbor (KNN). The classification models and validations were carried out with 40 and 11 test samples, respectively. Best results were obtained when KNN was used, with corrected predictions varying from 95% for Cd to 100% for Cr and Pb.

  20. Magnetic Nanocomposite Cilia Sensors

    KAUST Repository

    Alfadhel, Ahmed

    2016-01-01

    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

  1. Fruit production in three masting tree species does not rely on stored carbon reserves.

    Science.gov (United States)

    Hoch, Günter; Siegwolf, Rolf T W; Keel, Sonja G; Körner, Christian; Han, Qingmin

    2013-03-01

    Fruiting is typically considered to massively burden the seasonal carbon budget of trees. The cost of reproduction has therefore been suggested as a proximate factor explaining observed mast-fruiting patterns. Here, we used a large-scale, continuous (13)C labeling of mature, deciduous trees in a temperate Swiss forest to investigate to what extent fruit formation in three species with masting reproduction behavior (Carpinus betulus, Fagus sylvatica, Quercus petraea) relies on the import of stored carbon reserves. Using a free-air CO2 enrichment system, we exposed trees to (13)C-depleted CO2 during 8 consecutive years. By the end of this experiment, carbon reserve pools had significantly lower δ(13)C values compared to control trees. δ(13)C analysis of new biomass during the first season after termination of the CO2 enrichment allowed us to distinguish the sources of built-in carbon (old carbon reserves vs. current assimilates). Flowers and expanding leaves carried a significant (13)C label from old carbon stores. In contrast, fruits and vegetative infructescence tissues were exclusively produced from current, unlabeled photoassimilates in all three species, including F. sylvatica, which had a strong masting season. Analyses of δ(13)C in purified starch from xylem of fruit-bearing shoots revealed a complete turn-over of starch during the season, likely due to its usage for bud break. This study is the first to directly demonstrate that fruiting is independent from old carbon reserves in masting trees, with significant implications for mechanistic models that explain mast seeding.

  2. High sugar-induced insulin resistance in Drosophila relies on the lipocalin Neural Lazarillo.

    Directory of Open Access Journals (Sweden)

    Matthieu Y Pasco

    Full Text Available In multicellular organisms, insulin/IGF signaling (IIS plays a central role in matching energy needs with uptake and storage, participating in functions as diverse as metabolic homeostasis, growth, reproduction and ageing. In mammals, this pleiotropy of action relies in part on a dichotomy of action of insulin, IGF-I and their respective membrane-bound receptors. In organisms with simpler IIS, this functional separation is questionable. In Drosophila IIS consists of several insulin-like peptides called Dilps, activating a unique membrane receptor and its downstream signaling cascade. During larval development, IIS is involved in metabolic homeostasis and growth. We have used feeding conditions (high sugar diet, HSD that induce an important change in metabolic homeostasis to monitor possible effects on growth. Unexpectedly we observed that HSD-fed animals exhibited severe growth inhibition as a consequence of peripheral Dilp resistance. Dilp-resistant animals present several metabolic disorders similar to those observed in type II diabetes (T2D patients. By exploring the molecular mechanisms involved in Drosophila Dilp resistance, we found a major role for the lipocalin Neural Lazarillo (NLaz, a target of JNK signaling. NLaz expression is strongly increased upon HSD and animals heterozygous for an NLaz null mutation are fully protected from HSD-induced Dilp resistance. NLaz is a secreted protein homologous to the Retinol-Binding Protein 4 involved in the onset of T2D in human and mice. These results indicate that insulin resistance shares common molecular mechanisms in flies and human and that Drosophila could emerge as a powerful genetic system to study some aspects of this complex syndrome.

  3. The Integration of Realistic Episodic Memories Relies on Different Working Memory Processes: Evidence from Virtual Navigation

    Directory of Open Access Journals (Sweden)

    Gaën Plancher

    2018-01-01

    central elements. By contrast, the prevention of visuo-spatial maintenance interfered both with the encoding of the temporal context and with the binding. These results suggest that the integration of realistic episodic memories relies on different working memory processes that depend on the nature of the traces.

  4. The Integration of Realistic Episodic Memories Relies on Different Working Memory Processes: Evidence from Virtual Navigation.

    Science.gov (United States)

    Plancher, Gaën; Gyselinck, Valérie; Piolino, Pascale

    2018-01-01

    contrast, the prevention of visuo-spatial maintenance interfered both with the encoding of the temporal context and with the binding. These results suggest that the integration of realistic episodic memories relies on different working memory processes that depend on the nature of the traces.

  5. Object Categorization in Finer Levels Relies More on Higher Spatial Frequencies and Takes Longer.

    Science.gov (United States)

    Ashtiani, Matin N; Kheradpisheh, Saeed R; Masquelier, Timothée; Ganjtabesh, Mohammad

    2017-01-01

    The human visual system contains a hierarchical sequence of modules that take part in visual perception at different levels of abstraction, i.e., superordinate, basic, and subordinate levels. One important question is to identify the "entry" level at which the visual representation is commenced in the process of object recognition. For a long time, it was believed that the basic level had a temporal advantage over two others. This claim has been challenged recently. Here we used a series of psychophysics experiments, based on a rapid presentation paradigm, as well as two computational models, with bandpass filtered images of five object classes to study the processing order of the categorization levels. In these experiments, we investigated the type of visual information required for categorizing objects in each level by varying the spatial frequency bands of the input image. The results of our psychophysics experiments and computational models are consistent. They indicate that the different spatial frequency information had different effects on object categorization in each level. In the absence of high frequency information, subordinate and basic level categorization are performed less accurately, while the superordinate level is performed well. This means that low frequency information is sufficient for superordinate level, but not for the basic and subordinate levels. These finer levels rely more on high frequency information, which appears to take longer to be processed, leading to longer reaction times. Finally, to avoid the ceiling effect, we evaluated the robustness of the results by adding different amounts of noise to the input images and repeating the experiments. As expected, the categorization accuracy decreased and the reaction time increased significantly, but the trends were the same. This shows that our results are not due to a ceiling effect. The compatibility between our psychophysical and computational results suggests that the temporal

  6. You can't rely on color, yet we all do 2.0 (Manuscript Only)

    Science.gov (United States)

    van Nes, Floris L.

    2014-01-01

    Everybody views and uses color from early childhood onwards. But this magnificent property of all objects around us turns out to be elusive if you try to specify it and communicate it to another person. Also, people often don't know what effects color may have under different conditions. However, color is so important and omnipresent, that people can hardly avoid to 'rely on it' - so they do, in particular on its predictability. Thus, there is a discrepancy between the seeming self-evidence of color and the difficulty in specifying it accurately, for the prevailing circumstances. In order to analyze this situation, and possibly remedy it, a short historic perspective of the utilization and specification of color is given. The 'utilization' includes the emotional effects of color, which are important in, for instance, interior decorating but also play a role in literature and religion. 'Specification' begins with the early efforts by scientists, philosophers and artists to bring some order and understanding in what was observed with and while using color. Color has a number of basic functions: embellishment; attracting attention; coding; and bringing order in text by causing text parts presented in the same color to be judged as belonging together. People with a profession that involves color choices for many others, such as designers and manufacturers of products, including electronic visual displays, should have a fairly thorough knowledge of colorimetry and color perception. Unfortunately, they often don't, simply because for 'practitioners' whose work involves different aspects, applying color being only one of those, the available tools for specifying and applying color turn out to be too difficult to use. Two consequences of an insufficient knowledge of the effects color may have are given here. The first of these consequences, on color blindness, relates to 8% of the population, but the second one, on reading colored text, bears on everyone. Practical

  7. LRRC6 mutation causes primary ciliary dyskinesia with dynein arm defects.

    Directory of Open Access Journals (Sweden)

    Amjad Horani

    Full Text Available Despite recent progress in defining the ciliome, the genetic basis for many cases of primary ciliary dyskinesia (PCD remains elusive. We evaluated five children from two unrelated, consanguineous Palestinian families who had PCD with typical clinical features, reduced nasal nitric oxide concentrations, and absent dynein arms. Linkage analyses revealed a single common homozygous region on chromosome 8 and one candidate was conserved in organisms with motile cilia. Sequencing revealed a single novel mutation in LRRC6 (Leucine-rich repeat containing protein 6 that fit the model of autosomal recessive genetic transmission, leading to a change of a highly conserved amino acid from aspartic acid to histidine (Asp146His. LRRC6 was localized to the cytoplasm and was up-regulated during ciliogenesis in human airway epithelial cells in a Foxj1-dependent fashion. Nasal epithelial cells isolated from affected individuals and shRNA-mediated silencing in human airway epithelial cells, showed reduced LRRC6 expression, absent dynein arms, and slowed cilia beat frequency. Dynein arm proteins were either absent or mislocalized to the cytoplasm in airway epithelial cells from a primary ciliary dyskinesia subject. These findings suggest that LRRC6 plays a role in dynein arm assembly or trafficking and when mutated leads to primary ciliary dyskinesia with laterality defects.

  8. Value of transmission electron microscopy for primary ciliary dyskinesia diagnosis in the era of molecular medicine: Genetic defects with normal and non-diagnostic ciliary ultrastructure.

    Science.gov (United States)

    Shapiro, Adam J; Leigh, Margaret W

    2017-01-01

    Primary ciliary dyskinesia (PCD) is a genetic disorder causing chronic oto-sino-pulmonary disease. No single diagnostic test will detect all PCD cases. Transmission electron microscopy (TEM) of respiratory cilia was previously considered the gold standard diagnostic test for PCD, but 30% of all PCD cases have either normal ciliary ultrastructure or subtle changes which are non-diagnostic. These cases are identified through alternate diagnostic tests, including nasal nitric oxide measurement, high-speed videomicroscopy analysis, immunofluorescent staining of axonemal proteins, and/or mutation analysis of various PCD causing genes. Autosomal recessive mutations in DNAH11 and HYDIN produce normal TEM ciliary ultrastructure, while mutations in genes encoding for radial spoke head proteins result in some cross-sections with non-diagnostic alterations in the central apparatus interspersed with normal ciliary cross-sections. Mutations in nexin link and dynein regulatory complex genes lead to a collection of different ciliary ultrastructures; mutations in CCDC65, CCDC164, and GAS8 produce normal ciliary ultrastructure, while mutations in CCDC39 and CCDC40 cause absent inner dynein arms and microtubule disorganization in some ciliary cross-sections. Mutations in CCNO and MCIDAS cause near complete absence of respiratory cilia due to defects in generation of multiple cellular basal bodies; however, the scant cilia generated may have normal ultrastructure. Lastly, a syndromic form of PCD with retinal degeneration results in normal ciliary ultrastructure through mutations in the RPGR gene. Clinicians must be aware of these genetic causes of PCD resulting in non-diagnostic TEM ciliary ultrastructure and refrain from using TEM of respiratory cilia as a test to rule out PCD.

  9. Konfuciānisma, daoisma un budisma mantojums Ķīnas tautas reliģijā

    OpenAIRE

    Dudaļeva, Jūlija

    2014-01-01

    Šī bakalaura darba nosaukums ir „Konfuciānisma, daoisma un budisma mantojums Ķīnas tautas reliģijā”. Nosaukums ķīniešu tautas reliģijas ir pētnieku izveidots, un tas neatbilst nevienam tradicionālam ķīniešu nosaukumam. Tautas reliģija ir brīvi strukturēts ticību, prakses, dievību, mītu un vērtību savienojums, kas ietver sevī elementus no senču dievkalpojumiem, mirušo kulta, dabas pielūgsmes, animisma, vietējām tradīcijām, daoisma, konfuciānisma un budisma. Darba mērķis ir izpētīt konfuciān...

  10. Self-awareness in neurodegenerative disease relies on neural structures mediating reward-driven attention.

    Science.gov (United States)

    Shany-Ur, Tal; Lin, Nancy; Rosen, Howard J; Sollberger, Marc; Miller, Bruce L; Rankin, Katherine P

    2014-08-01

    Accurate self-awareness is essential for adapting one's tasks and goals to one's actual abilities. Patients with neurodegenerative diseases, particularly those with right frontal involvement, often present with poor self-awareness of their functional limitations that may exacerbate their already jeopardized decision-making and behaviour. We studied the structural neuroanatomical basis for impaired self-awareness among patients with neurodegenerative disease and healthy older adults. One hundred and twenty-four participants (78 patients with neurodegenerative diseases including Alzheimer's disease, behavioural variant frontotemporal dementia, right-temporal frontotemporal dementia, semantic variant and non-fluent variant primary progressive aphasia, and 46 healthy controls) described themselves on the Patient Competency Rating Scale, rating observable functioning across four domains (daily living activities, cognitive, emotional control, interpersonal). All participants underwent structural magnetic resonance imaging. Informants also described subjects' functioning on the same scale. Self-awareness was measured by comparing self and informant ratings. Group differences in discrepancy scores were analysed using general linear models, controlling for age, sex and disease severity. Compared with controls, patients with behavioural variant frontotemporal dementia overestimated their functioning in all domains, patients with Alzheimer's disease overestimated cognitive and emotional functioning, patients with right-temporal frontotemporal dementia overestimated interpersonal functioning, and patients with non-fluent aphasia overestimated emotional and interpersonal functioning. Patients with semantic variant aphasia did not overestimate functioning on any domain. To examine the neuroanatomic correlates of impaired self-awareness, discrepancy scores were correlated with brain volume using voxel-based morphometry. To identify the unique neural correlates of overlooking

  11. Early Career Researchers Demand Full-text and Rely on Google to Find Scholarly Sources

    Directory of Open Access Journals (Sweden)

    Richard Hayman

    2017-12-01

    Full Text Available A Review of: Nicholas, D., Boukacem-Zeghmouri, C., Rodríguez-Bravo, B., Xu, J., Watkinson, A., Abrizah, A., Herman, E., & Świgoń, M. (2017. Where and how early career researchers find scholarly information. Learned Publishing, 30(1, 19-29. http://dx.doi.org/10.1002/leap.1087 Abstract Objective – To examine the attitudes and information behaviours of early career researchers (ECRs when locating scholarly information. Design – Qualitative longitudinal study. Setting – Research participants from the United Kingdom, United States of America, China, France, Malaysia, Poland, and Spain. Subjects – A total 116 participants from various disciplines, aged 35 and younger, who were holding or had previously held a research position, but not in a tenured position. All participants held a doctorate or were in the process of earning one. Methods – Using structured interviews of 60-90 minutes, researchers asked 60 questions of each participant via face-to-face, Skype, or telephone interviews. The interview format and questions were formed via focus groups. Main Results – As part of a longitudinal project, results reported are limited to the first year of the study, and focused on three primary questions identified by the authors: where do ECRs find scholarly information, whether they use their smartphones to locate and read scholarly information, and what social media do they use to find scholarly information. Researchers describe how ECRs themselves interpreted the phrase scholarly information to primarily mean journal articles, while the researchers themselves had a much expanded definition to include professional and “scholarly contacts, ideas, and data” (p. 22. This research shows that Google and Google Scholar are widely used by ECRs for locating scholarly information regardless of discipline, language, or geography. Their analysis by country points to currency and the combined breadth-and-depth search experience that Google provides as

  12. 16 CFR 1115.5 - Reporting of failures to comply with a voluntary consumer product safety standard relied upon by...

    Science.gov (United States)

    2010-01-01

    ... voluntary consumer product safety standard relied upon by the Commission under section 9 of the CPSA. 1115.5 Section 1115.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SUBSTANTIAL PRODUCT HAZARD REPORTS General Interpretation § 1115.5 Reporting of failures to comply...

  13. Caution required when relying on a colleague's advice; a comparison between professional advice and evidence from the literature

    NARCIS (Netherlands)

    Schaafsma, Frederieke; Verbeek, Jos; Hulshof, Carel; van Dijk, Frank

    2005-01-01

    Background: Occupational Physicians rely especially on advice from colleagues when answering their information demands. On the other hand, Evidence-based Medicine (EBM) promotes the use of up-to-date research literature instead of experts. To find out if there was a difference between expert-based

  14. 78 FR 29392 - Embedded Digital Devices in Safety-Related Systems, Systems Important to Safety, and Items Relied...

    Science.gov (United States)

    2013-05-20

    ... NUCLEAR REGULATORY COMMISSION [NRC-2013-0098] Embedded Digital Devices in Safety-Related Systems, Systems Important to Safety, and Items Relied on for Safety AGENCY: Nuclear Regulatory Commission. ACTION... (NRC) is issuing for public comment Draft Regulatory Issue Summary (RIS) 2013-XX, ``Embedded Digital...

  15. Anemia predicts thromboembolic events, bleeding complications and mortality in patients with atrial fibrillation : insights from the RE-LY trial

    NARCIS (Netherlands)

    Westenbrink, B. D.; Alings, M.; Connolly, S. J.; Eikelboom, J.; Ezekowitz, M. D.; Oldgren, J.; Yang, S.; Pongue, J.; Yusuf, S.; Wallentin, L.; van Gilst, W. H.

    BackgroundAnemia may predispose to thromboembolic events or bleeding in anticoagulated patients with atrial fibrillation (AF). ObjectivesTo investigate whether anemia is associated with thromboembolic events and bleeding in patients with AF. Patients and methodsWe retrospectively analyzed the RE-LY

  16. Immobilization of α-Amylase from Anoxybacillus sp. SK3-4 on ReliZyme and Immobead Supports

    Directory of Open Access Journals (Sweden)

    Ummirul Mukminin Kahar

    2016-09-01

    Full Text Available α-Amylase from Anoxybacillus sp. SK3-4 (ASKA is a thermostable enzyme that produces a high level of maltose from starches. A truncated ASKA (TASKA variant with improved expression and purification efficiency was characterized in an earlier study. In this work, TASKA was purified and immobilized through covalent attachment on three epoxide (ReliZyme EP403/M, Immobead IB-150P, and Immobead IB-150A and an amino-epoxide (ReliZyme HFA403/M activated supports. Several parameters affecting immobilization were analyzed, including the pH, temperature, and quantity (mg of enzyme added per gram of support. The influence of the carrier surface properties, pore sizes, and lengths of spacer arms (functional groups on biocatalyst performances were studied. Free and immobilized TASKAs were stable at pH 6.0–9.0 and active at pH 8.0. The enzyme showed optimal activity and considerable stability at 60 °C. Immobilized TASKA retained 50% of its initial activity after 5–12 cycles of reuse. Upon degradation of starches and amylose, only immobilized TASKA on ReliZyme HFA403/M has comparable hydrolytic ability with the free enzyme. To the best of our knowledge, this is the first report of an immobilization study of an α-amylase from Anoxybacillus spp. and the first report of α-amylase immobilization using ReliZyme and Immobeads as supports.

  17. Amenorrhea - primary

    Science.gov (United States)

    ... of periods - primary Images Primary amenorrhea Normal uterine anatomy (cut section) Absence of menstruation (amenorrhea) References Bulun SE. The physiology and pathology of the female reproductive axis. In: ...

  18. Invitro genotoxicity, assessment of cytotoxicity and of Rely X luting cement on human lymphocyte cells before and after irradiation

    International Nuclear Information System (INIS)

    Shetty, Shilpa S.; Hegde, Mithra N.; Shabin; Hegde, Nidarsh D.; Suchetha Kumari; Sanjeev, Ganesh

    2013-01-01

    In dentistry, a luting agent is a viscous material placed between tooth structure and a prosthesis that by polymerization firmly attach the prosthesis to the tooth structure. Luting agents contact a large area of dentin when used for crown cementation. There is little information on biocompatibility tests, especially on the effect of electron beam irradiation on cytotoxicity for luting resin cements. To determine the in vitro cytotoxicity and genotoxicity of Rely X luting cement on human lymphocyte cells before and after irradiation. Rely X luting cement was obtained commercially. Samples were prepared as per the ISO standard size of 25x2x2 mm using polytetrafluoroethylene teflon mould and divided into two groups - non irradiated and irradiated groups. The samples in irradiated category were exposed to 200 Gy of electron beam irradiation at Microtron Centre, Mangalore University, Mangalore, India. For hemolysis the samples were immersed in phosphate buffer saline and incubated at 370℃ for 24 hrs, 7 days and 14 days. 200 μl of 24 hr material extract was mixed with human peripheral blood lymphocyte tested for comet assay by single cell DNA comet assay. Hemolytic activity of non irradiated Rely X luting cement after 24 hrs, 7 days and 14 days was 54.78±1.48, 69.91±2.41 and 43.21±0.92 respectively whereas hemolytic activity of irradiated Rely X luting cement after 24 hrs, 7 days and 14 days was 91.8±8.29, 56.95±19.7 and 41.34±12.30. The irradiation of Rely X luting cement with 200 Gy dose of electron beam irradiation caused an increase in the frequency of DNA damage when compared to that of the non-irradiated group. Based on the experimental condition, it is concluded that incomplete polymerization of the dental luting cements has resulted in the elution of the resin components which are responsible for the cytotoxicity and genotoxicity of Rely X luting cement on human lymphocyte cells. (author)

  19. Cilia walls influence on peristaltically induced motion of magneto-fluid through a porous medium at moderate Reynolds number: Numerical study

    Directory of Open Access Journals (Sweden)

    R.E. Abo-Elkhair

    2017-04-01

    Full Text Available This article addresses, effects of a magneto-fluid through a Darcy flow model with oscillatory wavy walled whose inner surface is ciliated. The equations that governing the flow are modeled without using any approximations. Adomian Decomposition Method (ADM is used to evaluate the solution of our system of nonlinear partial differential equations. Stream function, velocity and pressure gradient components are obtained by using the vorticity formula. The effects for our arbitrary physical parameters on flow characteristics are analyzed by plotting diagrams and discussed in details. With the help of stream lines the trapping mechanism has also been discussed. The major outcomes for the ciliated channel walls are: The axial velocity is higher without a ciliated walls than that for a ciliated walls and an opposite behaviour is shown near the ciliated channel walls. The pressure gradients in both directions are higher for a ciliated channel walls. More numbers of the trapped bolus in the absent of the eccentricity of the cilia elliptic path.

  20. Rely-Guarantee Protocols

    Science.gov (United States)

    2014-05-01

    University Pittsburgh, PA 15213 1School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA. 2Faculdade de Ciências e Tecnologia ...additional examples that are not in the ECOOP paper. This work was partially supported by Fundação para a Ciência e Tecnologia (Portuguese Foundation

  1. Einfluss von Flüssigkeitskontamination auf die Verbundfestigkeit von Wurzelkanalsealern (Adseal und RelyX Unicem)

    OpenAIRE

    Höfer, Margarita

    2010-01-01

    Ziel dieser Arbeit war es, eine Aussage über die Verbundfestigkeit des epoxidharz-basierten Wurzelkanalsealers Adseal und des selbstadhäsiven methacrylatbasierten Befestigungszements RelyX Unicem zum Wurzelkanaldentin in Abhängigkeit vom Verbleib der Spülflüssigkeit im Wurzelkanal zu treffen. Die Kontamination des Wurzelkanals wurde mittels dreier verschiedener Spüllösungen durchgeführt. Zu diesem Zweck wurden Scherfestigkeitsmessungen sowie lichtmikroskopische Untersuchungen der Sealer-Sprea...

  2. Primary ciliary dyskinesia: a report from ATS 2001, May 18–23, San Francisco

    Directory of Open Access Journals (Sweden)

    Noone Peadar G

    2001-06-01

    Full Text Available Abstract Primary ciliary dyskinesia (PCD is a genetic disorder of abnormal ciliary structure and function that leads to defective mucociliary clearance, resulting in oto-sino-pulmonary disease, and infertility. The disease is currently under intense investigation by a number of research groups worldwide. At the recent American Thoracic Society meeting in San Francisco in May 2001, two sessions focused on PCD; a symposium session on May 21 with several featured expert speakers was followed by a mini-symposium on Tuesday May 22, with one featured speaker and presentation of nine abstracts covering a range of research topics. Mattias Salathe (University of Miami, USA and Stephen Brody (Washington University, St Louis, USA chaired the symposium session. Presentations focused on the clinical spectrum of PCD, the genetics of PCD, a proteomics approach to detail the structure of cilia, the role of cilia in the embryology of situs laterality, and airway epithelial cell biology. The mini-symposium was chaired by Peadar Noone (University of North Carolina, USA and Malcolm King (University of Alberta, USA and included presentations on the use of PCD as a human disease model, accurate definition of the phenotype using clinical and cell biologic markers, and molecular studies. The latter reports ranged from isolation of a protein involved in ciliary structure and function to genetic studies using linkage analysis and the candidate gene approach. Clinicians and scientists alike displayed considerable interest at both sessions, and there were several lively question–answer sessions.

  3. Phonological memory in sign language relies on the visuomotor neural system outside the left hemisphere language network.

    Science.gov (United States)

    Kanazawa, Yuji; Nakamura, Kimihiro; Ishii, Toru; Aso, Toshihiko; Yamazaki, Hiroshi; Omori, Koichi

    2017-01-01

    Sign language is an essential medium for everyday social interaction for deaf people and plays a critical role in verbal learning. In particular, language development in those people should heavily rely on the verbal short-term memory (STM) via sign language. Most previous studies compared neural activations during signed language processing in deaf signers and those during spoken language processing in hearing speakers. For sign language users, it thus remains unclear how visuospatial inputs are converted into the verbal STM operating in the left-hemisphere language network. Using functional magnetic resonance imaging, the present study investigated neural activation while bilinguals of spoken and signed language were engaged in a sequence memory span task. On each trial, participants viewed a nonsense syllable sequence presented either as written letters or as fingerspelling (4-7 syllables in length) and then held the syllable sequence for 12 s. Behavioral analysis revealed that participants relied on phonological memory while holding verbal information regardless of the type of input modality. At the neural level, this maintenance stage broadly activated the left-hemisphere language network, including the inferior frontal gyrus, supplementary motor area, superior temporal gyrus and inferior parietal lobule, for both letter and fingerspelling conditions. Interestingly, while most participants reported that they relied on phonological memory during maintenance, direct comparisons between letters and fingers revealed strikingly different patterns of neural activation during the same period. Namely, the effortful maintenance of fingerspelling inputs relative to letter inputs activated the left superior parietal lobule and dorsal premotor area, i.e., brain regions known to play a role in visuomotor analysis of hand/arm movements. These findings suggest that the dorsal visuomotor neural system subserves verbal learning via sign language by relaying gestural inputs to

  4. Characterization of membrane protein trafficking and cellular signaling at the primary cilium

    DEFF Research Database (Denmark)

    Mogensen, Johanne Bay

    Primary cilia are microtubule-based, non-motile, sensory organelles emerging in a single copy from the surface of most quiescent cells in vertebrates. They emanate from the centrosomal mother centriole and are assembled and maintained by a bidirectional transport process termed intraflagellar...... transport. Specific receptors, ion channels and downstream signaling components are localized along the cilium-centrosome axis, enabling the cilium to function as a hot spot for the balanced coordination of multiple signaling pathways to control cell cycle entry, differentiation and migration during...... differentiation of mouse stem cells into cardiomyocytes. These results support the conclusion that Tab2 functions at the primary cilium to coordinate specified signaling events, which when defective may lead to congenital heart disease Collectively, the results presented in this PhD thesis provide new insights...

  5. NINL and DZANK1 Co-function in Vesicle Transport and Are Essential for Photoreceptor Development in Zebrafish

    NARCIS (Netherlands)

    Dona, M.; Bachmann-Gagescu, R.; Texier, Y.; Toedt, G.; Hetterschijt, L.; Tonnaer, E.L.; Peters, T.A.; Beersum, S.E.C. van; Bergboer, J.G.M.; Horn, N.; Vrieze, E. de; Slijkerman, R.W.N.; Reeuwijk, J. van; Flik, G.; Keunen, J.E.E.; Ueffing, M.; Gibson, T.J.; Roepman, R.; Boldt, K.; Kremer, H.; Wijk, E. van

    2015-01-01

    Ciliopathies are Mendelian disorders caused by dysfunction of cilia, ubiquitous organelles involved in fluid propulsion (motile cilia) or signal transduction (primary cilia). Retinal dystrophy is a common phenotypic characteristic of ciliopathies since photoreceptor outer segments are specialized

  6. Primary explosives

    Energy Technology Data Exchange (ETDEWEB)

    Matyas, Robert; Pachman, Jiri [Pardubice Univ. (Czech Republic). Faculty of Chemical Technology

    2013-06-01

    The first chapter provides background such as the basics of initiation and differences between requirements on primary explosives used in detonators and igniters. The authors then clarify the influence of physical characteristics on explosive properties, focusing on those properties required for primary explosives. Furthermore, the issue of sensitivity is discussed. All the chapters on particular groups of primary explosives are structured in the same way, including introduction, physical and chemical properties, explosive properties, preparation and documented use.

  7. Influence of Computerized Sounding Out on Spelling Performance for Children who do and not rely on AAC

    Science.gov (United States)

    McCarthy, Jillian H.; Hogan, Tiffany P.; Beukelman, David R.; Schwarz, Ilsa E.

    2015-01-01

    Purpose Spelling is an important skill for individuals who rely on augmentative alternative communication (AAC). The purpose of this study was to investigate how computerized sounding out influenced spelling accuracy of pseudo-words. Computerized sounding out was defined as a word elongated, thus providing an opportunity for a child to hear all the sounds in the word at a slower rate. Methods Seven children with cerebral palsy, four who use AAC and three who do not, participated in a single subject AB design. Results The results of the study indicated that the use of computerized sounding out increased the phonologic accuracy of the pseudo-words produced by participants. Conclusion The study provides preliminary evidence for the use of computerized sounding out during spelling tasks for children with cerebral palsy who do and do not use AAC. Future directions and clinical implications are discussed. PMID:24512195

  8. Humans rely on the same rules to assess emotional valence and intensity in conspecific and dog vocalizations.

    Science.gov (United States)

    Faragó, Tamás; Andics, Attila; Devecseri, Viktor; Kis, Anna; Gácsi, Márta; Miklósi, Adám

    2014-01-01

    Humans excel at assessing conspecific emotional valence and intensity, based solely on non-verbal vocal bursts that are also common in other mammals. It is not known, however, whether human listeners rely on similar acoustic cues to assess emotional content in conspecific and heterospecific vocalizations, and which acoustical parameters affect their performance. Here, for the first time, we directly compared the emotional valence and intensity perception of dog and human non-verbal vocalizations. We revealed similar relationships between acoustic features and emotional valence and intensity ratings of human and dog vocalizations: those with shorter call lengths were rated as more positive, whereas those with a higher pitch were rated as more intense. Our findings demonstrate that humans rate conspecific emotional vocalizations along basic acoustic rules, and that they apply similar rules when processing dog vocal expressions. This suggests that humans may utilize similar mental mechanisms for recognizing human and heterospecific vocal emotions.

  9. Primary fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, S; Jensen, L T; Foldager, M

    1990-01-01

    Serum concentrations of procollagen type III aminoterminal peptide have previously been reported to be low in some patients with primary fibromyalgia and the aim of this study was to determine if such patients differ clinically from primary fibromyalgia patients with normal levels of procollagen...... type III aminoterminal peptide. Subjective symptoms, tender points and dynamic muscle strength in 45 women with primary fibromyalgia were related to serum concentrations of procollagen type III aminoterminal peptide. Patients with low serum concentrations of procollagen type III aminoterminal peptide...... concentrations of procollagen type III aminoterminal peptide of primary fibromyalgia patients are connected to the disease impact....

  10. Primary cilium - antenna-like structure on the surface of most mammalian cell types

    International Nuclear Information System (INIS)

    Dvorak, J; Kasaova, L; Filip, S; Petera, J; Sitorova, V; Nikolov, D Hadzi; Ryska, A; Mokry, J; Richter, I

    2011-01-01

    The primary cilium is a sensory solitary non-motile microtubule-based organelle protruding in the quiescent phase of the cell cycle from the surface of the majority of human cells, including embryonic cells, stem cells and stromal cells of malignant tumors. The presence of a primary cilium on the surface of a cell is transient, limited to the quiescent G 1 (G 0 ) phase and the beginning of the S phase of the cell cycle. The primary cilium is formed from the mother centriole. Primary cilia are key coordinators of signaling pathways during development and tissue homeostasis and, when deffective, they are a major cause of human diseases and developmental disorders, now commonly referred to as ciliopathies. Most cancer cells do not possess a primary cilium. The loss of the primary cilium is a regular feature of neoplastic transformation in the majority of solid tumors. The primary cilium could serve as a tumor suppressor organelle. The aim of this paper was to provide a review of the current knowledge of the primary cilium.

  11. Primary cilium - antenna-like structure on the surface of most mammalian cell types

    Science.gov (United States)

    Dvorak, J.; Sitorova, V.; Hadzi Nikolov, D.; Mokry, J.; Richter, I.; Kasaova, L.; Filip, S.; Ryska, A.; Petera, J.

    2011-12-01

    The primary cilium is a sensory solitary non-motile microtubule-based organelle protruding in the quiescent phase of the cell cycle from the surface of the majority of human cells, including embryonic cells, stem cells and stromal cells of malignant tumors. The presence of a primary cilium on the surface of a cell is transient, limited to the quiescent G1(G0) phase and the beginning of the S phase of the cell cycle. The primary cilium is formed from the mother centriole. Primary cilia are key coordinators of signaling pathways during development and tissue homeostasis and, when deffective, they are a major cause of human diseases and developmental disorders, now commonly referred to as ciliopathies. Most cancer cells do not possess a primary cilium. The loss of the primary cilium is a regular feature of neoplastic transformation in the majority of solid tumors. The primary cilium could serve as a tumor suppressor organelle. The aim of this paper was to provide a review of the current knowledge of the primary cilium.

  12. Social plasticity relies on different neuroplasticity mechanisms across the brain social decision-making network in zebrafish

    Directory of Open Access Journals (Sweden)

    Magda C Teles

    2016-02-01

    Full Text Available Social living animals need to adjust the expression of their behavior to their status within the group and to changes in social context and this ability (social plasticity has an impact on their Darwinian fitness. At the proximate level social plasticity must rely on neuroplasticity in the brain social decision-making network (SDMN that underlies the expression of social behavior, such that the same neural circuit may underlie the expression of different behaviors depending on social context. Here we tested this hypothesis in zebrafish by characterizing the gene expression response in the SDMN to changes in social status of a set of genes involved in different types of neural plasticity: bdnf, involved in changes in synaptic strength; npas4, involved in contextual learning and dependent establishment of GABAergic synapses; neuroligins (nlgn1 and nlgn2 as synaptogenesis markers; and genes involved in adult neurogenesis (wnt3 and neurod. Four social phenotypes were experimentally induced: Winners and Losers of a real-opponent interaction; Mirror-fighters, that fight their own image in a mirror and thus do not experience a change in social status despite the expression of aggressive behavior; and non-interacting fish, which were used as a reference group. Our results show that each social phenotype (i.e. Winners, Losers and Mirror-fighters present specific patterns of gene expression across the SDMN, and that different neuroplasticity genes are differentially expressed in different nodes of the network (e.g. BDNF in the dorsolateral telencephalon, which is a putative teleost homologue of the mammalian hippocampus. Winners expressed unique patterns of gene co-expression across the SDMN, whereas in Losers and Mirror-fighters the co-expression patterns were similar in the dorsal regions of the telencephalon and in the supracommissural nucleus of the ventral telencephalic area, but differents in the remaining regions of the ventral telencephalon. These

  13. Social Plasticity Relies on Different Neuroplasticity Mechanisms across the Brain Social Decision-Making Network in Zebrafish.

    Science.gov (United States)

    Teles, Magda C; Cardoso, Sara D; Oliveira, Rui F

    2016-01-01

    Social living animals need to adjust the expression of their behavior to their status within the group and to changes in social context and this ability (social plasticity) has an impact on their Darwinian fitness. At the proximate level social plasticity must rely on neuroplasticity in the brain social decision-making network (SDMN) that underlies the expression of social behavior, such that the same neural circuit may underlie the expression of different behaviors depending on social context. Here we tested this hypothesis in zebrafish by characterizing the gene expression response in the SDMN to changes in social status of a set of genes involved in different types of neural plasticity: bdnf, involved in changes in synaptic strength; npas4, involved in contextual learning and dependent establishment of GABAergic synapses; neuroligins (nlgn1 and nlgn2) as synaptogenesis markers; and genes involved in adult neurogenesis (wnt3 and neurod). Four social phenotypes were experimentally induced: Winners and Losers of a real-opponent interaction; Mirror-fighters, that fight their own image in a mirror and thus do not experience a change in social status despite the expression of aggressive behavior; and non-interacting fish, which were used as a reference group. Our results show that each social phenotype (i.e., Winners, Losers, and Mirror-fighters) present specific patterns of gene expression across the SDMN, and that different neuroplasticity genes are differentially expressed in different nodes of the network (e.g., BDNF in the dorsolateral telencephalon, which is a putative teleost homolog of the mammalian hippocampus). Winners expressed unique patterns of gene co-expression across the SDMN, whereas in Losers and Mirror-fighters the co-expression patterns were similar in the dorsal regions of the telencephalon and in the supracommissural nucleus of the ventral telencephalic area, but differents in the remaining regions of the ventral telencephalon. These results

  14. Social Plasticity Relies on Different Neuroplasticity Mechanisms across the Brain Social Decision-Making Network in Zebrafish

    Science.gov (United States)

    Teles, Magda C.; Cardoso, Sara D.; Oliveira, Rui F.

    2016-01-01

    Social living animals need to adjust the expression of their behavior to their status within the group and to changes in social context and this ability (social plasticity) has an impact on their Darwinian fitness. At the proximate level social plasticity must rely on neuroplasticity in the brain social decision-making network (SDMN) that underlies the expression of social behavior, such that the same neural circuit may underlie the expression of different behaviors depending on social context. Here we tested this hypothesis in zebrafish by characterizing the gene expression response in the SDMN to changes in social status of a set of genes involved in different types of neural plasticity: bdnf, involved in changes in synaptic strength; npas4, involved in contextual learning and dependent establishment of GABAergic synapses; neuroligins (nlgn1 and nlgn2) as synaptogenesis markers; and genes involved in adult neurogenesis (wnt3 and neurod). Four social phenotypes were experimentally induced: Winners and Losers of a real-opponent interaction; Mirror-fighters, that fight their own image in a mirror and thus do not experience a change in social status despite the expression of aggressive behavior; and non-interacting fish, which were used as a reference group. Our results show that each social phenotype (i.e., Winners, Losers, and Mirror-fighters) present specific patterns of gene expression across the SDMN, and that different neuroplasticity genes are differentially expressed in different nodes of the network (e.g., BDNF in the dorsolateral telencephalon, which is a putative teleost homolog of the mammalian hippocampus). Winners expressed unique patterns of gene co-expression across the SDMN, whereas in Losers and Mirror-fighters the co-expression patterns were similar in the dorsal regions of the telencephalon and in the supracommissural nucleus of the ventral telencephalic area, but differents in the remaining regions of the ventral telencephalon. These results

  15. Primary Events in Olfactory Receptiom

    Science.gov (United States)

    1989-10-10

    phase after extraction with Triton X-1 14 and does not bind either concanavalin A or wheat germ agglutinin. When phosphorylation is allowed to proceed in...a low basal level of endogenous activity. Phosphorylation is reversible by treatment of phosphorylated cilia with alkaline phosphatase . Comparing...not with the non-phosphorylated peptide or individual phosphorylated amino acids , such as phosphoserine and phosphotyrosine. We will use these antisera

  16. Influence of computerized sounding out on spelling performance for children who do and do not rely on AAC.

    Science.gov (United States)

    McCarthy, Jillian H; Hogan, Tiffany P; Beukelman, David R; Schwarz, Ilsa E

    2015-05-01

    Spelling is an important skill for individuals who rely on augmentative and alternative communication (AAC). The purpose of this study was to investigate how computerized sounding out influenced spelling accuracy of pseudo-words. Computerized sounding out was defined as a word elongated, thus providing an opportunity for a child to hear all the sounds in the word at a slower rate. Seven children with cerebral palsy, four who use AAC and three who do not, participated in a single subject AB design. The results of the study indicated that the use of computerized sounding out increased the phonologic accuracy of the pseudo-words produced by participants. The study provides preliminary evidence for the use of computerized sounding out during spelling tasks for children with cerebral palsy who do and do not use AAC. Future directions and clinical implications are discussed. We investigated how computerized sounding out influenced spelling accuracy of pseudowords for children with complex communication needs who did and did not use augmentative and alternative communication (AAC). Results indicated that the use of computerized sounding out increased the phonologic accuracy of the pseudo-words by participants, suggesting that computerized sounding out might assist in more accurate spelling for children who use AAC. Future research is needed to determine how language and reading abilities influence the use of computerized sounding out with children who have a range of speech intelligibility abilities and do and do not use AAC.

  17. Catalytic ozonation not relying on hydroxyl radical oxidation: A selective and competitive reaction process related to metal-carboxylate complexes

    KAUST Repository

    Zhang, Tao

    2014-01-01

    Catalytic ozonation following non-hydroxyl radical pathway is an important technique not only to degrade refractory carboxylic-containing organic compounds/matter but also to avoid catalyst deactivation caused by metal-carboxylate complexation. It is unknown whether this process is effective for all carboxylates or selective to special molecule structures. In this work, the selectivity was confirmed using O3/(CuO/CeO2) and six distinct ozone-resistant probe carboxylates (i.e., acetate, citrate, malonate, oxalate, pyruvate and succinate). Among these probe compounds, pyruvate, oxalate, and citrate were readily degraded following the rate order of oxalate>citrate>pyruvate, while the degradation of acetate, malonate, and succinate was not promoted. The selectivity was independent on carboxylate group number of the probe compounds and solution pH. Competitive degradation was observed for carboxylate mixtures following the preference order of citrate, oxalate, and finally pyruvate. The competitive degradation was ascribed to competitive adsorption on the catalyst surface. It was revealed that the catalytically degradable compounds formed bidentate chelating or bridging complexes with surface copper sites of the catalyst, i.e., the active sites. The catalytically undegradable carboxylates formed monodentate complexes with surface copper sites or just electrostatically adsorbed on the catalyst surface. The selectivity, relying on the structure of surface metal-carboxylate complex, should be considered in the design of catalytic ozonation process. © 2013 Elsevier B.V.

  18. Spatial Reorganization of the Endoplasmic Reticulum during Mitosis Relies on Mitotic Kinase Cyclin A in the Early Drosophila Embryo

    Science.gov (United States)

    Bergman, Zane J.; Mclaurin, Justin D.; Eritano, Anthony S.; Johnson, Brittany M.; Sims, Amanda Q.; Riggs, Blake

    2015-01-01

    Mitotic cyclin-dependent kinase with their cyclin partners (cyclin:Cdks) are the master regulators of cell cycle progression responsible for regulating a host of activities during mitosis. Nuclear mitotic events, including chromosome condensation and segregation have been directly linked to Cdk activity. However, the regulation and timing of cytoplasmic mitotic events by cyclin:Cdks is poorly understood. In order to examine these mitotic cytoplasmic events, we looked at the dramatic changes in the endoplasmic reticulum (ER) during mitosis in the early Drosophila embryo. The dynamic changes of the ER can be arrested in an interphase state by inhibition of either DNA or protein synthesis. Here we show that this block can be alleviated by micro-injection of Cyclin A (CycA) in which defined mitotic ER clusters gathered at the spindle poles. Conversely, micro-injection of Cyclin B (CycB) did not affect spatial reorganization of the ER, suggesting CycA possesses the ability to initiate mitotic ER events in the cytoplasm. Additionally, RNAi-mediated simultaneous inhibition of all 3 mitotic cyclins (A, B and B3) blocked spatial reorganization of the ER. Our results suggest that mitotic ER reorganization events rely on CycA and that control and timing of nuclear and cytoplasmic events during mitosis may be defined by release of CycA from the nucleus as a consequence of breakdown of the nuclear envelope. PMID:25689737

  19. Sociological investigation Students of Universities' Social-Political Trust in Iran: relying on secondary analysis of some national surveys

    Directory of Open Access Journals (Sweden)

    Sayed Mahdi Etemadifard

    2013-12-01

    Full Text Available Social system based on mutual trust among members continues to exist. Social trust in modem era is more important than earlier periods. Subject of current report is focused on the trust of Iranian students in different aspects. Main question in this investigation is about social-political trust of these students (based on trust in Islamic Republic of Iran at the past and present. This matter explored by secondary analysis of data, Relying on secondary analysis of some national surveys. Based on data and consequences of other researches we are going to illustrate the objective aspects of student's trust in current decades. The main sources for data collection at this stage include: All the public surveys conducted in the past four decades, the general data about students and their related assays. Trust students were evaluated on the following dimensions: trust in trade unions and various groups, trust in the clergy, directors of public trust and confidence in judges. Furthermore, the level of political engagement and participation in elections, satisfaction with economic situation, political situation and level of satisfaction with confidence in radio and television news. Reduction of public trust leads to reduced maximum student trust especially in the social and political dimensions.

  20. The perception of (naked only) bodies and faceless heads relies on holistic processing: Evidence from the inversion effect.

    Science.gov (United States)

    Bonemei, Rob; Costantino, Andrea I; Battistel, Ilenia; Rivolta, Davide

    2018-05-01

    Faces and bodies are more difficult to perceive when presented inverted than when presented upright (i.e., stimulus inversion effect), an effect that has been attributed to the disruption of holistic processing. The features that can trigger holistic processing in faces and bodies, however, still remain elusive. In this study, using a sequential matching task, we tested whether stimulus inversion affects various categories of visual stimuli: faces, faceless heads, faceless heads in body context, headless bodies naked, whole bodies naked, headless bodies clothed, and whole bodies clothed. Both accuracy and inversion efficiency score results show inversion effects for all categories but for clothed bodies (with and without heads). In addition, the magnitude of the inversion effect for face, naked body, and faceless heads was similar. Our findings demonstrate that the perception of faces, faceless heads, and naked bodies relies on holistic processing. Clothed bodies (with and without heads), on the other side, may trigger clothes-sensitive rather than body-sensitive perceptual mechanisms. © 2017 The British Psychological Society.

  1. Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study.

    Science.gov (United States)

    Merege-Filho, Carlos Alberto Abujabra; Otaduy, Maria Concepción Garcia; de Sá-Pinto, Ana Lúcia; de Oliveira, Maira Okada; de Souza Gonçalves, Lívia; Hayashi, Ana Paula Tanaka; Roschel, Hamilton; Pereira, Rosa Maria Rodrigues; Silva, Clovis Artur; Brucki, Sonia Maria Dozzi; da Costa Leite, Claudia; Gualano, Bruno

    2017-02-01

    It has been hypothesized that dietary creatine could influence cognitive performance by increasing brain creatine in developing individuals. This double-blind, randomized, placebo-controlled, proof-of-principle study aimed to investigate the effects of creatine supplementation on cognitive function and brain creatine content in healthy youth. The sample comprised 67 healthy participants aged 10 to 12 years. The participants were given creatine or placebo supplementation for 7 days. At baseline and after the intervention, participants undertook a battery of cognitive tests. In a random subsample of participants, brain creatine content was also assessed in the regions of left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe by proton magnetic resonance spectroscopy (1H-MRS) technique. The scores obtained from verbal learning and executive functions tests did not significantly differ between groups at baseline or after the intervention (all p > 0.05). Creatine content was not significantly different between groups in left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe (all p > 0.05). In conclusion, a 7-day creatine supplementation protocol did not elicit improvements in brain creatine content or cognitive performance in healthy youth, suggesting that this population mainly relies on brain creatine synthesis rather than exogenous creatine intake to maintain brain creatine homeostasis.

  2. Symmetric Encryption Relying on Chaotic Henon System for Secure Hardware-Friendly Wireless Communication of Implantable Medical Systems

    Directory of Open Access Journals (Sweden)

    Taha Belkhouja

    2018-05-01

    Full Text Available Healthcare remote devices are recognized as a promising technology for treating health related issues. Among them are the wireless Implantable Medical Devices (IMDs: These electronic devices are manufactured to treat, monitor, support or replace defected vital organs while being implanted in the human body. Thus, they play a critical role in healing and even saving lives. Current IMDs research trends concentrate on their medical reliability. However, deploying wireless technology in such applications without considering security measures may offer adversaries an easy way to compromise them. With the aim to secure these devices, we explore a new scheme that creates symmetric encryption keys to encrypt the wireless communication portion. We will rely on chaotic systems to obtain a synchronized Pseudo-Random key. The latter will be generated separately in the system in such a way that avoids a wireless key exchange, thus protecting patients from the key theft. Once the key is defined, a simple encryption system that we propose in this paper will be used. We analyze the performance of this system from a cryptographic point of view to ensure that it offers a better safety and protection for patients.

  3. Primary productivity

    Digital Repository Service at National Institute of Oceanography (India)

    Verlecar, X.N.; Parulekar, A.H.

    Photosynthetic production in the oceans in relation to light, nutrients and mixing processes is discussed. Primary productivity in the estuarine region is reported to be high in comparison to coastal and oceanic waters. Upwelling phenomenon...

  4. Primary Hyperparathyroidism

    Science.gov (United States)

    ... Neoplasia Type 1 Thyroid Disease & Pregnancy Primary Hyperparathyroidism Prolactinoma National Hormone and Pituitary Program (NHPP): Information for ... qualified health care provider nearby. Eating, Diet, and Nutrition Eating, diet, and nutrition have not been shown ...

  5. Primary Myelofibrosis

    Science.gov (United States)

    ... attack is higher. Patients also have an increased risk of acute myeloid leukemia or primary myelofibrosis . Symptoms of polycythemia vera include headaches and a feeling of fullness below the ribs on the left ...

  6. If the results of an article are noteworthy, read the entire article; do not rely on the abstract alone.

    Science.gov (United States)

    Dal-Ré, R; Castell, M V; García-Puig, J

    2015-11-01

    Clinicians typically update their knowledge by reading articles on the Internet. Easy access to the articles' abstracts and a lack of time to access other information sources creates a risk that therapeutic or diagnostic decisions will be made after reading just the abstracts. Occasionally, however, the abstracts of articles from clinical trials that have not obtained statistically significant differences in the primary study endpoint have reported other positive results, for example, of a secondary endpoint or a subgroup analysis. The article, however, correctly reports all results, including those of the primary endpoint. In the abstract, the safety information of the experimental treatment is usually deficient. The whole article should be read if a clinical decision is to be made. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  7. Pitchfork and Gprasp2 Target Smoothened to the Primary Cilium for Hedgehog Pathway Activation.

    Directory of Open Access Journals (Sweden)

    Bomi Jung

    Full Text Available The seven-transmembrane receptor Smoothened (Smo activates all Hedgehog (Hh signaling by translocation into the primary cilia (PC, but how this is regulated is not well understood. Here we show that Pitchfork (Pifo and the G protein-coupled receptor associated sorting protein 2 (Gprasp2 are essential components of an Hh induced ciliary targeting complex able to regulate Smo translocation to the PC. Depletion of Pifo or Gprasp2 leads to failure of Smo translocation to the PC and lack of Hh target gene activation. Together, our results identify a novel protein complex that is regulated by Hh signaling and required for Smo ciliary trafficking and Hh pathway activation.

  8. Caution required when relying on a colleague's advice; a comparison between professional advice and evidence from the literature

    Directory of Open Access Journals (Sweden)

    Hulshof Carel

    2005-08-01

    Full Text Available Abstract Background Occupational Physicians rely especially on advice from colleagues when answering their information demands. On the other hand, Evidence-based Medicine (EBM promotes the use of up-to-date research literature instead of experts. To find out if there was a difference between expert-based practice and EBM we compared professional advice on occupational health topics with best evidence from the literature. Methods We asked 14 occupational physicians to consult their usual information sources on 12 pre-conceived occupational health problems. The problems were presented in the form of case vignettes which contained sufficient clinical information to be used by the occupational physicians for the consultation of their experts. We had searched the literature for the best available evidence on the 12 problems, which made it possible to answer the clinical questions with a clear yes or no. Results The cases could be used by the occupational physicians as arising from their own practice. All together the occupational physicians consulted 75 different experts. Almost half of the consulted experts were near colleagues, 10% were industrial hygienists, 8% medical specialists and the rest had a varied background. Fifty three percent (95% confidence interval 42% to 65% of all professional advice was not in line with the research literature. In 18 cases (24% professional advice explicitly referred to up-to-date research literature as their used source. These cases were substantially less incorrect (17% than advice that had not mentioned the literature as a source (65% (difference 48%, 95% Confidence Interval from 27% to 69%. Conclusion Advice that occupational physicians routinely get in their daily practice differs substantially from best evidence from the literature. Occupational physicians who ask professional advice should always ask about the evidence of this advice.

  9. Caution required when relying on a colleague's advice; a comparison between professional advice and evidence from the literature

    Science.gov (United States)

    Schaafsma, Frederieke; Verbeek, Jos; Hulshof, Carel; van Dijk, Frank

    2005-01-01

    Background Occupational Physicians rely especially on advice from colleagues when answering their information demands. On the other hand, Evidence-based Medicine (EBM) promotes the use of up-to-date research literature instead of experts. To find out if there was a difference between expert-based practice and EBM we compared professional advice on occupational health topics with best evidence from the literature. Methods We asked 14 occupational physicians to consult their usual information sources on 12 pre-conceived occupational health problems. The problems were presented in the form of case vignettes which contained sufficient clinical information to be used by the occupational physicians for the consultation of their experts. We had searched the literature for the best available evidence on the 12 problems, which made it possible to answer the clinical questions with a clear yes or no. Results The cases could be used by the occupational physicians as arising from their own practice. All together the occupational physicians consulted 75 different experts. Almost half of the consulted experts were near colleagues, 10% were industrial hygienists, 8% medical specialists and the rest had a varied background. Fifty three percent (95% confidence interval 42% to 65%) of all professional advice was not in line with the research literature. In 18 cases (24%) professional advice explicitly referred to up-to-date research literature as their used source. These cases were substantially less incorrect (17%) than advice that had not mentioned the literature as a source (65%) (difference 48%, 95% Confidence Interval from 27% to 69%). Conclusion Advice that occupational physicians routinely get in their daily practice differs substantially from best evidence from the literature. Occupational physicians who ask professional advice should always ask about the evidence of this advice. PMID:16131405

  10. Access to Grafts in a Liver Transplant Center: Does It Rely on the Severity of the Waiting List Population?

    Science.gov (United States)

    Daciuk, N I; Quiñonez, E G; Poupard, M; Vergara Sandoval, R M; Mattera, F J

    2018-03-01

    The number of transplants performed relies, partially, on recipients' variables on the waiting list. The goal of this study was to compare recipients from a high-volume liver center in Argentina with the rest of the country. This study was a retrospective analysis of liver transplant recipients nationally between January 2013 and April 2017. It involved extracting data from the open database CRESI-SINTRA (the Argentinian database of the National Procurement Organization, an equivalent to the United Network for Organ Sharing); expressing results by percentages, medians, and interquartile ranges (IQRs); and comparing the national population with the population transplanted at Hospital El Cruce (HEC). The Mann-Whitney U test was used for analysis. Nationally, 1434 liver transplants were performed. A total of 177 (12.34%) were emergency status; 811 (56.6%) were by the Model for End-Stage Liver Disease (MELD) (n = 759)/PELD (Pediatric End-Stage Liver Disease) (n = 52), with a median graft assignment position of 5 (IQR, 3-10) in 57.2 days (IQR, 11-217). Median MELD access was 29 points (IQR, 24-33). A total of 446 (31.1%) had MELD exceptions; 249 (55.8%) of these were due to Milan hepatocellular carcinoma. At the HEC, 167 liver transplantations were performed; 26 (15.6%) were emergency status and 97 (58.1%) by MELD (none PELD). Their median graft assignment position was 4 (IQR, 4-16) in 19.1 days (IQR, 4-90); median MELD access was 28 points (IQR, 24-31). Forty-five patients (26.9%) had MELD exceptions; 31 (68.9%) were due to hepatocellular carcinoma. Our center has a larger proportion of recipients transplanted by emergency status and MELD, similar MELD access, and less waiting list time, reflecting our wide policy of liver graft acceptance. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. An Overview of the Characteristics and Function of Vitamin C in Various Tissues: Relying on its Antioxidant Function

    Directory of Open Access Journals (Sweden)

    Abolfazl Akbari

    2016-10-01

    Full Text Available Vitamin C (L-ascorbic acid or ascorbate is a biomolecule that participates in many biochemical processes. It is an essential nutrient for humans, however, in some species such as rodents and guinea pigs is synthesized. It has a variety of functions in the body that we might venture to say make it a very important antioxidant nature and pro-oxidant. L-ascorbic acidic a reduced form of vitamin C and dehydroascorbic acid (DHA is the oxidized form of ascorbate, both L-ascorbic acid and dihydroascorbic acid retain the vitamin C activity. Dehydro-ascorbate is reconverted to ascorbate in the cytosol by cytochrome b reductase and thioredoxin reductase in reactions involving NADH and NADPH, respectively. Ascorbate is transported into the cell via the sodium-dependent vitamin C transporters (SVCTs, which causes accumulation of ascorbate within cells against a concentration gradient. Dehydroascorbic acid, the oxidized form of ascorbate, is transported via glucose transporters family (GLUTs. The highest concentrations of ascorbate in the body are found in brain and adrenal gland. Vitamin C also acts as a co-factor in several enzyme reactions. This vitamin is an essential biochemical factor in the reproductive process. The pharmacophore of vitamin C is the ascorbate, ascorbate is an antioxidant.Ascorbate is a neuromodulator of glutamatergic and dopaminergic system and related behaviors. It also improves components of the immune system. Given the wide role of ascorbate, further investigation is necessary to evaluate the exact mechanism(s underlying these effects. In this review we will consider a short overview of the characteristics and function of vitamin C (relying on antioxidant function in various tissues.

  12. Magnetic Nanocomposite Cilia Energy Harvester

    KAUST Repository

    Khan, Mohammed Asadullah; Alfadhel, Ahmed; Kosel, Jü rgen

    2016-01-01

    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

  13. Magnetic Nanocomposite Cilia Tactile Sensor

    KAUST Repository

    Alfadhel, Ahmed; Kosel, Jü rgen

    2015-01-01

    A multifunctional biomimetic nanocomposite tactile sensor is developed that can detect shear and vertical forces, feel texture, and measure flow with extremely low power consumption. The sensor's high performance is maintained within a wide operating range that can be easily adjusted. The concept works on rigid and flexible substrates and the sensors can be used in air or water without any modifications.

  14. Magnetic Nanocomposite Cilia Tactile Sensor

    KAUST Repository

    Alfadhel, Ahmed

    2015-10-21

    A multifunctional biomimetic nanocomposite tactile sensor is developed that can detect shear and vertical forces, feel texture, and measure flow with extremely low power consumption. The sensor\\'s high performance is maintained within a wide operating range that can be easily adjusted. The concept works on rigid and flexible substrates and the sensors can be used in air or water without any modifications.

  15. Imaging in primary osteosarcomas

    International Nuclear Information System (INIS)

    Davies, A.M.

    1998-01-01

    Osteosarcoma is the most common primary malignant bone tumour with the exception of myeloma. The majority of osteosarcoma cases arise within bone and are called conventional osteosarcoma. Intraosseous variants include telangiectatic, small-cell, low-grade intraosseous and cortical osteosarcoma. Less than 10% of osteosarcomas arise on the surface of bone and are subdivided into periosteal, high-grade surface and parosteal varieties. The imaging features of these subtypes of osteosarcoma are described and the impact on diagnosis highlighted. Using material from over 750 osteosarcomas treated at the author's centre, this article reviews the role of imaging in the management of this condition. Detection still relies principally on the conventional radiograph with bone scintigraphy and MR imaging useful in occult tumours. Establishing the radiological diagnosis depends on careful analysis of the radiographs, with particular attention paid to the nature and extent of bone destruction, periosteal new bone formation and matrix mineralization. The prudent radiologist will be wary of those bone conditions, such as stress fractures and osteomyelitis, which are frequently mistaken for osteosarcoma. Appropriate surgical staging requires MR imaging of the primary tumour to show the bony and soft tissue extent of the lesion and to confirm/exclude skip metastases and local lymph-node involvement. Staging should also include bone scintigraphy to confirm/exclude multiple lesions and chest CT to confirm/exclude pulmonary metastases. Following definitive surgery, imaging is used in the follow-up to monitor potential local recurrence and the development of pulmonary or osseous metastases. (orig.) [de

  16. [Hypertension: once primary, always primary?

    NARCIS (Netherlands)

    Braam, R.L.; Pieters, G.F.F.M.; Thien, Th.

    2002-01-01

    Three patients diagnosed with primary hypertension suddenly developed hard-to-treat blood pressure after several years of stable blood pressure. One patient, a man aged 48 years, had developed a renal artery stenosis, which had not been present five years earlier. The other two patients, a man aged

  17. Hyperthyroidism (primary)

    OpenAIRE

    Nygaard, Birte

    2010-01-01

    Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone (TSH). Thyrotoxicosis is the clinical effect of high levels of thyroid hormones, whether or not the thyroid gland is the primary source.The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma.About 20 times more women than men have hyperthyroidism.

  18. Do we really rely on fast for decision-making in the management of blunt abdominal trauma?

    Science.gov (United States)

    Carter, Jeffrey W; Falco, Mark H; Chopko, Michael S; Flynn, William J; Wiles Iii, Charles E; Guo, Weidun Alan

    2015-05-01

    The Focused Assessment with Sonography in Trauma examination (FAST) is currently taught and recommended in the ATLS(®), often as an addendum to the primary survey for patients with blunt abdominal trauma. Although it is non-invasive and rapidly performed at bedside, the utility of FAST in blunt abdominal trauma has been questioned. We designed this study to examine our hypothesis that FAST is not an efficacious screening tool for identifying intra-abdominal injuries. We performed a retrospective chart review of all patients with confirmatory diagnosis of blunt abdominal injuries with CT and/or laparotomy for a period of 1.5 years (from 7/2009 to 11/2010). FAST was performed by ED residents and considered positive when free intra-abdominal fluid was visualized. Abdominal CT, or exploratory laparotomy findings were used as confirmation of intra-abdominal injury. A total of 1671 blunt trauma patients were admitted to and evaluated in the Emergency Department during a 1½ year period and 146 patients were confirmed intra-abdominal injuries by CT and/or laparotomy. Intraoperative findings include injuries to the liver, spleen, kidneys, and bowels. In 114 hemodynamically stable patients, FAST was positive in 25 patients, with a sensitivity of 22%. In 32 hemodynamically unstable patients, FAST was positive in 9 patients, with a sensitivity of 28%. A free peritoneal fluid and splenic injury are associated with a positive FAST on univariate analysis, and are the independent predictors for a positive FAST on multiple logistic regression. FAST has a very low sensitivity in detecting blunt intraabdominal injury. In hemodynamically stable patients, a negative FAST without a CT may result in missed intra-abdominal injuries. In hemodynamically unstable blunt trauma patients, with clear physical findings on examination, the decision for exploratory laparotomy should not be distracted by a negative FAST. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Reliģijas, apmierinātības ar dzīvi un pašvērtējuma saistība.

    OpenAIRE

    Bērziņa, Annija

    2015-01-01

    Šī darba mērķis ir noskaidrot saistību starp reliģiju, apmierinātību ar dzīvi un pašvērtējumu. Apmierinātība ar dzīvi sevī ietver laimi, subjektīvo labklājību un pozitīvas emocijas. Šī darba ietvaros vairāk tiks apskatīta subjektīvā labklājība. Reliģija ir ticība kam mistiskam , kas sevī ietver reliģisku normu ievērošanu, rituālus, ticību un būšanu reliģiskā kopienā. Starp subjektīvo labklājību un reliģiju pastāv pozitīva korelācija. Pašvērtējums ir cilvēka subjektīvs viedoklis par...

  20. Clinical value of measurement of pulmonary radioaerosol mucociliary clearance in the work up of primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Munkholm, Mathias; Nielsen, Kim Gjerum; Mortensen, Jann

    2015-01-01

    BACKGROUND: We aimed to evaluate and define the general clinical applicability and impact of pulmonary radioaerosol mucociliary clearance (PRMC) on the work up of patients suspected of having primary ciliary dyskinesia (PCD). In addition, we wanted to evaluate the accuracy of the reference values...... primarily to results from nasal ciliary function testing, to electron microscopic (EM) examination of the ultrastructure of the cilia, and to the final clinical diagnosis. RESULTS: Of the 239 patients, 27 ended up with a final clinical diagnosis of definitive PCD. No patients with a PRMC test...... of the entire lung. Its greatest strength is its ability to reject a suspected PCD diagnosis with great certainty. In our material, this accounted for 2/3 of referred patients. In addition, the test has a high rate of conclusive results. According to our analyses, reference equations on children would benefit...

  1. CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium

    DEFF Research Database (Denmark)

    Mönnich, Maren; Borgeskov, Louise; Breslin, Loretta

    2018-01-01

    The centrosome is the main microtubule-organizing center in animal cells and comprises a mother and daughter centriole surrounded by pericentriolar material. During formation of primary cilia, the mother centriole transforms into a basal body that templates the ciliary axoneme. Ciliogenesis depends...... on mother centriole-specific distal appendages, whereas the role of subdistal appendages in ciliary function is unclear. Here, we identify CEP128 as a centriole subdistal appendage protein required for regulating ciliary signaling. Loss of CEP128 did not grossly affect centrosomal or ciliary structure...... but caused impaired transforming growth factor-β/bone morphogenetic protein (TGF-β/BMP) signaling in zebrafish and at the primary cilium in cultured mammalian cells. This phenotype is likely the result of defective vesicle trafficking at the cilium as ciliary localization of RAB11 was impaired upon loss...

  2. 12 CFR 714.5 - What is required if you rely on an estimated residual value greater than 25% of the original cost...

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false What is required if you rely on an estimated residual value greater than 25% of the original cost of the leased property? 714.5 Section 714.5 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS LEASING § 714.5 What is...

  3. Research Advances: Pacific Northwest National Laboratory Finds New Way to Detect Destructive Enzyme Activity--Hair Dye Relies on Nanotechnology--Ways to Increase Shelf Life of Milk

    Science.gov (United States)

    King, Angela G.

    2007-01-01

    Recent advances in various research fields are described. Scientists at the Pacific Northwest National Laboratory have found a new way to detect destructive enzyme activity, scientists in France have found that an ancient hair dye used by ancient people in Greece and Rome relied on nanotechnology and in the U.S. scientists are developing new…

  4. [Zeme, vara un reliģija viduslaikos un jaunajas laikos Baltijas jūras reģionā] / Marija Golubeva

    Index Scriptorium Estoniae

    Golubeva, Marija, 1973-

    2011-01-01

    Arvustus: Zeme, vara un reliģija viduslaikos un jaunajas laikos Baltijas jūras reģionā / Hrsg. von Andris Šnē. Acta Universitatis Latviensis ; 725. (Riga: Verlag Latvijas Universitātes Akadēmiskais apgāds, 2009)

  5. Biological adhesion of the flatworm Macrostomum lignano relies on a duo-gland system and is mediated by a cell type-specific intermediate filament protein

    NARCIS (Netherlands)

    Lengerer, Birgit; Pjeta, Robert; Wunderer, Julia; Rodrigues, Marcelo; Arbore, Roberto; Schaerer, Lukas; Berezikov, Eugene; Hess, Michael W.; Pfaller, Kristian; Egger, Bernhard; Obwegeser, Sabrina; Salvenmoser, Willi; Ladurner, Peter

    2014-01-01

    Background: Free-living flatworms, in both marine and freshwater environments, are able to adhere to and release from a substrate several times within a second. This reversible adhesion relies on adhesive organs comprised of three cell types: an adhesive gland cell, a releasing gland cell, and an

  6. Mass Spectrometry-Based Adrenal and Peripheral Venous Steroid Profiling for Subtyping Primary Aldosteronism

    NARCIS (Netherlands)

    Eisenhofer, G.; Dekkers, T.; Peitzsch, M.; Dietz, A.S.; Bidlingmaier, M.; Treitl, M.; Williams, T.A.; Bornstein, S.R.; Haase, M.; Rump, L.C.; Willenberg, H.S.; Beuschlein, F.; Deinum, J.; Lenders, J.W.; Reincke, M.

    2016-01-01

    BACKGROUND: Differentiating patients with primary aldosteronism caused by aldosterone-producing adenomas (APAs) from those with bilateral adrenal hyperplasia (BAH), which is essential for choice of therapeutic intervention, relies on adrenal venous sampling (AVS)-based measurements of aldosterone

  7. Diverticular Disease in the Primary Care Setting.

    Science.gov (United States)

    Wensaas, Knut-Arne; Hungin, Amrit Pali

    2016-10-01

    Diverticular disease is a chronic and common condition, and yet the impact of diverticular disease in primary care is largely unknown. The diagnosis of diverticular disease relies on the demonstration of diverticula in the colon, and the necessary investigations are often not available in primary care. The specificity and sensitivity of symptoms, clinical signs and laboratory tests alone are generally low and consequently the diagnostic process will be characterized by uncertainty. Also, the criteria for symptomatic uncomplicated diverticular disease in the absence of macroscopic inflammation are not clearly defined. Therefore both the prevalence of diverticular disease and the incidence of diverticulitis in primary care are unknown. Current recommendations for treatment and follow-up of patients with acute diverticulitis are based on studies where the diagnosis has been verified by computerized tomography. The results cannot be directly transferred to primary care where the diagnosis has to rely on the interpretation of symptoms and signs. Therefore, one must allow for greater diagnostic uncertainty, and safety netting in the event of unexpected development of the condition is an important aspect of the management of diverticulitis in primary care. The highest prevalence of diverticular disease is found among older patients, where multimorbidity and polypharmacy is common. The challenge is to remember the possible contribution of diverticular disease to the patient's overall condition and to foresee its implications in terms of advice and treatment in relation to other diseases.

  8. Lying relies on the truth

    NARCIS (Netherlands)

    Debey, E.; De Houwer, J.; Verschuere, B.

    2014-01-01

    Cognitive models of deception focus on the conflict-inducing nature of the truth activation during lying. Here we tested the counterintuitive hypothesis that the truth can also serve a functional role in the act of lying. More specifically, we examined whether the construction of a lie can involve a

  9. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial.

    Science.gov (United States)

    Wallentin, Lars; Yusuf, Salim; Ezekowitz, Michael D; Alings, Marco; Flather, Marcus; Franzosi, Maria Grazia; Pais, Prem; Dans, Antonio; Eikelboom, John; Oldgren, Jonas; Pogue, Janice; Reilly, Paul A; Yang, Sean; Connolly, Stuart J

    2010-09-18

    Effectiveness and safety of warfarin is associated with the time in therapeutic range (TTR) with an international normalised ratio (INR) of 2·0-3·0. In the Randomised Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, dabigatran versus warfarin reduced both stroke and haemorrhage. We aimed to investigate the primary and secondary outcomes of the RE-LY trial in relation to each centre's mean TTR (cTTR) in the warfarin population. In the RE-LY trial, 18 113 patients at 951 sites were randomly assigned to 110 mg or 150 mg dabigatran twice daily versus warfarin dose adjusted to INR 2·0-3·0. Median follow-up was 2·0 years. For 18 024 patients at 906 sites, the cTTR was estimated by averaging TTR for individual warfarin-treated patients calculated by the Rosendaal method. We compared the outcomes of RE-LY across the three treatment groups within four groups defined by the quartiles of cTTR. RE-LY is registered with ClinicalTrials.gov, number NCT00262600. The quartiles of cTTR for patients in the warfarin group were: less than 57·1%, 57·1-65·5%, 65·5-72·6%, and greater than 72·6%. There were no significant interactions between cTTR and prevention of stroke and systemic embolism with either 110 mg dabigatran (interaction p=0·89) or 150 mg dabigatran (interaction p=0·20) versus warfarin. Neither were any significant interactions recorded with cTTR with regards to intracranial bleeding with 110 mg dabigatran (interaction p=0·71) or 150 mg dabigatran (interaction p=0·89) versus warfarin. There was a significant interaction between cTTR and major bleeding when comparing 150 mg dabigatran with warfarin (interaction p=0·03), with less bleeding events at lower cTTR but similar events at higher cTTR, whereas rates of major bleeding were lower with 110 mg dabigatran than with warfarin irrespective of cTTR. There were significant interactions between cTTR and effects of both 110 mg and 150 mg dabigatran versus warfarin on the composite of all

  10. Do Local Contributions Affect the Efficacy of Public Primary Schools?

    Science.gov (United States)

    Jimenez, Emmanuel; Paqueo, Vicente

    1996-01-01

    Uses cost, financial sources, and student achievement data from Philippine primary schools (financed primarily from central sources) to discover if financial decentralization leads to more efficient schools. Schools that rely more heavily on local sources (contributions from local school boards, municipal government, parent-teacher associations,…

  11. Primary health eye care knowledge among general practitioners ...

    African Journals Online (AJOL)

    2010-05-10

    May 10, 2010 ... A significant percentage of patients seen at the primary health care level (district ... (GPs) are forced to rely on the knowledge acquired from their limited .... accurate in screening patients for diabetic retinopathy.4. In this study ...

  12. Cytotoxicity Comparison of Harvard Zinc Phosphate Cement Versus Panavia F2 and Rely X Plus Resin Cements on Rat L929-fibroblasts.

    Science.gov (United States)

    Mahasti, Sahabi; Sattari, Mandana; Romoozi, Elham; Akbar-Zadeh Baghban, Alireza

    2011-01-01

    Resin cements, regardless of their biocompatibility, have been widely used in restorative dentistry during the recent years. These cements contain hydroxy ethyl methacrylate (HEMA) molecules which are claimed to penetrate into dentinal tubules and may affect dental pulp. Since tooth preparation for metal ceramic restorations involves a large surface of the tooth, cytotoxicity of these cements would be more important in fixed prosthodontic treatments. The purpose of this study was to compare the cytotoxicity of two resin cements (Panavia F2 and Rely X Plus) versus zinc phosphate cement (Harvard) using rat L929-fibroblasts in vitro. In this experimental study, ninety hollow glass cylinders (internal diameter 5-mm, height 2-mm) were made and divided into three groups. Each group was filled with one of three experimental cements; Harvard Zinc Phosphate cement, Panavia F2 resin cement and Rely X Plus resin cement. L929- Fibroblast were passaged and subsequently cultured in 6-well plates of 5×10(5) cells each. The culture medium was RPMI_ 1640. All samples were incubated in CO2. Using enzyme-linked immune-sorbent assay (ELISA) and (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) (MTT) assay, the cytotoxicity of the cements was investigated at 1 hour, 24 hours and one week post exposure. Statistical analyses were performed via two-way ANOVA and honestly significant difference (HSD) Tukey tests. This study revealed significant differences between the three cements at the different time intervals. Harvard cement displayed the greatest cytotoxicity at all three intervals. After 1 hour Panavia F2 showed the next greatest cytotoxicity, but after 24-hours and oneweek intervals Rely X Plus showed the next greatest cytotoxicity. The results further showed that cytotoxicity decreased significantly in the Panavia F2 group with time (pHarvard cement group failed to showed no noticeable change in cytotoxicity with time. Although this study has limitations, it provides

  13. The description-experience gap and its relation to instructional control: Do people rely more on their experience than in objective descriptions?

    Directory of Open Access Journals (Sweden)

    Álvaro Viúdez

    2017-11-01

    Full Text Available The present work aims to reveal contradictory results obtained on two different fields; particularly from two studies conducted on the description-experience gap field showing that descriptions are neglected when personal experience is available (1,2, and several others conducted on the instructional control field getting to the opposite conclusion (3–8. To account for this contradiction, we hypothesized that participants from the studies of Jessup, Bishara and Busemeyer (1 and Lejarraga and Gonzalez (2 relied on their experience rather than on the descriptions because of the difficult, demanding nature of the probabilistic descriptions they faced. Enriched descriptions were created in our experiment to assess the contribution of this factor to the differential influence of the descriptions in choice behavior. Nonetheless, our hypothesis did not find support in the results and further research is needed to account for the aforementioned contradiction.

  14. Imputation of missing genotypes within LD-blocks relying on the basic coalescent and beyond: consideration of population growth and structure.

    Science.gov (United States)

    Kabisch, Maria; Hamann, Ute; Lorenzo Bermejo, Justo

    2017-10-17

    Genotypes not directly measured in genetic studies are often imputed to improve statistical power and to increase mapping resolution. The accuracy of standard imputation techniques strongly depends on the similarity of linkage disequilibrium (LD) patterns in the study and reference populations. Here we develop a novel approach for genotype imputation in low-recombination regions that relies on the coalescent and permits to explicitly account for population demographic factors. To test the new method, study and reference haplotypes were simulated and gene trees were inferred under the basic coalescent and also considering population growth and structure. The reference haplotypes that first coalesced with study haplotypes were used as templates for genotype imputation. Computer simulations were complemented with the analysis of real data. Genotype concordance rates were used to compare the accuracies of coalescent-based and standard (IMPUTE2) imputation. Simulations revealed that, in LD-blocks, imputation accuracy relying on the basic coalescent was higher and less variable than with IMPUTE2. Explicit consideration of population growth and structure, even if present, did not practically improve accuracy. The advantage of coalescent-based over standard imputation increased with the minor allele frequency and it decreased with population stratification. Results based on real data indicated that, even in low-recombination regions, further research is needed to incorporate recombination in coalescence inference, in particular for studies with genetically diverse and admixed individuals. To exploit the full potential of coalescent-based methods for the imputation of missing genotypes in genetic studies, further methodological research is needed to reduce computer time, to take into account recombination, and to implement these methods in user-friendly computer programs. Here we provide reproducible code which takes advantage of publicly available software to facilitate

  15. Automatic and Intentional Number Processing Both Rely on Intact Right Parietal Cortex: A Combined fMRI and Neuronavigated TMS Study

    Science.gov (United States)

    Cohen Kadosh, Roi; Bien, Nina; Sack, Alexander T.

    2012-01-01

    Practice and training usually lead to performance increase in a given task. In addition, a shift from intentional toward more automatic processing mechanisms is often observed. It is currently debated whether automatic and intentional processing is subserved by the same or by different mechanism(s), and whether the same or different regions in the brain are recruited. Previous correlational evidence provided by behavioral, neuroimaging, modeling, and neuropsychological studies addressing this question yielded conflicting results. Here we used transcranial magnetic stimulation (TMS) to compare the causal influence of disrupting either left or right parietal cortex during automatic and intentional numerical processing, as reflected by the size congruity effect and the numerical distance effect, respectively. We found a functional hemispheric asymmetry within parietal cortex with only the TMS-induced right parietal disruption impairing both automatic and intentional numerical processing. In contrast, disrupting the left parietal lobe with TMS, or applying sham stimulation, did not affect performance during automatic or intentional numerical processing. The current results provide causal evidence for the functional relevance of right, but not left, parietal cortex for intentional, and automatic numerical processing, implying that at least within the parietal cortices, automatic, and intentional numerical processing rely on the same underlying hemispheric lateralization. PMID:22347175

  16. Primary Progressive Aphasia

    Science.gov (United States)

    ... which cause different symptoms. Semantic variant primary progressive aphasia Symptoms include these difficulties: Comprehending spoken or written ... word meanings Naming objects Logopenic variant primary progressive aphasia Symptoms include: Having difficulty retrieving words Frequently pausing ...

  17. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  18. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  19. How and When Do Insects Rely on Endogenous Protein and Lipid Resources during Lethal Bouts of Starvation? A New Application for 13C-Breath testing.

    Science.gov (United States)

    McCue, Marshall D; Guzman, R Marena; Passement, Celeste A; Davidowitz, Goggy

    2015-01-01

    Most of our understanding about the physiology of fasting and starvation comes from studies of vertebrates; however, for ethical reasons, studies that monitor vertebrates through the lethal endpoint are scant. Insects are convenient models to characterize the comparative strategies used to cope with starvation because they have diverse life histories and have evolved under the omnipresent challenge of food limitation. Moreover, we can study the physiology of starvation through its natural endpoint. In this study we raised populations of five species of insects (adult grasshoppers, crickets, cockroaches, and larval beetles and moths) on diets labeled with either 13C-palmitic acid or 13C-leucine to isotopically enrich the lipids or the proteins in their bodies, respectively. The insects were allowed to become postabsorptive and then starved. We periodically measured the δ13C of the exhaled breath to characterize how each species adjusted their reliance on endogenous lipids and proteins as energy sources. We found that starving insects employ a wide range of strategies for regulating lipid and protein oxidation. All of the insects except for the beetle larvae were capable of sharply reducing reliance on protein oxidation; however, this protein sparing strategy was usually unsustainable during the entire starvation period. All insects increased their reliance on lipid oxidation, but while some species (grasshoppers, cockroaches, and beetle larvae) were still relying extensively on lipids at the time of death, other species (crickets and moth larvae) allowed rates of lipid oxidation to return to prestarvation levels. Although lipids and proteins are critical metabolic fuels for both vertebrates and insects, insects apparently exhibit a much wider range of strategies for rationing these limited resources during starvation.

  20. Moralized Rationality: Relying on Logic and Evidence in the Formation and Evaluation of Belief Can Be Seen as a Moral Issue

    Science.gov (United States)

    Skitka, Linda J.

    2016-01-01

    In the present article we demonstrate stable individual differences in the extent to which a reliance on logic and evidence in the formation and evaluation of beliefs is perceived as a moral virtue, and a reliance on less rational processes is perceived as a vice. We refer to this individual difference variable as moralized rationality. Eight studies are reported in which an instrument to measure individual differences in moralized rationality is validated. Results show that the Moralized Rationality Scale (MRS) is internally consistent, and captures something distinct from the personal importance people attach to being rational (Studies 1–3). Furthermore, the MRS has high test-retest reliability (Study 4), is conceptually distinct from frequently used measures of individual differences in moral values, and it is negatively related to common beliefs that are not supported by scientific evidence (Study 5). We further demonstrate that the MRS predicts morally laden reactions, such as a desire for punishment, of people who rely on irrational (vs. rational) ways of forming and evaluating beliefs (Studies 6 and 7). Finally, we show that the MRS uniquely predicts motivation to contribute to a charity that works to prevent the spread of irrational beliefs (Study 8). We conclude that (1) there are stable individual differences in the extent to which people moralize a reliance on rationality in the formation and evaluation of beliefs, (2) that these individual differences do not reduce to the personal importance attached to rationality, and (3) that individual differences in moralized rationality have important motivational and interpersonal consequences. PMID:27851777

  1. Moralized Rationality: Relying on Logic and Evidence in the Formation and Evaluation of Belief Can Be Seen as a Moral Issue.

    Directory of Open Access Journals (Sweden)

    Tomas Ståhl

    Full Text Available In the present article we demonstrate stable individual differences in the extent to which a reliance on logic and evidence in the formation and evaluation of beliefs is perceived as a moral virtue, and a reliance on less rational processes is perceived as a vice. We refer to this individual difference variable as moralized rationality. Eight studies are reported in which an instrument to measure individual differences in moralized rationality is validated. Results show that the Moralized Rationality Scale (MRS is internally consistent, and captures something distinct from the personal importance people attach to being rational (Studies 1-3. Furthermore, the MRS has high test-retest reliability (Study 4, is conceptually distinct from frequently used measures of individual differences in moral values, and it is negatively related to common beliefs that are not supported by scientific evidence (Study 5. We further demonstrate that the MRS predicts morally laden reactions, such as a desire for punishment, of people who rely on irrational (vs. rational ways of forming and evaluating beliefs (Studies 6 and 7. Finally, we show that the MRS uniquely predicts motivation to contribute to a charity that works to prevent the spread of irrational beliefs (Study 8. We conclude that (1 there are stable individual differences in the extent to which people moralize a reliance on rationality in the formation and evaluation of beliefs, (2 that these individual differences do not reduce to the personal importance attached to rationality, and (3 that individual differences in moralized rationality have important motivational and interpersonal consequences.

  2. How and When Do Insects Rely on Endogenous Protein and Lipid Resources during Lethal Bouts of Starvation? A New Application for 13C-Breath testing.

    Directory of Open Access Journals (Sweden)

    Marshall D McCue

    Full Text Available Most of our understanding about the physiology of fasting and starvation comes from studies of vertebrates; however, for ethical reasons, studies that monitor vertebrates through the lethal endpoint are scant. Insects are convenient models to characterize the comparative strategies used to cope with starvation because they have diverse life histories and have evolved under the omnipresent challenge of food limitation. Moreover, we can study the physiology of starvation through its natural endpoint. In this study we raised populations of five species of insects (adult grasshoppers, crickets, cockroaches, and larval beetles and moths on diets labeled with either 13C-palmitic acid or 13C-leucine to isotopically enrich the lipids or the proteins in their bodies, respectively. The insects were allowed to become postabsorptive and then starved. We periodically measured the δ13C of the exhaled breath to characterize how each species adjusted their reliance on endogenous lipids and proteins as energy sources. We found that starving insects employ a wide range of strategies for regulating lipid and protein oxidation. All of the insects except for the beetle larvae were capable of sharply reducing reliance on protein oxidation; however, this protein sparing strategy was usually unsustainable during the entire starvation period. All insects increased their reliance on lipid oxidation, but while some species (grasshoppers, cockroaches, and beetle larvae were still relying extensively on lipids at the time of death, other species (crickets and moth larvae allowed rates of lipid oxidation to return to prestarvation levels. Although lipids and proteins are critical metabolic fuels for both vertebrates and insects, insects apparently exhibit a much wider range of strategies for rationing these limited resources during starvation.

  3. Stepped MS(All) Relied Transition (SMART): An approach to rapidly determine optimal multiple reaction monitoring mass spectrometry parameters for small molecules.

    Science.gov (United States)

    Ye, Hui; Zhu, Lin; Wang, Lin; Liu, Huiying; Zhang, Jun; Wu, Mengqiu; Wang, Guangji; Hao, Haiping

    2016-02-11

    Multiple reaction monitoring (MRM) is a universal approach for quantitative analysis because of its high specificity and sensitivity. Nevertheless, optimization of MRM parameters remains as a time and labor-intensive task particularly in multiplexed quantitative analysis of small molecules in complex mixtures. In this study, we have developed an approach named Stepped MS(All) Relied Transition (SMART) to predict the optimal MRM parameters of small molecules. SMART requires firstly a rapid and high-throughput analysis of samples using a Stepped MS(All) technique (sMS(All)) on a Q-TOF, which consists of serial MS(All) events acquired from low CE to gradually stepped-up CE values in a cycle. The optimal CE values can then be determined by comparing the extracted ion chromatograms for the ion pairs of interest among serial scans. The SMART-predicted parameters were found to agree well with the parameters optimized on a triple quadrupole from the same vendor using a mixture of standards. The parameters optimized on a triple quadrupole from a different vendor was also employed for comparison, and found to be linearly correlated with the SMART-predicted parameters, suggesting the potential applications of the SMART approach among different instrumental platforms. This approach was further validated by applying to simultaneous quantification of 31 herbal components in the plasma of rats treated with a herbal prescription. Because the sMS(All) acquisition can be accomplished in a single run for multiple components independent of standards, the SMART approach are expected to find its wide application in the multiplexed quantitative analysis of complex mixtures. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Investigating Primary Source Literacy

    Science.gov (United States)

    Archer, Joanne; Hanlon, Ann M.; Levine, Jennie A.

    2009-01-01

    Primary source research requires students to acquire specialized research skills. This paper presents results from a user study testing the effectiveness of a Web guide designed to convey the concepts behind "primary source literacy". The study also evaluated students' strengths and weaknesses when conducting primary source research. (Contains 3…

  5. Primary Hyperparathyroidism: An Overview

    Directory of Open Access Journals (Sweden)

    Jessica MacKenzie-Feder

    2011-01-01

    Full Text Available Primary hyperparathyroidism is a common condition that affects 0.3% of the general population. Primary and tertiary care specialists can encounter patients with primary hyperparathyroidism, and prompt recognition and treatment can greatly reduce morbidity and mortality from this disease. In this paper we will review the basic physiology of calcium homeostasis and then consider genetic associations as well as common etiologies and presentations of primary hyperparathyroidism. We will consider emerging trends in detection and measurement of parathyroid hormone as well as available imaging modalities for the parathyroid glands. Surgical indications and approach will be reviewed as well as medical management of primary hyperparathyroidism with bisphosphonates and calcimimetics.

  6. Normocalcemic Primary Hyperparathyroidism

    Science.gov (United States)

    Cusano, Natalie E.; Silverberg, Shonni J.; Bilezikian, John P.

    2013-01-01

    Primary hyperparathyroidism, a common endocrine disorder, is traditionally defined by hypercalcemia and elevated levels of parathyroid hormone (PTH). A newer presentation of primary hyperparathyroidism has been described over the past decade, in which PTH is elevated but serum calcium is consistently normal, in the absence of secondary causes of hyperparathyroidism, such as renal disease or vitamin D deficiency. Recognition of this phenotype of primary hyperparathyroidism, normocalcemic primary hyperparathyroidism, supports a biphasic chronological time course in some individuals in which PTH levels are first elevated but serum calcium is normal, followed by the development of frank hypercalcemia. This review focuses on the available literature regarding this newly described phenotype of primary hyperparathyroidism. PMID:23374739

  7. An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells

    Science.gov (United States)

    Knies, Diana; Klobuch, Sebastian; Xue, Shao-An; Birtel, Matthias; Echchannaoui, Hakim; Yildiz, Oezlem; Omokoko, Tana; Guillaume, Philippe; Romero, Pedro; Stauss, Hans; Sahin, Ugur; Herr, Wolfgang; Theobald, Matthias; Thomas, Simone; Voss, Ralf-Holger

    2016-01-01

    Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells. PMID:27028870

  8. Biological adhesion of the flatworm Macrostomum lignano relies on a duo-gland system and is mediated by a cell type-specific intermediate filament protein.

    Science.gov (United States)

    Lengerer, Birgit; Pjeta, Robert; Wunderer, Julia; Rodrigues, Marcelo; Arbore, Roberto; Schärer, Lukas; Berezikov, Eugene; Hess, Michael W; Pfaller, Kristian; Egger, Bernhard; Obwegeser, Sabrina; Salvenmoser, Willi; Ladurner, Peter

    2014-02-12

    Free-living flatworms, in both marine and freshwater environments, are able to adhere to and release from a substrate several times within a second. This reversible adhesion relies on adhesive organs comprised of three cell types: an adhesive gland cell, a releasing gland cell, and an anchor cell, which is a modified epidermal cell responsible for structural support. However, nothing is currently known about the molecules that are involved in this adhesion process. In this study we present the detailed morphology of the adhesive organs of the free-living marine flatworm Macrostomum lignano. About 130 adhesive organs are located in a horse-shoe-shaped arc along the ventral side of the tail plate. Each organ consists of exactly three cells, an adhesive gland cell, a releasing gland cell, and an anchor cell. The necks of the two gland cells penetrate the anchor cell through a common pore. Modified microvilli of the anchor cell form a collar surrounding the necks of the adhesive- and releasing glands, jointly forming the papilla, the outer visible part of the adhesive organs. Next, we identified an intermediate filament (IF) gene, macif1, which is expressed in the anchor cells. RNA interference mediated knock-down resulted in the first experimentally induced non-adhesion phenotype in any marine animal. Specifically, the absence of intermediate filaments in the anchor cells led to papillae with open tips, a reduction of the cytoskeleton network, a decline in hemidesmosomal connections, and to shortened microvilli containing less actin. Our findings reveal an elaborate biological adhesion system in a free-living flatworm, which permits impressively rapid temporary adhesion-release performance in the marine environment. We demonstrate that the structural integrity of the supportive cell, the anchor cell, is essential for this adhesion process: the knock-down of the anchor cell-specific intermediate filament gene resulted in the inability of the animals to adhere. The RNAi

  9. Nanoscale Assembly of Actuating Cilia-Mimetic

    Science.gov (United States)

    Baird, Lance; Breidenich, Jennifer; Land, Bruce; Hayes, Allen; Benkoski, Jason; Keng, Pei; Pyun, Jeffrey

    2009-03-01

    The cilium is among the smallest mechanical actuators found in nature. We have taken inspiration from this design to create magnetic nanochains, measuring approximately 1-5 μm long and 25 nm in diameter. Fabricated from the self-assembly of cobalt nanoparticles, these flexible filaments actuate in an oscillating magnetic field. The cobalt nanoparticles were functionalized with a polystyrene/benzaldehyde surface coating, thus allowing the particles to form imine bonds with one another in the presence of a diamine terminated polyethylene glycol. These imine bonds effectively cross-linked the particles and held the nanochains together in the absence of a magnetic field. Using design of experiments (DOE) to efficiently screen the effects of cobalt nanoparticle concentration, crosslinker concentration, and surface chemistry, we determined that the morphology of the final structures could be explained primarily by physical interactions (i.e. magnetic forces) rather than chemistry.

  10. Immotile cilia syndrome in an aged dog

    International Nuclear Information System (INIS)

    Killingsworth, C.R.; Slocombe, R.F.; Wilsman, N.J.

    1987-01-01

    An 11-year-old Dalmatian was examined and treated for bilateral nasal discharge and cough of 6 months' duration. Response to medical treatment and surgical intervention was unsatisfactory. Histologic examination of lung tissue revealed chronic severe catarrhal bronchitis and bronchiolitis with bronchiectasis. Histologic findings and barium sulfate bronchography indicated abnormal mucociliary clearance in the respiratory tract. Electron microscopy revealed abnormalities or deletions of outer and/or inner dynein arms in 26% of the ciliary profiles from the affected dog. Similar abnormalities were not found in 500 ciliary profiles from age- and gender-matched control dogs

  11. Multiple primary cancer

    International Nuclear Information System (INIS)

    Jung, Gyu Sik; Lee, Ouk; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duck

    1989-01-01

    It is rare for one human being to be afflicted with more than one cancer. However with further advances in therapeutic regimens, histopathologic observation, diagnostic modalities, and increased curiosity, there are increasing number of case reports of multiple primary cancer. The present study evaluates 25 histologically confirmed cases of multiple primary cancer from 1974 to 1988 at Kosin Medical Center. The most frequent site of the first primary cancer in male was stomach and in female, uterine cervix. The first primary cancer in female occurred in endocrine-related organs (breast, uterus and thyroid) in 63.6 percent. Synchronous cancers are diagnosed simultaneously or within an interval of about six months and synchronous cancers were 16 out of 25 cases. Metachronous cancers are diagnosed at interval of more than six months. There were 9 metachronous cancers and average interval between the first and second primary cancer was 22.8 months. The incidence of multiple primary cancer was 0.11 percent. The average age was 51.9 years at the time of the first primary cancer (53.1 years in male and 50.3 years in female). CT scan was most helpful in early detection of multiple primary cancers facilitating biopsy and surgery. Multiple primary cancers are beyond the medical curiosity. Early diagnosis of the disease and careful follow-up study, based on an awareness of the possibility of second cancers, will substantially increase the survival of these patients

  12. Identification and location tasks rely on different mental processes: a diffusion model account of validity effects in spatial cueing paradigms with emotional stimuli.

    Science.gov (United States)

    Imhoff, Roland; Lange, Jens; Germar, Markus

    2018-02-22

    Spatial cueing paradigms are popular tools to assess human attention to emotional stimuli, but different variants of these paradigms differ in what participants' primary task is. In one variant, participants indicate the location of the target (location task), whereas in the other they indicate the shape of the target (identification task). In the present paper we test the idea that although these two variants produce seemingly comparable cue validity effects on response times, they rest on different underlying processes. Across four studies (total N = 397; two in the supplement) using both variants and manipulating the motivational relevance of cue content, diffusion model analyses revealed that cue validity effects in location tasks are primarily driven by response biases, whereas the same effect rests on delay due to attention to the cue in identification tasks. Based on this, we predict and empirically support that a symmetrical distribution of valid and invalid cues would reduce cue validity effects in location tasks to a greater extent than in identification tasks. Across all variants of the task, we fail to replicate the effect of greater cue validity effects for arousing (vs. neutral) stimuli. We discuss the implications of these findings for best practice in spatial cueing research.

  13. Using Primary Source Documents.

    Science.gov (United States)

    Mintz, Steven

    2003-01-01

    Explores the use of primary sources when teaching about U.S. slavery. Includes primary sources from the Gilder Lehrman Documents Collection (New York Historical Society) to teach about the role of slaves in the Revolutionary War, such as a proclamation from Lord Dunmore offering freedom to slaves who joined his army. (CMK)

  14. Medics in Primary School

    Science.gov (United States)

    Press, Colin

    2003-01-01

    Some time ago a flyer on "Medics in Primary School" came the author's way. It described a programme for making placements in primary schools available to medical students. The benefits of the program to medical students and participating schools were highlighted, including opportunities to develop communication skills and demystify…

  15. Short-term retention of a single word relies on retrieval from long-term memory when both rehearsal and refreshing are disrupted.

    Science.gov (United States)

    Rose, Nathan S; Buchsbaum, Bradley R; Craik, Fergus I M

    2014-07-01

    Many working memory (WM) models propose that the focus of attention (or primary memory) has a capacity limit of one to four items, and therefore, that performance on WM tasks involves retrieving some items from long-term (or secondary) memory (LTM). In the present study, we present evidence suggesting that recall of even one item on a WM task can involve retrieving it from LTM. The WM task required participants to make a deep (living/nonliving) or shallow ("e"/no "e") level-of-processing (LOP) judgment on one word and to recall the word after a 10-s delay on each trial. During the delay, participants either rehearsed the word or performed an easy or a hard math task. When the to-be-remembered item could be rehearsed, recall was fast and accurate. When it was followed by a math task, recall was slower, error-prone, and benefited from a deeper LOP at encoding, especially for the hard math condition. The authors suggest that a covert-retrieval mechanism may have refreshed the item during easy math, and that the hard math condition shows that even a single item cannot be reliably held in WM during a sufficiently distracting task--therefore, recalling the item involved retrieving it from LTM. Additionally, performance on a final free recall (LTM) test was better for items recalled following math than following rehearsal, suggesting that initial recall following math involved elaborative retrieval from LTM, whereas rehearsal did not. The authors suggest that the extent to which performance on WM tasks involves retrieval from LTM depends on the amounts of disruption to both rehearsal and covert-retrieval/refreshing maintenance mechanisms.

  16. Sclerodermiform basal cell carcinoma: how much can we rely on dermatoscopy to differentiate from non-aggressive basal cell carcinomas? Analysis of 1256 cases.

    Science.gov (United States)

    Husein-ElAhmed, Husein

    2018-03-01

    The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern. Among these aggressive lesions, sclerodermiform basal cell carcinomas are the most common type. This is a challenging-to-treat lesion due to its deep tissue invasion, rapid growth, risk of metastasis and overall poor prognosis if not diagnosed in early stages. To investigate if sclerodermiform basal cell carcinomas are diagnosed later compared to non-sclerodermiform basal cell carcinoma Method: All lesions excised from 2000 to 2010 were included. A pathologist classified the lesions in two cohorts: one with specimens of non-aggressive basal cell carcinoma (superficial, nodular and pigmented), and other with sclerodermiform basal cell carcinoma. For each lesion, we collected patient's information from digital medical records regarding: gender, age when first attending the clinic and the tumor location. 1256 lesions were included, out of which 296 (23.6%) corresponded to sclerodermiform basal cell carcinoma, whereas 960 (76.4%) were non-aggressive subtypes of basal cell carcinoma. The age of diagnosis was: 72.78±12.31 years for sclerodermiform basal cell and 69.26±13.87 years for non-aggressive basal cell carcinoma (Pbasal cell carcinomas are diagnosed on average 3.52 years later than non-aggressive basal cell carcinomas. Sclerodermiform basal cell carcinomas were diagnosed 3.40 years and 2.34 years later than non-aggressive basal cell carcinomas in younger and older patients respectively (P=.002 and P=.03, respectively). retrospective design. The diagnostic accuracy and primary clinic conjecture of sclerodermiform basal cell carcinomas is quite low compared to other forms of basal cell carcinoma such as nodular, superficial and pigmented. The dermoscopic vascular patterns, which is the basis for the diagnosis of non-melanocytic nonpigmented skin tumors, may not be particularly useful in identifying sclerodermiform basal cell carcinomas in early stages

  17. Whole-Exome Sequencing Identified a Novel Compound Heterozygous Mutation of LRRC6 in a Chinese Primary Ciliary Dyskinesia Patient

    Directory of Open Access Journals (Sweden)

    Lv Liu

    2018-01-01

    Full Text Available Primary ciliary dyskinesia (PCD is a clinical rare peculiar disorder, mainly featured by respiratory infection, tympanitis, nasosinusitis, and male infertility. Previous study demonstrated it is an autosomal recessive disease and by 2017 almost 40 pathologic genes have been identified. Among them are the leucine-rich repeat- (LRR- containing 6 (LRRC6 codes for a 463-amino-acid cytoplasmic protein, expressed distinctively in motile cilia cells, including the testis cells and the respiratory epithelial cells. In this study, we applied whole-exome sequencing combined with PCD-known genes filtering to explore the genetic lesion of a PCD patient. A novel compound heterozygous mutation in LRRC6 (c.183T>G/p.N61K; c.179-1G>A was identified and coseparated in this family. The missense mutation (c.183T>G/p.N61K may lead to a substitution of asparagine by lysine at position 61 in exon 3 of LRRC6. The splice site mutation (c.179-1G>A may cause a premature stop codon in exon 4 and decrease the mRNA levels of LRRC6. Both mutations were not present in our 200 local controls, dbSNP, and 1000 genomes. Three bioinformatics programs also predicted that both mutations are deleterious. Our study not only further supported the importance of LRRC6 in PCD, but also expanded the spectrum of LRRC6 mutations and will contribute to the genetic diagnosis and counseling of PCD patients.

  18. Primary Sclerosing Cholangitis (PSC)

    Science.gov (United States)

    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now Primary Sclerosing Cholangitis Back ...

  19. Primary cultures of astrocytes

    DEFF Research Database (Denmark)

    Lange, Sofie C; Bak, Lasse Kristoffer; Waagepetersen, Helle S

    2012-01-01

    During the past few decades of astrocyte research it has become increasingly clear that astrocytes have taken a central position in all central nervous system activities. Much of our new understanding of astrocytes has been derived from studies conducted with primary cultures of astrocytes...... subsequently found in vivo. Nevertheless, primary cultures of astrocytes are an in vitro model that does not fully mimic the complex events occurring in vivo. Here we present an overview of the numerous contributions generated by the use of primary astrocyte cultures to uncover the diverse functions...... of astrocytes. Many of these discoveries would not have been possible to achieve without the use of astrocyte cultures. Additionally, we address and discuss the concerns that have been raised regarding the use of primary cultures of astrocytes as an experimental model system....

  20. Primary Meningeal Rhabdomyosarcoma

    Science.gov (United States)

    Palta, Manisha; Riedel, Richard F.; Vredenburgh, James J.; Cummings, Thomas J.; Green, Scott; Chang, Zheng; Kirkpatrick, John P.

    2011-01-01

    Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy. PMID:21772793

  1. Primary Meningeal Rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    Manisha Palta

    2011-01-01

    Full Text Available Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13. Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC systemic therapy.

  2. Primary meningeal rhabdomyosarcoma.

    Science.gov (United States)

    Palta, Manisha; Riedel, Richard F; Vredenburgh, James J; Cummings, Thomas J; Green, Scott; Chang, Zheng; Kirkpatrick, John P

    2011-01-01

    Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy.

  3. Primary Nurse - Role Evolution

    Science.gov (United States)

    Mundinger, Mary O'Neil

    1973-01-01

    Primary nursing means that each patient has an individual nurse who is responsible for assessing his nursing needs and planning and evaluating his nursing care. The article describes the advantages and problems connected with this approach to patient care. (AG)

  4. Multiple Primary Tumors

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It is not very .... was estrogen receptor negative, progesterone receptor negative, and ... cervical, ovarian, and urinary bladder cancers. Multiple.

  5. Primary infertility (image)

    Science.gov (United States)

    Primary infertility is a term used to describe a couple that has never been able to conceive a pregnancy ... to do so through unprotected intercourse. Causes of infertility include a wide range of physical as well ...

  6. The value of rituximab treatment in primary Sjögren's syndrome

    NARCIS (Netherlands)

    Verstappen, Gwenny M.; van Nimwegen, Jolien F.; Vissink, Arjan; Kroese, Frans G. M.; Bootsma, Hendrika

    The rationale for B cell depletion therapy with rituximab in primary Sjogren's syndrome relies upon the well-established role of B cell hyperactivity in immunopathogenesis. In line with this notion, several biomarkers of B cell activity are significantly affected by treatment, both in the target

  7. Primary Intraorbital Ectopic Meningioma

    Science.gov (United States)

    Yokoyama, Tetsuo; Nishizawa, Shigeru; Sugiyama, Kenji; Yokota, Noki; Ohta, Seiji; Uemura, Kenichi; Hinokuma, Kaoru; Inenaga, Chikanori

    1999-01-01

    We report a case of intraorbital meningioma. Operative findings and histopathological examination revealed the tumoc to be meningothelial meningloma and to be located entirely outside the optic dura. This case demonstrates the occurrence of primary intraorbital ectopic meningioma, and the tumor was removed through a modified Dolenc approach. The primary intraorbital ectopic meningioma is discussed and the surgical approach to the orbital apex region is reviewed. ImagesFigure 1Figure 2Figure 4Figure 5 PMID:17171081

  8. Primary leiomyosarcoma of epididymis

    Directory of Open Access Journals (Sweden)

    Dillip Kumar Muduly

    2012-01-01

    Full Text Available Primary leiomyosarcomas rarely arise from epididymis. But they are the most common histopathological types of sarcoma arising from the epididymis. Primary epididymal leiomyosarcoma occurs usually in older patients. We report a young patient of 35 years presenting with leiomyosarcoma of left epididymis. He did not have any metastasis and underwent left high inguinal orchiectomy. He is on regular follow-up and disease free for last two years.

  9. Primary care ... where?

    Science.gov (United States)

    Adcock, G B

    1999-07-01

    Corporate-based nurse managed centers are not the national norm. More prevalent is the use of an occupational health or physician-directed medical model of care. The author describes how a 14-year-old primary care center at a North Carolina computer software company is just "business as usual" when viewed in the context of the company's philosophy, goals, and culture. Included are considerations for nurse practitioners interested in the successful transplantation of this primary care model to other settings.

  10. Other primary headaches

    Directory of Open Access Journals (Sweden)

    Anish Bahra

    2012-01-01

    Full Text Available The ′Other Primary Headaches′ include eight recognised benign headache disorders. Primary stabbing headache is a generally benign disorder which often co-exists with other primary headache disorders such as migraine and cluster headache. Primary cough headache is headache precipitated by valsalva; secondary cough has been reported particularly in association with posterior fossa pathology. Primary exertional headache can occur with sudden or gradual onset during, or immediately after, exercise. Similarly headache associated with sexual activity can occur with gradual evolution or sudden onset. Secondary headache is more likely with both exertional and sexual headache of sudden onset. Sudden onset headache, with maximum intensity reached within a minute, is termed thunderclap headache. A benign form of thunderclap headache exists. However, isolated primary and secondary thunderclap headache cannot be clinically differentiated. Therefore all headache of thunderclap onset should be investigated. The primary forms of the aforementioned paroxysmal headaches appear to be Indomethacin sensitive disorders. Hypnic headache is a rare disorder which is termed ′alarm clock headache′, exclusively waking patients from sleep. The disorder can be Indomethacin responsive, but can also respond to Lithium and caffeine. New daily persistent headache is a rare and often intractable headache which starts one day and persists daily thereafter for at least 3 months. The clinical syndrome more often has migrainous features or is otherwise has a chronic tension-type headache phenotype. Management is that of the clinical syndrome. Hemicrania continua straddles the disorders of migraine and the trigeminal autonomic cephalalgias and is not dealt with in this review.

  11. Axillary node metastatic carcinoma without definitive primary: a case report

    Directory of Open Access Journals (Sweden)

    Spencer R. Anderson

    2016-01-01

    Full Text Available Cancer of unknown primary (CUP is the finding of a metastatic cancerous lesion without an established primary source localized within the body. CUP can be of any cancer cell type, however, adenocarcinoma is most often identified by histology. Up to 5% of all malignant diagnoses are classified as CUP. PET is an imaging modality often utilized to distinguish a primary source in the setting of CUP, yet often a primary is never identified. CUP can be further stratified using specific qualifiers as favorable and unfavorable, indicating the potential therapeutic response to treatment regimens. Treatment approach to CUP relies heavily on the cell type identified by histology, the location of the lesion, and the amount of spread within the body. In the typical setting and presentation, per current literature, CUP arises in the 7th decade of life in patients with multiple comorbidities, and often has a poor prognostic value. This case report identifies an atypical presentation of CUP, a 38-year-old Caucasian female with an axillary mobile mass, and no associated systemic symptoms. Biopsy of the node and immunohistochemical staining showed histology consistent with metastatic carcinoma. Mammography, MRI, and PET scan found no evidence of tumor primary or distant metastasis. Further staining confirmed metastatic carcinoma consistent with breast origin, without an established breast primary. As in this case, CUP may present in an atypical manner, warranting a thorough investigation aiming to identify the tumor primary to aid in identification of a proper treatment regimen and approach.

  12. Sabiedriskās attiecības jauno reliģisko kustību praksē. Baznīcas "Jaunā paaudze" gadījuma analīze

    OpenAIRE

    Maļuha, Sandra

    2008-01-01

    Izstrādātā bakalaura darba nosaukums ir „Sabiedriskās attiecības jauno reliģisko kustību praksē: baznīcas „Jaunā paaudze” gadījuma analīze”. Darbā aplūkotā pētnieciskā problēma ir jauns, līdz šim maz pētīts fenomens - sabiedrisko attiecību mērķu realizācija jauno reliģisko kustību darbībā. Izvēlētais pētniecības objekts ir baznīca „Jaunā paaudze”, kura, pēc Tieslietu ministrijas Reliģisko lietu pārvaldes sniegtajiem datiem, šobrīd ir lielākā jaunā reliģiskā kustība Latvijā. Teorētiskā pama...

  13. Empirical and dynamic primary energy factors

    International Nuclear Information System (INIS)

    Wilby, Mark Richard; Rodríguez González, Ana Belén; Vinagre Díaz, Juan José

    2014-01-01

    Current legislation, standards, and scientific research in the field of energy efficiency often make use of PEFs (primary energy factors). The measures employed are usually fixed and based on theoretical calculations. However given the intrinsically variable nature of energy systems, these PEFs should rely on empirical data and evolve in time. Otherwise the obtained efficiencies may not be representative of the actual energy system. In addition, incorrect PEFs may cause a negative effect on the energy efficiency measures. For instance, imposing a high value on the PEF of electricity may discourage the use of renewable energy sources, which have an actual value close to 1. In order to provide a solution to this issue, we propose an application of the Energy Networks (ENs), described in a previous work, to calculate dynamic PEFs based on empirical data. An EN represents an entire energy system both numerically and graphically, from its primary energy sources to their final energy forms, and consuming sectors. Using ENs we can calculate the PEF of any energy form and depict it in a simple and meaningful graph that shows the details of the contribution of each primary energy and the efficiency of the associated process. The analysis of these PEFs leads to significant conclusions regarding the energy models adopted among countries, their evolution in time, the selection of viable ways to improve efficiency, and the detection of best practices that could contribute to the overall energy efficiency targets. - Highlights: • Primary Energy Factors (PEFs) are foundation of much energy legislation and research. • Traditionally, they have been treated as geotemporally invariant. • This work provides a systematic and transparent methodology for adding variability. • It also shows the variability between regions due to market, policy, and technology. • Finally it demonstrates the utility of extended PEFs as a tool in their own right

  14. Fast Appearance Modeling for Automatic Primary Video Object Segmentation.

    Science.gov (United States)

    Yang, Jiong; Price, Brian; Shen, Xiaohui; Lin, Zhe; Yuan, Junsong

    2016-02-01

    Automatic segmentation of the primary object in a video clip is a challenging problem as there is no prior knowledge of the primary object. Most existing techniques thus adapt an iterative approach for foreground and background appearance modeling, i.e., fix the appearance model while optimizing the segmentation and fix the segmentation while optimizing the appearance model. However, these approaches may rely on good initialization and can be easily trapped in local optimal. In addition, they are usually time consuming for analyzing videos. To address these limitations, we propose a novel and efficient appearance modeling technique for automatic primary video object segmentation in the Markov random field (MRF) framework. It embeds the appearance constraint as auxiliary nodes and edges in the MRF structure, and can optimize both the segmentation and appearance model parameters simultaneously in one graph cut. The extensive experimental evaluations validate the superiority of the proposed approach over the state-of-the-art methods, in both efficiency and effectiveness.

  15. Primary Ectopic Ethmoidal Craniopharyngioma.

    Science.gov (United States)

    Preti, Andrea; Karligkiotis, Apostolos; Facco, Carla; Ottini, Giorgia; Volpi, Luca; Castelnuovo, Paolo

    2017-06-01

    Craniopharyngiomas are benign but aggressive epithelial tumors usually originating in the anterior lobe of the pituitary gland from squamous remnants of an incompletely involuted craniopharingeal duct developing from the Rathke pouch. To the authors' knowledge only 1 patient of a primary isolated ethmoidal craniopharyngioma has been reported in the literature.The authors report the case of a 17-year-old boy with a primary extracranial ethmoidal craniopharyngioma. An endoscopic endonasal approach was employed to resect the tumor. After 2 years of clinical and radiological follow-up no recurrence of disease was observed.Primary ethmoidal craniopharyngiomas are rare entities and biopsy is necessary for diagnosis. However, a preoperative assessment by means of nasal endoscopy, computed tomography scan, and enhanced magnetic resonance imaging is mandatory to better evaluate the extension and characteristics of the tumor. The endoscopic endonasal technique is a safe and effective approach for the treatment of these lesions.

  16. Primary renal synovial sarcoma

    Directory of Open Access Journals (Sweden)

    Girish D. Bakhshi

    2012-03-01

    Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

  17. Primary headaches in children

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Pan

    2015-01-01

    Full Text Available Headache is a widespread clinical problem; the prevalence is high in all age groups, from which children and teenagers are not spared. It has been reported that, as many as 75% of school-age children may experience headache infrequently, among them 10% have recurrent headaches. [1],[2] The vast majority of headaches are primary and classified as migraine, tension-type headache (TTH, cluster headache, and other trigeminal autonomic cephalgias. The type of primary headaches could usually be diagnosed by a thorough and careful history taking, and physical examination. Once the diagnosis of migraine is established and appropriate reassurance provided, a balanced and individually tailored treatment plan can be instituted. The goal of treatment includes abortive or acute pain treatment, preventive long-term treatment, and biobehavioral therapy. Knowledge of precise impact of primary headaches on child′s quality of life helps to design a proper comprehensive treatment plan.

  18. Normocalcemic primary hyperparathyroidism

    Science.gov (United States)

    Bilezikian, John P.; Silverberg, Shonni J.

    2011-01-01

    SUMMARY Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. The historical view of this disease describes two distinct entities marked by two eras. When primary hyperparathyroidism was first discovered about 80 years ago, it was always symptomatic with kidney stones, bone disease and marked hypercalcemia. With the advent of the multichannel autoanalyzer about 40 years ago, the clinical phenotype changed to a disorder characterized by mild hypercalcemia and the absence of classical other features of the disease. We may now be entering a 3rd era in the history of this disease in which patients are being discovered with normal total and ionized serum calcium concentrations but with parathyroid hormone levels that are consistently elevated. In this article, we describe this new entity, normocalcemic primary hyperparathyroidism, a forme fruste of the disease. PMID:20485897

  19. [Primary care in Ireland].

    Science.gov (United States)

    Sánchez-Sagrado, T

    Spanish doctors are still leaving the country to look for quality work. Ireland is not a country with many Spanish professionals but it is interesting to know its particular Health care system. Ireland is one of the countries with a national health care system, although it has a mixture of private health care insurance schemes. People have a right to health care if they have been living in Ireland at least for a year. Access to the primary care health system depends on age and income: free of charge for Category 1 and co-payments for the rest. This division generates great inequalities among the population. Primary Care doctors are self-employed, and they work independently. However, since 2001 they have tended to work in multidisciplinary teams in order to strengthen the Primary Care practice. Salary is gained from a combination of public and private incomes which are not differentiated. The role of the General Practitioner consists in the treatment of acute and chronic diseases, minor surgery, child care, etc. There is no coordination between Primary and Secondary care. Access to specialised medicine is regulated by the price of consultation. Primary Care doctors are not gatekeepers. To be able to work here, doctors must have three years of training after medical school. After that, Continuing Medical Education is compulsory, and the college of general practitioners monitors it annually. The Irish health care system does not fit into the European model. Lack of a clear separation between public and private health care generates great inequalities. The non-existence of coordination between primary and specialised care leads to inefficiencies, which Ireland cannot allow itself after a decade of economic crisis. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Reactive carbonyl compounds impair wound healing by vimentin collapse and loss of the primary cilium.

    Science.gov (United States)

    Rodríguez-Ribera, Lara; Slattery, Craig; Mc Morrow, Tara; Marcos, Ricard; Pastor, Susana

    2017-10-01

    In renal pathologies tubulo-interstitial fibrosis results from an aberrant wound-healing ability where the normal epithelial tissue is substituted for scar tissue caused by accumulation of extracellular matrix proteins (ECM). During the wound-healing process, epithelial cells may undergo epithelial-mesenchymal transition (EMT) acquiring a mesenchymal-like phenotype that allows cells to migrate and re-epithelialize the wound site. It has been reported that chronic inflammation and uremic milieu are involved in wound-healing and enhanced kidney damage in chronic kidney disease (CKD) patients. In this study we evaluated reactive carbonyl compounds (RCC) effects on renal wound healing. The compounds resulting from carbonyl stress evaluated in this study were glyoxal (GO), methylglyoxal (MGO), malondialdehyde (MDA) and 4-hydroxy-hexenal (HHE). Wound repair ability was evaluated by the wound healing assay using HK-2 cells. EMT was evaluated by morphological, protein and transcriptional changes using microscopy, western blot, zymography and RT-qPCR. Changes in the vimentin network and primary cilia were assessed by immunofluorescence. Our data demonstrated that MDA and GO delay wound closure mediated by vimentin disruption, which caused collagen I mRNA decrease, and deciliation. In contrast, HHE treatment (and MGO to a minor degree) induced morphological changes and increased mesenchymal marker expression and gelatinase activity in HK-2 cells. In this study, we have demonstrated for the first time that exposure to RCC differentially affects wound healing in proximal tubular epithelia. A better comprehension of effects of uremic toxins on wound healing and fibrosis and migration is necessary to seek mechanisms to slow down renal fibrosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Thoughts on primary care.

    Science.gov (United States)

    Raskin, Lynne

    2010-01-01

    The uptake of family health teams in Ontario has been tremendous. And the creation of group practices in primary care has taken root in other provinces as well. For many people, being involved with something new is exciting. At the same time, once they are committed, they discover the challenges that can be simultaneously exhilarating and frustrating. This issue of Healthcare Quarterly offers two articles that provide interesting reflections on what has been learned so far from the perspectives of both team leadership and the team members themselves within a transforming primary care system.

  2. Primary lymphoma of the brain

    Science.gov (United States)

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  3. Surgery of Primary Melanomas

    Directory of Open Access Journals (Sweden)

    Piotr Rutkowski

    2010-05-01

    Full Text Available Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas.

  4. Surgery of Primary Melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Rutkowski, Piotr, E-mail: rutkowskip@coi.waw.pl; Zdzienicki, Marcin; Nowecki, Zbigniew I. [Soft Tissue/Bone Sarcoma and Melanoma Department, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Akkooi, Alexander C. J. van [Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2010-05-11

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas.

  5. Surgery of Primary Melanomas

    International Nuclear Information System (INIS)

    Rutkowski, Piotr; Zdzienicki, Marcin; Nowecki, Zbigniew I.; Akkooi, Alexander C. J. van

    2010-01-01

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas

  6. Primary intestinal lymphangiectasia.

    Science.gov (United States)

    Suresh, N; Ganesh, R; Sankar, Janani; Sathiyasekaran, Malathi

    2009-10-01

    Primary intestinal lymphangiectasia (PIL) is a rare disease of intestinal lymphatics presenting with hypoproteinemia, bilateral lower limb edema, ascites, and protein losing enteropathy. We report a series of 4 children from Chennai, India presenting with anasarca, recurrent diarrhea, hypoproteinemia and confirmatory features of PIL on endoscopy and histopathology.

  7. Healthcare is primary

    Directory of Open Access Journals (Sweden)

    Raman Kumar

    2015-01-01

    Full Text Available India is undergoing a rapid transformation in terms of governance, administrative reforms, newer policy develoment, and social movements. India is also considered one of the most vibrant economies in the world. The current discourse in public space is dominated by issues such as economic development, security, corruption free governance, gender equity, and women safety. Healthcare though remains a pressing need of population; seems to have taken a backseat. In the era of decreasing subsidies and cautious investment in social sectors, the 2 nd National Conference on Family Medicine and Primary Care 2015 (FMPC brought a focus on "healthcare" in India. The theme of this conference was "Healthcare is Primary." The conference participants discussed on the theme of why healthcare should be a national priority and why strong primary care should remain at the center of healthcare delivery system. The experts recommended that India needs to strengthen the "general health system" instead of focusing on disease based vertical programs. Public health system should have capacity and skill pool to be able to deliver person centered comprehensive health services to the community. Proactive implementation of policies towards human resource in health is the need of the hour. As the draft National Health Policy 2015 is being debated, "family medicine" (academic primary care, the unfinished agenda of National Health Policy 2002, remains a priority area of implementation.

  8. Multiple Primary Tumors

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... breast and ascending colon. KEYWORDS: Carcinoid, colorectal cancer, metachronous, synchronous. Multiple Primary Tumors. MA Adeyanju, AA Ilori. Address for correspondence: Dr. MA Adeyanju,. Department of Surgery, Federal Medical Centre, Ebute Metta,. Lagos, Nigeria. E-mail: mbadeyanju@yahoo.

  9. Primary malignant intramedullary lymphoma

    International Nuclear Information System (INIS)

    Orrego P, E.; Heinicke Y, H.; Arbaiza A, D.; Yepez R, V.

    1999-01-01

    A case of primary malignant intramedullary lymphoma, localized in the dorsal part of the spinal cord is presented. The clinical symptoms were associated with motor and sensitive deficit. Clinical investigations excluded the presence of lymphoma in other locations in the central nervous system and the extra neural organs. Postoperative radiotherapy and chemotherapy improved relict neurological symptoms. (authors)

  10. Primary black holes

    International Nuclear Information System (INIS)

    Novikov, I.; Polnarev, A.

    1981-01-01

    Proves are searched for of the formation of the so-called primary black holes at the very origin of the universe. The black holes would weigh less than 10 13 kg. The formation of a primary black hole is conditional on strong fluctuations of the gravitational field corresponding roughly to a half of the fluctuation maximally permissible by the general relativity theory. Only big fluctuations of the gravitational field can overcome the forces of the hot gas pressure and compress the originally expanding matter into a black hole. Low-mass black holes have a temperature exceeding that of the black holes formed from stars. A quantum process of particle formation, the so-called evaporation takes place in the strong gravitational field of a black hole. The lower the mass of the black hole, the shorter the evaporation time. The analyses of processes taking place during the evaporation of low-mass primary black holes show that only a very small proportion of the total mass of the matter in the universe could turn into primary black holes. (M.D.)

  11. Familial primary hyperparathyroidism

    International Nuclear Information System (INIS)

    Iqbal, P.; Javed, R.

    2007-01-01

    A case of primary hyperparathyroidism in a 17 years old female is described. Patient presented with severe abdominal and pelvic pains associate with discomfort. Diagnostic testing revealed multiple upper and lower limb fractures and renal stones. Case was self limiting. Patient's condition resolved on parathyroidectomy for adenoma and partial thyroidectomy. Follow-up showed familial links. (author)

  12. Multiple Primary Cancer Monograph

    Science.gov (United States)

    To identify groups of cancer survivors that are at increased risk for multiple primary cancers, investigators led an effort to provide the first comprehensive population-based analysis of the risk of subsequent cancer in the U.S., resulting in a monograph.

  13. Primary cosmic ray flux

    Energy Technology Data Exchange (ETDEWEB)

    Stanev, Todor

    2001-05-01

    We discuss the primary cosmic ray flux from the point of view of particle interactions and production of atmospheric neutrinos. The overall normalization of the cosmic ray flux and its time variations and site dependence are major ingredients of the atmospheric neutrino predictions and the basis for the derivation of the neutrino oscillation parameters.

  14. in primary care

    African Journals Online (AJOL)

    Claire van Deventer

    Keywords: child HIV, doctor involvement, primary health care, quality improvement ... expertise increased, PHC facilities are now expected to be able to .... organised patient documentation were revisited. .... Review: what can we learn from quality ... South Pacific: Review of evidence and lessons from an innovative.

  15. [Primary and secondary encopresis].

    Science.gov (United States)

    Lang-Langer, Ellen

    2007-01-01

    While the difficulty of the child to part with its faeces in primary encopresis is linked to the incapability to experience the object as separated and independent from himself, secondary encopresis is a progressed psychical state of development. In this case we have to deal with regression caused by conflict. Two case-studies show clearly the differences.

  16. Spirometry in primary care

    Science.gov (United States)

    Coates, Allan L; Graham, Brian L; McFadden, Robin G; McParland, Colm; Moosa, Dilshad; Provencher, Steeve; Road, Jeremy

    2013-01-01

    Canadian Thoracic Society (CTS) clinical guidelines for asthma and chronic obstructive pulmonary disease (COPD) specify that spirometry should be used to diagnose these diseases. Given the burden of asthma and COPD, most people with these diseases will be diagnosed in the primary care setting. The present CTS position statement was developed to provide guidance on key factors affecting the quality of spirometry testing in the primary care setting. The present statement may also be used to inform and guide the accreditation process for spirometry in each province. Although many of the principles discussed are equally applicable to pulmonary function laboratories and interpretation of tests by respirologists, they are held to a higher standard and are outside the scope of the present statement. PMID:23457669

  17. Cancer of unknown primary

    DEFF Research Database (Denmark)

    Dyrvig, Anne-Kirstine; Yderstræde, Knud Bonnet; Gerke, Oke

    2017-01-01

    210 (38.7%) had a CUP diagnosis confirmed. Within the cohort, 347 patients (64.0%) had a registration in CR matching with the NPR registration. Exposure to diagnostic procedures included biopsy (n = 439, 81.0%) and image modalities (n = 532, 98.2%). Survival was poor with 67 (12.4%) individuals alive...... after 4 years.The validity of a CUP diagnosis in NPR was low when using data from CR as reference. More than half the suspected CUP patients had a previous cancer diagnosis with CUP being the most frequent. Patients were diagnosed in compliance with guidelines indicating high external validity, but less...... than 1 quarter had their primary identified and the 1-year survival was approximately 20%. Research is needed to develop efficacious methods for primary detection....

  18. Primary omental pregnancy

    International Nuclear Information System (INIS)

    Yildizhan, R.; Kurdoglu, M.; Kolusari, A.; Erten, R.

    2008-01-01

    Omental pregnancy is a rare form of ectopic pregnancy and can be seen primarily or secondary to a tubal pregnancy. A 25-yeal-old woman presented with abdominal distention with pain and anemia without vaginal bleeding. After a provisional diagnosis of ruptured ectopic pregnancy, laparotomy was performed. On surgical exploration, the bilateral tubes and ovaries were intact, however, an omental pregnancy was detected as the cause of hemoperitoneum. Partial omentectomy was performed. Although most cases are secondary, presented here is an additional case of primary omental pregnancy at 12 weeks according to Studdiford's criteria. Histological evidence of neovascularization into the supporting tissue confirmed our diagnosis. A primary omental pregnancy should always be considered as a possible explanation for severe hemoperitoneum in ectopic pregnancies presenting with acute abdomen and with intact adnexes on surgical exploration. (author)

  19. Basics of primary immunodeficiencies

    Directory of Open Access Journals (Sweden)

    Claudia Hernández-Martínez

    2016-05-01

    Full Text Available Primary immunodeficiencies (PID are a heterogeneous group of inherited disorders, the etiology are the defects in the development or function of the immune system. The principal PID manifestations are the infections in early age, malignancy and diseases of immune dysregulation as autoimmunity and allergy. PIDs are genetics disorders and most of them are inherited as autosomal recessive, also this group of diseases is more prevalent in males and in childhood. The antibody immunodeficiency is the PID more common in adults. The more frequent disorders are the infections in the respiratory tract, abscesses, candidiasis, diarrhea, BCGosis etc. Initial approach included a complete blood count and quantification of immunoglobulins. The delay in diagnosis could be explained due to a perception that the recurrent infections are normal process or think that they are exclusively of childhood. The early diagnosis of PID by primary care physicians is important to opportune treatment and better prognosis.

  20. [Primary care in France].

    Science.gov (United States)

    Sánchez-Sagrado, T

    2016-01-01

    The poor planning of health care professionals in Spain has led to an exodus of doctors leaving the country. France is one of the chosen countries for Spanish doctors to develop their professional career. The French health care system belongs to the Bismarck model. In this model, health care system is financed jointly by workers and employers through payroll deduction. The right to health care is linked to the job, and provision of services is done by sickness-funds controlled by the Government. Primary care in France is quite different from Spanish primary care. General practitioners are independent workers who have the right to set up a practice anywhere in France. This lack of regulation has generated a great problem of "medical desertification" with problems of health care access and inequalities in health. French doctors do not want to work in rural areas or outside cities because "they are not value for money". Medical salary is linked to professional activity. The role of doctors is to give punctual care. Team work team does not exist, and coordination between primary and secondary care is lacking. Access to diagnostic tests, hospitals and specialists is unlimited. Duplicity of services, adverse events and inefficiencies are the norm. Patients can freely choose their doctor, and they have a co-payment for visits and hospital care settings. Two years training is required to become a general practitioner. After that, continuing medical education is compulsory, but it is not regulated. Although the French medical Health System was named by the WHO in 2000 as the best health care system in the world, is it not that good. While primary care in Spain has room for improvement, there is a long way for France to be like Spain. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  1. [Primary care in Italy].

    Science.gov (United States)

    Sánchez-Sagrado, T

    Italy is not a country where Spanish doctors emigrate, as there is an over-supply of health care professionals. The Italian Servizio Sanitario Nazionale has some differences compared to the Spanish National Health System. The Servizio Sanitario Nazionale is financed by national and regional taxes and co-payments. There are taxes earmarked for health, and Primary Care receives 50% of the total funds. Italian citizens and residents in Italy have the right to free health cover. However, there are co-payments for laboratory and imaging tests, pharmaceuticals, specialist ambulatory services, and emergencies. Co-payments vary in the different regions. The provision of services is regional, and thus fragmentation and major inequities are the norm. Doctors in Primary Care are self-employed and from 2000 onwards, there are incentives to work in multidisciplinary teams. Salary is regulated by a national contract and it is the sum of per-capita payments and extra resources for specific activities. Responsibilities are similar to those of Spanish professionals. However, medical care is more personal. Relationships between Primary Care and specialised care depend on the doctors' relationships. Primary Care doctors are gatekeepers for specialised care, except for gynaecology, obstetrics and paediatrics. Specialised training is compulsory in order to work as general practitioner. The Italian Health Care System is a national health system like the Spanish one. However, health care professionals are self-employed, and there are co-payments. In spite of co-payments, Italians have one of the highest average life expectancy, and they support a universal and publicly funded health-care system. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Primary Tunnel Junction Thermometry

    International Nuclear Information System (INIS)

    Pekola, Jukka P.; Holmqvist, Tommy; Meschke, Matthias

    2008-01-01

    We describe the concept and experimental demonstration of primary thermometry based on a four-probe measurement of a single tunnel junction embedded within four arrays of junctions. We show that in this configuration random sample specific and environment-related errors can be avoided. This method relates temperature directly to Boltzmann constant, which will form the basis of the definition of temperature and realization of official temperature scales in the future

  3. Primary stabbing headache.

    Science.gov (United States)

    Pareja, Juan A; Sjaastad, Ottar

    2010-01-01

    Primary stabbing headache is characterized by transient, cephalic ultrashort stabs of pain. It is a frequent complaint with a prevalence of 35.2%, a female preponderance, and a mean age of onset of 28 years (Vågå study). Attacks are generally characterized by moderate to severe, jabbing or stabbing pain, lasting from a fraction of a second to 3s. Attack frequency is generally low, with one or a few attacks per day. The paroxysms generally occur spontaneously, during daytime. Most patients exhibit a sporadic pattern, with an erratic, unpredictable alternation between symptomatic and non-symptomatic periods. Paroxysms are almost invariably unilateral. Temporal and fronto-ocular areas are most frequently affected. Attacks tend to move from one area to another, in either the same or the opposite hemicranium. Jabs may be accompanied by a shock-like feeling and even by head movement - "jolts" -or vocalization. On rare occasions, conjunctival hemorrhage and monocular vision loss have been described as associated features. Primary stabbing headache may concur, synchronously or independently, with other primary headaches. In contrast to what is the case in adults, in childhood it is not usually associated with other headaches. Treatment is rarely necessary. Indomethacin, 75-150 mg daily, may seem to be of some avail. Celecoxib, nifedipine, melatonin, and gabapentin have been reported to be effective in isolated cases and small series of patients. The drug studies need corroboration. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Implications of the Primary Cilium in Cellular Signaling and Brain Development

    DEFF Research Database (Denmark)

    Lindbæk, Louise

    neurogenesis. In addition, analysis of patient dermal fibroblasts show, that RRP7A localizes to nucleoli, centrosomes, and cilia, and that patient cells carrying a single amino acid substitution in RRP7A display reduced nucleoli localization. Moreover, patient-derived fibroblasts display defects in ribosomal...

  5. [Primary headache and depression].

    Science.gov (United States)

    Gesztelyi, Gyöngyi

    2004-11-28

    Primary headaches--mainly tension-type headache and migraine--affect a significant portion of the population. Depression is also highly prevalent. The co-existence of a primary headache and depression in the same patient therefore might be a coincidence due to the high prevalence of these conditions, but there might be a causal relationship between them, or headaches and depression might have a common background. This review of the literature summarizes the features of the relationship between primary headaches and depression. Depression is more prevalent in headache patients than in the headache-free population. Prospective epidemiological studies suggest a common genetic, biochemical or environmental background behind primary headaches and depression. This theory is supported by the role of the same neurotransmitter systems (mostly serotonin and dopamine) in headaches as well as in depression. Comorbid depression is associated with female gender, higher age, and higher frequency of headaches. Most depression inventories--questionnaires used to screen for the severity of depressive symptoms--contain transdiagnostic items, therefore their use in their original form is limited in organic diseases: due to the somatic items they might overestimate the severity of depression. When examining a headache patient special attention should be paid to the recognition of comorbid depression. The diagnosis of suspected mood disorder could be supported by using simple screening methods, such as the original or the abbreviated versions of standard depression inventories, but the final diagnosis of major depression needs psychiatric evaluation. Quality of life of the headache patient is affected not only by the characteristics of pain (frequency, duration, severity) but also by the disability caused by headache and the associating mood disorder. Recognizing coexisting mood disorder and disability helps to make the best treatment choice for the acute and preventive treatment of

  6. Localization of primary aldosteronism

    International Nuclear Information System (INIS)

    Pagny, J.Y.; Chatellier, G.; Raynaud, A.; Plouin, P.F.; Corvol, P.

    1988-01-01

    After diagnosis of primary aldosteronism on the basis of biochemical evidence, the detection of the tumour is of crucial importance in the management of the disease. The efficacy of CT-Scan, Iodo-Cholesterol Scintigraphy, digitalized phlebography, adrenal vein sampling for steroid measurements (AVS), and Nuclear Magnetic Resonance (NMR) in 160 hypertensive patients with primary aldosteronism was reviewed. Diagnosis of Conn's adenoma (n=96) or Adrenal Hyperplasia (n=40) was confirmed by surgery or at least two concordant tumour localization tests. Scintigraphy gave a correct diagnosis in 53% of the 51 exams, CT-Scan in 82% of the 85 exams, and phlebography in 79% of 61 exams. Plasma Aldosterone/ Cortisol ratio was 5 times higher on the side of adenoma in 55% of the 47 cases but this ratio was also present in 23% of 22 patients with adrenal hyperplasia. Each procedure exhibited few false positive and false negative cases. NMR performed in 15 patients with Conn's adenoma identified all the cases. But tumours displayed a signal close to the liver signal and identical to the normal adrenal. These results and the risk of invasive procedure (failure of catheterization of the right adrenal vein (n=6) and adrenal haematoma (n=2) lead to propose a schema of exploration of patients with primary aldosteronism. The CT-Scan could be performed at the first step once the biological diagnosis confirmed. Phlebography and AVS will be performed only if tumour was less than 1 cm at the CT-Scan despite important biological abnormalities. This schema requires to be validated by a prospective evaluation [fr

  7. Teacher of primary English

    CERN Multimedia

    2003-01-01

    Part-time teacher of primary English needed for September 2003 to teach English National Curriculum (KS2) and NLS to mother tongue or good second language English-speakers aged 7-10. 4 hours contact time per week, team planning, marking and meetings. Candidates should be English mother tongue qualified teachers, confident, flexible classroom practitioners and team players. For further details and how to apply see http://enpferney.org/staff_vacancies.htm English National Programme, Lycée International, Ferney-Voltaire (http://enpferney.org/)

  8. Primary isolated hepatic tuberculosis

    International Nuclear Information System (INIS)

    Sheikh, A.S.F.; Qureshi, I.H.; Saba, K.; Bukhari, M.H.

    2013-01-01

    Isolated hepatic tuberculosis without pulmonary or bowel involvement is a diagnostic challenge and can cause considerable morbidity. A young lady from Lahore presented with fever, pain in right hypochondria, nausea and weight loss. CT scan of abdomen showed multiple small hypodense non-enhancing lesions and a heterogeneous texture of liver. Biopsy confirmed the diagnosis of hepatic tuberculosis. It was concluded a case of isolated hepatic tuberculosis without evidence of other primary sites involvement. It is important to consider tuberculosis in the differential diagnosis when suspecting lymphoproliferative or metastatic diseases in a patient with vague symptoms and abnormal hepatic texture on CT. (author)

  9. PRIMARY CARIES: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Gaurav Solanki

    2012-01-01

    Full Text Available Primary caries is an initial lesions produced by direct extension from an external surface. Dental caries is called as tooth decay or a cavity is a disease in which bacterial processes changes carbohydrate to acid which than dematerializes the hard tooth structure like enamel, dentin and cementum. Streptococcus mutans and Lactobacillus are the bacteria responsible for the dental caries by acid production. This article throws light on the dental caries disease, its sign and symptoms, treatment and prevention of it. A review of some patents on dental caries is also provided that summarizes the recent technical advancements taken place in this area.

  10. Primary cutaneous lymphoma

    International Nuclear Information System (INIS)

    Nguyen, M. Connie; Cleary, Sean F.; Hoppe, Richard T.

    1995-01-01

    Purpose: A retrospective review analyzed the survival and freedom from relapse of patients with stage IE or IIE primary cutaneous lymphoma (non mycosis fungoides) after treatments with radiation therapy alone (XRT), chemotherapy alone (RX) or combined modality therapy (CMT). Methods and Materials: Fifty two patients with stage IE-IIE cutaneous lymphoma treated at Stanford University Hospital were reviewed. The median age was 57, with a range of 26 to 94 and a male to female ratio of 1.21:1. Patients were staged according to the Ann Arbor System. Pathology was classified according to the Working Formulation. Treatment outcomes were compared using Kaplan-Meier survival curves with a Gehan p-value test. Results: The follow up range was 6 months to 22 years (median 7 years.) Twenty one percent of patients had low grade, 63% had intermediate grade and 15% had high grade lymphoma. The most common histologic subtype was diffuse large cell lymphoma Thirty two patients received radiation alone as initial treatment and sixteen patients received combined modality as initial treatment. Four patients received chemotherapy alone. The only significant prognostic factor for survival was the stage at diagnosis. Patients with stage IE disease had a longer actuarial survival (5-yr=79%, 10-yr=71%), as compared to those with stage IIE (5-yr=49%, 10-yr=33%), (p=0.029). The only significant prognostic factor for freedom from relapse was the initial treatment. Initial combined modality treatment lead to a longer freedom from relapse compared to patients treated with radiation alone (p=0.002), (median 5 years vs. 1.2 years). Despite this, the actuarial overall survival in the combined modality group and the radiation alone group are similar (median survival 7.7 and 8 years). The efficacy of either radiation or chemotherapy as salvage treatment after radiation failure was equivalent and both salvage treatments lead to equally long survival and freedom from second relapse. Conclusion

  11. Bellefonte primary containment structure

    International Nuclear Information System (INIS)

    Olyniec, J.H.

    1981-01-01

    Construction of the reactor building primary containment structure at the Bellefonte Nuclear Plant involved several specialized construction techniques. This two unit plant is one of the nine nuclear units at six different sites now under construction by the Tennessee Valley Authority (TVA). The post-Tensioned, cast-in-place interior steel lined containment structure is unique within TVA. Problems during construction were identified at weekly planning meetings, and options were discussed. Close coordination between craft supervisors and on-site engineering personnel drew together ''hands-on''experience and technical background. Details of the construction techniques, problems, and solutions are presented

  12. Primary Carnitine Deficiency

    DEFF Research Database (Denmark)

    Rasmussen, Jan; Hougaard, David M; Sandhu, Noreen

    2017-01-01

    Primary carnitine deficiency (PCD) causes low levels of carnitine in patients potentially leading to metabolic and cardiac symptoms. Newborn screening for PCD is now routine in many countries by measuring carnitine levels in infants. In this study we report Apgar scores, length and weight...... scores, length and weight compared to controls. Newborns with PCD and newborns born to mothers with PCD had significantly lower levels of free carnitine (fC0) than controls. Screening algorithms focusing only on fC0 had a high rate of detection of newborns with PCD. Sample collection 4-9 days after birth...

  13. Aspirin for Primary Prevention.

    Science.gov (United States)

    Richman, Ilana B; Owens, Douglas K

    2017-07-01

    Aspirin reduces the risk of nonfatal myocardial infarction and stroke, and the risk of colorectal cancer. Aspirin increases the risk of gastrointestinal and intracranial bleeding. The best available evidence supports initiating aspirin in select populations. In 2016, the US Preventive Services Task Force recommended initiating aspirin for the primary prevention of both cardiovascular disease and colorectal cancer among adults ages 50 to 59 who are at increased risk for cardiovascular disease. Adults 60 to 69 who are at increased cardiovascular disease risk may also benefit. There remains considerable uncertainty about whether younger and older patients may benefit. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Primary cutaneous lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, M Connie; Cleary, Sean F; Hoppe, Richard T

    1995-07-01

    Purpose: A retrospective review analyzed the survival and freedom from relapse of patients with stage IE or IIE primary cutaneous lymphoma (non mycosis fungoides) after treatments with radiation therapy alone (XRT), chemotherapy alone (RX) or combined modality therapy (CMT). Methods and Materials: Fifty two patients with stage IE-IIE cutaneous lymphoma treated at Stanford University Hospital were reviewed. The median age was 57, with a range of 26 to 94 and a male to female ratio of 1.21:1. Patients were staged according to the Ann Arbor System. Pathology was classified according to the Working Formulation. Treatment outcomes were compared using Kaplan-Meier survival curves with a Gehan p-value test. Results: The follow up range was 6 months to 22 years (median 7 years.) Twenty one percent of patients had low grade, 63% had intermediate grade and 15% had high grade lymphoma. The most common histologic subtype was diffuse large cell lymphoma Thirty two patients received radiation alone as initial treatment and sixteen patients received combined modality as initial treatment. Four patients received chemotherapy alone. The only significant prognostic factor for survival was the stage at diagnosis. Patients with stage IE disease had a longer actuarial survival (5-yr=79%, 10-yr=71%), as compared to those with stage IIE (5-yr=49%, 10-yr=33%), (p=0.029). The only significant prognostic factor for freedom from relapse was the initial treatment. Initial combined modality treatment lead to a longer freedom from relapse compared to patients treated with radiation alone (p=0.002), (median 5 years vs. 1.2 years). Despite this, the actuarial overall survival in the combined modality group and the radiation alone group are similar (median survival 7.7 and 8 years). The efficacy of either radiation or chemotherapy as salvage treatment after radiation failure was equivalent and both salvage treatments lead to equally long survival and freedom from second relapse. Conclusion

  15. PRIMARY SCHOOL TEACHER

    CERN Multimedia

    Madeleine Dittus

    2002-01-01

    For January 2003, the A.P.E.G. has an opening for a primary school teacher in the German national language program. The position requires one afternoon of teaching (13:30 till 16:30) every Tuesday at the Collège in Prévessin. The candidate should be a native speaker of German and have some knowledge of French. If you are interested, please send your CV, a copy of your diploma, and a short letter of motivation, until December 9th, to the following address. Madeleine Dittus Présidente A.P.E.G. 5, La vie Destraz 01630 St. Genis-Pouilly (France)

  16. Epilepsy in Ireland: towards the primary-tertiary care continuum.

    Science.gov (United States)

    Varley, Jarlath; Delanty, Norman; Normand, Charles; Coyne, Imelda; McQuaid, Louise; Collins, Claire; Boland, Michael; Grimson, Jane; Fitzsimons, Mary

    2010-01-01

    Epilepsy is a chronic neurological disease affecting people of every age, gender, race and socio-economic background. The diagnosis and optimal management relies on contribution from a number of healthcare disciplines in a variety of healthcare settings. To explore the interface between primary care and specialist epilepsy services in Ireland. Using appreciative inquiry, focus groups were held with healthcare professionals (n=33) from both primary and tertiary epilepsy specialist services in Ireland. There are significant challenges to delivering a consistent high standard of epilepsy care in Ireland. The barriers that were identified are: the stigma of epilepsy, unequal access to care services, insufficient human resources, unclear communication between primary-tertiary services and lack of knowledge. Improving the management of people with epilepsy requires reconfiguration of the primary-tertiary interface and establishing clearly defined roles and formalised clinical pathways. Such initiatives require resources in the form of further education and training and increased usage of information communication technology (ICT). Epilepsy services across the primary-tertiary interface can be significantly enhanced through the implementation of a shared model of care underpinned by an electronic patient record (EPR) system and information communication technology (ICT). Better chronic disease management has the potential to halt the progression of epilepsy with ensuing benefits for patients and the healthcare system. Copyright 2009 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  17. Pattern of Primary Nocturnal Enuresis in Primary School Children ...

    African Journals Online (AJOL)

    Pattern of Primary Nocturnal Enuresis in Primary School Children (First Grade) in ... The control group consisting of 100 age-matched non-enuretic children ... was insignificantly associated with a positive family history, family size or birth rank.

  18. Primary iris leiomyoma.

    Science.gov (United States)

    Yeaney, Gabrielle A; Platt, Sean; Singh, Arun D

    Intraocular leiomyomas are uncommon and usually occur in the ciliary body. Primary leiomyoma of the iris is both rare and a difficult diagnosis to make, given melanocytic tumors are more common and may be amelanotic. The somewhat controversial diagnosis of iris leiomyoma requires further confirmation by immunohistochemistry and electron microscopy. Herein, we describe a 58-year-old man with a 2-mm round translucent pink lesion of the iris. The tumor was excised by sector iridectomy. Immunohistochemistry showed positivity for both smooth muscle actin and desmin and negativity for S-100, HMB45, SOX10, MelanA, CD31, CD34, and h-caldesmon. Epstein-Barr virus-associated smooth muscle tumor was excluded by chromogenic in situ hybridization-Epstein-Barr virus-encoded RNA. Ultrastructural analysis showed cytoplasmic myofilaments with focal fusiform densities and micropinocytotic vesicles. Our review of previous literature confirmed the unusual nature of this tumor. Primary iris leiomyoma should be considered in the differential of an amelanotic S-100-immunonegative iris tumor. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. [Normocalcemic primary hyperparathyroidism].

    Science.gov (United States)

    Spivacow, Francisco R; Sapag Durán, Ana; Zanchetta, María B

    2014-01-01

    This report shows our conclusions on the clinical, biochemical and densitometry characteristics of 35 normocalcemic primary hyperparathyroidism (PHPT) patients. This condition is defined by a high level of intact parathyroid hormone (iPTHI) with persistently normal serum and ionized calcium in the absence of secondary hyperparathyroidism. Our selection consisted of 30 women (90%) and 5 men (10%). The control group of 55 hypercalcemic patients with primary hyperparathyroidism included 51 women (93%) and 4 men (7%). The average age at diagnosis of normocalcemic PHPT was 61.4 ± 11.7 years and 56.4 ± 11.3 years in hypercalcemic PHPT. Besides the expected differences in serum calcium, ionized calcium, phosphorus and 24 h urinary calcium, we found no significant changes in other biochemical variables, and no differences in densitometry evaluations such as the presence of osteopenia or osteoporosis and the number of fractures in the two types of PHPT. But there was a significant difference in the presence of renal lithiasis between normocalcemic PHPT (11.4%) and clasic PHPT (49.1%) p < 0.0005, to some extent associated to the presence of hypercalciuria in classic PHPT. Two of the 35 patients with normocalcemic PHPT became classic hypercalcemic PHPT over a 4 year follow-up period. Our findings support the hypothesis that the normocalcemic PHPT could be an early stage of the classic PHPT, both having similar clinical effects to metabolic renal and bone levels.

  20. Asymptomatic Primary Hyperparathyroidism

    Science.gov (United States)

    Silverberg, Shonni J.; Walker, Marcella D.; Bilezikian, John P.

    2014-01-01

    The clinical profile of primary hyperparathyroidism (PHPT) as it is seen in the United States and most Western countries has evolved significantly over the past half century. The introduction of the multichannel serum autoanalyzer in the 1970s led to the recognition of a cohort of individuals with asymptomatic hypercalcemia, in whom evaluation led to the diagnosis of PHPT. The term “asymptomatic primary hyperparathyroidism” was introduced to describe patients who lack obvious signs and symptoms referable to either excess calcium or parathyroid hormone. Although it was expected that asymptomatic patients would eventually develop classical symptoms of PHPT, observational data suggest that most patients do not evolve over time to become overtly symptomatic. In most parts of the world, the asymptomatic phenotype of PHPT has replaced classical PHPT. This report is a selective review of data on asymptomatic PHPT: its demographic features, presentation and natural history, as well as biochemical, skeletal, neuromuscular, psychological, and cardiovascular manifestations. In addition, we will summarize available information on treatment indications and options for those with asymptomatic disease. PMID:23374736

  1. Decentralized DC Microgrid Monitoring and Optimization via Primary Control Perturbations

    Science.gov (United States)

    Angjelichinoski, Marko; Scaglione, Anna; Popovski, Petar; Stefanovic, Cedomir

    2018-06-01

    We treat the emerging power systems with direct current (DC) MicroGrids, characterized with high penetration of power electronic converters. We rely on the power electronics to propose a decentralized solution for autonomous learning of and adaptation to the operating conditions of the DC Mirogrids; the goal is to eliminate the need to rely on an external communication system for such purpose. The solution works within the primary droop control loops and uses only local bus voltage measurements. Each controller is able to estimate (i) the generation capacities of power sources, (ii) the load demands, and (iii) the conductances of the distribution lines. To define a well-conditioned estimation problem, we employ decentralized strategy where the primary droop controllers temporarily switch between operating points in a coordinated manner, following amplitude-modulated training sequences. We study the use of the estimator in a decentralized solution of the Optimal Economic Dispatch problem. The evaluations confirm the usefulness of the proposed solution for autonomous MicroGrid operation.

  2. COMMUNITY MEDICINE & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    Journal of Community Medicine and Primary Health Care. ... Ladoke Akintola University of Technology, PMB 4400, Osogbo, Osun State. ... weak management and poor adherence to the basic infrastructure e.g. primary, secondary and tertiary.

  3. Bezafibrate for primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Rudic, Jelena S; Poropat, Goran; Krstic, Miodrag N

    2012-01-01

    Treatment of primary biliary cirrhosis is complicated. There are studies suggesting that bezafibrate, alone or in combination with ursodeoxycholic acid (UDCA), is effective in the treatment of primary biliary cirrhosis, but no systematic review has summarised the evidence yet....

  4. BR-5 primary circuit decontamination

    International Nuclear Information System (INIS)

    Efimov, I.A.; Nikulin, M.P.; Smirnov-Averin, A.P.; Tymosh, B.S.; Shereshkov, V.S.

    1976-01-01

    Results and methodology of steam-water and acid decontamination of the primary coolant circuit SBR-5 reactor in 1971 are discussed. Regeneration process in a cold trap of the primary coolant circuit is discussed

  5. The role of mental health in primary prevention of sexual and gender-based violence.

    Science.gov (United States)

    Gevers, Aník; Dartnall, Elizabeth

    2014-01-01

    In this short communication, we assert that mental health has a crucial role in the primary prevention of sexual and gender-based violence (SGBV). However, we found that most research and practice to date has focused on the role of mental health post-violence, and SGBV primary prevention is relying on public health models that do not explicitly include mental health. Yet, key concepts, processes, and competencies in the mental health field appear essential to successful SGBV primary prevention. For example, empathy, self-esteem, compassion, emotional regulation and resilience, stress management, relationship building, and challenging problematic social norms are crucial. Furthermore, competencies such as rapport building, group processing, emotional nurturing, modelling, and the prevention of vicarious trauma among staff are important for the successful implementation of SGBV primary prevention programmes. SGBV primary prevention work would benefit from increased collaboration with mental health professionals and integration of key mental health concepts, processes, and skills in SGBV research.

  6. The role of mental health in primary prevention of sexual and gender-based violence

    Directory of Open Access Journals (Sweden)

    Aník Gevers

    2014-09-01

    Full Text Available In this short communication, we assert that mental health has a crucial role in the primary prevention of sexual and gender-based violence (SGBV. However, we found that most research and practice to date has focused on the role of mental health post-violence, and SGBV primary prevention is relying on public health models that do not explicitly include mental health. Yet, key concepts, processes, and competencies in the mental health field appear essential to successful SGBV primary prevention. For example, empathy, self-esteem, compassion, emotional regulation and resilience, stress management, relationship building, and challenging problematic social norms are crucial. Furthermore, competencies such as rapport building, group processing, emotional nurturing, modelling, and the prevention of vicarious trauma among staff are important for the successful implementation of SGBV primary prevention programmes. SGBV primary prevention work would benefit from increased collaboration with mental health professionals and integration of key mental health concepts, processes, and skills in SGBV research.

  7. Peritoneal dialysis: a primary care perspective.

    Science.gov (United States)

    Saxena, Ramesh; West, Cheryl

    2006-01-01

    As the population of chronic kidney disease (CKD) and end-stage renal disease (ESRD) grows at an alarming rate, primary care physicians will increasingly be involved in the management of these patients. Early recognition of CKD and timely referral to a nephrologist when glomerular filtration rate approaches 30 mL/min/1.73 m(2) is extremely important to improve ESRD outcome and appropriate selection of dialysis modality. Peritoneal dialysis (PD) remains a viable treatment option for ESRD patients. PD is less expensive dialysis modality and may provide a survival advantages over hemodialysis in first 2 to 4 years of treatment. Preserving residual renal function (RRF) is of paramount importance to prolong the survival outcomes in PD patients. Thus preservation of RRF is an important goal in the management of PD patients. Every effort should be made to avoid nephrotoxic drugs like aminoglycosides and nonsteroidal anti-inflammatory drugs, and limit the use of radiocontrast agents in PD patients with RRF. Judicious use of prophylactic antibiotics to prevent peritonitis would further help to reduce morbidity from PD. Protecting peritoneal membrane from long-term toxic and metabolic effects of the conventional glucose-based solutions is another objective to further improve PD outcome. Development of new, more biocompatible PD solutions holds promise for the future. One such solution, icodextrin, is now approved for use in the United States. Although extremely safe to use, it is associated with unique metabolic effects that may concern primary care physicians. They include false elevation of blood glucose, a reversible increase in serum alkaline phosphatase and a false decline in serum amylase. Monitoring of glycemia by assays that use glucose dehydrogenase pyrroloquinoline quinone enzymes should be avoided and serum amylase alone should not be relied on in diagnosing pancreatitis in patients on icodextrin.

  8. Primary Prevention With Statins

    DEFF Research Database (Denmark)

    Mortensen, Martin B; Afzal, Shoaib; Nordestgaard, Børge G

    2015-01-01

    BACKGROUND: Guidelines recommend initiating primary prevention for atherosclerotic cardiovascular disease (ASCVD) with statins based on absolute ASCVD risk assessment. Recently, alternative trial-based and hybrid approaches were suggested for statin treatment eligibility. OBJECTIVES: This study...... the population studied, 42% were eligible for statin therapy according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) risk assessment and cholesterol treatment guidelines approach, versus 56% with the trial-based approach and 21% with the hybrid approach. Among these statin......-eligible subjects, the ASCVD event rate per 1,000 person-years was 9.8, 6.8, and 11.2, respectively. The ACC/AHA-recommended absolute risk score was well calibrated around the 7.5% 10-year ASCVD risk treatment threshold and discriminated better than the trial-based or hybrid approaches. Compared with the ACC...

  9. Primary care guidelines

    DEFF Research Database (Denmark)

    Ijäs, Jarja; Alanen, Seija; Kaila, Minna

    2009-01-01

    OBJECTIVE: To describe the adoption of the national Hypertension Guideline in primary care and to evaluate the consistency of the views of the health centre senior executives on the guideline's impact on clinical practices in the treatment of hypertension in their health centres. DESIGN: A cross...... Guideline. RESULTS: Data were available from 143 health centres in Finland (49%). The views of head physicians and senior nursing officers on the adoption of the Hypertension Guideline were not consistent. Head physicians more often than senior nursing officers (44% vs. 29%, p ...: Hypertension Guideline recommendations that require joint agreements between professionals are less often adopted than simple, precise recommendations. More emphasis on effective multidisciplinary collaboration is needed....

  10. Adrenal incidentalomas. Primary hyperaldosteronism

    International Nuclear Information System (INIS)

    Murat, A.; Dupas, B.; Zenatti, M.; Aupetit-Faisant, B.; Tenenbaum, F.; Tabarin, A.; Barrat, J.L.; Gosse, P.; Olivier-Puel, F.; Leprat, F.; Trouette, H.; Laurent, F.; Roger, P.

    1993-01-01

    Adrenal incidentalomas are masses incidentally discovered at X rays, ultrasound or MRI examination of the abdomen. In 100 CT scans, one can expect to find two incidentalomas on average. The article by Murat and Dupas is dealing with the strategy of biological, morphological and scintigraphic examinations to be performed in such patients, to assess whether the tumor is of a benign or a malignant nature. Zenatti et al propose a detailed exploration of the aldosterone pathways, since adrenal carcinoma may be responsible for a specific profile of the serum concentrations of mineralo-steroids, compatible with a blockade of the last step of the aldosterone synthesis. The exploration of primary hyperaldosteronism requires biological and imaging techniques. Tabarin et al summarize the main biological parameters and tests available for the diagnosis of this condition and delineate the indications of imaging techniques, associated to hormonal tests to distinguish between adenoma and bilateral adrenal hyperplasia. (author). 104 refs

  11. Primary Anorectal Melanoma

    Directory of Open Access Journals (Sweden)

    Maliha Khan

    2014-03-01

    Full Text Available Primary malignant melanoma of the anus and rectum is a rare and aggressive neoplasm that tends to invade locally and metastasize early in the course of the disease. It is often misdiagnosed as hemorrhoids or as one of the other benign anorectal conditions and is thus linked to an overall poor prognosis and a 5-year survival rate of less than 20%. Optimal treatment is still controversial, and current evidence does not show any preferential survival benefit from abdominoperineal resection over wide local excision. Chemotherapy or radiotherapy may be used for advanced disease. We report a 71-year-old female presenting with painful bowel movements and blood in stools. She was eventually found to have a mass arising from the anorectal junction with regional lymph node involvement. The patient underwent an abdominoperineal resection and is currently scheduled for chemotherapy.

  12. Primary conjunctival amyloidosis

    Directory of Open Access Journals (Sweden)

    Chandana Chakraborti

    2014-01-01

    Full Text Available A 19-year-old previously healthy male presented with a 4 year history of painless drooping of right upper eyelid.On eversion of the right upper eyelid, a yellowish pink mass was seen in the tarsal region. Rest of the ocular examination was normal in both the eyes. Initial biopsy showed chronic inflammation. Subsequently, the entire mass was excised and histopathological examination showed the presence of amyloid in the subconjunctival stroma. At 3 months follow-up, similar lesion was detected in the right lower, left upper, and lower lid, which were treated with cryotherapy, with partial resolution. Patient has been followed up for more than 2 years without any complaints. To our knowledge, this is the first case report of an isolated primary conjunctival amyloidosis with involvement of both the upper and lower palpebral conjunctiva of either eye. It was treated successfully by excision and cryotherapy.

  13. Prostaglandins and primary dysmenorrhea

    International Nuclear Information System (INIS)

    Seifert, B.; Liedtke, M.P.; Kempf, H.J.; Richter, H.; Alexander, H.; Herter, U.

    1978-01-01

    In 100 patients a total of 171 PG determinations in the menstrual blood was performed under standardized conditions. The primary PGE 1 and PGFsub(2α) were determined by RIA. The evaluation of the analysis of the sexual hormones resulted in a group with a biphasic cycle without dysmenorrhea and a group with a biphasic cycle with dysmenorrhea. Highly significant differences (p < 0.01) were found in the PGFsub(2α) concentration in menstrual blood between a group of healthy women and one of patients with dysmenorrhea. In dysmenorrhea the ratio of the PGs investigated is shifted in favor of PGFsub(2α). Indomethacin can decrease the PGFsub(2α) levels in dysmenorrhea up to 15% (p < 0.01). All treated patients reported that their conditions had improved. Five out of seven women were completely without any complaints. (author)

  14. PRIMARY SCHOOL TEACHER

    CERN Multimedia

    Madeleine Dittus

    2002-01-01

    For the beginning of the school year 2002/2003, the A.P.E.G. has an opening for a primary school teacher in the German national language program. The position requires one afternoon of teaching (13:30 till 16:30) every Tuesday at the Collège in Prévessin. The candidate should be a native speaker of German and have some knowledge of French. If you are interested, please send your CV, a copy of your diploma, and a short letter of motivation, until March 10th, to the following address. Madeleine Dittus - Présidente A.P.E.G. 5, La vie Destraz 01630 St. Genis-Pouilly - France

  15. Primary Fallopian Tube Carcinoma

    Directory of Open Access Journals (Sweden)

    Prasad K Shetty

    2011-01-01

    Full Text Available Primary Fallopian Tube Carcinoma (PFTC is rare and accounts for about 0.3% of all gynecologic cancers. Less than 1500 cases have been reported in the literature. It arises in postmenopausal women and typically presents with abdominal pelvic pain, vaginal bleeding and watery discharge. However, a correct diagnosis is rarely achieved preoperative, and in many cases, the diagnosis is made after incidental surgery for unrelated conditions commonly being ovarian carcinoma . Compared with ovarian carcinoma, PFTC more often presents at early stages, but it has a worse prognosis. PFTC is usually managed in the same manner as ovarian cancer. We report a case of Left PFTC that presented as Left ovarian mass, and we briefly review the literature.

  16. Primary aldosteronism. Clinical management

    International Nuclear Information System (INIS)

    Grant, C.S.; Carpenter, P.; van Heerden, J.A.; Hamberger, B.

    1984-01-01

    We retrospectively reviewed the clinical features, methods of diagnosis and localization, and results of treatment in 105 patients with primary aldosteronism seen between 1969 and 1981. Coincident with the use of computed tomography (CT), 131 I-6-beta-iodomethyl norcholesterol scans (NP-59), and postural response studies, the study group was temporally divided into pre-1976 and post-1976 groups, and subdivided into groups with aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia. Our results indicate that aldosterone postural response studies and CT differentiate and localize APA and IHA reliably. Adrenalectomy is a safe and effective treatment for APA, whereas medical treatment alone is preferable for IHA

  17. Primary Identity in Literature

    DEFF Research Database (Denmark)

    Graham, Brian Russell

    In our times, literary criticism, as well as larger political and cultural developments, is characterized by identity politics, meaning that our discourses are structured around the notion of different socially identifiable populations in society. In relation to literature, this results in our...... viewing the characters in literature in terms of these political identities. Literature is consequently discussed in relation to political causes. Literary criticism is animated by the same causes, and is viewed as having a direct intervention in society in relation to them. In this paper, I will discuss......, in relation to Frye’s works, the idea that the primary identities of characters in literature were and, to a considerable extent, continue to be those of family-member identities. As such, literature should not be appropriated to a political context too readily. Whereas viewing characters in terms of...

  18. Treating Teen Depression in Primary Care.

    Science.gov (United States)

    Santiago, Sabrina

    2015-11-01

    I recently had an adolescent patient who presented with a chief complaint of depression. He had classic symptoms of difficulty sleeping, dysthymia, and anhedonia (loss of interest in things that used to bring him joy). He was a very smart and self-aware 17-year-old, and was able to describe his symptoms easily. There were no concerns for manic episodes or psychosis, and he met diagnostic criteria for unipolar major depressive disorder. He denied suicidal ideation, and was already seeing a therapist weekly for the last several months. He had a strong family history of depression, with his father, aunts, and grandmother who also carried a diagnosis of depression. He presented with the support of his mother, asking about next steps, and specifically, pharmacotherapy. This patient is a perfect example of an adolescent who is a good candidate for initiation of antidepressant medication. Primary care pediatricians should feel comfortable with first-line agents for major depressive disorder in certain adolescents with depression, but many feel hesitant and rely on child and adolescent psychiatry colleagues for prescriptions. Copyright 2015, SLACK Incorporated.

  19. [Primary care in Belgium].

    Science.gov (United States)

    Sánchez-Sagrado, T

    2017-09-01

    Belgium is an attractive country to work in, not just for doctors but for all Spanish workers, due to it having the headquarters of European Union. The health job allure is double; on the one hand, the opportunity to find a decent job, and on the other, because it is possible to develop their professional abilities with patients of the same nationality in a health system with a different way of working. The Belgium health care system is based on security social models. Health care is financed by the government, social security contributions, and voluntary private health insurance. Primary care in Belgium is very different to that in Spain. Citizens may freely choose their doctor (general practitioner or specialist) increasing the lack of coordination between primary and specialized care. This leads to serious patient safety problems and loss of efficiency within the system. Belgium is a European country with room to improve preventive coverage. General practitioners are self-employed professionals with free choice of setting, and their salary is linked to their professional activity. Ambulatory care is subjected to co-payment, and this fact leads to great inequities on access to care. The statistics say that there is universal coverage but, in 2010, 14% of the population did not seek medical contact due to economic problems. It takes 3 years to become a General Practitioner and continuing medical education is compulsory to be revalidated. In general, Belgian and Spaniards living and working in Belgium are happy with the functioning of the health care system. However, as doctors, we should be aware that it is a health care system in which access is constrained for some people, and preventive coverage could be improved. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Primary Teacher Education in Malaysia

    Science.gov (United States)

    Ching, Chin Phoi; Yee, Chin Peng

    2012-01-01

    In Malaysia the training of primary school teachers is solely carried out by teacher training institutes which offer the Bachelor of Teaching with Honors (Primary education) program and was first launched in 2007. This program prepares primary school teachers specializing in various subjects or major and is carried out in 27 teacher training…

  1. Bilateral supernumerary primary maxillary canines

    Directory of Open Access Journals (Sweden)

    Santanu Mukhopadhyay

    2018-01-01

    Full Text Available Supernumerary teeth are more common in the permanent than in primary dentition. In the primary dentition, the anomaly is most frequently observed in the maxillary lateral incisor region, followed by the maxillary midline where they are termed as mesiodens. Supernumerary teeth in the primary canine region are rare. This paper describes a rare case of nonsyndromic supernumerary primary maxillary canine distributed bilaterally in a 4-year-old boy. Both the supernumeraries resembled size and shape of normal primary canine. The right supplemental canine is high labially placed, whereas the left one is seen normally aligned in the dental arch distal to lateral incisor. One of the most significant sequelae of primary supernumerary teeth is their duplication in the permanent series. Radiographic examination of supernumerary primary canine did not indicate any such anomaly in the permanent dentition. The patient was kept under observation.

  2. Comparison between Primary Teacher Educators' and Primary School Teachers' Beliefs of Primary Geography Education Quality

    Science.gov (United States)

    Bent, Gert Jan; Bakx, Anouke; den Brok, Perry

    2016-01-01

    In this study teacher educators' beliefs concerning primary geography education have been investigated and compared with primary school teachers' beliefs. In this study 45 teacher educators and 489 primary school teachers completed a questionnaire, and nine teacher educators have been interviewed as well. It has been found that teacher educators…

  3. Primary hepatic pheochromocytoma

    International Nuclear Information System (INIS)

    Rimmelin, A.; Hartheiser, M.; Gangi, A.; Welsch, M.; Jeung, M.Y.; Jaeck, D.; Tongio, J.; Dietemann, J.L.

    1996-01-01

    Pheochromocytomas are uncommon tumors that represent a potentially curable cause of hypertension. They are usually located in the adrenal glands, but 10% arise from extra-adrenal sites, located along the paravertebral sympathetic chains. We report a case of primary hepatic pheochromocytoma responsible for a severe hypertension in a 24-year-old man. Echotomography showed a lightly heterogeneous mass located in the segment 8 of the liver. Iodine 131 -metaiodobenzylguanidine scintigraphy showed a large hepatic concentration of the tracer and no other localization. This tumor appeared highly vascularized on enhanced CT scan and on aortic angiography. Magnetic resonance imaging revealed a hepatic tumor with a high signal intensity on T2-weighted images and with a signal isointense to the liver on T1-weighted images. The hepatic venous sampling contained the highest catecholamine level, whereas the adrenal venous samping was normal. After surgical resection of the hepatic tumor, the tension level and catecholamines plasmatic level normalized. No recurrent symptoms appeared during a 3-year follow-up. (orig.)

  4. Primary intestinal lymphangiectasia: Minireview

    Science.gov (United States)

    Ingle, Sachin B; Hinge (Ingle), Chitra R

    2014-01-01

    Primary idiopathic intestinal lymphangiectasia is an unusual disease featured by the presence of dilated lymphatic channels which are located in the mucosa, submucosa or subserosa leading to protein loosing enteropathy.Most often affected were children and generally diagnosed before third year of life but may be rarely seen in adults too. Bilateral pitting oedema of lower limb is the main clinical manifestation mimicking the systemic disease and posing a real diagnostic dilemma to the clinicians to differentiate it from other common systemic diseases like Congestive cardiac failure, Nephrotic Syndrome, Protein Energy Malnutrition, etc. Diagnosis can be made on capsule endoscopy which can localise the lesion but unable to take biopsy samples. Thus, recently double-balloon enteroscopy and biopsy in combination can be used as an effective diagnostic tool to hit the correct diagnosis. Patients respond dramatically to diet constituting low long chain triglycerides and high protein content with supplements of medium chain triglyceride. So early diagnosis is important to prevent untoward complications related to disease or treatment for the sake of accurate pathological diagnosis. PMID:25325063

  5. Primary hyperoxaluria in infants

    Directory of Open Access Journals (Sweden)

    Manel Jellouli

    2016-01-01

    Full Text Available The infantile form of primary hyperoxaluria type-1 (PH-1 is characterized by a rapid progression to the end-stage renal disease (ESRD due to both increased oxalate load and reduced glomerular filtration rate. In the literature, data on this form are limited. The purpose of this study is to analyze retrospectively the clinical, biological, and radiological features of children who were diagnosed with PH-1 during the 1styear of life. We reviewed the records of all children with PH-1 diagnosed and followed-up at our department between January 1995 and December 2013. Among them, only infants younger than 12 months of age were retrospectively enrolled in the study. Fourteen infants with the median age of two months were enrolled in the study. At diagnosis, 11 patients had ESRD. All patients had nephrocalcinosis and two of them had calculi. The diagnosis was established in nine patients on the basis of the positive family history of PH-1, bilateral nephrocalcinosis, and quantitative crystalluria. In four patients, the diagnosis was made with molecular analysis of DNA. Kidney biopsy contributed to the diagnosis in one patient. During follow-up, two patients were pyridoxine sensitive and preserved renal function. Seven among 11 patients who had ESRD died, four patients are currently undergoing peritoneal dialysis. Children with infantile PH and ESRD are at high risk of early death. Peritoneal dialysis is not a treatment of choice. Combined liver-kidney transplantation is mandatory.

  6. Primary hyperparathyroidism: recent advances.

    Science.gov (United States)

    Walker, Marcella D; Bilezikian, John P

    2018-07-01

    The purpose of this review is to describe recent advances and changes in the evaluation and management of primary hyperparathyroidism (PHPT). Although it has long been recognized that asymptomatic PHPT is associated with bone loss, particularly at cortical skeletal sites when evaluated with dual-energy X-ray absorptiometry, new imaging techniques suggest that trabecular skeletal deterioration as well as clinically silent vertebral fractures and nephrolithiasis are common. Nonclassical targets of asymptomatic PHPT as well as the effect of vitamin D deficiency and treatment upon PHPT presentation have been the subject of recent intense investigation. Randomized clinical trials are now available regarding the effect of parathyroidectomy (PTX) upon both classical and nonclassical target organs. They have confirmed results from observational studies with regard to the skeletal benefits of PTX but have not consistently shown improvements in nonclassical symptoms. These findings have led to recommendations for more extensive renal and skeletal evaluation and broader criteria for PTX in PHPT. In addition to dual-energy X-ray absorptiometry, vertebral and renal imaging is recommended. When available, trabecular imaging techniques may be helpful. PTX criteria now include subclinical kidney stones, vertebral fractures and hypercalciuria, in addition to those based on age, serum calcium, bone densitometry and renal function.

  7. Primary sclerosing cholangitis

    Directory of Open Access Journals (Sweden)

    Marina G Silveira

    2008-01-01

    Full Text Available Primary sclerosing cholangitis (PSC is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphatase, nonspecific autoantibodies such as perinuclear antineutrophilic antibody, antinuclear antibodies and smooth muscle antibodies, and diffuse multifocal biliary strictures, resulting in a ‘beaded’ appearance on radiographic studies, are the hallmarks of the disease. No effective medical therapy is currently available, although clinical studies are in progress. Ursodeoxycholic acid at high doses (28 mg/kg/day to 30 mg/kg/day is the most promising agent but is unproven so far. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease, although recurrent disease can be observed in the transplanted liver. The multiple complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, peristomal varices, bacterial cholangitis, dominant biliary strictures, gallbladder stones and polyps, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of PSC.

  8. Primary sclerosing cholangitis

    Directory of Open Access Journals (Sweden)

    Chapman Roger

    2006-10-01

    Full Text Available Abstract Primary sclerosing cholangitis (PSC is a chronic cholestatic liver disease of unknown aetiology characterised by inflammation and fibrosis of the biliary tree. The mean age at diagnosis is 40 years and men are affected twice as often as women. There is a reported annual incidence of PSC of 0.9–1.31/100,000 and point prevalence of 8.5–13.6/100,000. The onset of PSC is usually insidious and many patients are asymptomatic at diagnosis or have mild symptoms only such as fatigue, abdominal discomfort and pruritus In late stages, splenomegaly and jaundice may be a feature. In most, the disease progresses to cirrhosis and liver failure. Cholangiocarcinoma develops in 8–30% of patients. PSC is thought to be immune mediated and is often associated with inflammatory bowel disease, especially ulcerative colitis. The disease is diagnosed on typical cholangiographic and histological findings and after exclusion of secondary sclerosing cholangitis. Median survival has been estimated to be 12 years from diagnosis in symptomatic patients. Patients who are asymptomatic at diagnosis, the majority of whom will develop progressive disease, have a survival rate greater than 70% at 16 years after diagnosis. Liver transplantation remains the only effective therapeutic option for patients with end-stage liver disease from PSC, although high dose ursodeoxycholic acid may have a beneficial effect.

  9. Consanguinity and primary immunodeficiencies.

    Science.gov (United States)

    Al-Herz, Waleed; Aldhekri, Hasan; Barbouche, Mohamed-Ridha; Rezaei, Nima

    2014-01-01

    Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders caused by defects in the immune system that predispose patients to infections, autoimmune diseases, lymphoproliferation and malignancies. Most PIDs are inherited in an autosomal recessive pattern; therefore, they are more common in areas with high rates of consanguineous marriage. Reports about PIDs from these areas have demonstrated a peculiar prevalence of more severe forms of diseases compared to other regions, and patients born to consanguineous parents have increased rates of morbidity and mortality compared to other patients. Individuals at high risk of having a child with a PID who wish to have a healthy child have limited options, these include prenatal diagnosis and pre-implantation genetic diagnosis. However, these options require a collaborative team of specialists and may not always be implemented due to geographic, religious, financial or social factors. The recent introduction of newborn-screening programs for a number of T and B lymphocyte deficiencies will facilitate early diagnosis and therapeutic interventions, which may include hematopoietic stem cell transplantation and intravenous immunoglobulin treatment. There is a need for the implementation of strategies to increase public awareness of the health risks associated with consanguineous marriage. It should be stressed that genetic counseling should be an important component of the care of patients with PIDs as well as their families. © 2014 S. Karger AG, Basel.

  10. Idiopathic (primary achalasia

    Directory of Open Access Journals (Sweden)

    Vaezi Michael F

    2007-09-01

    Full Text Available Abstract Idiopathic achalasia is a primary esophageal motor disorder characterized by esophageal aperistalsis and abnormal lower esophageal sphincter (LES relaxation in response to deglutition. It is a rare disease with an annual incidence of approximately 1/100,000 and a prevalence rate of 1/10,000. The disease can occur at any age, with a similar rate in men and women, but is usually diagnosed between 25 and 60 years. It is characterized predominantly by dysphagia to solids and liquids, bland regurgitation, and chest pain. Weight loss (usually between 5 to 10 kg is present in most but not in all patients. Heartburn occurs in 27%–42% of achalasia patients. Etiology is unknown. Some familial cases have been reported, but the rarity of familial occurrence does not support the hypothesis that genetic inheritance is a significant etiologic factor. Association of achalasia with viral infections and auto-antibodies against myenteric plexus has been reported, but the causal relationship remains unclear. The diagnosis is based on history of the disease, radiography (barium esophagogram, and esophageal motility testing (esophageal manometry. Endoscopic examination is important to rule out malignancy as the cause of achalasia. Treatment is strictly palliative. Current medical and surgical therapeutic options (pneumatic dilation, surgical myotomy, and pharmacologic agents aimed at reducing the LES pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids. Although it cannot be permanently cured, excellent palliation is available in over 90% of patients.

  11. Idiopathic (primary) achalasia

    Science.gov (United States)

    Farrokhi, Farnoosh; Vaezi, Michael F

    2007-01-01

    Idiopathic achalasia is a primary esophageal motor disorder characterized by esophageal aperistalsis and abnormal lower esophageal sphincter (LES) relaxation in response to deglutition. It is a rare disease with an annual incidence of approximately 1/100,000 and a prevalence rate of 1/10,000. The disease can occur at any age, with a similar rate in men and women, but is usually diagnosed between 25 and 60 years. It is characterized predominantly by dysphagia to solids and liquids, bland regurgitation, and chest pain. Weight loss (usually between 5 to 10 kg) is present in most but not in all patients. Heartburn occurs in 27%–42% of achalasia patients. Etiology is unknown. Some familial cases have been reported, but the rarity of familial occurrence does not support the hypothesis that genetic inheritance is a significant etiologic factor. Association of achalasia with viral infections and auto-antibodies against myenteric plexus has been reported, but the causal relationship remains unclear. The diagnosis is based on history of the disease, radiography (barium esophagogram), and esophageal motility testing (esophageal manometry). Endoscopic examination is important to rule out malignancy as the cause of achalasia. Treatment is strictly palliative. Current medical and surgical therapeutic options (pneumatic dilation, surgical myotomy, and pharmacologic agents) aimed at reducing the LES pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids. Although it cannot be permanently cured, excellent palliation is available in over 90% of patients. PMID:17894899

  12. Achieving Value in Primary Care: The Primary Care Value Model.

    Science.gov (United States)

    Rollow, William; Cucchiara, Peter

    2016-03-01

    The patient-centered medical home (PCMH) model provides a compelling vision for primary care transformation, but studies of its impact have used insufficiently patient-centered metrics with inconsistent results. We propose a framework for defining patient-centered value and a new model for value-based primary care transformation: the primary care value model (PCVM). We advocate for use of patient-centered value when measuring the impact of primary care transformation, recognition, and performance-based payment; for financial support and research and development to better define primary care value-creating activities and their implementation; and for use of the model to support primary care organizations in transformation. © 2016 Annals of Family Medicine, Inc.

  13. Does the Spatial Distribution of the Parasitic Mite Varroa jacobsoni Oud. (Mesostigmata: Varroidae) in Worker Brood of Honey Bee Apis Mellifera L. (Hymenoptera: Apidae) Rely on an Aggregative Process?

    Science.gov (United States)

    Salvy, M.; Capowiez, Y.; Le Conte, Y.; Salvy, M.; Clément, J.-L.

    Varroa jacobsoni is an ectoparasite of honey bees which reproduces in capped brood cells. Multi-infestation is frequently observed in worker brood and can be interpreted as an aggregative phenomenon. The aim of this study was to determine whether the distribution of V. jacobsoni in worker brood cells relies on a random or an aggregative process. We studied the distribution of Varroa females in capped worker brood at similar age by comparing, by a Monte Carlo test, the observed frequency distribution of mites per cell to simulated distributions based on a random process. A complementary approach, using the "nearest neighbor distances" (NND) with Monte Carlo tests, was investigated to study the spatial distribution (a) between mites in different cells and (b) between infested cells in brood. The observed distributions did not differ significantly from that expected by a random process, and we conclude that there is no aggregation during invasion of V. jacobsoni in worker brood.

  14. Primary intracranial malignant lymphoma

    International Nuclear Information System (INIS)

    Matsumoto, Mikiro; Ohtsuka, Takatsugu; Kuroki, Takao; Shibata, Iekado; Terao, Hideo; Kudo, Motoshige

    1988-01-01

    Nine cases of primary intracranial malignant lymphoma, which accounts for 3.3 % of all intracranial tumors seen in the authors' institution, were studied in terms of diagnostic computed tomographic (CT) features, the tumors' histologic appearance, treatment, post-treatment blood immunologic and cerebrospinal fluid (CSF) characteristics, and outcome. The patients were seven males and two females aged 42 to 67 years. Their chief signs and symptoms on admission were intracranial hypertension, focal signs, and disturbance of consciousness. CT, which proved the most useful preoperative diagnostic technique, demonstrated multiple lesions in seven cases and, in all cases, regions of isodensity or slight high density that were enhanced by contrast medium. According to the patterns of enhancement, the tumors were classed as diffuse (three cases) or nodular (six cases). The former is considered typical of malignant lymphoma, whereas the latter type was sometimes indistinguishable from metastatic tumor and meningioma. At surgery, one patient underwent radical tumor excision, two partial removal, and six biopsy only. Histologic examination revealed one tumor to be of the diffuse small cell type, three of the medium cell type, and five of the large cell type (Lymphoma Study Group classification). Of seven tumors in which lymphocytes were examined by peroxidase-antiperoxidase staining, four were of the B cell type. Postoperatively, whole brain irradiation with 29 to 46 Gy was followed by local irradiation with 15 to 50 Gy. If the tumor persisted, one of three chemotherapies was administered. In one case, methotrexate was given intrathecally. Seven patients were divided into two groups: long remission (three) and recurrence (four). These two groups were compared in terms of serum immunoglobulin levels, T and B cell ratios, CSF characteristics, CT features, tumor cell type, and treatment. No clear differences were found. (author)

  15. Primary cosmic radiation

    International Nuclear Information System (INIS)

    Anderson, H.R.

    1972-01-01

    The term cosmic radiation means the charged particle flux that reaches the earth from outside its magnetosphere with energies above the solar wind energy of a few keV. There are two sources of flux. Sporadically the sun produces such particles, generally within the energy range 1--200 MeV, and these solar cosmic rays arrive at the earth for a period ranging from hours to days. There may be a small, rather constant flux from the sun also, but the bulk of the steady flux originates outside the earth's orbit. Although some have conjectured that part of this latter flux may be accelerated in the outer portions of the solar system where the outward flowing interplanetary medium meets the interstellar medium, it is generally thought that most or all of it arises in unique systems such as supernovae, and is distributed throughout the galaxy. These galactic particles range in energy from a few MeV to at least 10 13 MeV and consist primarily of protons with significant numbers of heavier nuclei, positrons and electrons. They are supposed to fill our galaxy, or at least the disc, more or less uniformly. However, the flux with energies below a few GeV that reaches earth's orbit is modulated by the interplanetary medium so that the number at earth varies inversely with solar activity and is always somewhat below the interstellar flux. A discussion is presented of primary galactic radiation at earth, its modulation by solar activity, and its interaction with the geomagnetic field. (U.S.)

  16. [Primary care in Portugal].

    Science.gov (United States)

    Sánchez-Sagrado, T

    2018-04-01

    The economic crisis and deterioration of the Portuguese National Health service has forced professionals to leave the country. The Portuguese National Health System was introduced in 1976, but it has been unable to provide citizens with the social and health advantages of an equality of access and free national health system. The Portuguese National Health System is financed by taxes. However, a 35% of its incomes are from private sources. The health minister decides the budget, and it is based on an historical financing plus a per capita system. Portuguese citizens and immigrants are entitled to free health care, but there is a co-payment for care, diagnostic, pharmacy, and emergency care. Health care provision is a mixture of public and private health care at a regional level. It leads to fragmentation of services and greater inequalities. Doctors are civil servants. Salary is regulated and it depends on seniority and on-call shifts. Primary care activities are similar to those of their Spanish counterparts. General practitioners have gatekeeper function, but the system is imperfect, and patients with private insurance get direct access to the specialist. Specialist training is similar to the training system in Spain. Continuing education is not regulated. The Portuguese Health System has been trying to become a national health system since 1979. Political instability, fragmentation of services, lack of clarity between public and private and co-payments are important constraints. Inequalities are an important problem to reconsider while discussing a national health system. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Spatial imagery relies on a sensory independent, though sensory sensitive, functional organization within the parietal cortex: a fMRI study of angle discrimination in sighted and congenitally blind individuals.

    Science.gov (United States)

    Bonino, Daniela; Ricciardi, Emiliano; Bernardi, Giulio; Sani, Lorenzo; Gentili, Claudio; Vecchi, Tomaso; Pietrini, Pietro

    2015-02-01

    Although vision offers distinctive information to space representation, individuals who lack vision since birth often show perceptual and representational skills comparable to those found in sighted individuals. However, congenitally blind individuals may result in impaired spatial analysis, when engaging in 'visual' spatial features (e.g., perspective or angle representation) or complex spatial mental abilities. In the present study, we measured behavioral and brain responses using functional magnetic resonance imaging in sighted and congenitally blind individuals during spatial imagery based on a modified version of the mental clock task (e.g., angle discrimination) and a simple recognition control condition, as conveyed across distinct sensory modalities: visual (sighted individuals only), tactile and auditory. Blind individuals were significantly less accurate during the auditory task, but comparable-to-sighted during the tactile task. As expected, both groups showed common neural activations in intraparietal and superior parietal regions across visual and non-visual spatial perception and imagery conditions, indicating the more abstract, sensory independent functional organization of these cortical areas, a property that we named supramodality. At the same time, however, comparisons in brain responses and functional connectivity patterns across experimental conditions demonstrated also a functional lateralization, in a way that correlated with the distinct behavioral performance in blind and sighted individuals. Specifically, blind individuals relied more on right parietal regions, mainly in the tactile and less in the auditory spatial processing. In sighted, spatial representation across modalities relied more on left parietal regions. In conclusions, intraparietal and superior parietal regions subserve supramodal spatial representations in sighted and congenitally blind individuals. Differences in their recruitment across non-visual spatial processing in

  18. Formative and summative assessment of science in English primary schools: evidence from the Primary Science Quality Mark

    Science.gov (United States)

    Earle, Sarah

    2014-05-01

    Background:Since the discontinuation of Standard Attainment Tests (SATs) in science at age 11 in England, pupil performance data in science reported to the UK government by each primary school has relied largely on teacher assessment undertaken in the classroom. Purpose:The process by which teachers are making these judgements has been unclear, so this study made use of the extensive Primary Science Quality Mark (PSQM) database to obtain a 'snapshot' (as of March 2013) of the approaches taken by 91 English primary schools to the formative and summative assessment of pupils' learning in science. PSQM is an award scheme for UK primary schools. It requires the science subject leader (co-ordinator) in each school to reflect upon and develop practice over the course of one year, then upload a set of reflections and supporting evidence to the database to support their application. One of the criteria requires the subject leader to explain how science is assessed within the school. Sample:The data set consists of the electronic text in the assessment section of all 91 PSQM primary schools which worked towards the Quality Mark in the year April 2012 to March 2013. Design and methods:Content analysis of a pre-existing qualitative data set. Text in the assessment section of each submission was first coded as describing formative or summative processes, then sub-coded into different strategies used. Results:A wide range of formative and summative approaches were reported, which tended to be described separately, with few links between them. Talk-based strategies are widely used for formative assessment, with some evidence of feedback to pupils. Whilst the use of tests or tracking grids for summative assessment is widespread, few schools rely on one system alone. Enquiry skills and conceptual knowledge were often assessed separately. Conclusions:There is little consistency in the approaches being used by teachers to assess science in English primary schools. Nevertheless

  19. African Primary Care Research: qualitative interviewing in primary care.

    Science.gov (United States)

    Reid, Steve; Mash, Bob

    2014-06-05

    This article is part of a series on African Primary Care Research and focuses on the topic of qualitative interviewing in primary care. In particular it looks at issues of study design, sample size, sampling and interviewing in relation to individual and focus group interviews.There is a particular focus on helping postgraduate students at a Masters level to write their research proposals.

  20. Primary epiploic appendagitis

    Directory of Open Access Journals (Sweden)

    Carlos Augusto Real Martinez

    2013-07-01

    Full Text Available Primary epiploic appendagitis (PEA is a seldom reported disease caused by spontaneous torsion of one or more epiploic appendices. The aim of this study is to describe two cases of PEA reviewing the main aspects of the diagnosis and treatment of disease. Case report: Case 1 Male patient, 55 years old, obese, with abdominal right iliac fossa (RIF pain for two days. Abdominal examination showed pain on palpation in the RIF with rebound tenderness. Abdominal computed tomography identified lobulated lesion in the cecum, measuring 4.5 cm in diameter, which was suggestive of PEA or early neoplasm of the colon wall. The lapa- roscopic assessment confirmed the diagnosis of PEA and the appendix was removed. The pa- tient had a satisfactory outcome, being discharged on the second postoperative day. Case 2 Female patient, obese, 47 years old, with abdominal pain for six days, with sudden RIF onset. She had pain at palpation with rebound tenderness. Acute diverticulitis was suspected and patient underwent abdominal CT that identified PEA in the sigmoid colon. After expectant management, the patient showed progressive improvement resuming her activities in seven days. PEA is a rarely recalled condition during the investigation of inflammatory acute abdo- men which can be easily recognized by modern imaging methods of assessment. Resumo: Apendagite epiplóica primária (AEP é uma enfermidade raramente descrita, ocasionada pela torção espontânea de um ou mais apêndices epiplóicos. O objetivo deste estudo é descrever dois casos de AEP revisando os principais aspectos do diagnóstico e tratamento da doença. Relato dos Casos: 1° Homem, 55 anos, obeso com dor abdominal em FID há dois dias. No exame do abdômen apresentava dor à palpação na FID e descompressão brusca presente. A tomografia computadorizada do abdômen identificou lesão expansiva no ceco, lobulada, medindo 4,5 cm de diâmetro, suspeitando-se de AEP ou neoplasia primitiva da parede c

  1. Primary ectopic frontotemporal extradural craniopharyngioma

    Directory of Open Access Journals (Sweden)

    Reza Pourkhalili

    2016-01-01

    Full Text Available We present a case of primary ectopic frontotemporal extradural craniopharyngioma. Primary ectopic craniopharyngiomas are very rare and have been reported involving the fourth ventricle, infrasellar region, lateral ventricle, temporal area, cerebellopontine angle, clivus, corpus callosum, and prepontine cistern. There was just 1 case of craniopharyngioma previously presented in the literature, with nearly same location as the presenting case.

  2. Methotrexate for primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Giljaca, Vanja; Poropat, Goran; Stimac, Davor

    2010-01-01

    Methotrexate has been used to treat patients with primary biliary cirrhosis as it possesses immunosuppressive properties. The previously prepared version of this review from 2005 showed that methotrexate seemed to significantly increase mortality in patients with primary biliary cirrhosis. Since...... that last review version, follow-up data of the included trials have been published....

  3. Primary Science Interview: Science Sparks

    Science.gov (United States)

    Bianchi, Lynne

    2016-01-01

    In this "Primary Science" interview, Lynne Bianchi talks with Emma Vanstone about "Science Sparks," which is a website full of creative, fun, and exciting science activity ideas for children of primary-school age. "Science Sparks" started with the aim of inspiring more parents to do science at home with their…

  4. Cardiovascular Risk in Primary Hyperaldosteronism

    NARCIS (Netherlands)

    Prejbisz, A.; Warchol-Celinska, E.; Lenders, J.W.M.; Januszewicz, A.

    2015-01-01

    After the first cases of primary aldosteronism were described and characterized by Conn, a substantial body of experimental and clinical evidence about the long-term effects of excess aldosterone on the cardiovascular system was gathered over the last 5 decades. The prevalence of primary

  5. Primary care research in Denmark

    DEFF Research Database (Denmark)

    Vedsted, Peter; Kallestrup, Per

    2016-01-01

    International Perspectives on Primary Care Research examines how the evidence base from primary care research can strengthen health care services and delivery, tackle the growing burden of disease, improve quality and safety, and increase a person-centred focus to health care. Demonstrating...... the inter-professional nature of the discipline, the book also features a section on cross-nation organisations and primary care networks supporting research. National perspectives are offered from researchers in 20 countries that form part of the World Organization of Family Doctors, providing case...... histories from research-rich to resource-poor nations that illustrate the range of research development and capacity building. This book argues the importance of primary care research, especially to policy makers, decision makers and funders in informing best practice, training primary health care providers...

  6. Spatial integration in mouse primary visual cortex.

    Science.gov (United States)

    Vaiceliunaite, Agne; Erisken, Sinem; Franzen, Florian; Katzner, Steffen; Busse, Laura

    2013-08-01

    Responses of many neurons in primary visual cortex (V1) are suppressed by stimuli exceeding the classical receptive field (RF), an important property that might underlie the computation of visual saliency. Traditionally, it has proven difficult to disentangle the underlying neural circuits, including feedforward, horizontal intracortical, and feedback connectivity. Since circuit-level analysis is particularly feasible in the mouse, we asked whether neural signatures of spatial integration in mouse V1 are similar to those of higher-order mammals and investigated the role of parvalbumin-expressing (PV+) inhibitory interneurons. Analogous to what is known from primates and carnivores, we demonstrate that, in awake mice, surround suppression is present in the majority of V1 neurons and is strongest in superficial cortical layers. Anesthesia with isoflurane-urethane, however, profoundly affects spatial integration: it reduces the laminar dependency, decreases overall suppression strength, and alters the temporal dynamics of responses. We show that these effects of brain state can be parsimoniously explained by assuming that anesthesia affects contrast normalization. Hence, the full impact of suppressive influences in mouse V1 cannot be studied under anesthesia with isoflurane-urethane. To assess the neural circuits of spatial integration, we targeted PV+ interneurons using optogenetics. Optogenetic depolarization of PV+ interneurons was associated with increased RF size and decreased suppression in the recorded population, similar to effects of lowering stimulus contrast, suggesting that PV+ interneurons contribute to spatial integration by affecting overall stimulus drive. We conclude that the mouse is a promising model for circuit-level mechanisms of spatial integration, which relies on the combined activity of different types of inhibitory interneurons.

  7. Primary care providers' experiences caring for complex patients in primary care: a qualitative study.

    Science.gov (United States)

    Loeb, Danielle F; Bayliss, Elizabeth A; Candrian, Carey; deGruy, Frank V; Binswanger, Ingrid A

    2016-03-22

    Complex patients are increasingly common in primary care and often have poor clinical outcomes. Healthcare system barriers to effective care for complex patients have been previously described, but less is known about the potential impact and meaning of caring for complex patients on a daily basis for primary care providers (PCPs). Our objective was to describe PCPs' experiences providing care for complex patients, including their experiences of health system barriers and facilitators and their strategies to enhance provision of effective care. Using a general inductive approach, our qualitative research study was guided by an interpretive epistemology, or way of knowing. Our method for understanding included semi-structured in-depth interviews with internal medicine PCPs from two university-based and three community health clinics. We developed an interview guide, which included questions on PCPs' experiences, perceived system barriers and facilitators, and strategies to improve their ability to effectively treat complex patients. To focus interviews on real cases, providers were asked to bring de-identified clinical notes from patients they considered complex to the interview. Interview transcripts were coded and analyzed to develop categories from the raw data, which were then conceptualized into broad themes after team-based discussion. PCPs (N = 15) described complex patients with multidimensional needs, such as socio-economic, medical, and mental health. A vision of optimal care emerged from the data, which included coordinating care, preventing hospitalizations, and developing patient trust. PCPs relied on professional values and individual care strategies to overcome local and system barriers. Team based approaches were endorsed to improve the management of complex patients. Given the barriers to effective care described by PCPs, individual PCP efforts alone are unlikely to meet the needs of complex patients. To fulfill PCP's expressed concepts of

  8. An Investigation on the impact of using problem-based trainings in the in-service courses on the teachers' performance and capabilities, by relying on the elementary sixth grade mathematics book (case study: the city of Ahvaz

    Directory of Open Access Journals (Sweden)

    Pari Cheraq

    2017-02-01

    Full Text Available Changes in the administrative structure of the education system and the need to coordinate with the world of science and technology and hence, the need to update the general and technical information and knowledge, have doubled the importance and necessity of holding the new and efficient in-service trainings for the teachers. In this study, the attempt was taken to examine and analyze the impact of using problem-based trainings during the in-service courses on the teachers' performance and capabilities, by relying on the mathematics book of the sixth grade elementary level (case study: the city of Ahvaz. To do so, using a quasi-experimental study, 37 teachers of the sixth grade were selected from the elementary schools of Ahvaz city. For the in-service training courses on the teaching of mathematics, the problem-based learning method was used. After conducting the problem-based teaching method and the traditional method of teaching, through using the test and the standard questionnaire, the data about the teaching practice and the capabilities of the teachers were collected. Using t-test for the paired and independent samples, it was demonstrated that the problem-based in-service trainings, enhance the teachers' capabilities and performance regarding the problem-solving skills.

  9. The Coming Primary Care Revolution.

    Science.gov (United States)

    Ellner, Andrew L; Phillips, Russell S

    2017-04-01

    The United States has the most expensive, technologically advanced, and sub-specialized healthcare system in the world, yet it has worse population health status than any other high-income country. Rising healthcare costs, high rates of waste, the continued trend towards chronic non-communicable disease, and the growth of new market entrants that compete with primary care services have set the stage for fundamental change in all of healthcare, driven by a revolution in primary care. We believe that the coming primary care revolution ought to be guided by the following design principles: 1) Payment must adequately support primary care and reward value, including non-visit-based care. 2) Relationships will serve as the bedrock of value in primary care, and will increasingly be fostered by teams, improved clinical operations, and technology, with patients and non-physicians assuming an ever-increasing role in most aspects of healthcare. 3) Generalist physicians will increasingly focus on high-acuity and high-complexity presentations, and primary care teams will increasingly manage conditions that specialists managed in the past. 4) Primary care will refocus on whole-person care, and address health behaviors as well as vision, hearing, dental, and social services. Design based on these principles should lead to higher-value healthcare, but will require new approaches to workforce training.

  10. Identification and characterization of a novel allele of Caenorhabditis elegans bbs-7.

    Directory of Open Access Journals (Sweden)

    Kara Braunreiter

    Full Text Available Primary cilia play a role in the sensation of and response to the surrounding environment. Caenorhabditis elegans (C. elegans have primary cilia only on the distal tips of some dendrites. In order to better understand the relationship between receptor localization to cilia, cilia structure and cilia function, we have characterized a mutation originally identified in a forward genetic screen for mutants with defective PKD-2 ciliary localization. Through behavioral assays and examination of the structure of cilia in the cil-5 (my13 mutant animals, we have found that my13 disrupts not only receptor localization, but also some cilia-mediated sensory behaviors and cilia structural integrity. We have identified the my13 lesion and found that it is a missense mutation in bbs-7, an ortholog of human BBS-7, a gene known to affect human cilia and to be involved in Bardet-Biedl syndrome. Finally, we show that bbs-7(my13 also affects the glia cells which support the cilia.

  11. Primary amenorrhea: diagnosis and management.

    Science.gov (United States)

    Marsh, Courtney A; Grimstad, Frances W

    2014-10-01

    Puberty is a defining time of many adolescents' lives. It is a series of events that includes thelarche, pubarche, and menarche. Primary amenorrhea is the absence of menarche. There are numerous etiologies including outflow tract obstructions, gonadal dysgenesis, and anomalies of the hypothalamic axis. This review's aims are to define primary amenorrhea and describe the various causes, their workups, associated comorbidities, and treatment options. At the end, a generalist should be able to perform an assessment of an adolescent who presents with primary amenorrhea and, if warranted, begin initial treatment.

  12. Primary vertebral tumours in children

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Beluffi, G.; Masel, J.; Diard, F.; Ferrari-Ciboldi, F.; Le Dosseur, P.; Labatut, J.

    1984-03-01

    20 cases of primary benign and malignant bone tumours in children were reported. The most common tumours were Ewing's sarcoma, aneurismal bone cyst, benign osteoblastoma and osteoid osteoma. Some rare primary bone tumours in children (osteochondroma, chondroblastoma 6F, primary lymphoma of bone and neurofibromatosis with unusual cervical spinal changes) were also reported. The authors believe that radiographic findings together with clinical history and clinical examination may yield a high percentage of accurate diagnoses. Although microscopy is essential in the final diagnosis, the microscopic report should be also accepted with caution.

  13. Primary Productivity (PP_Master)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set included primary production for each subregion in the study (Georges Bank, Gulf of Maine, Southern New England, Middle Atlantic Bight) . The data came...

  14. Problems of Primary Education Today

    Science.gov (United States)

    Dubova, M. V.

    2014-01-01

    Primary education in Russia has failed to adapt to the needs of post-Soviet society, and is still based on rote learning and memorization instead of learning through discovery and learning to use and apply what is learned.

  15. Primary sclerosing cholangitis and pregnancy

    Directory of Open Access Journals (Sweden)

    Casper Q. Kammeijer

    2011-08-01

    Full Text Available Primary sclerosing cholangitis is a progressive disease, and coincidentally in pregnancy it is rare. It is characterized by progressive inflammation and destruction of bile ducts finally resulting in liver failure. A rare case of primary sclerosing cholangitis in pregnancy is presented. The course of the pregnancy was marked by threatened preterm delivery and exacerbation of cholestasis. She was successfully treated with ursodeoxycholic acid (UDCA. Although, primary sclerosing cholangitis has both maternal and fetal effects on pregnancy, the overall outcome is favorable. Only few cases have been reported using high dose ursodeoxycholic acid for primary sclerosing cholangitis in pregnancy, it often improves pruritus but has no protection against stillbirth. Data on the safety to the fetus or neonate and long-term outcome are scarce.

  16. COMMUNITY HEALTH & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    adedamla

    Quarry industry has become a major means of livelihood in Ebonyi state, but insufficient data exists on their operations ... of Dust Mask among Crushers of Selected Quarry (Crushed ... Journal of Community Medicine and Primary Health Care.

  17. Primary intracerebral lymphoma: Case report

    Directory of Open Access Journals (Sweden)

    Olcay Eser

    2012-09-01

    Full Text Available We describe a case of primary central nervous lymphoma (PCNSL that may be confused with magnetic resonance imaging (MRI findings of high grade glioma. Primary central nervous lymphoma is a rare tumour and it account for 0.3-3% of intracranial tumours. A 61 year’s old woman was admitted to our clinic with a severe headache, vomiting, left hemiparesia and transient loss of consciousness. Primary central nervous lymphoma may show various biological and radiological characteristics. We herein emphasized being confused with MRI findings of PCNSL and high grade glioma. J Clin Exp Invest 2012; 3 (3: 409-411Key words: Primary central nervous lymphoma, high grade glioma, B-cell, diagnosis

  18. Structures in the primary spectrum

    International Nuclear Information System (INIS)

    Kempa, J.; Knurenko, S.P.; Malecki, R.

    2009-01-01

    Structures in the energy spectrum of primary cosmic rays at the 'knee' region and for energies higher than 1 EeV are obtained through studying extensive air showers (EAS). The main problem of the research is the fact that we work in the ranges of highly fluctuating parameters used to obtain the primary energy spectrum. In this paper the log-normal distribution for the error function has been used in convolution with the power spectrum to explain the Yakutsk experimental data. Similar results have been obtained for the gamma distribution as the error function. Using the power law primary spectrum in the energy region around 10 19 eV we will argue that the primary Yakutsk spectrum is overestimated. In the best case this overestimation is not less than 42%.

  19. COMMUNITY MEDICINE & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    ajiboro

    3Department of Community and Primary Health Care, College of Medicine, University of Lagos, Idiaraba, ... Some of the participants (45.3%) carry out physical exercises such as walking ..... hypertension, continuous effective management of.

  20. COMMUNITY HEALTH & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    2Primary Health Care Department, Ikpoba Okha Local Government Area, Benin City, ... selected from each of the ten wards in the LGA using multistage sampling technique. ..... Knowledge of HIV/AIDS Insurance Companies in Lagos State.

  1. COMMUNITY MEDICINE & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    Client Satisfaction with Antenatal Care Services in Primary Health Care. Centres in Sabon ... important information about how well clinicians and the population of women within child bearing. 8 ..... model. Health and Quality of Life outcomes.

  2. Primary optic nerve sheath meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Jeremic, Branislav [International Atomic Energy Agency, Vienna (Austria); Pitz, Susanne (eds.) [University Eye Hospital, Mainz (Germany)

    2008-07-01

    Optic nerve sheath meningioma (ONSM) is a rare tumour. Cases are usually separated into primary ONSM, which arises either intraorbitally or, less commonly, intracanalicularly, and secondary ONSM, which arises intracranially and subsequently invades the optic canal and orbit. This is the first book to cover all important aspects of the diagnosis and treatment of primary ONSM. After a general introduction, individual chapters discuss the clinical presentation, clinical examination and diagnosis, imaging, and histology. Treatment options are then addressed in detail, with special emphasis on external beam radiation therapy, and in particular stereotactic fractionated radiation therapy. The latter has recently produced consistently good results and is now considered the emerging treatment of choice for the vast majority of patients with primary ONSM. This well-illustrated book will prove invaluable to all practitioners who encounter primary ONSM in their clinical work. (orig.)

  3. Allegheny County Primary Care Access

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — The data on health care facilities includes the name and location of all the hospitals and primary care facilities in Allegheny County. The current listing of...

  4. & PRIMARY HEALTH CARE COMMUNITY MEDICINE

    African Journals Online (AJOL)

    Family planning is an important preventive measure against maternal and child ... users of the services, desire for more children, fear of side effects and partner's ... It is an essential component of primary development across the regions .

  5. Characteristics of Sissi primary beam

    International Nuclear Information System (INIS)

    Nghiem, P.; Payet, J.; Tkatchenko, A.

    1994-01-01

    This study concerns the definition of the Sissi primary beam characteristics. The calculations have been carried out in two steps : -a study of primary and secondary order with the help of BETA matrix code -a study of superior orders with the help of ZGOUBI code which is able to take into consideration the measured fields and in which the movement equations are integrated numerically. (O.L.). 9 figs., 3 tabs

  6. Insomnia (primary) in older people

    OpenAIRE

    Alessi, Cathy; Vitiello, Michael V

    2011-01-01

    Up to 40% of older adults have insomnia, with difficulty getting to sleep, early waking, or feeling unrefreshed on waking. The prevalence of insomnia increases with age. Other risk factors include medical and psychiatric illnesses, psychological factors, stress, daytime napping, and hyperarousal.Primary insomnia is a chronic and relapsing condition that may increase the risks of accidents.Primary insomnia is chronic insomnia without specific underlying medical, psychiatric, or other sleep ...

  7. Hyperuricemia in Childhood Primary Hypertension

    OpenAIRE

    Feig, Daniel I.; Johnson, Richard J.

    2003-01-01

    Experimental animal models suggest that uric acid might have a pathogenic role in the early development of primary hypertension. We hypothesized that serum uric acid is correlated with blood pressure in children with new-onset, untreated, primary hypertension. We evaluated 125 consecutive children referred to the Baylor Pediatric Renal Program for evaluation of hypertension. None of the subjects had previously been evaluated or treated for hypertension. The children ranged in age from 6 to 18...

  8. Glucocorticosteroids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Giljaca, Vanja; Poropat, Goran; Stimac, Davor

    2010-01-01

    Primary sclerosing cholangitis is a chronic cholestatic disease of intrahepatic and extrahepatic biliary ducts, characterised by chronic periductal inflammation and sclerosis of the ducts, which results in segmental stenoses of bile ducts, cholestasis, fibrosis, and ultimately, liver cirrhosis...... sclerosing cholangitis, like ursodeoxycholic acid, glucocorticosteroids, and immunomodulatory agents, but none has been successful in reversing the process of the disease. To date, liver transplantation is the only definite therapeutic solution for patients with advanced primary sclerosing cholangitis...

  9. Primary system boron dilution analysis

    International Nuclear Information System (INIS)

    Crump, R.J.; Naretto, C.J.; Borgen, R.A.; Rockhold, H.C.

    1978-01-01

    The results are presented for an analysis conducted to determine the potential paths through which nonborated water or water with insufficient boron concentration might enter the LOFT primary coolant piping system or reactor vessel to cause dilution of the borated primary coolant water. No attempt was made in the course of this analysis to identify possible design modifications nor to suggest changes in administrative procedures or controls

  10. Ege bölgesi standart süreli yıllık maksimum yağışları için en uygun dağılımlar

    Directory of Open Access Journals (Sweden)

    Halil Karahan

    2013-03-01

    Full Text Available Su kaynaklarının temel girdisi olan yağışların; miktarı, süresi, şiddeti, alansal ve zamansal değişimi v.b. özelliklerinin bilinmesi; su kaynakları, tarım, kentleşme, drenaj, taşkın kontrolü ve ulaşım gibi farklı sektörlere ait planlama, tasarım, inşaat ve işletme çalışmaları için gereklidir. Belirtilen faaliyetlerin gerçekleştirilebilmesi için; mevcut gözlemlere dayalı, güvenilir ve gerçekçi tahminlerin yapılması gerekir. Güvenilir tahmin yapabilmenin ilk aşaması ise mevcut gözlemlerin güvenirliğinin test edilmesidir. Bu çalışmada; DMİ Genel Müdürlüğü tarafından işletilen Ege Bölgesi il ve ilçe merkezlerinde yer alan meteoroloji istasyonlarında (1929-2005 yıllarında ölçülen standart süreli maksimum yağış değerlerinin hangi dağılıma uyduklarını belirlemek için; Kolmogorov-Smirnov, Anderson-Darling ve Ki-Kare dağılım uygunluk testleri uygulanmıştır. Anderson-Darling testine göre gözlemlerin tümüne yakını GEV dağılımına uyum gösterirken, Kolmogorov-Smirnov ve Ki-Kare testlerine göre kısa, orta ve uzun süreli yağış gözlemleri için genellikle GEV, Gamma ve Log-Normal dağılımın uygun olduğu görülmüştür. Seçilen olasılık dağılımının parametrelerini belirlemek için farklı dağılımlara göre maksimum olabilirlik (LN2, LN3, EXP2, Gamma3, olasılık-ağırlıklı momentler (LP3,Gamma2, L-momentler (GEV ve en küçük kareler (Weibull2 yöntemleri kullanılmıştır.

  11. Gender equality in primary immunisation

    Directory of Open Access Journals (Sweden)

    Deepak S Khismatrao

    2015-01-01

    Full Text Available Context: Immunization, a well-known and effective method of preventing childhood illnesses is basic service under primary health care. Most surveys in India measure primary immunization coverage and quality, but no "Gender Equality." Aims: Assess "Gender Equality" in primary immunization with reference to coverage, quality, and place of immunization. Settings and Design: Cross-sectional survey in a primary health center, Pune, Maharashtra using World Health Organization 30-cluster sampling method with 14 beneficiaries (7 girls and 7 boys to be selected from each cluster. Instead of 420 children, data collected for 345 children, as requisite numbers of children were not available in low population villages and also children whose mothers were not present during survey were excluded. Materials and Methods: Vaccination data collected from either records and/or history by mother. Children born on or between 13-09-2009 and 13-09-2010, were included. Statistical Analysis Used: SPSS 14.01 version with Chi-square as test of significance. Results: Of the study population, 171 (49.6% were females and 174 (50.4% males. A total of 64.1% children had immunization records with female proportion 69.0% and males 59.2%. Primary immunization coverage was 80.0%, with female proportion 82.5% and males 77.6%. One male child was completely unimmunized and remaining partially immunized, with unaware of schedule and illness of child being major reasons for partial immunization. There was no gender wise statistically significant difference observed in Primary Immunization with reference to coverage, quality, and place of immunization. Conclusions: Immunization coverage is nearing 85% benchmark with major contribution from Universal Immunization Program. Gender Equality observed in primary immunization. Preservation of immunization records by community and timely vaccinations are areas for improvement.

  12. CO_2 emission trends of China's primary aluminum industry: A scenario analysis using system dynamics model

    International Nuclear Information System (INIS)

    Li, Qiang; Zhang, Wenjuan; Li, Huiquan; He, Peng

    2017-01-01

    China announced its promise on CO_2 emission peak. When and what level of CO_2 emission peak China's primary aluminum industry will reach is in suspense. In this paper, a system dynamic model is established, with five subsystems of economy development, primary aluminum production, secondary aluminum production, CO_2 emission intensity and policies making involved. The model is applied to examine potential CO_2 emission trends of China's primary aluminum industry in next fifteen years with three scenarios of “no new policies”, “13th five-year plan” and “additional policies”. Simulation results imply that: merely relying on rapid expansion of domestic scarps recycling and reuse could not mitigate CO_2 emission continuously. Combination of energy-saving technology application and electrolytic technology innovation, as well as promoting hydropower utilization in primary aluminum industry are necessary for long term low-carbon development. From a global prospective, enhancing international cooperation on new primary aluminum capacity construction in other countries, especially with rich low-carbon energy, could bring about essential CO_2 emission for both China's and global primary aluminum industry. - Highlights: • A system dynamic model is established for future CO_2 emission trend of China's primary aluminum industry. • Three potential policy scenarios are simulated. • The impacts of potential policies implication on the CO_2 emission trend are discussed.

  13. Evaluation of Organic Proxies for Quantifying Past Primary Productivity

    Science.gov (United States)

    Raja, M.; Rosell-Melé, A.; Galbraith, E.

    2017-12-01

    Ocean primary productivity is a key element of the marine carbon cycle. However, its quantitative reconstruction in the past relies on the use of biogeochemical models as the available proxy approaches are qualitative at best. Here, we present an approach that evaluates the use of phytoplanktonic biomarkers (i.e. chlorins and alkenones) as quantitative proxies to reconstruct past changes in marine productivity. We compare biomarkers contents in a global suite of core-top sediments to sea-surface chlorophyll-a abundance estimated by satellites over the last 20 years, and the results are compared to total organic carbon (TOC). We also assess satellite data and detect satellite limitations and biases due to the complexity of optical properties and the actual defined algorithms. Our findings show that sedimentary chlorins can be used to track total sea-surface chlorophyll-a abundance as an indicator for past primary productivity. However, degradation processes restrict the application of this proxy to concentrations below a threshold value (1µg/g). Below this threshold, chlorins are a useful tool to identify reducing conditions when used as part of a multiproxy approach to assess redox sedimentary conditions (e.g. using Re, U). This is based on the link between anoxic/disoxic conditions and the flux of organic matter from the sea-surface to the sediments. We also show that TOC is less accurate than chlorins for estimating sea-surface chlorophyll-a due to the contribution of terrigenous organic matter, and the different degradation pathways of all organic compounds that TOC includes. Alkenones concentration also relates to primary productivity, but they are constrained by different processes in different regions. In conclusion, as lons as specific constraints are taken into account, our study evaluates the use of chlorins and alkenones as quantitative proxies of past primary productivity, with more accuracy than by using TOC.

  14. Primary Headache in Yemen: Prevalence and Common Medications Used

    Directory of Open Access Journals (Sweden)

    Salah A. Abdo

    2014-01-01

    Full Text Available Background and Objective. Primary headaches is a major medical concern in certain Arabic countries, for example Oman, Jordan, and Qatar. This study was aimed at increasing understanding of the prevalence of headache in Arabic countries and identifying common medications used for treatment because of the lack of research done in this field in Yemen. Methods. This is a cross-sectional observational study conducted by recruiting case-series of adults and elderly who have primary headache within the age group from 18 to 85 years. 12640 subjects received a simple explanation for the aim of the study as ethical issue. The subjects were allowed to complete a self-conducted screening questionnaire. The data were diagnosed according to the International Headache Society’s diagnostic criteria (2004. Results. The results showed that 76.5% of the primary headache is prevalent at least once per year, 27.1% of the tension type headache (TTH was the maximum percentage of type of headache, and 14.48% of the migraine headache (MH was the minimum percentage. On the other hand, the relationship between the primary headache and age of subjects was statistically significant (P0.05. In addition, 70.15% of the subjects said that headache attacks affected their activity of daily livings (ADL. 62.26% of the subjects used the medications without medical advice regarding their headache. 37.73% of the subjects relied on medical professionals (physicians and pharmacist regarding analgesics use. The most common agent used among the medications was paracetamol (38.4%. Others included ibuprofen, aspirin, diclofenac sodium, naproxen, mefenamic acid, ergotamine and (11.45% were unknown agents. Conclusion. We concluded that absence of health attention from the Yemeni Community and education from the health system in the country regarding analgesics use and their potential risk led to abuse of such medications and could be a reason beyond high prevalence of headache in Yemen.

  15. Cardiovascular Risk in Primary Hyperaldosteronism.

    Science.gov (United States)

    Prejbisz, A; Warchoł-Celińska, E; Lenders, J W M; Januszewicz, A

    2015-12-01

    After the first cases of primary aldosteronism were described and characterized by Conn, a substantial body of experimental and clinical evidence about the long-term effects of excess aldosterone on the cardiovascular system was gathered over the last 5 decades. The prevalence of primary aldosteronism varies considerably between different studies among hypertensive patients, depending on patient selection, the used diagnostic methods, and the severity of hypertension. Prevalence rates vary from 4.6 to 16.6% in those studies in which confirmatory tests to diagnose primary aldosteronism were used. There is also growing evidence indicating that prolonged exposure to elevated aldosterone concentrations is associated with target organ damage in the heart, kidney, and arterial wall, and high cardiovascular risk in patients with primary aldosteronism. Therefore, the aim of treatment should not be confined to BP normalization and hypokalemia correction, but rather should focus on restoring the deleterious effects of excess aldosterone on the cardiovascular system. Current evidence convincingly demonstrates that both surgical and medical treatment strategies beneficially affect cardiovascular outcomes and mortality in the long term. Further studies can be expected to provide better insight into the relationship between cardiovascular risk and complications and the genetic background of primary aldosteronism. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Haber Üretiminde Göreli Özerklik Problemi: Bir Saha Araştırması / The Relative Autonomy Problem in Newsmaking Process: A Field Research

    Directory of Open Access Journals (Sweden)

    Deniz Tansel İLİC

    2014-09-01

    Full Text Available Kültürel simgelerin üretim sürecinde görev yapan enformasyon işçilerinin özerkliği, sosyal bilimler açısından önemli bir tartışma konusudur. Üretim sürecini sadece sahiplik üzerinden değerlendiren yaklaşımlar, mülkiyet ilişkilerinin, simge üreticisinin özerklik alanını tamamen kısıtlayacağını savunurlar. Yine de, zihinsel emekleri ile çalışan simge üreticilerinin, belli oranda özerkliğe sahip olduğu iddiası sınamaya değerdir. Bu çalışmada, David Hesmondhalgh ve Mike Wayne’deki göreli özerklik vurgusundan yola çıkarak, Türkiye’de anaakım televizyon haberciliğinde bir saha araştırması yapılmıştır. Fox TV, TGRT Haber ve Kanal D’de gerçekleştirilen katılımlı gözlemlerle, birer simge üreticisi olan habercilerin, hangi oranda özerk oldukları saptanmaya çalışılmıştır. / The autonomy of information workers who work in the production process of cultural symbols is an important issue for social sciences. The approaches that evaluate the production process only in the context of ownership claim that these relationships will restrain the autonomy field of the symbol producer. Still the suggestion that symbol producers who work with their mental labours have a certain amount of autonomy is worth testing. In this study a field research is conducted in mainstream broadcasting in Turkey by using the relative autonomy emphasis in David Hesmondhalgh and Mike Wayne as a starting point. In the participant observation that is conducted in Fox TV, TGRT Haber and Kanal D Televisions it is tried to determine at what level the journalists as symbol producers are autonomous.

  17. Early LC3 lipidation induced by d-limonene does not rely on mTOR inhibition, ERK activation and ROS production and it is associated with reduced clonogenic capacity of SH-SY5Y neuroblastoma cells.

    Science.gov (United States)

    Berliocchi, Laura; Chiappini, Carlotta; Adornetto, Annagrazia; Gentile, Debora; Cerri, Silvia; Russo, Rossella; Bagetta, Giacinto; Corasaniti, Maria Tiziana

    2018-02-01

    d-Limonene is a natural monoterpene abundant in Citrus essential oils. It is endowed with several biological activities, including inhibition of carcinogenesis and promotion of tumour regression. Recently, d-limonene has been shown to modulate autophagic markers in vitro at concentrations found in vivo, in clinical pharmacokinetic studies. Autophagy is an intracellular catabolic process serving as both an adaptive metabolic response and a quality control mechanism. Because autophagy defects have been linked to a wide range of human pathologies, including neurodegeneration and cancer, there is a need for new pharmacological tools to control deregulated autophagy. To better understand the effects of d-limonene on autophagy, to identify the molecular mechanisms through which this monoterpene rapidly triggers LC3 lipidation and to evaluate the role for autophagy in long-term effects of d-limonene. Human SH-SY5Y neuroblastoma, HepG2 hepatocellular carcinoma and MCF7 breast cancer cells were used. Endogenous LC3-II levels were evaluated by western blotting. Autophagic flux assay was performed using bafilomycin A1 and chloroquine. Intracellular distribution of LC3 protein was studied by confocal microscopy analysis of LC3B-GFP transduced cells. Expression of lysosomal-membrane protein LAMP-1 was assessed by immunofluorescence analysis. Phosphorylated levels of downstream substrates of mTOR kinase (p70S6 kinase, 4E-BP1, and ULK1) and ERK were analyzed by western blotting. Production of reactive oxygen species (ROS) was assessed by live confocal microscopy of cells loaded with CellROX ® Green Reagent. Clonogenic assay was used to evaluate the ability of treated cells to proliferate and form colonies. LC3 lipidation promoted by d-limonene correlates with autophagosome formation and stimulation of basal autophagy. LC3 lipidation does not rely on inhibition of mTOR kinase, which instead appears to be transiently activated. In addition, d-limonene rapidly activates ERK and

  18. A case of "order insensitivity"? Natural and artificial language processing in a man with primary progressive aphasia.

    OpenAIRE

    Zimmerer, V. C.; Varley, R. A.

    2015-01-01

    Processing of linear word order (linear configuration) is important for virtually all languages and essential to languages such as English which have little functional morphology. Damage to systems underpinning configurational processing may specifically affect word-order reliant sentence structures. We explore order processing in WR, a man with primary progressive aphasia (PPA). In a previous report, we showed how WR showed impaired processing of actives, which rely strongly on word order, b...

  19. Primary malignant small bowel tumor

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk [Kosin College, Pusan (Korea, Republic of)

    1990-07-15

    Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings.

  20. Primary malignant small bowel tumor

    International Nuclear Information System (INIS)

    Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk

    1990-01-01

    Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings