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Sample records for adam melhem alishia

  1. What's an Adam's Apple?

    MedlinePlus

    ... Help White House Lunch Recipes What's an Adam's Apple? KidsHealth > For Kids > What's an Adam's Apple? Print A A A Text Size You're ... the throat. This is what's called an Adam's apple. Everyone's larynx grows during puberty, but a girl's ...

  2. The ADAMS interactive interpreter

    SciTech Connect

    Rietscha, E.R.

    1990-12-17

    The ADAMS (Advanced DAta Management System) project is exploring next generation database technology. Database management does not follow the usual programming paradigm. Instead, the database dictionary provides an additional name space environment that should be interactively created and tested before writing application code. This document describes the implementation and operation of the ADAMS Interpreter, an interactive interface to the ADAMS data dictionary and runtime system. The Interpreter executes individual statements of the ADAMS Interface Language, providing a fast, interactive mechanism to define and access persistent databases. 5 refs.

  3. Ansel Adams: early works

    NASA Astrophysics Data System (ADS)

    Throckmorton, Jodi

    2010-02-01

    Ansel Adams (1902-1984), photographer, musician, naturalist, explorer, critic, and teacher, was a giant in the field of landscape photography. In his images of the unspoiled Western landscape, he strove to capture the sublime: the transcendentalist concept that nature can generate the experience of awe for the viewer. Many viewers are familiar with the heroic, high-contrast prints on high-gloss paper that Adams made to order beginning in the 1970s; much less well known are the intimate prints that the artist crafted earlier in his career. This exhibition focuses on these masterful small prints from the 1920s into the 1950s. During this time period, Adams's printing style changed dramatically. The painterly, soft-focus, warm-toned style of the Parmelian Prints of the High Sierras from the 1920s evolved into the sharp-focus style of the f/64 school of photography that Adams co-founded in the 1930s with Edward Weston and Imogen Cunningham. After World War II, Adams opted for a cooler, higher-contrast look for his prints. Throughout the various styles in which he chose to work, Adams explored the power of nature and succeeded in establishing landscape photography as a legitimate form of modern art.

  4. Was Adam a Real Person?

    ERIC Educational Resources Information Center

    Lamoureux, Denis O.

    2011-01-01

    Belief in the historicity of Adam has been held firmly throughout the history of the church. In the light of modern biblical criticism and the evolutionary sciences, some conservative Christians are now questioning whether or not Adam was a real person. This paper argues that the existence of Adam in the opening chapters of scripture reflects an…

  5. All about Adam.

    ERIC Educational Resources Information Center

    Bradley, Ann

    1992-01-01

    Rochester Teachers Association President Adam Urbanski is kingpin of a new breed of union leaders who want to be partners, not adversaries, in the school improvement crusade. Despite his good intentions, many people in his hometown are disgruntled with him. The article describes his work over the past five years. (SM)

  6. The Adams Family

    ERIC Educational Resources Information Center

    Douven, Igor; Verbrugge, Sara

    2010-01-01

    According to Adams's Thesis, the acceptability of an indicative conditional sentence goes by the conditional probability of its consequent given its antecedent. We test, for the first time, whether this thesis is descriptively correct and show that it is not; in particular, we show that it yields the wrong predictions for people's judgments of the…

  7. ADAM Proteases and Gastrointestinal Function.

    PubMed

    Jones, Jennifer C; Rustagi, Shelly; Dempsey, Peter J

    2016-01-01

    A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g., inflammation) and play a central role in coordinating intercellular communication within the local microenvironment. ADAM10 and ADAM17 are the most studied members of the ADAM family in the gastrointestinal tract. ADAMs regulate many cellular processes associated with intestinal development, cell fate specification, and the maintenance of intestinal stem cell/progenitor populations. Several signaling pathway molecules that undergo ectodomain shedding by ADAMs [e.g., ligands and receptors from epidermal growth factor receptor (EGFR)/ErbB and tumor necrosis factor α (TNFα) receptor (TNFR) families] help drive and control intestinal inflammation and injury/repair responses. Dysregulation of these processes through aberrant ADAM expression or sustained ADAM activity is linked to chronic inflammation, inflammation-associated cancer, and tumorigenesis. PMID:26667078

  8. ADAM Proteases and Gastrointestinal Function

    PubMed Central

    Jones, Jennifer C.; Rustagi, Shelly; Dempsey, Peter J.

    2016-01-01

    A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g., inflammation) and play a central role in coordinating intercellular communication within the local microenvironment. ADAM10 and ADAM17 are the most studied members of the ADAM family in the gastrointestinal tract. ADAMs regulate many cellular processes associated with intestinal development, cell fate specification, and the maintenance of intestinal stem cell/progenitor populations. Several signaling pathway molecules that undergo ectodomain shedding by ADAMs [e.g., ligands and receptors from epidermal growth factor receptor (EGFR)/ErbB and tumor necrosis factor α (TNFα) receptor (TNFR) families] help drive and control intestinal inflammation and injury/repair responses. Dysregulation of these processes through aberrant ADAM expression or sustained ADAM activity is linked to chronic inflammation, inflammation-associated cancer, and tumorigenesis. PMID:26667078

  9. New Mathematical Dimensions: Adam's Story

    ERIC Educational Resources Information Center

    Manizade, Agida

    2009-01-01

    Adam, an 11th grader, was identified as gifted and accepted into a two week summer enrichment program. He signed up for "Geometry with Flash Programming." He had no prior programming experience but had a strong and healthy self-image as mathematics student. Although Adam had a positive attitude toward mathematics and saw himself as a successful…

  10. Evolution of Vertebrate Adam Genes; Duplication of Testicular Adams from Ancient Adam9/9-like Loci

    PubMed Central

    Wei, Shuo

    2015-01-01

    Members of the disintegrin metalloproteinase (ADAM) family have important functions in regulating cell-cell and cell-matrix interactions as well as cell signaling. There are two major types of ADAMs: the somatic ADAMs (sADAMs) that have a significant presence in somatic tissues, and the testicular ADAMs (tADAMs) that are expressed predominantly in the testis. Genes encoding tADAMs can be further divided into two groups: group I (intronless) and group II (intron-containing). To date, tAdams have only been reported in placental mammals, and their evolutionary origin and relationship to sAdams remain largely unknown. Using phylogenetic and syntenic tools, we analyzed the Adam genes in various vertebrates ranging from fishes to placental mammals. Our analyses reveal duplication and loss of some sAdams in certain vertebrate species. In particular, there exists an Adam9-like gene in non-mammalian vertebrates but not mammals. We also identified putative group I and group II tAdams in all amniote species that have been examined. These tAdam homologues are more closely related to Adams 9 and 9-like than to other sAdams. In all amniote species examined, group II tAdams lie in close vicinity to Adam9 and hence likely arose from tandem duplication, whereas group I tAdams likely originated through retroposition because of their lack of introns. Clusters of multiple group I tAdams are also common, suggesting tandem duplication after retroposition. Therefore, Adam9/9-like and some of the derived tAdam loci are likely preferred targets for tandem duplication and/or retroposition. Consistent with this hypothesis, we identified a young retroposed gene that duplicated recently from Adam9 in the opossum. As a result of gene duplication, some tAdams were pseudogenized in certain species, whereas others acquired new expression patterns and functions. The rapid duplication of Adam genes has a major contribution to the diversity of ADAMs in various vertebrate species. PMID:26308360

  11. Adam Smith and dependency.

    PubMed

    Ozler, Sule

    2012-06-01

    The focus of this paper is the works and life of Adam Smith, who is widely recognized as the father and founder of contemporary economics. Latent content analysis is applied to his seminal text in economics, An Inquiry into the Nature and Causes of the Wealth of Nations (1776). The results reveal that Smith considers dependence on others a problem and sees the solution to this problem in impersonalized interdependence. In addition, his views on social dependency and personal dependency, reflected in his Lectures on Jurisprudence (1963) and The Theory of Moral Sentiments (1759), are analyzed. This analysis suggests a central tension between dependence and independence in Smith's writings. The personal dependency patterns he exhibited in his life, which also suggest a tension between dependence and independence, are identified through a reading of his biographies. Based on insights from psychoanalytic literature, this paper proposes that developing the ideas in the Wealth of Nations was part of Smith's creative solution to this tension. In particular, his solution to one individual's dependence on another was through a system of impersonalized interdependence. In other words, Smith defended against his personal dependence through his economic theorizing. PMID:22712591

  12. The ADAM environment and transputers

    NASA Technical Reports Server (NTRS)

    Kelly, B. D.; Stewart, J. M.; Mcnally, B. V.

    1992-01-01

    The ADAM environment is both used for data analysis by Starlink and for data acquisition by the UK-involved observatories in Australia, Hawaii, and the Canary Islands. ADAM was originally hosted under VAX/VMS but is now at an advanced stage of a Unix port. ADAM comprises a parameter system, hierarchical data system, noticeboard system, error handling system, and other components. Originally a multi-tasking single processor environment, it has been enhanced to a multiprocessor environment using local or wide area networking. The Royal Observatory Edinburgh is producing a transputer version of the ADAM kernel to allow instruments which make use of transputers for data acquisition/control to integrate more closely with the ADAM software running at the telescopes. Communication into the transputer system is based on Ethernet carrying TCP/IP, which eases development toward a network of mixed VMS/Unix/transputer Telescope systems. The transputer system is being applied to instruments under development for the UKIRT and JCMT telescopes.

  13. Franklin-Adams, John (1843-1912)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    English businessman and amateur astronomer; compiled the Franklin-Adams Photographic Atlas of Star Positions (1913). The Franklin-Adams camera was a 25 cm aperture, 10 degree field telescope, later re-erected in Johannesburg....

  14. Children's Literature. Adams State College.

    ERIC Educational Resources Information Center

    Myers, Susan L.

    This is one of a series of eight Teacher Education Modules developed by Adams State College Teacher Corps Program. The dual purpose of these modules is stated as follows: trying to understand children and their needs and becoming familiar with and developing criteria for evaluating children's literature. The objectives of the modules, which are…

  15. John Couch Adams, the astronomer.

    NASA Astrophysics Data System (ADS)

    Foster, N.

    1989-03-01

    The planet Neptune was discovered more than 140 years ago. The circumstances of the discovery gave rise to great controversy, and very nearly led to an international incident between Britain and France, but this was only one of John Couch Adams' many contributions to astronomical science.

  16. ADAMS: AIRLAB data management system user's guide

    NASA Technical Reports Server (NTRS)

    Conrad, C. L.; Ingogly, W. F.; Lauterbach, L. A.

    1986-01-01

    The AIRLAB Data Management System (ADAMS) is an online environment that supports research at NASA's AIRLAB. ADAMS provides an easy to use interactive interface that eases the task of documenting and managing information about experiments and improves communication among project members. Data managed by ADAMS includes information about experiments, data sets produced, software and hardware available in AIRLAB as well as that used in a particular experiment, and an on-line engineer's notebook. The User's Guide provides an overview of the ADAMS system as well as details of the operations available within ADAMS. A tutorial section takes the user step-by-step through a typical ADAMS session. ADAMS runs under the VAX/VMS operating system and uses the ORACLE database management system and DEC/FMS (the Forms Management System). ADAMS can be run from any VAX connected via DECnet to the ORACLE host VAX. The ADAMS system is designed for simplicity, so interactions within the underlying data management system and communications network are hidden from the user.

  17. Adam receives Fred Whipple Award

    NASA Astrophysics Data System (ADS)

    McCord, Thomas B.; Adams, John B.

    John B. Adams was presented with the Fred Whipple Award at the AGU Fall Meeting in December in San Francisco, California. The award, established in 1989 by the Planetary Sciences Section, is presented to an individual who makes an outstanding contribution to the field of planetary science.In the beginning, scientists including Galileo studied the solar system by staring through a tube with glass elements called a telescope. This panchromatic instrument demonstrated existence and motion of objects and revealed features such as craters and clouds. However, it required approximately another 400 years to develop the physics and technology necessary to determine remotely the composition of these objects.

  18. Asteroid shape modelling with ADAM

    NASA Astrophysics Data System (ADS)

    Viikinkoski, Matti; Kaasalainen, Mikko; Durech, Josef

    2015-08-01

    Technological advancements have made it possible to obtain highly detailed images of asteroids, yet 3-D shape reconstruction remains a challenge. Shape inversion is an ill-posed inverse problem as systematic errors, shadowing effects due to non-convex features, and the limitations of the imaging systems render the direct inversion impossible. Moreover, the coverage of one observation session alone is seldom sufficient for 3-D reconstruction, necessitating a method for the integration of widely different, complementary data sources into a coherent shape solution.We present a new 3-D shape reconstruction method for asteroid models. ADAM, an acronym for all-data asteroid modelling, is a general procedure for combining disk-resolved observational data into a shape model. ADAM handles all disk-resolved data in a uniform manner via 2-D Fourier Transform. Almost all disk-resolved data sources are supported: adaptive optics and other images, range-Doppler radar data, and thermal infrared interferometry.As case studies, we examine the shape of (41) Daphne using the adaptive optics images and photometry, and create a model of the asteroid 2000 ET70 from the range-Doppler radar images. Finally, we combine ALMA science verification data, adaptive optics images, occultations, and lightcurve data to study the shape of the large main-belt asteroid (3) Juno.

  19. Marguerite Arnet Residence, exterior window detail, looking north. Adam ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Marguerite Arnet Residence, exterior window detail, looking north. - Adam & Bessie Arnet Homestead, Marguerite Arnet Residence, 560 feet northeast of Adam & Bessie Arnet Residence, Model, Las Animas County, CO

  20. Marguerite Arnet Residence, exterior door detail, looking north. Adam ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Marguerite Arnet Residence, exterior door detail, looking north. - Adam & Bessie Arnet Homestead, Marguerite Arnet Residence, 560 feet northeast of Adam & Bessie Arnet Residence, Model, Las Animas County, CO

  1. Cleavage Site Localization Differentially Controls Interleukin-6 Receptor Proteolysis by ADAM10 and ADAM17

    PubMed Central

    Riethmueller, Steffen; Ehlers, Johanna C.; Lokau, Juliane; Düsterhöft, Stefan; Knittler, Katharina; Dombrowsky, Gregor; Grötzinger, Joachim; Rabe, Björn; Rose-John, Stefan; Garbers, Christoph

    2016-01-01

    Limited proteolysis of the Interleukin-6 Receptor (IL-6R) leads to the release of the IL-6R ectodomain. Binding of the cytokine IL-6 to the soluble IL-6R (sIL-6R) results in an agonistic IL-6/sIL-6R complex, which activates cells via gp130 irrespective of whether the cells express the IL-6R itself. This signaling pathway has been termed trans-signaling and is thought to mainly account for the pro-inflammatory properties of IL-6. A Disintegrin And Metalloprotease 10 (ADAM10) and ADAM17 are the major proteases that cleave the IL-6R. We have previously shown that deletion of a ten amino acid long stretch within the stalk region including the cleavage site prevents ADAM17-mediated cleavage, whereas the receptor retained its full biological activity. In the present study, we show that deletion of a triple serine (3S) motif (Ser-359 to Ser-361) adjacent to the cleavage site is sufficient to prevent IL-6R cleavage by ADAM17, but not ADAM10. We find that the impaired shedding is caused by the reduced distance between the cleavage site and the plasma membrane. Positioning of the cleavage site in greater distance towards the plasma membrane abrogates ADAM17-mediated shedding and reveals a novel cleavage site of ADAM10. Our findings underline functional differences in IL-6R proteolysis by ADAM10 and ADAM17. PMID:27151651

  2. John Quincy Adams's rhetorical crusade for astronomy.

    PubMed

    Portolano, M

    2000-09-01

    Astronomy thrived in Europe during the early nineteenth century, but in the United States a utilitarian mind-set opposed it. John Quincy Adams's oratory in support of American astronomical discovery reached its peak during congressional debate over the Smithsonian Institution (1838-1846). During this debate Adams countered proposals to found a university with plans for an observatory. His addresses to congressional and public audiences about observatories and astronomy were intended to foster interest in the science and encourage the growing astronomical community in America. Although the U.S. Naval Observatory in Washington, D.C., was established before the Smithsonian debate ended, many considered Adams its political father. Adams composed his speeches on astronomy in a systematic manner, following neoclassical principles of rhetoric that he had taught at Harvard University. His speeches both in and outside of Congress show evidence of the rhetorical principles he conscientiously used in the service of astronomy. PMID:11143785

  3. A Conversation with Adam Heller.

    PubMed

    Heller, Adam; Cairns, Elton J

    2015-01-01

    Adam Heller, Ernest Cockrell Sr. Chair in Engineering Emeritus of the John J. McKetta Department of Chemical Engineering at The University of Texas at Austin, recalls his childhood in the Holocaust and his contributions to science and technology that earned him the US National Medal of Technology and Innovation in a conversation with Elton J. Cairns, Professor of Chemical and Biomolecular Engineering at the University of California, Berkeley. Dr. Heller, born in 1933, describes the enslavement of his father by Hungarians in 1942; the confiscation of his family's home, business, and all its belongings in 1944; and his incarceration in a brick factory with 18,000 Jews who were shipped by the Hungarians to be gassed by Germans in Auschwitz. Dr. Heller and his immediate family survived the Holocaust and arrived in Israel in 1945. He studied under Ernst David Bergmann at the Hebrew University, and then worked at Bell Laboratories and GTE Laboratories, where he headed Bell Lab's Electronic Materials Research Department. At GTE Laboratories, he built in 1966 the first neodymium liquid lasers and in 1973 with Jim Auborn conceived and engineered the lithium thionyl chloride battery, one of the first to be manufactured lithium batteries, which is still in use. After joining the faculty of engineering of The University of Texas at Austin, he cofounded with his son Ephraim Heller TheraSense, now a major part of Abbott Diabetes Care, which produced a microcoulometer that made the monitoring of glucose painless by accurately measuring the blood glucose concentration in 300 nL of blood. He also describes the electrical wiring of enzymes, the basis for Abbott's state-of-the-art continuous glucose monitoring system. He discusses his perspective of reducing the risk of catastrophic global warming in a wealth-accumulating, more-energy-consuming world and provides advice for students entering careers in science or engineering. PMID:26247288

  4. ADAM: automated data management for research datasets

    PubMed Central

    Woodbridge, Mark; Tomlinson, Christopher D.; Butcher, Sarah A.

    2013-01-01

    Existing repositories for experimental datasets typically capture snapshots of data acquired using a single experimental technique and often require manual population and continual curation. We present a storage system for heterogeneous research data that performs dynamic automated indexing to provide powerful search, discovery and collaboration features without the restrictions of a structured repository. ADAM is able to index many commonly used file formats generated by laboratory assays and therefore offers specific advantages to the experimental biology community. However, it is not domain specific and can promote sharing and re-use of working data across scientific disciplines. Availability and implementation: ADAM is implemented using Java and supported on Linux. It is open source under the GNU General Public License v3.0. Installation instructions, binary code, a demo system and virtual machine image and are available at http://www.imperial.ac.uk/bioinfsupport/resources/software/adam. Contact: m.woodbridge@imperial.ac.uk PMID:23109181

  5. Women in History--Abigail Adams: Life, Accomplishments, and Ideas

    ERIC Educational Resources Information Center

    Kenan, Sharon K.

    2008-01-01

    This article profiles the life, accomplishments, and ideas of Abigail Adams. Born in 1944, Adams lacked a formal education, but she more than made up for that shortcoming with her love of reading, especially literature, and her interests in politics and events surrounding the young colonies. Adams was supportive of the advancement of women. She…

  6. Adam Smith and the Rhetoric of Style.

    ERIC Educational Resources Information Center

    Moran, Michael G.

    Historians of rhetoric have generally accepted the view that Adam Smith rejected the principles of classical rhetoric. However, while there can be no doubt that Smith greatly truncated the five classical arts of rhetoric (invention, arrangement, style, memory, and delivery) by reducing his concerns largely to style and arrangement, he did not…

  7. Adam Smith, Religion, and Tuition Tax Credits.

    ERIC Educational Resources Information Center

    Alexander, Kern

    1983-01-01

    Examines tuition tax credit programs in framework of Adam Smith's ideas on the economic impact of established churches. Finds that tuition tax credits would amount to state expenditures to relieve the financial burden of parochial school parents and would allow churches to invest commercially to maintain their charitable functions. (JW)

  8. Paraprofessional of the Year 2009: Tina Adams

    ERIC Educational Resources Information Center

    Berry, John N., III

    2009-01-01

    There is no doubt among the staff and managers at North Carolina State University (NCSU) Libraries, Raleigh, that advanced library technician Tina Adams deserves to be the winner of the "Library Journal's "Paraprofessional of the Year Award for 2009." "Certainly this library has never seen anyone like her before, not in my nine years on staff,"…

  9. ADAM "sequence" part II: hypothesis and speculation.

    PubMed

    Opitz, John M; Johnson, Dennis R; Gilbert-Barness, Enid F

    2015-03-01

    Noted for centuries in humans, a relatively hairless mammal [e.g., Hallero, 1766; Hohl, 1828 in Klunker, 2003], the so-called amniotic deformities, adhesions, mutilations (ADAM) sequence remains causally and pathogenetically incognito. In 1930 Streeter stated " apodictically" that no evidence has been found that intra-uterine amputation is due to amniotic bands or adhesions …" and that his 16 cases provided (histological) evidence for a "germinal origin." He concluded that an amniotic cord was "not an adhesion or inflammatory product but … an anomalous developmental structure and present from the outset." In survivors the "traces" of damaged limb-buds "reveal the scars of poor germ-plasm." In 1958, Willis, in dismissing the amniotic origin of the ADAM defects (or "Streeter" or "Simonart" bands) quoted Keith [1940] to the effect that "(a)mniotic adhesions … are always produced by … the fetus – as a result of dysplasia in foetal tissues. They are the result, not the cause, of foetal malformations." Streeter [1930] mentions a potential familial case (56-year-old man and his mother), not controlled by photographs or other records and concluded "that the (ADAM) deformity is not easily transmissible," but "due to the constitution of the germ-plasm." Torpin [1968] concluded, as apodictically as Streeter and Willis, that "… proof of amnion rupture without damage to the chorionic sac is no longer "in question." Considering Torpin's decades-long study of the ADAM phenomenon and review of 494 references (missing many) it is surprising that he does not discuss the relationship between the apparent ADAM defects and other, internal anomalies that maybe present in an affected fetus or infant not evidently caused by the amniotic disruptions, adhesions or mutilations, unless his mind was made up. Our review of these internal and other presumed primary malformations in ADAM is ongoing. However, on a preliminary basis, it seems likely to us that: (1) there is an increased

  10. Illnesses of the brain in John Quincy Adams.

    PubMed

    Paulson, George

    2004-12-01

    John Quincy Adams, the sixth and perhaps most scholarly American president, served courageously despite familial essential tremor, depression, and cerebrovascular disease. His cousin Samuel Adams and his father John Adams also had essential tremor, which the later called "quiveration". Alcoholism and depression affected several members of J.Q. Adams's family. Following his own time as president, J.Q. Adams returned to duty as the congressman who most assiduously fought slavery, a fight he continued even after he had suffered a major left hemispheric stroke. His fatal collapse in Congress, protesting the Mexican War, is legendary among the final illnesses of American statesmen. PMID:15545105

  11. ADAM: An Axisymmetric Duct Aeroacoustic Modeling system

    NASA Astrophysics Data System (ADS)

    Abrahamson, A. L.

    1983-01-01

    An interconnected system of computer programs for analyzing the propagation and attenuation of sound in aeroengine ducts containing realistic compressible subsonic mean flows, ADAM was developed primarily for research directed towards the reduction of noise emitted from turbofan aircraft engines. The two basic components are a streamtube curvature program for determination of the mean flow, and a finite element code for solution of the acoustic propagation problem. The system, which has been specifically tailored for ease of use, is presently installed at NASA Langley Reseach Center on a Control Data Cyber 175 Computer under the NOS Operating system employing a Tektronix terminal for interactive graphics. The scope and organization of the ADAM system is described. A users guide, examples of input data, and results for selected cases are included.

  12. Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain

    NASA Astrophysics Data System (ADS)

    Miller, Miles A.; Moss, Marcia L.; Powell, Gary; Petrovich, Robert; Edwards, Lori; Meyer, Aaron S.; Griffith, Linda G.; Lauffenburger, Douglas A.

    2015-10-01

    Dysregulation of ErbB-family signaling underlies numerous pathologies and has been therapeutically targeted through inhibiting ErbB-receptors themselves or their cognate ligands. For the latter, “decoy” antibodies have been developed to sequester ligands including heparin-binding epidermal growth factor (HB-EGF); however, demonstrating sufficient efficacy has been difficult. Here, we hypothesized that this strategy depends on properties such as ligand-receptor binding affinity, which varies widely across the known ErbB-family ligands. Guided by computational modeling, we found that high-affinity ligands such as HB-EGF are more difficult to target with decoy antibodies compared to low-affinity ligands such as amphiregulin (AREG). To address this issue, we developed an alternative method for inhibiting HB-EGF activity by targeting its cleavage from the cell surface. In a model of the invasive disease endometriosis, we identified A Disintegrin and Metalloproteinase 12 (ADAM12) as a protease implicated in HB-EGF shedding. We designed a specific inhibitor of ADAM12 based on its recombinant prodomain (PA12), which selectively inhibits ADAM12 but not ADAM10 or ADAM17. In endometriotic cells, PA12 significantly reduced HB-EGF shedding and resultant cellular migration. Overall, specific inhibition of ligand shedding represents a possible alternative to decoy antibodies, especially for ligands such as HB-EGF that exhibit high binding affinity and localized signaling.

  13. Iterative Mechanism Solutions with Scenario and ADAMS

    NASA Technical Reports Server (NTRS)

    Rhoades, Daren

    2006-01-01

    This slide presentation reviews the use of iterative solutions using Scenario for Motion (UG NX 2 Motion) to assist in designing the Mars Science Laboratory (MSL). The MSL will have very unique design requirements, and in order to meet these requirements the system must have the ability to design for static stability, simulate mechanism kinematics, simulate dynamic behaviour and be capable of reconfiguration, and iterations as designed. The legacy process used on the Mars Exploration rovers worked, but it was cumbersome using multiple tools, limited configuration control, with manual process and communication, and multiple steps. The aim is to develop a mechanism that would reduce turn around time, and make more reiterations possible, to improve the quality and quantity of data, and to enhance configuration control. Currently for NX Scenario for Motion uses are in the articulation studies, the simulations of traverse motions,and subsystem simulations. The design of the Rover landing model requires accurate results, flexible elements, such as beams, and the use of the full ADAMS solver has been used. In order to achieve this, when required, there has been a direct translation from Scenario to ADAMS, with additional data in ascii format. The process that has been designed to move from Scenario to ADAMS is reviewed.

  14. Regional expression of ADAM19 during chicken embryonic development.

    PubMed

    Yan, Xin; Lin, Juntang; Markus, Annett; Rolfs, Arndt; Luo, Jiankai

    2011-04-01

    ADAM19 (also named meltrin β) is a member of the ADAM (a disintegrin and metalloprotease) family of metalloproteases and is involved in morphogenesis and tissue formation during embryonic development. In the present study, chicken ADAM19 is cloned by reverse transcription-polymerase chain reaction and identified by sequencing. Its expression patterns in different parts of the developing chicken embryo are investigated by Western blot analysis and immunohistochemistry. Results show that ADAM19 protein is widely expressed in chicken embryos. It is detectable in the central nervous system, including the brain, spinal cord, cochlea, and retina. Furthermore, ADAM19 protein is also found in other tissues and organs such as digestive organs, the thymus, the lung bud, the dorsal aorta, the kidney, the gonad, muscles, and in the feather buds. All these data suggest that ADAM19 plays an important role in the embryonic development of chicken. PMID:21492148

  15. From Adam Swift to Adam Smith: How the "Invisible Hand" Overcomes Middle Class Hypocrisy

    ERIC Educational Resources Information Center

    Tooley, James

    2007-01-01

    This paper challenges Richard Pring's suggestion that parents using private education may be undermining the desire for social justice and equality, using recent arguments of Adam Swift as a springboard. Swift's position on the banning of private schools, which uses a Rawlsian "veil of ignorance" argument, is explored, and it is suggested that, if…

  16. Connective tissue growth factor is a substrate of ADAM28

    SciTech Connect

    Mochizuki, Satsuki; Tanaka, Rena; Shimoda, Masayuki; Onuma, Junko; Fujii, Yutaka; Jinno, Hiromitsu; Okada, Yasunori

    2010-11-26

    Research highlights: {yields} The hyper-variable region in the cysteine-rich domain of ADAM28 binds to C-terminal domain of CTGF. {yields} ADAM28 cleaves CTGF alone and CTGF in the CTGF/VEGF{sub 165} complex. {yields} CTGF digestion by ADAM28 releases biologically active VEGF{sub 165} from the complex. {yields} ADAM28, CTGF and VEGF{sub 165} are commonly co-expressed by carcinoma cells in human breast carcinoma tissues. {yields} These suggest that ADAM28 promotes VEGF{sub 165}-induced angiogenesis in the breast carcinomas by selective CTGF digestion in the CTGF/VEGF{sub 165} complex. -- Abstract: ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinoma cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala{sup 181}-Tyr{sup 182} and Asp{sup 191}-Pro{sup 192} bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor{sub 165} (VEGF{sub 165}), releasing biologically active VEGF{sub 165} from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF{sub 165}-induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF{sub 165} complex.

  17. The Failed Educations of John Stuart Mill and Henry Adams.

    ERIC Educational Resources Information Center

    Crossley, Robert

    1979-01-01

    Analyzes and contrasts Mill's "Autobiography" and Adams'"The Education of Henry Adams" in order to present two approaches to the nature of education and of failure. Maintains that their perspectives may serve as catalysts and cautions for contemporary theories of education and its utility and relevance. (CAM)

  18. ADAM8 as a drug target in Pancreatic Cancer

    PubMed Central

    Schlomann, Uwe; Koller, Garrit; Conrad, Catharina; Ferdous, Taheera; Golfi, Panagiota; Garcia, Adolfo Molejon; Höfling, Sabrina; Parsons, Maddy; Costa, Patricia; Soper, Robin; Bossard, Maud; Hagemann, Thorsten; Roshani, Rozita; Sewald, Norbert; Ketchem, Randal R.; Moss, Marcia L.; Rasmussen, Fred H.; Miller, Miles A.; Lauffenburger, Douglas A.; Tuveson, David A.; Nimsky, Christopher; Bartsch, Jörg W.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a grim prognosis with less than 5% survivors after 5 years. High expression levels of ADAM8, a metalloprotease-disintegrin, are correlated with poor clinical outcome. We show that ADAM8 expression is associated with increased migration and invasiveness of PDAC cells caused by activation of ERK 1/2 and higher MMP activities. For biological function, ADAM8 requires multimerisation and associates with β1-integrin on the cell surface. A peptidomimetic ADAM8 inhibitor, BK-1361, designed by structural modelling of the disintegrin domain, prevents ADAM8 multimerisation. In PDAC cells, BK-1361 affects ADAM8 function leading to reduced invasiveness, and less ERK 1/2 and MMP activation. BK-1361 application in mice decreased tumour burden and metastasis of implanted pancreatic tumour cells and provides improved metrics of clinical symptoms and survival in a KrasG12D-driven mouse model of PDAC. Thus, our data integrate ADAM8 in pancreatic cancer signalling and validate ADAM8 as a target for PDAC therapy. PMID:25629724

  19. "Adam of the Road" by Elizabeth Janet Gray. Literature Unit.

    ERIC Educational Resources Information Center

    Robbins, Mari Lu

    Intended as an aid to classroom teachers, this 48-page handbook presents a literature unit based on the children's book, "Adam of the Road" by Elizabeth Janet Gray. It begins with sample lesson plans, pre-reading activities, author information, a book summary, and vocabulary lists and suggested vocabulary activities. Next, chapters of "Adam of the…

  20. ADAM8 in asthma. Friend or foe to airway inflammation?

    PubMed

    Chen, Jun; Jiang, Xuemei; Duan, Yiyuan; Long, Jiaoyue; Bartsch, Jörg W; Deng, Linhong

    2013-12-01

    Airway inflammation has been suggested as the pathological basis in asthma pathogenesis. Recruitment of leukocytes from the vasculature into airway sites is essential for induction of airway inflammation, a process thought to be mediated by a disintegrin and metalloprotease 8 (ADAM8). However, there is an apparent controversy about whether ADAM8 helps or hampers transmigration of leukocytes through endothelium in airway inflammation of asthma. This review outlines the current contradictory concepts concerning the role of ADAM8 in airway inflammation, particularly focusing on the recruitment of leukocytes during asthma, and attempts to bridge the existing experimental data on the basis of the functional analysis of different domains of ADAM8 and their endogenous processing in vivo. We suggest a possible hypothesis for the specific mechanism by which ADAM8 regulates the transmigration of leukocytes to explain the disparity existing in current studies, and we also raise some questions that require future investigations. PMID:23837412

  1. A Disintegrin and Metalloproteinase10 (ADAM10) Regulates NOTCH Signaling during Early Retinal Development

    PubMed Central

    Toonen, Joseph A.; Ronchetti, Adam; Sidjanin, D. J.

    2016-01-01

    ADAM10 and ADAM17 are two closely related members of the ADAM (a disintegrin and metalloprotease) family of membrane-bound sheddases, which proteolytically cleave surface membrane proteins. Both ADAM10 and ADAM17 have been implicated in the proteolytic cleavage of NOTCH receptors and as such regulators of NOTCH signaling. During retinal development, NOTCH signaling facilitates retinal neurogenesis by maintaining progenitor cells in a proliferative state and by mediating retinal cell fates. However, the roles of ADAM10 and ADAM17 in the retina are not well defined. In this study, we set out to clarify the roles of ADAM10 and ADAM17 during early retinal development. The retinal phenotype of conditionally abated Adam17 retinae (Adam17 CKO) did not differ from the controls whereas conditionally ablated Adam10 retinae (Adam10 CKO) exhibited abnormal morphogenesis characterized by the formation of rosettes and a loss of retinal laminae phenotypically similar to morphological abnormalities identified in mice with retinal NOTCH signaling deficiency. Additionally, Adam10 CKO retinae exhibited abnormal neurogenesis characterized by fewer proliferating progenitor cells and greater differentiation of early photoreceptors and retinal ganglion cells. Moreover, constitutive activation of the NOTCH1-intracellular domain (N1-ICD) rescued Adam10 CKO abnormal neurogenesis, as well as abnormal retinal morphology by maintaining retinal cells in the progenitor state. Collectively these findings provide in vivo genetic evidence that ADAM10, and not ADAM17, is indispensable for proper retinal development as a regulator of NOTCH signaling. PMID:27224017

  2. Human and Murine Interleukin 23 Receptors Are Novel Substrates for A Disintegrin and Metalloproteases ADAM10 and ADAM17.

    PubMed

    Franke, Manuel; Schröder, Jutta; Monhasery, Niloufar; Ackfeld, Theresa; Hummel, Thorben M; Rabe, Björn; Garbers, Christoph; Becker-Pauly, Christoph; Floss, Doreen M; Scheller, Jürgen

    2016-05-13

    IL-23 (interleukin 23) regulates immune responses against pathogens and plays a major role in the differentiation and maintenance of TH17 cells and the development of autoimmune diseases and cancer. The IL-23 receptor (IL-23R) complex consists of the unique IL-23R and the common IL-12 receptor β1 (IL-12Rβ1). Differential splicing generates antagonistic soluble IL-23R (sIL-23R) variants, which might limit IL-23-mediated immune responses. Here, ectodomain shedding of human and murine IL-23R was identified as an alternative pathway for the generation of sIL-23R. Importantly, proteolytically released sIL-23R has IL-23 binding activity. Shedding of IL-23R was induced by stimulation with the phorbol ester phorbol 12-myristate 13-acetate (PMA), but not by ionomycin. PMA-induced shedding was abrogated by an ADAM (A disintegrin and metalloprotease) 10 and 17 selective inhibitor, but not by an ADAM10 selective inhibitor. ADAM17-deficient but not ADAM10-deficient HEK293 cells failed to shed IL-23R after PMA stimulation, demonstrating that ADAM17 but not ADAM10 cleaves the IL-23R. Constitutive shedding was, however, inhibited by an ADAM10 selective inhibitor. Using deletions and specific amino acid residue exchanges, we identified critical determinants of ectodomain shedding within the stalk region of the IL-23R. Finally, interaction studies identified domains 1 and 3 of the IL-23R as the main ADAM17 binding sites. In summary, we describe human and murine IL-23R as novel targets for protein ectodomain shedding by ADAM10 and ADAM17. PMID:26961870

  3. Luhmann Receives 2007 John Adam Fleming Medal

    NASA Astrophysics Data System (ADS)

    Russell, Christopher T.; Luhmann, Janet G.

    2008-02-01

    This year's John Adam Fleming medalist quickly established a reputation as an innovative and productive scientist with a broad range of interests. She made early and seminal contributions to aeronomy, cosmic rays, and magnetospheric and planetary physics. She contributed importantly to the understanding of the interaction of the solar wind with the atmosphere and magnetic fields of Mercury, Venus, Earth, and Mars. She has examined the behavior of planetary rings, the interaction of interstellar neutrals with heliospheric plasmas, as well as the interaction of planetary neutrals with the heliosphere. She has led in the study of the interaction of the moon Titan with the Saturn magnetosphere, and most recently she developed a vigorous solar physics effort, leading the implementation of the IMPACT particle and field package on the twin STEREO mission, now entering its second year of successful operation.

  4. John Adams and CERN: Personal Recollections

    NASA Astrophysics Data System (ADS)

    Brianti, G.; Plane, D. E.

    2014-02-01

    By any standards, John Adams had a most remarkable career. He was involved in three important, emerging technologies, radar, particle accelerators and controlled fusion, and had an outstanding impact on the last two. Without a university education, he attained hierarchical positions of the highest level in prestigious national and international organizations. This article covers the CERN part of his career, by offering some personal insights into the different facets of his contributions to major accelerator projects, from the first strong-focusing synchrotron, the PS, to the SPS and its conversion to a proton--antiproton collider. In particular, it outlines his abilities as a leader of an international collaboration, which has served as an example for international initiatives in other disciplines.

  5. ADAM17 mediates OSCC development in an orthotopic murine model

    PubMed Central

    2014-01-01

    Background ADAM17 is one of the main sheddases of the cells and it is responsible for the cleavage and the release of ectodomains of important signaling molecules, such as EGFR ligands. Despite the known crosstalk between ADAM17 and EGFR, which has been considered a promising targeted therapy in oral squamous cell carcinoma (OSCC), the role of ADAM17 in OSCC development is not clear. Method In this study the effect of overexpressing ADAM17 in cell migration, viability, adhesion and proliferation was comprehensively appraised in vitro. In addition, the tumor size, tumor proliferative activity, tumor collagenase activity and MS-based proteomics of tumor tissues have been evaluated by injecting tumorigenic squamous carcinoma cells (SCC-9) overexpressing ADAM17 in immunodeficient mice. Results The proteomic analysis has effectively identified a total of 2,194 proteins in control and tumor tissues. Among these, 110 proteins have been down-regulated and 90 have been up-regulated in tumor tissues. Biological network analysis has uncovered that overexpression of ADAM17 regulates Erk pathway in OSCC and further indicates proteins regulated by the overexpression of ADAM17 in the respective pathway. These results are also supported by the evidences of higher viability, migration, adhesion and proliferation in SCC-9 or A431 cells in vitro along with the increase of tumor size and proliferative activity and higher tissue collagenase activity as an outcome of ADAM17 overexpression. Conclusion These findings contribute to understand the role of ADAM17 in oral cancer development and as a potential therapeutic target in oral cancer. In addition, our study also provides the basis for the development of novel and refined OSCC-targeting approaches. PMID:24495306

  6. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    SciTech Connect

    Ungerer, Christopher; Doberstein, Kai; Boehm, Beate; Pfeilschifter, Josef; Mihic-Probst, Daniela; Gutwein, Paul

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  7. TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization.

    PubMed

    Jouannet, Stéphanie; Saint-Pol, Julien; Fernandez, Laurent; Nguyen, Viet; Charrin, Stéphanie; Boucheix, Claude; Brou, Christel; Milhiet, Pierre-Emmanuel; Rubinstein, Eric

    2016-05-01

    The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Aβ, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the endoplasmic reticulum. Here we show that 4 of these TspanC8 (Tspan5, Tspan14, Tspan15 and Tspan33) which positively regulate ADAM10 surface expression levels differentially impact ADAM10-dependent Notch activation and the cleavage of several ADAM10 substrates, including APP, N-cadherin and CD44. Sucrose gradient fractionation, single molecule tracking and quantitative mass-spectrometry analysis of the repertoire of molecules co-immunoprecipitated with Tspan5, Tspan15 and ADAM10 show that these two tetraspanins differentially regulate ADAM10 membrane compartmentalization. These data represent a unique example where several tetraspanins differentially regulate the function of a common partner protein through a distinct membrane compartmentalization. PMID:26686862

  8. 7. Historic American Buildings Survey, C. C. Adams, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Historic American Buildings Survey, C. C. Adams, Photographer August 1931, SEED PACKING ROOM, Gift of New York State Department of Education. - Shaker North Family Washhouse (first), Shaker Road, New Lebanon, Columbia County, NY

  9. Alternative mRNA Splicing Generates Two Distinct ADAM12 Prodomain Variants

    PubMed Central

    Duhachek-Muggy, Sara; Li, Hui; Qi, Yue; Zolkiewska, Anna

    2013-01-01

    Human ADAM12, transcript variant 1 (later on referred to as Var-1b), present in publicly available databases contains the sequence 5′-GTAATTCTG-3′ at the nucleotide positions 340–348 of the coding region, at the 3′ end of exon 4. The translation product of this variant, ADAM12-Lb, includes the three amino acid motif 114VIL116 in the prodomain. This motif is not conserved in ADAM12 from different species and is not present in other human ADAMs. Currently, it is not clear whether a shorter variant, Var-1a, encoding the protein version without the 114VIL116 motif, ADAM12-La, is expressed in human. In this work, we have established that human mammary epithelial cells and breast cancer cells express both Var-1a and Var-1b transcripts. Importantly, the proteolytic processing and intracellular trafficking of the corresponding ADAM12-La and ADAM12-Lb proteins are different. While ADAM12-La is cleaved and trafficked to the cell surface in a manner similar to ADAM12 in other species, ADAM12-Lb is retained in the ER and is not proteolytically processed. Furthermore, the relative abundance of ADAM12-La and ADAM12-Lb proteins detected in several breast cancer cell lines varies significantly. We conclude that the canonical form of transmembrane ADAM12 is represented by Var-1a/ADAM12-La, rather than Var-1b/ADAM12-Lb currently featured in major sequence databases. PMID:24116070

  10. The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity

    PubMed Central

    Abbruzzese, Genevieve; Gorny, Anne-Kathrin; Kaufmann, Lilian T.; Cousin, Hélène; Kleino, Iivari; Steinbeisser, Herbert; Alfandari, Dominique

    2015-01-01

    ABSTRACT Cranial neural crest (CNC) cells are a transient population of stem cells that originate at the border of the neural plate and the epidermis, and migrate ventrally to contribute to most of the facial structures including bones, cartilage, muscles and ganglia. ADAM13 is a cell surface metalloprotease that is essential for CNC cell migration. Here, we show in Xenopus laevis embryos that the Wnt receptor Fz4 binds to the cysteine-rich domain of ADAM13 and negatively regulates its proteolytic activity in vivo. Gain of Fz4 function inhibits CNC cell migration and can be rescued by gain of ADAM13 function. Loss of Fz4 function also inhibits CNC cell migration and induces a reduction of mature ADAM13, together with an increase in the ADAM13 cytoplasmic fragment that is known to translocate into the nucleus to regulate gene expression. We propose that Fz4 associates with ADAM13 during its transport to the plasma membrane to regulate its proteolytic activity. PMID:25616895

  11. ADAM10 as a target for anti-cancer therapy.

    PubMed

    Moss, Marcia L; Stoeck, Alexander; Yan, Wenbo; Dempsey, Peter J

    2008-02-01

    There is a great unmet medical need in the area of cancer treatment. A potential therapeutic target for intervention in cancer is ADAM10. ADAM10 is a disintegrin-metalloproteinase that processes membrane bound proteins from the cell surface to yield soluble forms. Pharmaceutical companies are actively seeking out inhibitors of ADAM10 for treatments in cancer as the enzyme is known to release the ErbB receptor, HER2/ErbB2 from the cell membrane, an event that is necessary for HER2 positive tumor cells to proliferate. ADAM10 is also capable of processing betacellulin indicating that an inhibitor could be used against EGFR/ErbB1 and/or HER4/ErbB4 receptor positive tumor cells that are betacellulin-dependent. ADAM10 is the principle sheddase for several other molecules associated with cancer proliferation, differentiation, adhesion and migration such as Notch, E-cadherin, CD44 and L1 adhesion molecule indicating that targeting ADAM10 with specific inhibitors could be beneficial. PMID:18289051

  12. Adam Politzer-Father of Modern Otology.

    PubMed

    Dhungat, J V Pai; Gore, Geeta

    2015-09-01

    Adam Politzer (1835-1920) was born in Alberti near the city of Budapest in Hungary. He studied medicine at the University of Vienna and obtained his Doctorate degree in 1859. Some of his teachers belonged to the famous second "Vienna School" such as Joseph Skoda, Karl Rokitansky, Von Hebra, Josef Hyrtil, Johann Von Oppolzer and famous physiologist Carl Ludwig -who took special interest in him and was influential in his subsequent career. Politzer showed unusual interest in diseases of the ear and started to work in Carl Ludwig's laboratory. His interest at that time was mainly the physics of the auditory system. He studied the innervations of the intrinsic muscles of the ear There he was the first to demonstrate that the innervations of the tensor tympani muscle was by trigeminal nerve and that of the stapedial muscle was by facial nerve. He studied the air movement in the Eustachian tube and variation of air pressure in the tympanic cavity by connecting two manometers- one placed in the external auditory canal meatus, and another in the pharynx. He showed valve near the opening into the middle ear which controls the process. It is usually closed to keep the bacteria and other things away from the mouth and nose. PMID:27608882

  13. The Cytoplasmic Domain of A Disintegrin and Metalloproteinase 10 (ADAM10) Regulates Its Constitutive Activity but Is Dispensable for Stimulated ADAM10-dependent Shedding*

    PubMed Central

    Maretzky, Thorsten; Evers, Astrid; Le Gall, Sylvain; Alabi, Rolake O.; Speck, Nancy; Reiss, Karina; Blobel, Carl P.

    2015-01-01

    The membrane-anchored metalloproteinase a disintegrin and metalloprotease 10 (ADAM10) is required for shedding of membrane proteins such as EGF, betacellulin, the amyloid precursor protein, and CD23 from cells. ADAM10 is constitutively active and can be rapidly and post-translationally enhanced by several stimuli, yet little is known about the underlying mechanism. Here, we use ADAM10-deficient cells transfected with wild type or mutant ADAM10 to address the role of its cytoplasmic and transmembrane domain in regulating ADAM10-dependent protein ectodomain shedding. We report that the cytoplasmic domain of ADAM10 negatively regulates its constitutive activity through an ER retention motif but is dispensable for its stimulated activity. However, chimeras with the extracellular domain of ADAM10 and the transmembrane domain of ADAM17 with or without the cytoplasmic domain of ADAM17 show reduced stimulated shedding of the ADAM10 substrate betacellulin, whereas the ionomycin-stimulated shedding of the ADAM17 substrates CD62-L and TGFα is not affected. Moreover, we show that influx of extracellular calcium activates ADAM10 but is not essential for its activation by APMA and BzATP. Finally, the rapid stimulation of ADAM10 is not significantly affected by incubation with proprotein convertase inhibitors for up to 8 h, arguing against a major role of increased prodomain removal in the rapid stimulation of ADAM10. Thus, the cytoplasmic domain of ADAM10 negatively influences constitutive shedding through an ER retention motif, whereas the cytoplasmic domain and prodomain processing are not required for the rapid activation of ADAM10-dependent shedding events. PMID:25605720

  14. Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein

    PubMed Central

    Xu, Daosong; Sharma, Chandan; Hemler, Martin E.

    2009-01-01

    Using mass spectrometry, we identified ADAM10 (a membrane-associated metalloproteinase) as a partner for TSPAN12, a tetraspanin protein. TSPAN12-ADAM10 interaction was confirmed by reciprocal coimmunoprecipitation in multiple tumor cell lines. TSPAN12, to a greater extent than other tetraspanins (CD81, CD151, CD9, and CD82), associated with ADAM10 but not with ADAM17. Overexpression of TSPAN12 enhanced ADAM10-dependent shedding of amyloid precursor protein (APP) in MCF7 (breast cancer) and SH-SY5Y (neuroblastoma) cell lines. Conversely, siRNA ablation of endogenous TSPAN12 markedly diminished APP proteolysis in both cell lines. Furthermore, TSPAN12 overexpression enhanced ADAM10 prodomain maturation, whereas TSPAN12 ablation diminished ADAM10 maturation. A palmitoylation-deficient TSPAN12 mutant failed to associate with ADAM10, inhibited ADAM10-dependent proteolysis of APP, and inhibited ADAM10 maturation, most likely by interfering with endogenous wild-type TSPAN12. In conclusion, TSPAN12 serves as a novel and robust partner for ADAM10 and promotes ADAM10 maturation, thereby facilitating ADAM10-dependent proteolysis of APP. This novel mode of regulating APP cleavage is of relevance to Alzheimer’s disease therapy.—Xu, D., Sharma, C., Hemler, M. E. Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein. PMID:19587294

  15. LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology

    PubMed Central

    Owuor, Katherine; Harel, Noam Y.; Englot, Dario C.; Hisama, Fuki; Blumenfeld, Hal; Strittmatter, Stephen M.

    2009-01-01

    Most epilepsy genes encode ion channels, but the LGI1 gene responsible for Autosomal Dominant Partial Epilepsy with Auditory Features produces a secreted protein. LGI1 is suggested to regulate PSD-95 via ADAM22. However, no unbiased screen of LGI1 action has been conducted. Here, we searched for brain genes supporting high affinity LGI-1 binding. ADAM23 was the only LGI1 interactor identified. The related proteins, ADAM22 and ADAM11, but not ADAM12, bind LGI1. Neither ADAM23 nor ADAM11, nor some forms of ADAM22, contain PDZ-interacting sequences, suggesting PSD-95-independent mechanisms in ADPEAF. Because ADAMs modulate integrins, we examined LGI1 effect on neurite outgrowth. LGI1 increases outgrowth from wild type but not ADAM23-/- neurons. Furthermore, CA1 pyramidal neurons of ADAM23-/- hippocampi have reduced dendritic arborization. ADAM23-/- mice exhibit spontaneous seizures, while ADAM23+/- mice have decreased seizure thresholds. Thus, LGI1 binding to ADAM23 is necessary to correctly pattern neuronal morphology and altered anatomical patterning contributes to ADPEAF. PMID:19796686

  16. Taking Charge: Walter Sydney Adams and the Mount Wilson Observatory

    NASA Astrophysics Data System (ADS)

    Brashear, R.

    2004-12-01

    The growing preeminence of American observational astronomy in the first half of the 20th century is a well-known story and much credit is given to George Ellery Hale and his skill as an observatory-building entrepreneur. But a key figure who has yet to be discussed in great detail is Walter Sydney Adams (1876-1956), Hale's Assistant Director at Mount Wilson Observatory. Due to Hale's illnesses, Adams was Acting Director for much of Hale's tenure, and he became the second Director of Mount Wilson from 1923 to 1946. Behind his New England reserve Adams was instrumental in the growth of Mount Wilson and thus American astronomy in general. Adams was hand-picked by Hale to take charge of stellar spectroscopy work at Yerkes and Mount Wilson and the younger astronomer showed tremendous loyalty to Hale and Hale's vision throughout his career. As Adams assumed the leadership role at Mount Wilson he concentrated on making the observatory a place where researchers worked with great freedom but maintain a high level of cooperation. This paper will concentrate on Adams's early years and look at his growing relationship with Hale and how he came to be the central figure in the early history of Mount Wilson as both a solar and stellar observatory. His education, his years at Dartmouth and Yerkes (including his unfortunate encounter with epsilon Leonis), and his formative years on Mount Wilson are all important in learning how he shaped the direction of Mount Wilson and the development of American astronomy in the first half of the 20th century. This latter history cannot be complete until we bring Adams into better focus.

  17. Characterization of Mammalian ADAM2 and Its Absence from Human Sperm

    PubMed Central

    Choi, Heejin; Jin, Sora; Kwon, Jun Tae; Kim, Jihye; Jeong, Juri; Kim, Jaehwan; Jeon, Suyeon; Park, Zee Yong; Jung, Kang-Jin; Park, Kwangsung; Cho, Chunghee

    2016-01-01

    The members of the ADAM (a disintegrin and metalloprotease) family are membrane-anchored multi-domain proteins that play prominent roles in male reproduction. ADAM2, which was one of the first identified ADAMs, is the best studied ADAM in reproduction. In the male germ cells of mice, ADAM2 and other ADAMs form complexes that contribute to sperm-sperm adhesion, sperm-egg interactions, and the migration of sperm in the female reproductive tract. Here, we generated specific antibodies against mouse and human ADAM2, and investigated various features of ADAM2 in mice, monkeys and humans. We found that the cytoplasmic domain of ADAM2 might enable the differential association of this protein with other ADAMs in mice. Western blot analysis with the anti-human ADAM2 antibodies showed that ADAM2 is present in the testis and sperm of monkeys. Monkey ADAM2 was found to associate with chaperone proteins in testis. In humans, we identified ADAM2 as a 100-kDa protein in the testis, but failed to detect it in sperm. This is surprising given the results in mice and monkeys, but it is consistent with the failure of ADAM2 identification in the previous proteomic analyses of human sperm. These findings suggest that the reproductive functions of ADAM2 differ between humans and mice. Our protein analysis showed the presence of potential ADAM2 complexes involving yet-unknown proteins in human testis. Taken together, our results provide new information regarding the characteristics of ADAM2 in mammalian species, including humans. PMID:27341348

  18. Phosphatidylserine exposure is required for ADAM17 sheddase function

    PubMed Central

    Sommer, Anselm; Kordowski, Felix; Büch, Joscha; Maretzky, Thorsten; Evers, Astrid; Andrä, Jörg; Düsterhöft, Stefan; Michalek, Matthias; Lorenzen, Inken; Somasundaram, Prasath; Tholey, Andreas; Sönnichsen, Frank D.; Kunzelmann, Karl; Heinbockel, Lena; Nehls, Christian; Gutsmann, Thomas; Grötzinger, Joachim; Bhakdi, Sucharit; Reiss, Karina

    2016-01-01

    ADAM17, a prominent member of the ‘Disintegrin and Metalloproteinase' (ADAM) family, controls vital cellular functions through cleavage of transmembrane substrates. Here we present evidence that surface exposure of phosphatidylserine (PS) is pivotal for ADAM17 to exert sheddase activity. PS exposure is tightly coupled to substrate shedding provoked by diverse ADAM17 activators. PS dependency is demonstrated in the following: (a) in Raji cells undergoing apoptosis; (b) in mutant PSA-3 cells with manipulatable PS content; and (c) in Scott syndrome lymphocytes genetically defunct in their capacity to externalize PS in response to intracellular Ca2+ elevation. Soluble phosphorylserine but not phosphorylcholine inhibits substrate cleavage. The isolated membrane proximal domain (MPD) of ADAM17 binds to PS but not to phosphatidylcholine liposomes. A cationic PS-binding motif is identified in this domain, replacement of which abrogates liposome-binding and renders the protease incapable of cleaving its substrates in cells. We speculate that surface-exposed PS directs the protease to its targets where it then executes its shedding function. PMID:27161080

  19. Phosphatidylserine exposure is required for ADAM17 sheddase function.

    PubMed

    Sommer, Anselm; Kordowski, Felix; Büch, Joscha; Maretzky, Thorsten; Evers, Astrid; Andrä, Jörg; Düsterhöft, Stefan; Michalek, Matthias; Lorenzen, Inken; Somasundaram, Prasath; Tholey, Andreas; Sönnichsen, Frank D; Kunzelmann, Karl; Heinbockel, Lena; Nehls, Christian; Gutsmann, Thomas; Grötzinger, Joachim; Bhakdi, Sucharit; Reiss, Karina

    2016-01-01

    ADAM17, a prominent member of the 'Disintegrin and Metalloproteinase' (ADAM) family, controls vital cellular functions through cleavage of transmembrane substrates. Here we present evidence that surface exposure of phosphatidylserine (PS) is pivotal for ADAM17 to exert sheddase activity. PS exposure is tightly coupled to substrate shedding provoked by diverse ADAM17 activators. PS dependency is demonstrated in the following: (a) in Raji cells undergoing apoptosis; (b) in mutant PSA-3 cells with manipulatable PS content; and (c) in Scott syndrome lymphocytes genetically defunct in their capacity to externalize PS in response to intracellular Ca(2+) elevation. Soluble phosphorylserine but not phosphorylcholine inhibits substrate cleavage. The isolated membrane proximal domain (MPD) of ADAM17 binds to PS but not to phosphatidylcholine liposomes. A cationic PS-binding motif is identified in this domain, replacement of which abrogates liposome-binding and renders the protease incapable of cleaving its substrates in cells. We speculate that surface-exposed PS directs the protease to its targets where it then executes its shedding function. PMID:27161080

  20. Structural Characterization of the Ectodomain of a Disintegrin and Metalloproteinase-22 (ADAM22), a Neural Adhesion Receptor Instead of Metalloproteinase INSIGHTS ON ADAM FUNCTION

    SciTech Connect

    Liu, Heli; Shim, Ann H.R.; He, Xiaolin

    2009-12-01

    ADAMs (adisintegrin and metalloproteinases) are a family of multidomain transmembrane glycoproteins with diverse roles in physiology and diseases, with several members being drug targets for cancer and inflammation therapies. The spatial organization of the ADAM extracellular segment and its influence on the function of ADAMs have been unclear. Although most members of the ADAM family are active zinc metalloproteinases, 8 of 21 ADAMs lack functional metalloproteinase domains and are implicated in protein-protein interactions instead of membrane protein ectodomain shedding. One of such non-proteinase ADAMs, ADAM22, acts as a receptor on the surface of the postsynaptic neuron to regulate synaptic signal transmission. The crystal structure of the full ectodomain of mature human ADAM22 shows that it is a compact four-leaf clover with the metalloproteinase-like domain held in the concave face of a rigid module formed by the disintegrin, cysteine-rich, and epidermal growth factor-like domains. The loss of metalloproteinase activity is ensured by the absence of critical catalytic residues, the filling of the substrate groove, and the steric hindrance by the cysteine-rich domain. The structure, combined with calorimetric experiments, suggests distinct roles of three putative calcium ions bound to ADAM22, with one in the metalloproteinase-like domain being regulatory and two in the disintegrin domain being structural. The metalloproteinase-like domain contacts the rest of ADAM22 with discontinuous, hydrophilic, and poorly complemented interactions, suggesting the possibility of modular movement of ADAM22 and other ADAMs. The ADAM22 structure provides a framework for understanding how different ADAMs exert their adhesive function and shedding activities.

  1. The Adam language: Ada extended with support for multiway activities

    NASA Technical Reports Server (NTRS)

    Charlesworth, Arthur

    1993-01-01

    The Adam language is an extension of Ada that supports multiway activities, which are cooperative activities involving two or more processes. This support is provided by three new constructs: diva procedures, meet statements, and multiway accept statements. Diva procedures are recursive generic procedures having a particular restrictive syntax that facilitates translation for parallel computers. Meet statements and multiway accept statements provide two ways to express a multiway rendezvous, which is an n-way rendezvous generalizing Ada's 2-way rendezvous. While meet statements tend to have simpler rules than multiway accept statements, the latter approach is a more straightforward extension of Ada. The only nonnull statements permitted within meet statements and multiway accept statements are calls on instantiated diva procedures. A call on an instantiated diva procedure is also permitted outside a multiway rendezvous; thus sequential Adam programs using diva procedures can be written. Adam programs are translated into Ada programs appropriate for use on parallel computers.

  2. Aberrant ADAM10 expression correlates with osteosarcoma progression

    PubMed Central

    2014-01-01

    Background Osteosarcoma is the most common type of bone cancer and is notorious for its rapid progression. The Notch signaling pathway has recently been shown to be involved in osteosarcoma. As a major sheddase of Notch receptors, ADAM10 has been implicated in many types of cancers, but its role in osteosarcoma has not been investigated. Previous studies have shown that the expression of CD31 was significantly elevated in metastatic osteosarcoma; however, its expression in nonmetastatic groups is not known. In addition, the mysterious multinucleated giant cell in giant cell-rich osteosarcoma was previously regarded as an osteoclast-like cell, but its exact identity is unclear. Method Tissue chip samples from 40 cases of nonmetastatic osteosarcoma were stained for cytoplasmic ADAM10, activated Notch1 and CD31. Osteoclasts in tumor sections were also stained for tartrate-resistant acid phosphatase (TRAP). Results Immunofluorescence staining revealed that ADAM10 expression significantly increased with the progression of osteosarcoma as well as in osteoblastic osteosarcoma, whereas the expression of the Notch intracellular domain (NICD) and CD31 was not significantly altered between different pathological stages. In addition, multinucleated giant cells in giant cell-rich osteosarcoma were also found to coexpress CD31, ADAM10 and NICD, but were negative for TRAP staining. Conclusions Our results highlight the importance of ADAM10 in the progression of osteosarcoma and suggest that the protein might be a potential therapeutic target in osteosarcoma treatment. This study also demonstrates that the multinucleated giant cell is an angiogenic tumor cell, rather than an osteoclast, and involves ADAM10/Notch1 signaling activation. PMID:24548763

  3. Shedding of klotho by ADAMs in the kidney.

    PubMed

    van Loon, Ellen P M; Pulskens, Wilco P; van der Hagen, Eline A E; Lavrijsen, Marla; Vervloet, Marc G; van Goor, Harry; Bindels, René J M; Hoenderop, Joost G J

    2015-08-15

    The anti-aging gene klotho plays an important role in Ca(2+) and phosphate homeostasis. Membrane-bound klotho is an essential coreceptor for fibroblast growth factor-23 and can be cleaved by proteases, including a disintegrin and metalloproteinase (ADAM)10 and ADAM17. Cleavage of klotho occurs at a site directly above the plasma membrane (α-cut) or between the KL1 and KL2 domain (β-cut), resulting in soluble full-length klotho or KL1 and KL2 fragments, respectively. The aim of the present study was to gain insights into the mechanisms behind klotho cleavage processes in the kidney. Klotho shedding was demonstrated using a Madin-Darby canine kidney cell line stably expressing klotho and human embryonic kidney-293 cells transiently transfected with klotho. Here, we report klotho expression on both the basolateral and apical membrane, with a higher abundance of klotho at the apical membrane and in the apical media. mRNA expression of ADAM17 and klotho were enriched in mouse distal convoluted and connecting tubules. In vitro ADAM/matrix metalloproteinase inhibition by TNF484 resulted in a concentration-dependent inhibition of the α-cut, with a less specific effect on β-cut shedding. In vivo TNF484 treatment in wild-type mice did not change urinary klotho levels. However, ADAM/matrix metalloproteinase inhibition did increase renal and duodenal mRNA expression of phosphate transporters, whereas serum phosphate levels were significantly decreased. In conclusion, our data show that renal cells preferentially secrete klotho to the apical side and suggest that ADAMs are responsible for α-cut cleavage. PMID:26155844

  4. Photograph of photogrammetric plate LCHABSGS11IL1124S06R. SOUTH (ADAMS STREET) ELEVATION, UPPER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photograph of photogrammetric plate LC-HABS-GS11-IL-1124-S06R. SOUTH (ADAMS STREET) ELEVATION, UPPER LEVEL, INCLINED 30; Upper right section of elevation - Phelps-Dodge-Palmer Building, 200 West Adams Street, Chicago, Cook County, IL

  5. Photograph of photogrammetric plate LCHABSGS11IL1124S02R. SOUTH (ADAMS STREET) ELEVATION, GROUND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photograph of photogrammetric plate LC-HABS-GS11-IL-1124-S02R. SOUTH (ADAMS STREET) ELEVATION, GROUND LEVEL Lower right section of elevation - Phelps-Dodge-Palmer Building, 200 West Adams Street, Chicago, Cook County, IL

  6. Photograph of photogrammetric plate LCHABSGS11IL1124S04R. SOUTH (ADAMS STREET) ELEVATION, UPPER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photograph of photogrammetric plate LC-HABS-GS11-IL-1124-S04R. SOUTH (ADAMS STREET) ELEVATION, UPPER LEVEL Middle right section of elevation - Phelps-Dodge-Palmer Building, 200 West Adams Street, Chicago, Cook County, IL

  7. Photograph of photogrammetric plate LCHABSGS11IL1124S05R. SOUTH (ADAMS STREET) ELEVATION, UPPER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photograph of photogrammetric plate LC-HABS-GS11-IL-1124-S05R. SOUTH (ADAMS STREET) ELEVATION, UPPER LEVEL, INCLINED 30; Upper left section of elevation - Phelps-Dodge-Palmer Building, 200 West Adams Street, Chicago, Cook County, IL

  8. Photograph of photogrammetric plate LCHABSGS11IL1124S01R. SOUTH (ADAMS STREET) ELEVATION, GROUND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photograph of photogrammetric plate LC-HABS-GS11-IL-1124-S01R. SOUTH (ADAMS STREET) ELEVATION, GROUND LEVEL Lower left section of elevation - Phelps-Dodge-Palmer Building, 200 West Adams Street, Chicago, Cook County, IL

  9. Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice

    PubMed Central

    Chalaris, Athena; Adam, Nina; Sina, Christian; Rosenstiel, Philip; Lehmann-Koch, Judith; Schirmacher, Peter; Hartmann, Dieter; Cichy, Joanna; Gavrilova, Olga; Schreiber, Stefan; Jostock, Thomas; Matthews, Vance; Häsler, Robert; Becker, Christoph; Neurath, Markus F.; Reiß, Karina; Saftig, Paul

    2010-01-01

    The protease a disintegrin and metalloprotease (ADAM) 17 cleaves tumor necrosis factor (TNF), L-selectin, and epidermal growth factor receptor (EGF-R) ligands from the plasma membrane. ADAM17 is expressed in most tissues and is up-regulated during inflammation and cancer. ADAM17-deficient mice are not viable. Conditional ADAM17 knockout models demonstrated proinflammatory activities of ADAM17 in septic shock via shedding of TNF. We used a novel gene targeting strategy to generate mice with dramatically reduced ADAM17 levels in all tissues. The resulting mice called ADAM17ex/ex were viable, showed compromised shedding of ADAM17 substrates from the cell surface, and developed eye, heart, and skin defects as a consequence of impaired EGF-R signaling caused by failure of shedding of EGF-R ligands. Unexpectedly, although the intestine of unchallenged homozygous ADAM17ex/ex mice was normal, ADAM17ex/ex mice showed substantially increased susceptibility to inflammation in dextran sulfate sodium colitis. This was a result of impaired shedding of EGF-R ligands resulting in failure to phosphorylate STAT3 via the EGF-R and, consequently, in defective regeneration of epithelial cells and breakdown of the intestinal barrier. Besides regulating the systemic availability of the proinflammatory cytokine TNF, our results demonstrate that ADAM17 is needed for vital regenerative activities during the immune response. Thus, our mouse model will help investigate ADAM17 as a potential drug target. PMID:20603312

  10. 3. Aerial view southeast, State Route 92 bottom left, Adams ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Aerial view southeast, State Route 92 bottom left, Adams Dam Road center, Brandywine Creek State Park and J. Chandler Farm in center left, duck pond bottom right and reservoir bottom left. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

  11. 4. Aerial view southwest, Adams Dam Road bottom left, State ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Aerial view southwest, Adams Dam Road bottom left, State Route 100 center, back gates to Winterthur and Wilmington Country Club upper center, duck pond and reservoir bottom right and center, and State Route 92 center bottom. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

  12. 5. Aerial view west, Adams Dam Road bottom center, State ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Aerial view west, Adams Dam Road bottom center, State Route 100 center, duck pond and reservoir center, State Route 100 center right, State Route 92 below center right, Brandywine Creek State Park center bottom. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

  13. The ADaptation and Anticipation Model (ADAM) of sensorimotor synchronization

    PubMed Central

    van der Steen, M. C. (Marieke); Keller, Peter E.

    2013-01-01

    A constantly changing environment requires precise yet flexible timing of movements. Sensorimotor synchronization (SMS)—the temporal coordination of an action with events in a predictable external rhythm—is a fundamental human skill that contributes to optimal sensory-motor control in daily life. A large body of research related to SMS has focused on adaptive error correction mechanisms that support the synchronization of periodic movements (e.g., finger taps) with events in regular pacing sequences. The results of recent studies additionally highlight the importance of anticipatory mechanisms that support temporal prediction in the context of SMS with sequences that contain tempo changes. To investigate the role of adaptation and anticipatory mechanisms in SMS we introduce ADAM: an ADaptation and Anticipation Model. ADAM combines reactive error correction processes (adaptation) with predictive temporal extrapolation processes (anticipation) inspired by the computational neuroscience concept of internal models. The combination of simulations and experimental manipulations based on ADAM creates a novel and promising approach for exploring adaptation and anticipation in SMS. The current paper describes the conceptual basis and architecture of ADAM. PMID:23772211

  14. WEISER RIVER STUDY, ADAMS AND WASHINGTON COUNTIES, IDAHO, 1979

    EPA Science Inventory

    During the 1979 water year, a water quality study was conducted on the Weiser and Little Weiser Rivers (17050124) in Washington and Adams Counties, Idaho. The study was completed to obtain background information on effluent limitations for the cities of Cambridge and Council and...

  15. Adam Smith and the Teaching of English Literature.

    ERIC Educational Resources Information Center

    Court, Franklin E.

    1985-01-01

    Adam Smith used selections from English literature in his classroom during the eighteenth century because he believed that vernacular literature could provide a ready context for the teaching of ideological, social, and moral lessons. He believed that higher education should prepare students for the real business of the real world. (RM)

  16. Adam Smith and the Moral Economy of the Classroom System.

    ERIC Educational Resources Information Center

    Hamilton, D.

    1980-01-01

    Traces the development of mass schooling to its origins in 19th-century Glasgow. Its importance as an intellectual and economic center enabled Glasgow to invent a solution to the problem of urban schooling, while the association of scholars like Adam Smith with Glasgow University made Scottish educational theories acceptable around the world. (DB)

  17. Father Knows Best: Using Adam Smith to Teach Transactions Costs

    ERIC Educational Resources Information Center

    Dupont, Brandon

    2014-01-01

    Adam Smith's moral philosophy can be used to introduce economics students to the important idea of transactions costs. The author provides a brief background in this article to Smith's moral philosophy and connects it to the costs of transacting in a way that fits easily into the standard principles of microeconomics classroom. By doing…

  18. An Informal Report on Collegiate Successes with "The Adams Chronicles."

    ERIC Educational Resources Information Center

    Goldsberry, Gary G.

    In the spring of 1976, "The Adams Chronicles", a bicentennial television course developed by Coast Community College District and the University of California at San Diego, was distributed to colleges nationwide at no charge with the understanding that each college would return information regarding promotion, enrollment, and form of offering this…

  19. John Adams High School First Year Report, 1969-1970.

    ERIC Educational Resources Information Center

    Adams High School, Portland, OR.

    This report is an assessment of the events of the first year of operation of John Adams High School, Portland, Oregon. The primary goal of the school was to provide an educational experience relevant to the needs and interests of all adolescents, regardless of their intentions about pursuing further formal education. The report is oriented toward…

  20. Research and Evaluation at John Adams High School.

    ERIC Educational Resources Information Center

    Adams High School, Portland, OR.

    We at Adams have committed ourselves (1) to search for new ways to make the inquiry into our own activities and the evaluation of our programs relevant and consistent with our notions of humanistic and personal education, and (2) to seek a mechanism for using research and evaluation to improve the operation of the school at every level and for…

  1. What Ever Happened to . . . John Adams High School?

    ERIC Educational Resources Information Center

    Doremus, Richard R.

    1981-01-01

    First in a series, this article describes the rise and fall of John Adams High School, an experimental school in Portland (Oregon) that was recently closed after 12 years of operation. The experiences of those who tried to make the experiment work may help others interested in educational innovation. (WD)

  2. Cloning and characterization of ADAM28: evidence for autocatalytic pro-domain removal and for cell surface localization of mature ADAM28.

    PubMed Central

    Howard, L; Maciewicz, R A; Blobel, C P

    2000-01-01

    The metalloprotease disintegrins are a family of membrane-anchored glycoproteins with diverse functions in fertilization, myoblast fusion, neurogenesis and protein ectodomain shedding. Here we report a cDNA sequence, encoding a metalloprotease disintegrin, termed ADAM28 ('a disintegrin and metalloprotease 28'), which was cloned from mouse lung. From protein sequence comparisons, ADAM28 is more closely related to snake venom metalloproteases (SVMPs) than to other ADAMs, and hence may cleave similar substrates to SVMPs, perhaps including components of the extracellular matrix. Northern blot analysis of selected mouse tissues revealed that ADAM28 is expressed highly and in alternatively spliced forms in the epididymis, suggesting a possible role in sperm maturation, and at lower levels in lung. The intracellular maturation of ADAM28 expressed in COS-7 cells resembles that of other ADAMs, in that ADAM28 is made as a precursor and processed to a mature form in a late Golgi compartment of the secretory pathway. Most or all of the mature, and thus presumably catalytically active, form of ADAM28 in COS-7 cells is accessible to cell surface trypsinization, suggesting that ADAM28 functions mainly on the cell surface. A mutation converting the catalytic-site glutamate residue into alanine abolishes pro-domain removal, even though this mutant form of ADAM28 can be transported to the cell surface in a manner similar to the wild-type protein. This suggests that pro-domain removal and maturation of ADAM28 may be, at least in part, autocatalytic. This is in contrast with several other ADAMs, for which furin-like proprotein convertases are involved in pro-domain removal, and in which a glutamate-to-alanine mutation in the catalytic site does not alter pro-domain removal. PMID:10794709

  3. ADAM8 in squamous cell carcinoma of the head and neck: a retrospective study

    PubMed Central

    2012-01-01

    Background A disintegrin and metalloproteinase (ADAMs) have been associated with multiple malignancies. ADAMs are involved in cell fusion, cell migration, membrane protein shedding and proteolysis. ADAM8 has been found to be overexpressed in squamous cell carcinomas of the lung. A new study showed that ADAM8 is significantly overexpressed in metastasis of squamous cell carcinomas of the head and neck (HNSCC). Methods We determined ADAM8 levels in the serum of 79 HNSCC patients at the time of diagnosis, in 35 patients 3 months after treatment and in 10 patients 1 year after therapy and compared the results to the sera of 31 healthy volunteers. We also constructed tissue microarrays to detect ADAM8 immunohistochemically in 100 patients. The results were correlated with the survival data of the patients to determine the diagnostic and prognostic value. Results The data demonstrated that patients with high ADAM8 expression in the tumor have worse survival rates. We found that high ADAM8 serum levels correlated with high ADAM8 expression in tumor samples. Soluble ADAM8 levels did not show any prognostic or diagnostic properties. Conclusion In summary ADAM8 expression is a prognostic factor for survival of patients with head and neck squamous cell carcinoma. PMID:22369429

  4. A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis

    PubMed Central

    Köhn-Gaone, Julia; Chalupsky, Karel; Lüllmann-Rauch, Renate; Barikbin, Roja; Bergmann, Juri; Wöhner, Birte; Zbodakova, Olga; Leuschner, Ivo; Martin, Gregor; Tiegs, Gisa; Rose-John, Stefan; Sedlacek, Radislav; Tirnitz-Parker, Janina E.E.; Saftig, Paul; Schmidt-Arras, Dirk

    2016-01-01

    A Disintegrin And Metalloprotease (ADAM) 10 exerts essential roles during organ development and tissue integrity in different organs, mainly through activation of the Notch pathway. However, only little is known about its implication in liver tissue physiology. Here we show that in contrast to its role in other tissues, ADAM10 is dispensable for the Notch2-dependent biliary tree formation. However, we demonstrate that expression of bile acid transporters is dependent on ADAM10. Consequently, mice deficient for Adam10 in hepatocytes, cholangiocytes and liver progenitor cells develop spontaneous hepatocyte necrosis and concomitant liver fibrosis. We furthermore observed a strongly augmented ductular reaction in 15-week old ADAM10Δhep/Δch mice and demonstrate that c-Met dependent liver progenitor cell activation is enhanced. Additionally, liver progenitor cells are primed to hepatocyte differentiation in the absence of ADAM10. These findings show that ADAM10 is a novel central node controlling liver tissue homeostasis. Highlights: Loss of ADAM10 in murine liver results in hepatocyte necrosis and concomitant liver fibrosis. ADAM10 directly regulates expression of bile acid transporters but is dispensable for Notch2-dependent formation of the biliary system. Activation of liver progenitor cells is enhanced through increased c-Met signalling, in the absence of ADAM10. Differentiation of liver progenitor cells to hepatocytes is augmented in the absence of ADAM10. PMID:26942887

  5. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

    PubMed

    Mężyk-Kopeć, Renata; Wyroba, Barbara; Stalińska, Krystyna; Próchnicki, Tomasz; Wiatrowska, Karolina; Kilarski, Witold W; Swartz, Melody A; Bereta, Joanna

    2015-01-01

    Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC). When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i) single-cell motility, (ii) cell migration through a 3D Matrigel/collagen type I matrix, and (iii) their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy. PMID:26176220

  6. Adam8 Limits the Development of Allergic Airway Inflammation in Mice

    PubMed Central

    Knolle, Martin D.; Nakajima, Takahiro; Hergrueter, Anja; Gupta, Kushagra; Polverino, Francesca; Craig, Vanessa J.; Fyfe, Susanne E.; Zahid, Muhammad; Permaul, Perdita; Cernadas, Manuela; Montano, Gilbert; Tesfaigzi, Yohannes; Sholl, Lynette; Kobzik, Lester; Israel, Elliot; Owen, Caroline A.

    2013-01-01

    To determine whether a disintegrin and a metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyper-responsiveness (AHR), we compared AAI and AHR in wild type (WT) versus Adam8−/− mice in different genetic backgrounds sensitized and challenged with ovalbumin (OVA) or house dust mite protein extract (HDM). OVA- and HDM-treated Adam8−/− mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some TH2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8’s anti-inflammatory activities in murine airways. Airway eosinophils and macrophages both expressed Adam8 in WT mice with AAI. Adam8 limited AAI and AHR in mice by reducing leukocyte survival because: 1) Adam8−/− mice with AAI had fewer apoptotic eosinophils and macrophages in their airways than WT mice with AAI; and 2) Adam8−/− macrophages and eosinophils had reduced rates of apoptosis compared with WT leukocytes when the intrinsic (but not the extrinsic) apoptosis pathway was triggered in the cells in vitro. ADAM8 was robustly expressed by airway granulocytes in lung sections from human asthma patients but, surprisingly, airway macrophages had less ADAM8 staining than airway eosinophils. Thus, ADAM8 has anti-inflammatory activities during AAI in mice by activating the intrinsic apoptosis pathway in myeloid leukocytes. Strategies that increase ADAM8 levels in myeloid leukocytes may have therapeutic efficacy in asthma. PMID:23670189

  7. Adams-Based Rover Terramechanics and Mobility Simulator - ARTEMIS

    NASA Technical Reports Server (NTRS)

    Trease, Brian P.; Lindeman, Randel A.; Arvidson, Raymond E.; Bennett, Keith; VanDyke, Lauren P.; Zhou, Feng; Iagnemma, Karl; Senatore, Carmine

    2013-01-01

    The Mars Exploration Rovers (MERs), Spirit and Opportunity, far exceeded their original drive distance expectations and have traveled, at the time of this reporting, a combined 29 kilometers across the surface of Mars. The Rover Sequencing and Visualization Program (RSVP), the current program used to plan drives for MERs, is only a kinematic simulator of rover movement. Therefore, rover response to various terrains and soil types cannot be modeled. Although sandbox experiments attempt to model rover-terrain interaction, these experiments are time-intensive and costly, and they cannot be used within the tactical timeline of rover driving. Imaging techniques and hazard avoidance features on MER help to prevent the rover from traveling over dangerous terrains, but mobility issues have shown that these methods are not always sufficient. ARTEMIS, a dynamic modeling tool for MER, allows planned drives to be simulated before commands are sent to the rover. The deformable soils component of this model allows rover-terrain interactions to be simulated to determine if a particular drive path would take the rover over terrain that would induce hazardous levels of slip or sink. When used in the rover drive planning process, dynamic modeling reduces the likelihood of future mobility issues because high-risk areas could be identified before drive commands are sent to the rover, and drives planned over these areas could be rerouted. The ARTEMIS software consists of several components. These include a preprocessor, Digital Elevation Models (DEMs), Adams rover model, wheel and soil parameter files, MSC Adams GUI (commercial), MSC Adams dynamics solver (commercial), terramechanics subroutines (FORTRAN), a contact detection engine, a soil modification engine, and output DEMs of deformed soil. The preprocessor is used to define the terrain (from a DEM) and define the soil parameters for the terrain file. The Adams rover model is placed in this terrain. Wheel and soil parameter files

  8. Adams-Oliver Syndrome: A Case with Full Expression

    PubMed Central

    Dehdashtian, Amir; Dehdashtian, Masoud

    2016-01-01

    Adams-Oliver syndrome (AOS) is characterized by the combination of congenital scalp defects (aplasia cutis congenita) and terminal transverse limb defects of variable severity. It is believed that Adams-Oliver syndrome without major organ abnormalities does not necessarily alter the normal lifespan. We present a case without detectable major organ abnormality contrary to life but with poor weight gain. A male infant with scalp and skin cutis aplasia, generalized cutis aplasia, dilated veins over scalp and trunk, hypoplastic toes and nails of feet, glaucoma, poor feeding and poor weight gain. This report shows a case of AOS without major multiple organ abnormalities but with poor feeding and abnormal weight gain that may be alter the normal lifespan. PMID:27433307

  9. ADAM: An Axisymmetric Duct Aeroacoustic Modeling system. [aircraft turbofan engines

    NASA Technical Reports Server (NTRS)

    Abrahamson, A. L.

    1983-01-01

    An interconnected system of computer programs for analyzing the propagation and attenuation of sound in aeroengine ducts containing realistic compressible subsonic mean flows, ADAM was developed primarily for research directed towards the reduction of noise emitted from turbofan aircraft engines. The two basic components are a streamtube curvature program for determination of the mean flow, and a finite element code for solution of the acoustic propagation problem. The system, which has been specifically tailored for ease of use, is presently installed at NASA Langley Reseach Center on a Control Data Cyber 175 Computer under the NOS Operating system employing a Tektronix terminal for interactive graphics. The scope and organization of the ADAM system is described. A users guide, examples of input data, and results for selected cases are included.

  10. Application of the ADAMS program to deployable space truss structures

    NASA Technical Reports Server (NTRS)

    Calleson, R. E.

    1985-01-01

    The need for a computer program to perform kinematic and dynamic analyses of large truss structures while deploying from a packaged configuration in space led to the evaluation of several existing programs. ADAMS (automatic dynamic analysis of mechanical systems), a generalized program from performing the dynamic simulation of mechanical systems undergoing large displacements, is applied to two concepts of deployable space antenna units. One concept is a one cube folding unit of Martin Marietta's Box Truss Antenna and the other is a tetrahedral truss unit of a Tetrahedral Truss Antenna. Adequate evaluation of dynamic forces during member latch-up into the deployed configuration is not yet available from the present version of ADAMS since it is limited to the assembly of rigid bodies. Included is a method for estimating the maximum bending stress in a surface member at latch-up. Results include member displacement and velocity responses during extension and an example of member bending stresses at latch-up.

  11. Automatic Dynamic Aircraft Modeler (ADAM) for the Computer Program NASTRAN

    NASA Technical Reports Server (NTRS)

    Griffis, H.

    1985-01-01

    Large general purpose finite element programs require users to develop large quantities of input data. General purpose pre-processors are used to decrease the effort required to develop structural models. Further reduction of effort can be achieved by specific application pre-processors. Automatic Dynamic Aircraft Modeler (ADAM) is one such application specific pre-processor. General purpose pre-processors use points, lines and surfaces to describe geometric shapes. Specifying that ADAM is used only for aircraft structures allows generic structural sections, wing boxes and bodies, to be pre-defined. Hence with only gross dimensions, thicknesses, material properties and pre-defined boundary conditions a complete model of an aircraft can be created.

  12. User's manual for ADAM (Advanced Dynamic Airfoil Model)

    SciTech Connect

    Oler, J.W.; Strickland, J.H.; Im, B.J.

    1987-06-01

    The computer code for an advanced dynamic airfoil model (ADAM) is described. The code is capable of calculating steady or unsteady flow over two-dimensional airfoils with allowances for boundary layer separation. Specific types of airfoil motions currently installed are steady rectilinear motion, impulsively started rectilinear motion, constant rate pitching, sinusoidal pitch oscillations, sinusoidal lateral plunging, and simulated Darrieus turbine motion. Other types of airfoil motion may be analyzed through simple modifications of a single subroutine. The code has a built-in capability to generate the geometric parameters for a cylinder, the NACA four-digit series of airfoils, and a NASA NLF-0416 laminar airfoil. Other types of airfoils are easily incorporated. The code ADAM is currently in a state of development. It is theoretically consistent and complete. However, further work is needed on the numerical implementation of the method.

  13. Distal Limb Defects and Aplasia Cutis: Adams-Oliver Syndrome.

    PubMed

    Renfree, Kevin J; Dell, Paul C

    2016-07-01

    Adams-Oliver syndrome is a rare congenital condition that should be considered in persons with terminal transverse limb deficiencies and scalp defects (aplasia cutis congenita). Broad phenotypic variability exists in this condition. In its more severe forms, Adams-Oliver syndrome can involve the cardiovascular system, central nervous system, gastrointestinal tract, and genitourinary system and should require prompt evaluation by appropriate subspecialists. Extremity involvement is typically bilateral and asymmetrical, with lower extremities involved more than upper extremities. Brachydactyly is the most common limb defect, and severity ranges from hypoplastic nails to complete absence of the distal limb. The syndrome has been described as resulting from autosomal dominant and recessive modes of inheritance, but most cases are sporadic. No gene has been identified. Although the exact pathogenic mechanism is unknown, a common hypothesis is that a vascular disturbance occurs in watershed areas, such as cranial vertex and limbs, during fetal development. PMID:27178874

  14. System Verification of MSL Skycrane Using an Integrated ADAMS Simulation

    NASA Technical Reports Server (NTRS)

    White, Christopher; Antoun, George; Brugarolas, Paul; Lih, Shyh-Shiuh; Peng, Chia-Yen; Phan, Linh; San Martin, Alejandro; Sell, Steven

    2012-01-01

    Mars Science Laboratory (MSL) will use the Skycrane architecture to execute final descent and landing maneuvers. The Skycrane phase uses closed-loop feedback control throughout the entire phase, starting with rover separation, through mobility deploy, and through touchdown, ending only when the bridles have completely slacked. The integrated ADAMS simulation described in this paper couples complex dynamical models created by the mechanical subsystem with actual GNC flight software algorithms that have been compiled and linked into ADAMS. These integrated simulations provide the project with the best means to verify key Skycrane requirements which have a tightly coupled GNC-Mechanical aspect to them. It also provides the best opportunity to validate the design of the algorithm that determines when to cut the bridles. The results of the simulations show the excellent performance of the Skycrane system.

  15. A Disintegrin and Metalloprotease (ADAM): Historical Overview of Their Functions.

    PubMed

    Giebeler, Nives; Zigrino, Paola

    2016-04-01

    Since the discovery of the first disintegrin protein from snake venom and the following identification of a mammalian membrane-anchored metalloprotease-disintegrin implicated in fertilization, almost three decades of studies have identified additional members of these families and several biochemical mechanisms regulating their expression and activity in the cell. Most importantly, new in vivo functions have been recognized for these proteins including cell partitioning during development, modulation of inflammatory reactions, and development of cancers. In this review, we will overview the a disintegrin and metalloprotease (ADAM) family of proteases highlighting some of the major research achievements in the analysis of ADAMs' function that have underscored the importance of these proteins in physiological and pathological processes over the years. PMID:27120619

  16. ADAMS GAP AND SHINBONE CREEK ROADLESS AREAS, ALABAMA.

    USGS Publications Warehouse

    Klein, T.L.; Harrison, Donald K.

    1984-01-01

    The Adams Gap and Shinbone Creek Roadless Areas in Alabama were evaluated for their mineral potential. The only resource within the established boundary of the roadless area is quartzite suitable for crushed rock or refractory-grade aggregate. The quartzite contains deleterious impurities and is found in abundance outside the areas. Natural gas or petroleum may exist at depth. Detailed seismic studies and deep drilling tests are needed before a reasonable estimate of hydrocarbon potential can be made.

  17. ADAM-mediated amphiregulin shedding and EGFR transactivation

    PubMed Central

    Kasina, S.; Scherle, P. A.; Hall, C. L.; Macoska, J. A.

    2011-01-01

    Introduction The ectodomain shedding of epidermal growth factor receptor (EGFR) ligands, such as amphiregulin (AREG), by ADAMs (A Disintegrin And Metalloproteases) can be stimulated by G protein-coupled receptor (GPCR) agonists. Interactions between the CXCR4 GPCR and the CXCL12 chemokine have been shown to mediate gene transcription and cellular proliferation in non-transformed and transformed prostate epithelial cells, as well as motility/invasiveness in transformed cells. Objectives In this report, we investigated the ability of CXCL12 to stimulate amphiregulin ectodomain shedding in non-transformed and transformed prostate epithelial cells that respond proliferatively to sub-nanomolar levels of CXCL12 and amphiregulin. Materials and Methods Non-transformed N15C6 and transformed PC3 prostate epithelial cells were assessed for amphiregulin shedding, ADAM activation, Src phosphorylation and EGFR activation using ELISA, immunoblot, and immunoprecipitation techniques, and for proliferation using cell counting after stimulation with CXCL12 or vehicle. Results The results of these studies identify CXCL12 as a novel inducer of amphiregulin ectodomain shedding and show that both basal and CXCL12-mediated amphiregulin shedding are ADAM10- and Src kinase-dependent in non-transformed N15C6 cells. In contrast, amphiregulin shedding is not amplified subsequent to stimulation with exogenous CXCL12, and is not reduced subsequent to metalloprotease- or Src kinase-inhibition, in highly aggressive PC3 prostate cancer cells. These data also show that CXCL12-mediated cellular proliferation requires EGFR transactivation in a Src-and ADAM-dependent manner in non-transformed prostate epithelial cells. However, these same mechanisms are dysfunctional in highly transformed prostate cancer cells, which secrete amphiregulin in an autocrine manner that cannot be repressed through metalloprotease- or Src kinase inhibition. Conclusion These findings show that non-transformed and transformed

  18. Evaluation of ADAM/1 model for advanced coal extraction concepts

    NASA Technical Reports Server (NTRS)

    Deshpande, G. K.; Gangal, M. D.

    1982-01-01

    Several existing computer programs for estimating life cycle cost of mining systems were evaluated. A commercially available program, ADAM/1 was found to be satisfactory in relation to the needs of the advanced coal extraction project. Two test cases were run to confirm the ability of the program to handle nonconventional mining equipment and procedures. The results were satisfactory. The model, therefore, is recommended to the project team for evaluation of their conceptual designs.

  19. Circulating ADAM17 Level Reflects Disease Activity in Proteinase-3 ANCA-Associated Vasculitis.

    PubMed

    Bertram, Anna; Lovric, Svjetlana; Engel, Alissa; Beese, Michaela; Wyss, Kristin; Hertel, Barbara; Park, Joon-Keun; Becker, Jan U; Kegel, Johanna; Haller, Hermann; Haubitz, Marion; Kirsch, Torsten

    2015-11-01

    ANCA-associated vasculitides are characterized by inflammatory destruction of small vessels accompanied by enhanced cleavage of membrane-bound proteins. One of the main proteases responsible for ectodomain shedding is disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Given its potential role in aggravating vascular dysfunction, we examined the role of ADAM17 in active proteinase-3 (PR3)-positive ANCA-associated vasculitis (AAV). ADAM17 concentration was significantly increased in plasma samples from patients with active PR3-AAV compared with samples from patients in remission or from other controls with renal nonvascular diseases. Comparably, plasma levels of the ADAM17 substrate syndecan-1 were significantly enhanced in active AAV. We also observed that plasma-derived ADAM17 retained its specific proteolytic activity and was partly located on extracellular microparticles. Transcript levels of ADAM17 were increased in blood samples of patients with active AAV, but those of ADAM10 or tissue inhibitor of metalloproteinases 3, which inhibits ADAMs, were not. We also performed a microRNA (miR) screen and identified miR-634 as significantly upregulated in blood samples from patients with active AAV. In vitro, miR-634 mimics induced a proinflammatory phenotype in monocyte-derived macrophages, with enhanced expression and release of ADAM17 and IL-6. These data suggest that ADAM17 has a prominent role in AAV and might account for the vascular complications associated with this disease. PMID:25788529

  20. Dr. Lytle Adams' incendiary "bat bomb" of World War II.

    PubMed

    Christen, Arden G; Christen, Joan A

    2004-11-01

    On December 7, 1941, a 60-year old dentist from Irwin, Pennsylvania, Dr. Lytle S. Adams, was driving home from a vacation at Carlsbad Caverns in New Mexico. Hours earlier, he had been gripped with amazement as he witnessed millions of bats exiting the caves of Carlsbad. Listening to his car radio on his return trip, he was shocked to hear that Japan had just attacked Pearl Harbor. Dr. Adams, outraged over this travesty, began to mentally construct a plan for U.S. retaliation. As his thoughts returned to the countless bats that had awed him, he formed a tentative plan: millions of these small, flying mammals could be connected to tiny, time-fused incendiary bombs, and then released to land on the flimsily constructed structures which dotted the cities of Japan. Within a few minutes, the bombs would explode and enflame the entire urban areas. He postulated that these immeasurable numbers of fires, spreading their devastation over such vast areas within Japanese cities would result in the enemy's speedy surrender. This article documents the futile efforts of Dr. Adams, his team and the U.S. government to develop and employ an effective, incendiary bat bomb. The recently developed atom bomb, a far more deadly weapon was used in its place. PMID:15666497

  1. ADAM23 is downregulated in side population and suppresses lung metastasis of lung carcinoma cells.

    PubMed

    Ota, Masahide; Mochizuki, Satsuki; Shimoda, Masayuki; Abe, Hitoshi; Miyamae, Yuka; Ishii, Ken; Kimura, Hiroshi; Okada, Yasunori

    2016-04-01

    Cancer cells contain a small population of cancer stem cells or cancer initiating cells, which can be enriched in the side population (SP) after fluorescence activated cell sorting. To examine the members of the ADAM, ADAMTS and MMP gene families related to phenotypes of the SP and the main population (MP), we screened the expression of all the members in the propagated SP and MP of A549 lung adenocarcinoma cells, and found that the relative expression ratio of ADAM23 in the MP to the SP is most highly increased, but none of them are increased in the SP. A similar result on the ADAM23 expression was obtained with another cell line, Calu-3 cells. Overexpression of ADAM23 inhibited colony formation, cell adhesion and migration, and knockdown of ADAM23 by shRNA showed the reverse effects. ADAM23-mediated suppression of colony formation, cell adhesion and migration was greatly reduced by treatment with neutralizing anti-ADAM23 antibody, anti-αvβ3 integrin antibody and/or ADAM23 disintegrin peptide. Expression of cancer stem cell-related genes, including AKRC1/2, TM4SF1 and NR0B1, was increased by knockdown of ADAM23. In addition, lung metastasis of A549 transfectants with different levels of ADAM23 expression was negatively regulated by the ADAM23 expression levels. Our data provide evidence that ADAM23 plays a role in suppression of cancer cell progression through interaction with αvβ3 integrin, and suggest that downregulation of ADAM23 in SP cells may contribute toward providing a cancer stem cell phenotype by facilitating the activity of integrin αvβ3. PMID:26800504

  2. iRhoms 1 and 2 are essential upstream regulators of ADAM17-dependent EGFR signaling

    PubMed Central

    Li, Xue; Maretzky, Thorsten; Weskamp, Gisela; Monette, Sébastien; Qing, Xiaoping; Issuree, Priya Darshinee A.; Crawford, Howard C.; McIlwain, David R.; Mak, Tak W.; Salmon, Jane E.; Blobel, Carl P.

    2015-01-01

    The metalloproteinase ADAM17 (a disintegrin and metalloprotease 17) controls EGF receptor (EGFR) signaling by liberating EGFR ligands from their membrane anchor. Consequently, a patient lacking ADAM17 has skin and intestinal barrier defects that are likely caused by lack of EGFR signaling, and Adam17−/− mice die perinatally with open eyes, like Egfr−/− mice. A hallmark feature of ADAM17-dependent EGFR ligand shedding is that it can be rapidly and posttranslationally activated in a manner that requires its transmembrane domain but not its cytoplasmic domain. This suggests that ADAM17 is regulated by other integral membrane proteins, although much remains to be learned about the underlying mechanism. Recently, inactive Rhomboid 2 (iRhom2), which has seven transmembrane domains, emerged as a molecule that controls the maturation and function of ADAM17 in myeloid cells. However, iRhom2−/− mice appear normal, raising questions about how ADAM17 is regulated in other tissues. Here we report that iRhom1/2−/− double knockout mice resemble Adam17−/− and Egfr−/− mice in that they die perinatally with open eyes, misshapen heart valves, and growth plate defects. Mechanistically, we show lack of mature ADAM17 and strongly reduced EGFR phosphorylation in iRhom1/2−/− tissues. Finally, we demonstrate that iRhom1 is not essential for mouse development but regulates ADAM17 maturation in the brain, except in microglia, where ADAM17 is controlled by iRhom2. These results provide genetic, cell biological, and biochemical evidence that a principal function of iRhoms1/2 during mouse development is to regulate ADAM17-dependent EGFR signaling, suggesting that iRhoms1/2 could emerge as novel targets for treatment of ADAM17/EGFR-dependent pathologies. PMID:25918388

  3. Dissecting the role of ADAM10 as a mediator of Staphylococcus aureus α-toxin action.

    PubMed

    von Hoven, Gisela; Rivas, Amable J; Neukirch, Claudia; Klein, Stefan; Hamm, Christian; Qin, Qianqian; Meyenburg, Martina; Füser, Sabine; Saftig, Paul; Hellmann, Nadja; Postina, Rolf; Husmann, Matthias

    2016-07-01

    Staphylococcus aureus is a leading cause of bacterial infections in humans, including life-threatening diseases such as pneumonia and sepsis. Its small membrane-pore-forming α-toxin is considered an important virulence factor. By destroying cell-cell contacts through cleavage of cadherins, the metalloproteinase ADAM10 (a disintegrin and metalloproteinase 10) critically contributes to α-toxin-dependent pathology of experimental S. aureus infections in mice. Moreover, ADAM10 was proposed to be a receptor for α-toxin. However, it is unclear whether the catalytic activity or specific domains of ADAM10 are involved in mediating binding and/or subsequent cytotoxicity of α-toxin. Also, it is not known how α-toxin triggers ADAM10's enzymatic activity, and whether ADAM10 is invariably required for all α-toxin action on cells. In the present study, we show that efficient cleavage of the ADAM10 substrate epithelial cadherin (E-cadherin) requires supra-cytotoxic concentrations of α-toxin, leading to significant increases in intracellular [Ca(2+)]; the fall in cellular ATP levels, typically following membrane perforation, became observable at far lower concentrations. Surprisingly, ADAM10 was dispensable for α-toxin-dependent xenophagic targeting of S. aureus, whereas a role for α-toxin attack on the plasma membrane was confirmed. The catalytic site of ADAM10, furin cleavage site, cysteine switch and intracellular domain of ADAM10 were not required for α-toxin binding and subsequent cytotoxicity. In contrast, an essential role for the disintegrin domain and the prodomain emerged. Thus, co-expression of the prodomain with prodomain-deficient ADAM10 reconstituted binding of α-toxin and susceptibility of ADAM10-deficient cells. The results of the present study may help to inform structural analyses of α-toxin-ADAM10 interactions and to design novel strategies to counteract S. aureus α-toxin action. PMID:27147619

  4. ADAM10 Is Involved in Cell Junction Assembly in Early Porcine Embryo Development

    PubMed Central

    Kwon, Jeongwoo; Jeong, Sung-min; Choi, Inchul; Kim, Nam-Hyung

    2016-01-01

    ADAM10 (A Disintegrin and Metalloprotease domain-containing protein 10) is a cell surface protein with a unique structure possessing both potential adhesion and protease domains. However, the role of ADAM10 in preimplantation stage embryos is not clear. In this study, we examined the expression patterns and functional roles of ADAM10 in porcine parthenotes during preimplantation development. The transcription level of ADAM10 dramatically increased from the morula stage onward. Immunostaining revealed that ADAM10 was present in both the nucleus and cytoplasm in early cleavage stage embryos, and localized to the apical region of the outer cells in morula and blastocyst embryos. Knockdown (KD) of ADAM10 using double strand RNA did not alter preimplantation embryo development until morula stage, but resulted in significantly reduced development to blastocyst stage. Moreover, the KD blastocyst showed a decrease in gene expression of adherens and tight junction (AJ/TJ), and an increase in trophectoderm TJ permeability by disrupting TJ assembly. Treatment with an ADAM10 specific chemical inhibitor, GI254023X, at the morula stage also inhibited blastocyst development and led to disruption of TJ assembly. An in situ proximity ligation assay demonstrated direct interaction of ADAM10 with coxsackie virus and adenovirus receptor (CXADR), supporting the involvement of ADAM10 in TJ assembly. In conclusion, our findings strongly suggest that ADADM10 is important for blastocyst formation rather than compaction, particularly for TJ assembly and stabilization in preimplantation porcine parthenogenetic development. PMID:27043020

  5. ADAM10 Is Involved in Cell Junction Assembly in Early Porcine Embryo Development.

    PubMed

    Kwon, Jeongwoo; Jeong, Sung-min; Choi, Inchul; Kim, Nam-Hyung

    2016-01-01

    ADAM10 (A Disintegrin and Metalloprotease domain-containing protein 10) is a cell surface protein with a unique structure possessing both potential adhesion and protease domains. However, the role of ADAM10 in preimplantation stage embryos is not clear. In this study, we examined the expression patterns and functional roles of ADAM10 in porcine parthenotes during preimplantation development. The transcription level of ADAM10 dramatically increased from the morula stage onward. Immunostaining revealed that ADAM10 was present in both the nucleus and cytoplasm in early cleavage stage embryos, and localized to the apical region of the outer cells in morula and blastocyst embryos. Knockdown (KD) of ADAM10 using double strand RNA did not alter preimplantation embryo development until morula stage, but resulted in significantly reduced development to blastocyst stage. Moreover, the KD blastocyst showed a decrease in gene expression of adherens and tight junction (AJ/TJ), and an increase in trophectoderm TJ permeability by disrupting TJ assembly. Treatment with an ADAM10 specific chemical inhibitor, GI254023X, at the morula stage also inhibited blastocyst development and led to disruption of TJ assembly. An in situ proximity ligation assay demonstrated direct interaction of ADAM10 with coxsackie virus and adenovirus receptor (CXADR), supporting the involvement of ADAM10 in TJ assembly. In conclusion, our findings strongly suggest that ADADM10 is important for blastocyst formation rather than compaction, particularly for TJ assembly and stabilization in preimplantation porcine parthenogenetic development. PMID:27043020

  6. ADAM12-deficient zebrafish exhibit retardation in body growth at the juvenile stage without developmental defects.

    PubMed

    Tokumasu, Yudai; Iida, Atsuo; Wang, Zi; Ansai, Satoshi; Kinoshita, Masato; Sehara-Fujisawa, Atsuko

    2016-05-01

    ADAM (a disintegrin and metalloprotease) constitutes a family of multi-domain proteins that are involved in development, homeostasis, and disease. ADAM12 plays important roles in myogenesis and adipogenesis in mice; however, the precise physiological mechanisms are not known, and the function of this gene in other vertebrates has not been examined. In this study, we used a simple model vertebrate, the zebrafish, to investigate the functions of ADAM12 during development. Zebrafish adam12 is conserved with those of mammals in the synteny and the amino-acid sequence. We examined adam12 expression in zebrafish embryos by whole mount in situ hybridization and the promoter activity of the adam12 upstream sequence. We found that adam12 is strongly expressed in the cardiovascular system, erythroid progenitors, brain, and jaw cartilage during zebrafish development, and adam12-knockout zebrafish exhibited reduced body size in the juvenile stage without apparent morphological defects. Taken together, these results suggest that adam12 plays a significant role in the regulation of body growth during juvenile stage in zebrafish, although the precise molecular mechanisms await further study. PMID:27185351

  7. Effects of ADAM10 upregulation on progression, migration, and prognosis of nasopharyngeal carcinoma.

    PubMed

    You, Bo; Shan, Ying; Shi, Si; Li, Xingyu; You, Yiwen

    2015-11-01

    A disintegrin and metalloprotease 10 (ADAM10) is a typical member of the ADAMs family, which has been reported to be upregulated in various types of cancers and contribute to cancer progression and metastasis. However, little is known about the role of ADAM10 in nasopharyngeal carcinoma (NPC). The purpose of this study is to explore ADAM10 expression status and its biological functions in NPC. We first examined the expression of ADAM10 in NPC tissues and cell lines by immunohistochemistry, Western blotting, PCR, and immunofluorescence analysis. We observed that ADAM10 was significantly elevated in NPC and its expression level was correlated with T classification (P = 0.044), distant metastasis (P = 0.016), TNM clinical stage (P = 0.013), and proliferation marker Ki-67 expression (P = 0.001). Patients with NPC with high expression of ADAM10 had shorter overall survival rates. In addition, knockdown of ADAM10 by RNAi was found to inhibit the CNE-2 cell proliferation and migration. Our findings hinted that overexpression of ADAM10 promotes the progression and migration of NPC, which makes it a potential therapeutic target for the treatment of tumor metastases in NPC. PMID:26310711

  8. The "delivery" of Adam: a medical interpretation of Michelangelo.

    PubMed

    Di Bella, Stefano; Taglietti, Fabrizio; Iacobuzio, Andrea; Johnson, Emma; Baiocchini, Andrea; Petrosillo, Nicola

    2015-04-01

    This article describes what we believe to be the key to interpreting the concept represented by Michelangelo's painting the Creation of Adam. This fresco, one of his most famous masterpieces, is situated in the heart of the Sistine Chapel and is viewed by millions of people every year. A man of many talents, Michelangelo's proficiency in anatomical dissection is reflected in his artwork. As such, analyses of hidden meanings in this fresco have been ascribed, including the concept of the "Brain-God." However, we see a postpartum uterus and adjacent anatomy, justifying our interpretation that Michelangelo was depicting something far more fundamental: the birth of mankind. PMID:25841253

  9. ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

    PubMed Central

    2009-01-01

    Background ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer. Methods First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR) treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP). Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test. Results The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR) demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM); tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC) was 76.2% compared with 25.5% in invasive ductal carcinoma (IDC), and this

  10. Metalloproteinases ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas.

    PubMed

    Wang, Junwen; Voellger, Benjamin; Benzel, Julia; Schlomann, Uwe; Nimsky, Christopher; Bartsch, Jörg W; Carl, Barbara

    2016-09-15

    Invasion of tumor cells critically depends on cell-cell or cell-extracellular matrix interactions. Enzymes capable of modulating these interactions belong to the proteinase families of ADAM (a disintegrin and metalloprotease) and MMP (matrix metalloprotease) proteins. Our objective is to examine their expression levels and evaluate the relationship between expression levels and cavernous sinus invasion in pituitary adenomas. Tissue samples from 35 patients with pituitary adenomas were analyzed. Quantitative real-time polymerase chain reaction (qPCR) was employed to assess mRNA expression levels for ADAM and MMP genes. Protein levels were examined using immunohistochemistry and Western Blot. Correlation analyses between expression levels and clinical parameters were performed. By silencing ADAM12 and MMP-14 with siRNA in a mouse pituitary adenoma cell line (TtT/GF), their cellular effects were investigated. In our study, nine women and 26 men were included, with a mean age of 53.1 years (range 15-84 years) at the time of surgery. There were 19 cases with cavernous sinus invasion. The proteins ADAM12 and MMP-14 were significantly up-regulated in invasive adenomas compared to noninvasive adenomas. Both human isoforms of ADAM12 (ADAM12L and ADAM12s) were involved in tumor invasion; moreover, ADAM12L was found to correlate positively with Ki-67 proliferation index in pituitary adenomas. In TtT/GF pituitary adenoma cells, silencing of ADAM12 and MMP-14 significantly inhibited cell invasion and migration, respectively, whereas only silencing of ADAM12 suppressed cell proliferation. We conclude that ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas, which qualifies these proteins in diagnosis and therapy. PMID:27144841

  11. ADAM15 Is Functionally Associated with the Metastatic Progression of Human Bladder Cancer

    PubMed Central

    Rubin, John R.; Hayward, Alexandra; Cates, Angelica L.; Day, Kathleen C.; El-Sawy, Layla; Kunju, L. Priya; Daignault, Stephanie; Lee, Cheryl T.; Liebert, Monica; Hussain, Maha; Day, Mark L.

    2016-01-01

    ADAM15 is a member of a family of catalytically active disintegrin membrane metalloproteinases that function as molecular signaling switches, shed membrane bound growth factors and/or cleave and inactivate cell adhesion molecules. Aberrant metalloproteinase function of ADAM15 may contribute to tumor progression through the release of growth factors or disruption of cell adhesion. In this study, we utilized human bladder cancer tissues and cell lines to evaluate the expression and function of ADAM15 in the progression of human bladder cancer. Examination of genome and transcriptome databases revealed that ADAM15 ranked in the top 5% of amplified genes and its mRNA was significantly overexpressed in invasive and metastatic bladder cancer compared to noninvasive disease. Immunostaining of a bladder tumor tissue array designed to evaluate disease progression revealed increased ADAM15 immunoreactivity associated with increasing cancer stage and exhibited significantly stronger staining in metastatic samples. About half of the invasive tumors and the majority of the metastatic cases exhibited high ADAM15 staining index, while all low grade and noninvasive cases exhibited negative or low staining. The knockdown of ADAM15 mRNA expression significantly inhibited bladder tumor cell migration and reduced the invasive capacity of bladder tumor cells through MatrigelTM and monolayers of vascular endothelium. The knockdown of ADAM15 in a human xenograft model of bladder cancer inhibited tumor growth by 45% compared to controls. Structural modeling of the catalytic domain led to the design of a novel ADAM15-specific sulfonamide inhibitor that demonstrated bioactivity and significantly reduced the viability of bladder cancer cells in vitro and in human bladder cancer xenografts. Taken together, the results revealed an undescribed role of ADAM15 in the invasion of human bladder cancer and suggested that the ADAM15 catalytic domain may represent a viable therapeutic target in

  12. Levatiracetam for the management of Lance-Adams syndrome

    PubMed Central

    ILIK, Faik; Kemal ILIK, Mustafa; ÇÖVEN, İlker

    2014-01-01

    Chronic post-hypoxic myoclonus, also known as Lance-Adams syndrome (LAS) is a neurological complication characterized by uncontrolled myoclonic jerks following cardiac arrest. In this article, clinical manifestation and symptomatic treatment options are discussed especially concerning the rationale of use of levatiracetam in patients with Lance-Adams syndrome. Clinical presentation is action myoclonus associated with cerebellar ataxia, postural imbalance, and very mild intellectual deficit. An 18-year-old female patient was admitted to our intensive care unit in a coma. She had a cardiorespiratory arrest after a splenectomy in a local hospital. Then, myoclonic movements were continuously observed over the entire body, including the face. On day 14 of hospitalization, we started levatiracetam 1000 mg daily. The frequency of convulsion movements was reduced. The patient level of consciousness was 15 on the Glasgow coma scale (GCS) on the Mini-Mental State Examination (MMSE) score was 23 out of 30. She was later transferred to the rehabilitation department. Vigilance is required to ensure early diagnosis and timely intervention for the myoclonic jerks. We would like to emphasize that LAS should be considered in patients with the myoclonic jerks following cardiac arrest and that levatiracetam therapy may be useful as treatment. PMID:24949053

  13. The futility of utility: how market dynamics marginalize Adam Smith

    NASA Astrophysics Data System (ADS)

    McCauley, Joseph L.

    2000-10-01

    Economic theorizing is based on the postulated, nonempiric notion of utility. Economists assume that prices, dynamics, and market equilibria are supposed to be derived from utility. The results are supposed to represent mathematically the stabilizing action of Adam Smith's invisible hand. In deterministic excess demand dynamics I show the following. A utility function generally does not exist mathematically due to nonintegrable dynamics when production/investment are accounted for, resolving Mirowski's thesis. Price as a function of demand does not exist mathematically either. All equilibria are unstable. I then explain how deterministic chaos can be distinguished from random noise at short times. In the generalization to liquid markets and finance theory described by stochastic excess demand dynamics, I also show the following. Market price distributions cannot be rescaled to describe price movements as ‘equilibrium’ fluctuations about a systematic drift in price. Utility maximization does not describe equilibrium. Maximization of the Gibbs entropy of the observed price distribution of an asset would describe equilibrium, if equilibrium could be achieved, but equilibrium does not describe real, liquid markets (stocks, bonds, foreign exchange). There are three inconsistent definitions of equilibrium used in economics and finance, only one of which is correct. Prices in unregulated free markets are unstable against both noise and rising or falling expectations: Adam Smith's stabilizing invisible hand does not exist, either in mathematical models of liquid market data, or in real market data.

  14. DEVELOPMENT OF THE HUMAN LUNG MEASURED BY AEROSOL-DERIVED AIRWAY MORPHEMETRY (ADAM).

    EPA Science Inventory

    We measured, in vivo, the airspace calibers of the small airways and alveoli by ADAM in the lungs of children of ages 6 to 18 years and adults aged 18 to 80 years. ADAM utilizes the gravitational settling time of inhaled monodisperse particles to infer the vertical distance to th...

  15. ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease.

    PubMed

    Letronne, Florent; Laumet, Geoffroy; Ayral, Anne-Marie; Chapuis, Julien; Demiautte, Florie; Laga, Mathias; Vandenberghe, Michel E; Malmanche, Nicolas; Leroux, Florence; Eysert, Fanny; Sottejeau, Yoann; Chami, Linda; Flaig, Amandine; Bauer, Charlotte; Dourlen, Pierre; Lesaffre, Marie; Delay, Charlotte; Huot, Ludovic; Dumont, Julie; Werkmeister, Elisabeth; Lafont, Franck; Mendes, Tiago; Hansmannel, Franck; Dermaut, Bart; Deprez, Benoit; Hérard, Anne-Sophie; Dhenain, Marc; Souedet, Nicolas; Pasquier, Florence; Tulasne, David; Berr, Claudine; Hauw, Jean-Jacques; Lemoine, Yves; Amouyel, Philippe; Mann, David; Déprez, Rebecca; Checler, Frédéric; Hot, David; Delzescaux, Thierry; Gevaert, Kris; Lambert, Jean-Charles

    2016-07-01

    Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30(mut)) did not affect Aβ secretion. Proteomics/cell-based experiments showed that ADAM30-dependent regulation of APP metabolism required both cathepsin D (CTSD) activation and APP sorting to lysosomes. Accordingly, in Alzheimer-like transgenic mice, neuronal ADAM30 over-expression lowered Aβ42 secretion in neuron primary cultures, soluble Aβ42 and amyloid plaque load levels in the brain and concomitantly enhanced CTSD activity and finally rescued long term potentiation alterations. Our data thus indicate that lowering ADAM30 expression may favor Aβ production, thereby contributing to Alzheimer's disease development. PMID:27333034

  16. The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling

    PubMed Central

    Weber, Silvio; Niessen, Michaela T.; Prox, Johannes; Lüllmann-Rauch, Renate; Schmitz, Annika; Schwanbeck, Ralf; Blobel, Carl P.; Jorissen, Ellen; de Strooper, Bart; Niessen, Carien M.; Saftig, Paul

    2011-01-01

    The disintegrin and metalloproteinase Adam10 has been implicated in the regulation of key signaling pathways that determine skin morphogenesis and homeostasis. To address the in vivo relevance of Adam10 in the epidermis, we have selectively disrupted Adam10 during skin morphogenesis and in adult skin. K14-Cre driven epidermal Adam10 deletion leads to perinatal lethality, barrier impairment and absence of sebaceous glands. A reduction of spinous layers, not associated with differences in either proliferation or apoptosis, indicates that loss of Adam10 triggers a premature differentiation of spinous keratinocytes. The few surviving K14-Adam10-deleted mice and mice in which Adam10 was deleted postnatally showed loss of hair, malformed vibrissae, epidermal hyperproliferation, cyst formation, thymic atrophy and upregulation of the cytokine thymic stromal lymphopoetin (TSLP), thus indicating non cell-autonomous multi-organ disease resulting from a compromised barrier. Together, these phenotypes closely resemble skin specific Notch pathway loss-of-function phenotypes. Notch processing is indeed strongly reduced resulting in decreased levels of Notch intracellular domain fragment and functional Notch signaling. The data identify Adam10 as the major Site-2 processing enzyme for Notch in the epidermis in vivo, and thus as a central regulator of skin development and maintenance. PMID:21205794

  17. The shedding activity of ADAM17 is sequestered in lipid rafts

    SciTech Connect

    Tellier, Edwige; Canault, Matthias; Rebsomen, Laure; Bonardo, Bernadette; Juhan-Vague, Irene; Nalbone, Gilles; Peiretti, Franck . E-mail: Franck.Peiretti@medecine.univ-mrs.fr

    2006-12-10

    The tumor necrosis factor-alpha (TNF) converting enzyme (ADAM17) is a metalloprotease-disintegrin responsible for the cleavage of several biologically active transmembrane proteins. However, the substrate specificity of ADAM17 and the regulation of its shedding activity are still poorly understood. Here, we report that during its transport through the Golgi apparatus, ADAM17 is included in cholesterol-rich membrane microdomains (lipid rafts) where its prodomain is cleaved by furin. Consequently, ADAM17 shedding activity is sequestered in lipid rafts, which is confirmed by the fact that metalloproteinase inhibition increases the proportion of ADAM17 substrates (TNF and its receptors TNFR1 and TNFR2) in lipid rafts. Membrane cholesterol depletion increases the ADAM17-dependent shedding of these substrates demonstrating the importance of lipid rafts in the control of this process. Furthermore, ADAM17 substrates are present in different proportions in lipid rafts, suggesting that the entry of each of these substrates in these particular membrane microdomains is specifically regulated. Our data support the idea that one of the mechanisms regulating ADAM17 substrate cleavage involves protein partitioning in lipid rafts.

  18. Tumorigenicity of cortical astrocyte cell line induced by the protease ADAM17

    PubMed Central

    Katakowski, Mark; Jiang, Feng; Zheng, XuGuang; Gutierrez, Jorge A.; Szalad, Alexandra; Chopp, Michael

    2009-01-01

    The metalloprotease ADAM17 (a.k.a. TACE) plays a pivotal role in the cleavage and activation of membrane-anchored receptor ligands. More recently, it has been revealed that ADAM17 is a potent sheddase of the epidermal growth factor (EGF) family of ligands and regulates epidermal growth factor receptor (EGFR) activity in a variety of tumors. EGFR is a key component of autonomous growth signaling in several tumors, and correlates with the malignancy grade of astrocytoma. In this study, we tested the hypothesis that over-expression of ADAM17 in cortical astrocytes derived from normal brain would induce a progression towards a malignant phenotype. Over-expression of human ADAM17 (hADAM17) in the CTX-TNA2 cortical astrocyte cell line resulted in non-adherent growth, increased proliferation, invasiveness, production of angiogenic factors, and expression of genes associated with immature and/or neoplastic cells. hADAM17 up-regulated EGFR and AKT phosphorylation, and increased proliferation and cell invasion were significantly dependent upon EGFR activity. When implanted in the nude mouse brain, CTX-TNA2 cells induced low histological grade, benign intraventricular gliomas. In contrast, the same astrocytes with hADAM17 formed large malignant gliomas. Taken together, these findings suggest that unregulated ADAM17 activity induces functional changes in astrocytes that significantly advance the malignant phenotype. PMID:19515085

  19. Cell surface annexins regulate ADAM-mediated ectodomain shedding of proamphiregulin

    PubMed Central

    Nakayama, Hironao; Fukuda, Shinji; Inoue, Hirofumi; Nishida-Fukuda, Hisayo; Shirakata, Yuji; Hashimoto, Koji; Higashiyama, Shigeki

    2012-01-01

    A disintegrin and metalloproteinase (ADAM) is a family of enzymes involved in ectodomain shedding of various membrane proteins. However, the molecular mechanism underlying substrate recognition by ADAMs remains unknown. In this study, we successfully captured and analyzed cell surface transient assemblies between the transmembrane amphiregulin precursor (proAREG) and ADAM17 during an early shedding phase, which enabled the identification of cell surface annexins as components of their shedding complex. Annexin family members annexin A2 (ANXA2), A8, and A9 interacted with proAREG and ADAM17 on the cell surface. Shedding of proAREG was increased when ANXA2 was knocked down but decreased with ANXA8 and A9 knockdown, because of enhanced and impaired association with ADAM17, respectively. Knockdown of ANXA2 and A8 in primary keratinocytes altered wound-induced cell migration and ultraviolet B–induced phosphorylation of epidermal growth factor receptor (EGFR), suggesting that annexins play an essential role in the ADAM-mediated ectodomain shedding of EGFR ligands. On the basis of these data, we propose that annexins on the cell surface function as “shedding platform” proteins to determine the substrate selectivity of ADAM17, with possible therapeutic potential in ADAM-related diseases. PMID:22438584

  20. 77 FR 5291 - The Designation of Monir Chouka, also Known as Mounir Chouka, Also Known as Abu Adam, Also Known...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ... Germany, also Known as Abu Adam aus Deutschland, as a Specially Designated Global Terrorist Pursuant to... Monir Chouka, also known as Mounir Chouka, also known as Abu Adam from Germany, also known as Abu...

  1. The role of CXCL16 and its processing metalloproteinases ADAM10 and ADAM17 in the proliferation and migration of human mesangial cells

    SciTech Connect

    Schramme, Anja; Abdel-Bakky, Mohamed Sadek; Kaempfer-Kolb, Nicole; Pfeilschifter, Josef

    2008-05-30

    In this study, we analyzed the regulation and functional role of CXCL16 in human mesangial cells (hMCs). We can show, that CXCL16 is constitutively expressed in hMCs and is further up-regulated by cytokine mix (IFN{gamma}, TNF{alpha}, and IL1{beta}). The constitutive release of CXCL16 from hMCs was rapidly induced by the stimulation with cytokines. We identified ADAM10 and ADAM17 as being responsible for the cytokine-induced shedding of CXCL16. Notably, targeting ADAM10 and ADAM17 in hMCs decreased the chemotaxis of T-Jurkat cells, whereas the inhibition of CXCL16 had no significant influence. This suggests that both proteases are important players in the recruitment of immune cells into the glomerulus, but other substrates than CXCL16 are involved in this process. Finally, we could show that the inhibition of CXCL16, ADAM10, and ADAM17 led to a strong reduction of cell proliferation and migration of hMCs. This finding could be important to develop novel diagnostic and therapeutic strategies to treat mesangial proliferative kidney diseases.

  2. A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma.

    PubMed

    Kanzaki, Hiroyuki; Shinohara, Fumiaki; Suzuki, Maiko; Wada, Satoshi; Miyamoto, Yutaka; Yamaguchi, Yuuki; Katsumata, Yuta; Makihira, Seicho; Kawai, Toshi; Taubman, Martin A; Nakamura, Yoshiki

    2016-01-01

    Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption. Peptidases of the a-disintegrin and metalloproteinase (ADAM) family are implicated in cancer cell proliferation and tumor progression. We hypothesized that the ADAM enzymes expressed by cancer cells degrades IFN-γ and attenuates IFN-γ-mediated anti-tumorigenic and anti-osteoclastogenic effects. Recombinant ADAM17 degraded IFN-γ into small fragments. The addition of ADAM17 to the culture supernatant of stimulated mouse splenocytes decreased IFN-γ concentration. However, ADAM17 inhibition in the stimulated mouse T-cells prevented IFN-γ degradation. ADAM17-expressing human breast cancer cell lines MCF-7 and MDA-MB-453 also degraded recombinant IFN-γ, but this was attenuated by ADAM17 inhibition. Degraded IFN-γ lost the functionality including the inhibititory effect on osteoclastogenesis. This is the first study to demonstrate the extracellular proteolytic degradation of IFN-γ by ADAM17. These results suggest that ADAM17-mediated degradation of IFN-γ may block the anti-tumorigenic and anti-osteoclastogenic effects of IFN-γ. ADAM17 inhibition may be useful for the treatment of attenuated cancer immune surveillance and/or bone metastases. PMID:27573075

  3. A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma

    PubMed Central

    Kanzaki, Hiroyuki; Shinohara, Fumiaki; Suzuki, Maiko; Wada, Satoshi; Miyamoto, Yutaka; Yamaguchi, Yuuki; Katsumata, Yuta; Makihira, Seicho; Kawai, Toshi; Taubman, Martin A.; Nakamura, Yoshiki

    2016-01-01

    Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption. Peptidases of the a-disintegrin and metalloproteinase (ADAM) family are implicated in cancer cell proliferation and tumor progression. We hypothesized that the ADAM enzymes expressed by cancer cells degrades IFN-γ and attenuates IFN-γ-mediated anti-tumorigenic and anti-osteoclastogenic effects. Recombinant ADAM17 degraded IFN-γ into small fragments. The addition of ADAM17 to the culture supernatant of stimulated mouse splenocytes decreased IFN-γ concentration. However, ADAM17 inhibition in the stimulated mouse T-cells prevented IFN-γ degradation. ADAM17-expressing human breast cancer cell lines MCF-7 and MDA-MB-453 also degraded recombinant IFN-γ, but this was attenuated by ADAM17 inhibition. Degraded IFN-γ lost the functionality including the inhibititory effect on osteoclastogenesis. This is the first study to demonstrate the extracellular proteolytic degradation of IFN-γ by ADAM17. These results suggest that ADAM17-mediated degradation of IFN-γ may block the anti-tumorigenic and anti-osteoclastogenic effects of IFN-γ. ADAM17 inhibition may be useful for the treatment of attenuated cancer immune surveillance and/or bone metastases. PMID:27573075

  4. Identification of Novel Interaction between ADAM17 (a Disintegrin and Metalloprotease 17) and Thioredoxin-1*

    PubMed Central

    Aragão, Annelize Z. B.; Nogueira, Maria Luiza C.; Granato, Daniela C.; Simabuco, Fernando M.; Honorato, Rodrigo V.; Hoffman, Zaira; Yokoo, Sami; Laurindo, Francisco R. M.; Squina, Fabio M.; Zeri, Ana Carolina M.; Oliveira, Paulo S. L.; Sherman, Nicholas E.; Paes Leme, Adriana F.

    2012-01-01

    ADAM17, which is also known as TNFα-converting enzyme, is the major sheddase for the EGF receptor ligands and is considered to be one of the main proteases responsible for the ectodomain shedding of surface proteins. How a membrane-anchored proteinase with an extracellular catalytic domain can be activated by inside-out regulation is not completely understood. We characterized thioredoxin-1 (Trx-1) as a partner of the ADAM17 cytoplasmic domain that could be involved in the regulation of ADAM17 activity. We induced the overexpression of the ADAM17 cytoplasmic domain in HEK293 cells, and ligands able to bind this domain were identified by MS after protein immunoprecipitation. Trx-1 was also validated as a ligand of the ADAM17 cytoplasmic domain and full-length ADAM17 recombinant proteins by immunoblotting, immunolocalization, and solid phase binding assay. In addition, using nuclear magnetic resonance, it was shown in vitro that the titration of the ADAM17 cytoplasmic domain promotes changes in the conformation of Trx-1. The MS analysis of the cross-linked complexes showed cross-linking between the two proteins by lysine residues. To further evaluate the functional role of Trx-1, we used a heparin-binding EGF shedding cell model and observed that the overexpression of Trx-1 in HEK293 cells could decrease the activity of ADAM17, activated by either phorbol 12-myristate 13-acetate or EGF. This study identifies Trx-1 as a novel interaction partner of the ADAM17 cytoplasmic domain and suggests that Trx-1 is a potential candidate that could be involved in ADAM17 activity regulation. PMID:23105116

  5. A new species of Spiroberotha Adams 1989 (Neuroptera: Berothidae) and the first record of the genus in Brazil.

    PubMed

    Machado, Renato Jose Pires; Krolow, Tiago Kütter

    2016-01-01

    The genus Spiroberotha Adams, 1989 is classified in Berothidae (Neuroptera) with two described species: S. fernandezi Adams, 1989 from Venezuela and S. sanctarosae Adams, 1989 from Colombia, Costa Rica and Venezuela. Here we describe a new species, S. tocantinensis n. sp., from Palmas, Tocantins, Brazil. This is the first record of the genus in Brazil, extending its geographical distribution. PMID:27394485

  6. Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain

    SciTech Connect

    Endsley, Mark A.; Somasunderam, Anoma D.; Li, Guangyu; Oezguen, Numan; Thiviyanathan, Varatharasa; Murray, James L.; Rubin, Donald H.; Hodge, Thomas W.; and others

    2014-04-15

    Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary human macrophages and immortalized cell lines. Silencing ADAM10 expression interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA. Furthermore, our data indicated that HIV-1 replication depends on the expression of ADAM15 and γ-secretase, which proteolytically processes ADAM10. Silencing ADAM15 or γ-secretase expression inhibits HIV-1 replication between reverse transcription and nuclear entry. Here, we show that ADAM10 expression also supports replication in CD4{sup +} T lymphocytes. The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm and immunoprecipitates and co-localizes with HIV-1 integrase, a key component of PIC. Taken together, our data support a model whereby ADAM15/γ-secretase processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel therapeutic target for inhibiting HIV-1 prior to nuclear entry. - Highlights: • Nuclear trafficking of the HIV-1 pre-integration complex depends on ADAM10. • ADAM10 associates with HIV-1 integrase in the pre-integration complex. • HIV-1 replication depends on the expression of ADAM15 and γ-secretase. • Silencing ADAM15 or γ-secretase expression inhibits nuclear import of viral cDNA. • ADAM10 is important for HIV-1 replication in human macrophages and CD4{sup +} T lymphocytes.

  7. Econophysical visualization of Adam Smith’s invisible hand

    NASA Astrophysics Data System (ADS)

    Cohen, Morrel H.; Eliazar, Iddo I.

    2013-02-01

    Consider a complex system whose macrostate is statistically observable, but yet whose operating mechanism is an unknown black-box. In this paper we address the problem of inferring, from the system’s macrostate statistics, the system’s intrinsic force yielding the observed statistics. The inference is established via two diametrically opposite approaches which result in the very same intrinsic force: a top-down approach based on the notion of entropy, and a bottom-up approach based on the notion of Langevin dynamics. The general results established are applied to the problem of visualizing the intrinsic socioeconomic force-Adam Smith’s invisible hand-shaping the distribution of wealth in human societies. Our analysis yields quantitative econophysical representations of figurative socioeconomic forces, quantitative definitions of “poor” and “rich”, and a quantitative characterization of the “poor-get-poorer” and the “rich-get-richer” phenomena.

  8. Defenses and morality: Adam Smith, Sigmund Freud, and contemporary psychoanalysis.

    PubMed

    Gabrinetti, Paul A; Özler, Sule

    2014-10-01

    In this paper we follow the development and transmission of moral learning from Adam Smith's impartial spectator to Sigmund Freud's superego and then to contemporary psychoanalysis. We argue that defenses are an integral component in the acquisition of any moral system. Elaborating on this argument, we assert that there is a progression from defensive systems that are "closed" to defensive systems that are "open," as defined in a recent work by Novick and Novick. The former system is "static, avoids reality, and is characterized by power dynamics, sadomasochism, and omnipotent defense." The latter, on the other hand, is a system that allows for "joy, creativity, spontaneity, love and it is attuned to reality." Furthermore, while Smith and Freud's systems are more one-person systems of defense, contemporary psychoanalysis has moved to more of a two-person system. PMID:25247288

  9. A Disintegrin and Metalloprotease (ADAM): Historical Overview of Their Functions

    PubMed Central

    Giebeler, Nives; Zigrino, Paola

    2016-01-01

    Since the discovery of the first disintegrin protein from snake venom and the following identification of a mammalian membrane-anchored metalloprotease-disintegrin implicated in fertilization, almost three decades of studies have identified additional members of these families and several biochemical mechanisms regulating their expression and activity in the cell. Most importantly, new in vivo functions have been recognized for these proteins including cell partitioning during development, modulation of inflammatory reactions, and development of cancers. In this review, we will overview the a disintegrin and metalloprotease (ADAM) family of proteases highlighting some of the major research achievements in the analysis of ADAMs’ function that have underscored the importance of these proteins in physiological and pathological processes over the years. PMID:27120619

  10. Neptune's Discovery: Le Verrier, Adams, and the Assignment of Credit

    NASA Astrophysics Data System (ADS)

    Sheehan, William

    2011-01-01

    As one of the most significant achievements of 19th century astronomy, the discovery of Neptune has been the subject of a vast literature. A large part of this literature--beginning with the period immediately after the optical discovery in Berlin--has been the obsession with assigning credit to the two men who attempted to calculate the planet's position (and initially this played out against the international rivalry between France and England). Le Verrier and Adams occupied much different positions in the Scientific Establishments of their respective countries; had markedly different personalities; and approached the investigation using different methods. A psychiatrist and historian of astronomy tries to provide some new contexts to the familiar story of the discovery of Neptune, and argues that the personalities of these two men played crucial roles in their approaches to the problem they set themselves and the way others reacted to their stimuli. Adams had features of high-functioning autism, while Le Verrier's domineering, obsessive, orderly personality--though it allowed him to be immensely productive--eventually led to serious difficulties with his peers (and an outright revolt). Though it took extraordinary smarts to calculate the position of Neptune, the discovery required social skills that these men lacked--and thus the process to discovery was more bumbling and adventitious than it might have been. The discovery of Neptune occurred at a moment when astronomy was changing from that of heroic individuals to team collaborations involving multiple experts, and remains an object lesson in the sociological aspects of scientific endeavor.

  11. ADAM10 is essential for cranial neural crest-derived maxillofacial bone development.

    PubMed

    Tan, Yu; Fu, Runqing; Liu, Jiaqiang; Wu, Yong; Wang, Bo; Jiang, Ning; Nie, Ping; Cao, Haifeng; Yang, Zhi; Fang, Bing

    2016-07-01

    Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. PMID:27221046

  12. Activation of peroxisome proliferator-activated receptor α stimulates ADAM10-mediated proteolysis of APP.

    PubMed

    Corbett, Grant T; Gonzalez, Frank J; Pahan, Kalipada

    2015-07-01

    Amyloid precursor protein (APP) derivative β-amyloid (Aβ) plays an important role in the pathogenesis of Alzheimer's disease (AD). Sequential proteolysis of APP by β-secretase and γ-secretase generates Aβ. Conversely, the α-secretase "a disintegrin and metalloproteinase" 10 (ADAM10) cleaves APP within the eventual Aβ sequence and precludes Aβ generation. Therefore, up-regulation of ADAM10 represents a plausible therapeutic strategy to combat overproduction of neurotoxic Aβ. Peroxisome proliferator-activated receptor α (PPARα) is a transcription factor that regulates genes involved in fatty acid metabolism. Here, we determined that the Adam10 promoter harbors PPAR response elements; that knockdown of PPARα, but not PPARβ or PPARγ, decreases the expression of Adam10; and that lentiviral overexpression of PPARα restored ADAM10 expression in Ppara(-/-) neurons. Gemfibrozil, an agonist of PPARα, induced the recruitment of PPARα:retinoid x receptor α, but not PPARγ coactivator 1α (PGC1α), to the Adam10 promoter in wild-type mouse hippocampal neurons and shifted APP processing toward the α-secretase, as determined by augmented soluble APPα and decreased Aβ production. Accordingly, Ppara(-/-) mice displayed elevated SDS-stable, endogenous Aβ and Aβ1-42 relative to wild-type littermates, whereas 5XFAD mice null for PPARα (5X/α(-/-)) exhibited greater cerebral Aβ load relative to 5XFAD littermates. These results identify PPARα as an important factor regulating neuronal ADAM10 expression and, thus, α-secretase proteolysis of APP. PMID:26080426

  13. An improved fluorescent substrate for assaying soluble and membrane-associated ADAM family member activities.

    PubMed

    Moss, Marcia L; Minond, Dmitriy; Yoneyama, Toshie; Hansen, Hinrich P; Vujanovic, Nikola; Rasmussen, Fred H

    2016-08-15

    A fluorescent resonance energy transfer substrate with improved sensitivity for ADAM17, -10, and -9 (where ADAM represents a disintegrin and metalloproteinase) has been designed. The new substrate, Dabcyl-Pro-Arg-Ala-Ala-Ala-Homophe-Thr-Ser-Pro-Lys(FAM)-NH2, has specificity constants of 6.3 (±0.3) × 10(4) M(-1) s(-1) and 2.4 (±0.3) × 10(3) M(-1) s(-1) for ADAM17 and ADAM10, respectively. The substrate is more sensitive than widely used peptides based on the precursor tumor necrosis factor-alpha (TNF-alpha) cleavage site, PEPDAB010 or Dabcyl-Ser-Pro-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser-Lys(FAM)-NH2 and Mca-Pro-Leu-Ala-Gln-Ala-Val-Dpa-Arg-Ser-Ser-Arg-NH2. ADAM9 also processes the new peptide more than 18-fold better than the TNF-alpha-based substrates. The new substrate has a unique selectivity profile because it is processed less efficiently by ADAM8 and MMP1, -2, -3, -8, -9, -12, and -14. This substrate provides a unique tool in which to assess ADAM17, -10, and -9 activities. PMID:27177841

  14. SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation

    PubMed Central

    Saraceno, C; Marcello, E; Di Marino, D; Borroni, B; Claeysen, S; Perroy, J; Padovani, A; Tramontano, A; Gardoni, F; Di Luca, M

    2014-01-01

    A disintegrin and metalloproteinase 10 (ADAM10) is the major α-secretase that catalyzes the amyloid precursor protein (APP) ectodomain shedding in the brain and prevents amyloid formation. Its activity depends on correct intracellular trafficking and on synaptic membrane insertion. Here, we describe that in hippocampal neurons the synapse-associated protein-97 (SAP97), an excitatory synapse scaffolding element, governs ADAM10 trafficking from dendritic Golgi outposts to synaptic membranes. This process is mediated by a previously uncharacterized protein kinase C phosphosite in SAP97 SRC homology 3 domain that modulates SAP97 association with ADAM10. Such mechanism is essential for ADAM10 trafficking from the Golgi outposts to the synapse, but does not affect ADAM10 transport from the endoplasmic reticulum. Notably, this process is altered in Alzheimer's disease brains. These results help in understanding the mechanism responsible for the modulation of ADAM10 intracellular path, and can constitute an innovative therapeutic strategy to finely tune ADAM10 shedding activity towards APP. PMID:25429624

  15. ADAM10-Notch signaling governs the recruitment of ovarian pregranulosa cells and controls folliculogenesis in mice.

    PubMed

    Feng, Lizhao; Wang, Yijing; Cai, Han; Sun, Guanghong; Niu, Wanbao; Xin, Qiliang; Tang, Xiaofang; Zhang, Jiawei; Wang, Chao; Zhang, Hua; Xia, Guoliang

    2016-06-01

    Ovarian follicles are the basic functional units of female reproduction in the mammalian ovary. We show here that the protein a disintegrin and metalloproteinase domain 10 (ADAM10), a cell surface sheddase, plays an indispensable role in controlling primordial follicle formation by regulating the recruitment of follicle supporting cells in mice. We demonstrate that suppressing ADAM10 in vitro or deletion of Adam10 in vivo disrupts germline cyst breakdown and primordial follicle formation. Using a cell lineage tracing approach, we show that ADAM10 governs the recruitment of ovarian follicle cells by regulating the differentiation and proliferation of LGR5-positive follicle supporting progenitor cells. By detecting the development of FOXL2-positive pregranulosa cells, we found that inhibiting ADAM10 reduced the number of FOXL2-positive cells in perinatal ovaries. Furthermore, inhibiting ADAM10 suppressed the activation of Notch signaling, and blocking Notch signaling also disrupted the recruitment of follicle progenitor cells. Taken together, these results show that ADAM10-Notch signaling in ovarian somatic cells governs the primordial follicle formation by controlling the development of ovarian pregranulosa cells. The proper recruitment of ovarian follicle supporting cells is essential for establishment of the ovarian reserve in mice. PMID:27084580

  16. Regulation of adult hematopoiesis by the a disintegrin and metalloproteinase 10 (ADAM10).

    PubMed

    Weber, Silvio; Wetzel, Sebastian; Prox, Johannes; Lehmann, Tobias; Schneppenheim, Janna; Donners, Marjo; Saftig, Paul

    2013-12-13

    Adult hematopoiesis requires tightly regulated cell-cell interactions between hematopoietic cells and the bone marrow stromal microenvironment. We addressed the question if the ectodomain sheddase ADAM10 is essential to regulate adult hematopoiesis. Induced ADAM10 deletion in hematopoietic cells resulted in morphological and histological abnormalities that resemble an unclassified myeloproliferative disorder (MPD). The MPD was characterized by an expansion of granulocytic subpopulations and their infiltration of peripheral hematopoietic tissues, the development of hepatosplenomegaly with extramedullary erythropoiesis, lymphnodepathy and death of the mice around 20weeks after induction. ADAM10 expression analysis during the different stages of the MPD revealed that non-targeted hematopoietic cells repopulated the immune system of the ADAM10-deficient mice. Examination of mice with a myeloid- or epidermis-specific deletion of ADAM10 and bone marrow transplantation (BMT) experiments indicated that the development of the MPD can be triggered by non-cell autonomous effects. We found that plasma levels of clinical markers for MPD such as G-CSF, TIMP-1 and IL-16 were significantly elevated in ADAM10-deficient mice. Our findings indicate that a tightly controlled ADAM10 expression is needed to balance hematopoietic cell-fate decisions in adult mice. PMID:24239882

  17. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life

    PubMed Central

    Davies, Elizabeth R.; Kelly, Joanne F.C.; Howarth, Peter H.; Wilson, David I.; Holgate, Stephen T.; Davies, Donna E.; Whitsett, Jeffrey A.; Haitchi, Hans Michael

    2016-01-01

    Asthma is a chronic inflammatory airways disease that usually begins in early life and involves gene-environment interactions. Although most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Here, we report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma. We show that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and plays a role in airway remodeling, independent of inflammation. Furthermore, remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. When induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps to explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, we show that sADAM33-induced airway remodeling is reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma. PMID:27489884

  18. ADAM17 Controls Endochondral Ossification by Regulating Terminal Differentiation of Chondrocytes

    PubMed Central

    Hall, Katherine C.; Hill, Daniel; Otero, Miguel; Plumb, Darren A.; Froemel, Dara; Dragomir, Cecilia L.; Maretzky, Thorsten; Boskey, Adele; Crawford, Howard C.; Selleri, Licia; Goldring, Mary B.

    2013-01-01

    Endochondral ossification is a highly regulated process that relies on properly orchestrated cell-cell interactions in the developing growth plate. This study is focused on understanding the role of a crucial regulator of cell-cell interactions, the membrane-anchored metalloproteinase ADAM17, in endochondral ossification. ADAM17 releases growth factors, cytokines, and other membrane proteins from cells and is essential for epidermal growth factor receptor (EGFR) signaling and for processing tumor necrosis factor alpha. Here, we report that mice lacking ADAM17 in chondrocytes (A17ΔCh) have a significantly expanded zone of hypertrophic chondrocytes in the growth plate and retarded growth of long bones. This abnormality is caused by an accumulation of the most terminally differentiated type of chondrocytes that produces a calcified matrix. Inactivation of ADAM17 in osteoclasts or endothelial cells does not affect the zone of hypertrophic chondrocytes, suggesting that the main role of ADAM17 in the growth plate is in chondrocytes. This notion is further supported by in vitro experiments showing enhanced hypertrophic differentiation of primary chondrocytes lacking Adam17. The enlarged zone of hypertrophic chondrocytes in A17ΔCh mice resembles that described in mice with mutant EGFR signaling or lack of its ligand transforming growth factor α (TGFα), suggesting that ADAM17 regulates terminal differentiation of chondrocytes during endochondral ossification by activating the TGFα/EGFR signaling axis. PMID:23732913

  19. ADAM12-directed ectodomain shedding of E-cadherin potentiates trophoblast fusion.

    PubMed

    Aghababaei, M; Hogg, K; Perdu, S; Robinson, W P; Beristain, A G

    2015-12-01

    Trophoblasts, placental cells of epithelial lineage, undergo extensive differentiation to form the cellular components of the placenta. Trophoblast progenitor cell differentiation into the multinucleated syncytiotrophoblast is a key developmental process required for placental function, where defects in syncytiotrophoblast formation and turnover associate with placental pathologies and link to poor pregnancy outcomes. The cellular and molecular processes governing syncytiotrophoblast formation are poorly understood, but require the activation of pathways that direct cell fusion. The protease, A Disintegrin and Metalloproteinase 12 (ADAM12), controls cell fusion in myoblasts and is highly expressed in the placenta localizing to multiple trophoblast populations. However, the importance of ADAM12 in regulating trophoblast fusion is unknown. Here, we describe a function for ADAM12 in regulating trophoblast fusion. Using two distinct trophoblast models of cell fusion, we show that ADAM12 is dynamically upregulated and is under the transcriptional control of protein kinase A. siRNA-directed loss of ADAM12 impedes spontaneous fusion of primary cytotrophoblasts, whereas overexpression of the secreted variant, ADAM12S, potentiates cell fusion in the Bewo trophoblast cell line. Mechanistically, both ectopic and endogenous levels of ADAM12 were shown to control trophoblast fusion through E-cadherin ectodomain shedding and remodeling of intercellular boundaries. This study describes a novel role for ADAM12 in placental development, specifically highlighting its importance in controlling the differentiation of villous cytotrophoblasts into multinucleated cellular structures. Moreover, this work identifies E-cadherin as a novel ADAM12 substrate, and highlights the significance that cell adhesion molecule ectodomain shedding has in normal development. PMID:25909890

  20. Xenopus ADAM19 is involved in neural, neural crest and muscle development

    PubMed Central

    Neuner, Russell; Cousin, Hélène; McCusker, Catherine; Coyne, Michael; Alfandari, Dominique

    2009-01-01

    ADAM19 is a member of the meltrin subfamily of ADAM metalloproteases. In Xenopus, ADAM19 is present as a maternal transcript. Zygotic expression starts during gastrulation and is apparent in the dorsal blastopore lip. ADAM19 expression through neurulation and tailbud formation becomes enriched in dorsal structures such as the neural tube, the notochord and the somites. Using morpholino knock-down, we show that a reduction of ADAM19 protein in gastrula stage embryos results in a decrease of Brachyury expression in the notochord concomitant with an increase in the dorsal markers, Goosecoid and Chordin. These changes in gene expression are accompanied by a decrease in phosphorylated AKT, a downstream target of the EGF signaling pathway, and occur while the blastopore closes at the same rate as the control embryos. During neurulation and tailbud formation, ADAM19 knock-down induces a reduction of the neural markers N-tubulin and NRP1 but not Sox2. In the somitic mesoderm, the expression of MLC is also decreased while MyoD is not. ADAM19 knockdown also reduces neural crest markers prior to cell migration. Neural crest induction is also decreased in embryos treated with an EGF receptor inhibitor suggesting that this pathway is necessary for neural crest cell induction. Using targeted knockdown of ADAM19 we show that the reduction of neural and neural crest markers is cell autonomous and that the migration if the cranial neural crest is perturbed. We further show that ADAM19 protein reduction affects somite organization, reduces 12–101 expression and perturbs fibronectin localization at the intersomitic boundary. PMID:19027850

  1. Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

    PubMed

    Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

    2015-10-01

    Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness. PMID:24798404

  2. Recombinant disintegrin domain of ADAM15 inhibits the proliferation and migration of Bel-7402 cells

    SciTech Connect

    Hou, Y.; Chu, M.; Du, F.F.; Lei, J.Y.; Chen, Y.; Zhu, R.Y.; Gong, X.H.; Ma, X.; Jin, J.

    2013-06-14

    Highlights: •rhddADAM15 inhibited the proliferation and migration of Bel-7402 cells. •rhddADAM15 inhibited growth and metastasis of Bel-7402 cells in zebrafish xenograft. •rhddADAM15 induced apoptosis in Bel-7402 cells and somatic cells of zebrafish. •Cell-cycle in Bel-7402 cells showed a partial G{sub 2}/S arrest. •Activity of caspases 8, 9 and 3 was increased in rhddADAM15-treated Bel-7402 cells. -- Abstract: ADAM15 (A Disintegrin And Metalloproteinase 15), a transmembrane protein containing seven domains, interacts with some integrins via its disintegrin domain and overexpresses in many solid tumors. In this study, the effect of the recombinant human disintegrin domain (rhddADAM15) on the proliferation and migration of Bel-7402 cells was evaluated in vitro and in vivo in zebrafish xenografts. rhddADAM15 (4 μM) severely inhibited the proliferation and migration of Bel-7402 cells, inducing a partial G{sub 2}/S arrest and morphological nucleus changes of apoptosis. Moreover, the activity of caspases 8, 9 and 3 in Bel-7402 cells was increased. In addition, the zebrafish was used as a model for apoptosis-induction and tumor-xenograft. rhddADAM15 (1 pM) inhibited the growth and metastasis of Bel-7402 cell xenografts in zebrafish and a lower concentration (0.1 pM) induced severe apoptosis in the somatic cells of zebrafish. In conclusion, our data identified rhddADAM15 as a potent inhibitor of tumor growth and metastasis, making it a promising tool for use in anticancer treatment.

  3. Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

    PubMed Central

    Kuhn, Peer-Hendrik; Colombo, Alessio Vittorio; Schusser, Benjamin; Dreymueller, Daniela; Wetzel, Sebastian; Schepers, Ute; Herber, Julia; Ludwig, Andreas; Kremmer, Elisabeth; Montag, Dirk; Müller, Ulrike; Schweizer, Michaela; Saftig, Paul; Bräse, Stefan; Lichtenthaler, Stefan F

    2016-01-01

    Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain. DOI: http://dx.doi.org/10.7554/eLife.12748.001 PMID:26802628

  4. A comment on Adams' measurement of the gravitational redshift of Sirius B

    NASA Astrophysics Data System (ADS)

    Wesemael, F.

    1985-09-01

    Hetherington's contention that Adams' 1925 determination of the gravitational redshift of Sirius B is the result of a deliberate effort to reproduce the value predicted earlier on theoretical grounds is examined. It is emphasized that Adams' measurement may instead be the result of spectral contamination by scattered light from Sirius A, and the plausibility of that suggestion is confirmed by numerical simulations. There is thus, at present, no evidence to support the contention that Adams may not have acted objectively in this particular scientific endeavor.

  5. iRhom2 controls the substrate selectivity of stimulated ADAM17-dependent ectodomain shedding

    PubMed Central

    Maretzky, Thorsten; McIlwain, David R.; Issuree, Priya Darshinee A.; Li, Xue; Malapeira, Jordi; Amin, Sadaf; Lang, Philipp A.; Mak, Tak W.; Blobel, Carl P.

    2013-01-01

    Protein ectodomain shedding by ADAM17 (a disintegrin and metalloprotease 17), a principal regulator of EGF-receptor signaling and TNFα release, is rapidly and posttranslationally activated by a variety of signaling pathways, and yet little is known about the underlying mechanism. Here, we report that inactive rhomboid protein 2 (iRhom2), recently identified as essential for the maturation of ADAM17 in hematopoietic cells, is crucial for the rapid activation of the shedding of some, but not all substrates of ADAM17. Mature ADAM17 is present in mouse embryonic fibroblasts (mEFs) lacking iRhom2, and yet ADAM17 is unable to support stimulated shedding of several of its substrates, including heparin-binding EGF and Kit ligand 2 in this context. Stimulated shedding of other ADAM17 substrates, such as TGFα, is not affected in iRhom2−/− mEFs but can be strongly reduced by treating iRhom2−/− mEFs with siRNA against iRhom1. Activation of heparin-binding EGF or Kit ligand 2 shedding by ADAM17 in iRhom2−/− mEFs can be rescued by wild-type iRhom2 but not by iRhom2 lacking its N-terminal cytoplasmic domain. The requirement for the cytoplasmic domain of iRhom2 for stimulated shedding by ADAM17 may help explain why the cytoplasmic domain of ADAM17 is not required for stimulated shedding. The functional relevance of iRhom2 in regulating shedding of EGF receptor (EGFR) ligands is established by a lack of lysophasphatidic acid/ADAM17/EGFR-dependent crosstalk with ERK1/2 in iRhom2−/− mEFs, and a significant reduction of FGF7/ADAM17/EGFR-stimulated migration of iRhom2−/− keratinocytes. Taken together, these findings uncover functions for iRhom2 in the regulation of EGFR signaling and in controlling the activation and substrate selectivity of ADAM17-dependent shedding events. PMID:23801765

  6. Molecular design and structural optimization of potent peptide hydroxamate inhibitors to selectively target human ADAM metallopeptidase domain 17.

    PubMed

    Wang, Zhengting; Wang, Lei; Fan, Rong; Zhou, Jie; Zhong, Jie

    2016-04-01

    Human ADAMs (a disintegrin and metalloproteinases) have been established as an attractive therapeutic target of inflammatory disorders such as inflammatory bowel disease (IBD). The ADAM metallopeptidase domain 17 (ADAM17 or TACE) and its close relative ADAM10 are two of the most important ADAM members that share high conservation in sequence, structure and function, but exhibit subtle difference in regulation of downstream cell signaling events. Here, we described a systematic protocol that combined computational modeling and experimental assay to discover novel peptide hydroxamate derivatives as potent and selective inhibitors for ADAM17 over ADAM10. In the procedure, a virtual combinatorial library of peptide hydroxamate compounds was generated by exploiting intermolecular interactions involved in crystal and modeled structures. The library was examined in detail to identify few promising candidates with both high affinity to ADAM17 and low affinity to ADAM10, which were then tested in vitro with enzyme inhibition assay. Consequently, two peptide hydroxamates Hxm-Phe-Ser-Asn and Hxm-Phe-Arg-Gln were found to exhibit potent inhibition against ADAM17 (Ki=92 and 47nM, respectively) and strong selectivity for ADAM17 over ADAM10 (∼7-fold and ∼5-fold, S=0.86 and 0.71, respectively). The structural basis and energetic property of ADAM17 and ADAM10 interactions with the designed inhibitors were also investigated systematically. It is found that the exquisite network of nonbonded interactions involving the side chains of peptide hydroxamates is primarily responsible for inhibitor selectivity, while the coordination interactions and hydrogen bonds formed by the hydroxamate moiety and backbone of peptide hydroxamates confer high affinity to inhibitor binding. PMID:26709988

  7. TspanC8 Tetraspanins and A Disintegrin and Metalloprotease 10 (ADAM10) Interact via Their Extracellular Regions

    PubMed Central

    Noy, Peter J.; Yang, Jing; Reyat, Jasmeet S.; Matthews, Alexandra L.; Charlton, Alice E.; Furmston, Joanna; Rogers, David A.; Rainger, G. Ed; Tomlinson, Michael G.

    2016-01-01

    A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitously expressed transmembrane metalloprotease that cleaves the extracellular regions from its transmembrane substrates. ADAM10 is essential for embryonic development and is implicated in cancer, Alzheimer, and inflammatory diseases. The tetraspanins are a superfamily of 33 four-transmembrane proteins in mammals, of which the TspanC8 subgroup (Tspan5, 10, 14, 15, 17, and 33) promote ADAM10 intracellular trafficking and enzymatic maturation. However, the interaction between TspanC8s and ADAM10 has only been demonstrated in overexpression systems and the interaction mechanism remains undefined. To address these issues, an antibody was developed to Tspan14, which was used to show co-immunoprecipitation of Tspan14 with ADAM10 in primary human cells. Chimeric Tspan14 constructs demonstrated that the large extracellular loop of Tspan14 mediated its co-immunoprecipitation with ADAM10, and promoted ADAM10 maturation and trafficking to the cell surface. Chimeric ADAM10 constructs showed that membrane-proximal stalk, cysteine-rich, and disintegrin domains of ADAM10 mediated its co-immunoprecipitation with Tspan14 and other TspanC8s. This TspanC8-interacting region was required for ADAM10 exit from the endoplasmic reticulum. Truncated ADAM10 constructs revealed differential TspanC8 binding requirements for the stalk, cysteine-rich, and disintegrin domains. Moreover, Tspan15was the only TspanC8 to promote cleavage of the ADAM10 substrate N-cadherin, whereas Tspan14 was unique in reducing cleavage of the platelet collagen receptor GPVI. These findings suggest that ADAM10 may adopt distinct conformations in complex with different TspanC8s, which could impact on substrate selectivity. Furthermore, this study identifies regions of TspanC8s and ADAM10 for potential interaction-disrupting therapeutic targeting. PMID:26668317

  8. Differential expression of ADAM (a disintegrin and metalloproteinase) genes between human first trimester villous and extravillous trophoblast cells.

    PubMed

    Takahashi, Hironori; Yuge, Kazuya; Matsubara, Shigeki; Ohkuchi, Akihide; Kuwata, Tomoyuki; Usui, Rie; Suzuki, Mitsuaki; Takizawa, Toshihiro

    2014-01-01

    A disintegrin and metalloproteinases (ADAMs) are members of the metzincin family of zinc-dependent metalloproteinases that play pivotal roles in the proteolytic degradation of the extracellular matrix for cell invasion. Few studies have investigated the ADAM subtypes that are expressed in first trimester trophoblast cells. The purpose of this study was to elucidate the differential expression profiles of ADAMs between first trimester villous trophoblast cells (VTs) and extravillous trophoblast cells (EVTs). We isolated EVTs from explanted human first trimester chorionic villi and investigated the mRNA expression levels of five members of the ADAM family (ADAMTS1, ADAMTS2, ADAM10, ADAM12, and ADAM17) using real-time PCR. Chorionic villous tips were defined as first trimester VTs. Of the differentially expressed ADAM genes between first trimester VTs and EVTs, ADAMTS1 was expressed at a significantly higher level in EVTs than in VTs. In contrast, both ADAM10 and ADAM12 were expressed at significantly higher levels in VTs than in EVTs. No differences were found in the mRNA levels of ADAMTS2 and ADAM17 between the two cell types. Moreover, we demonstrated that in VTs, the expression level of ADAM12 was significantly downregulated in the late first trimester (10-13 gestational weeks) compared to the middle first trimester (7-8 weeks). These results suggest that first trimester trophoblast cells express ADAM genes in cell type- and gestational age-dependent manners. Our data provide additional insight into the functions of ADAMs in the human placenta. PMID:24998958

  9. Modulation of CD163 Expression by Metalloprotease ADAM17 Regulates Porcine Reproductive and Respiratory Syndrome Virus Entry

    PubMed Central

    Guo, Longjun; Niu, Junwei; Yu, Haidong; Gu, Weihong; Li, Ren; Luo, Xiaolei; Huang, Mingming; Tian, Zhijun; Feng, Li

    2014-01-01

    ABSTRACT As a consequence of their effects on ectodomain shedding, members of the A disintegrin and metalloprotease (ADAM) family have been implicated in the control of various cellular processes. Although ADAM family members are also involved in cancer, inflammation, and other pathologies, it is unclear whether they affect porcine reproductive and respiratory syndrome virus (PRRSV) infection. Here, we demonstrate for the first time that inhibition of ADAM17 enhances PRRSV entry in Marc-145 and porcine alveolar macrophages (PAMs). We also demonstrate that the inhibition of ADAM17 upregulates membrane CD163 expression, a putative PRRSV receptor that is exogenously expressed in BHK-21 and endogenously expressed in Marc-145 and PAMs. Furthermore, overexpression of ADAM17 induced downregulation of CD163 expression and a reduction in PRRSV infection, whereas ablation of ADAM17 expression using specific small interfering RNA resulted in upregulation of CD163 expression with a corresponding increase in PRRSV infection. These ADAM17-mediated effects were confirmed with PRRSV nonpermissive BHK-21 cells transfected with CD163 cDNA. Overall, these findings indicate that ADAM17 downregulates CD163 expression and hinders PRRSV entry. Hence, downregulation of ADAM17 particular substrates may be an additional component of the anti-infection defenses. IMPORTANCE ADAM17 is one of the important membrane-associated metalloproteases that mediate various cellular events, as well as inflammation, cancer, and other pathologies. Here, we investigate for the first time the role of the metalloprotease ADAM17 in PRRSV infection. By using inhibitor and genetic modification methods, we demonstrate that ADAM17 negatively regulate PRRSV entry by regulating its substrate(s). More specifically, ADAM 17 mediates the downregulation of the PRRSV cellular receptor CD163. The reduction in CD163 expression represents another component of the anti-infection response initiated by ADAM17. PMID:24965453

  10. The Fall of Adam Osborne: Why His Company Failed and What It Means for Personal Computing.

    ERIC Educational Resources Information Center

    Immel, A. Richard

    1984-01-01

    Discusses some of the reasons for the failure of the Osborne Computer Corporation, including Adam Osborne's personality and background, the people he selected to run the company, and lack of financial controls. (MBR)

  11. ISS Update: Adam Naids on Creating "€œNASA Johnson Style"

    NASA Video Gallery

    Public Affairs Officer Dan Huot talks to Adam Naids, Hardware Development Engineer, one of the creators of the successful "€œGangnam Style" parody video "€œNASA Johnson Style."€ Featured on NASAâ€...

  12. A novel peptide ADAM8 inhibitor attenuates bronchial hyperresponsiveness and Th2 cytokine mediated inflammation of murine asthmatic models.

    PubMed

    Chen, Jun; Deng, Linhong; Dreymüller, Daniela; Jiang, Xuemei; Long, Jiaoyue; Duan, Yiyuan; Wang, Yue; Luo, Mingzhi; Lin, Feng; Mao, Lizhen; Müller, Bernd; Koller, Garrit; Bartsch, Jörg W

    2016-01-01

    A disintegrin and metalloproteinase 8 (ADAM8) has been identified as a signature gene associated with moderate and severe asthma. Studies in mice have demonstrated that the severity of asthma can be reduced by either transgenic knock-out or by antibodies blocking ADAM8 function, highlighting ADAM8 as potential drug target for asthma therapy. Here, we examined the therapeutic effect of an ADAM8 inhibitor peptide (BK-1361) that specifically blocks cellular ADAM8 activity in ovalbumin-sensitized and challenged Balb/c mice. We found that BK-1361 (25 μg/g body weight) attenuated airway responsiveness to methacholine stimulation by up to 42%, concomitantly reduced tissue remodeling by 50%, and decreased inflammatory cells (e.g. eosinophils down by 54%)/inflammatory factors (e.g. sCD23 down by 50%)/TH2 cytokines (e.g. IL-5 down by 70%)/ADAM8-positive eosinophils (down by 60%) in the lung. We further verified that BK-1361 specifically targets ADAM8 in vivo as the peptide caused significantly reduced levels of soluble CD23 in wild-type but not in ADAM8-deficient mice. These findings suggest that BK-1361 blocks ADAM8-dependent asthma effects in vivo by inhibiting infiltration of eosinophils and TH2 lymphocytes, thus leading to reduction of TH2-mediated inflammation, tissue remodeling and bronchial hyperresponsiveness. Taken together, pharmacological ADAM8 inhibition appears as promising novel therapeutic strategy for the treatment of asthma. PMID:27458083

  13. The sorting protein PACS-2 promotes ErbB signalling by regulating recycling of the metalloproteinase ADAM17

    PubMed Central

    Dombernowsky, Sarah Louise; Samsøe-Petersen, Jacob; Petersen, Camilla Hansson; Instrell, Rachael; Hedegaard, Anne-Mette Bornhardt; Thomas, Laurel; Atkins, Katelyn Mae; Auclair, Sylvain; Albrechtsen, Reidar; Mygind, Kasper Johansen; Fröhlich, Camilla; Howell, Michael; Parker, Peter; Thomas, Gary; Kveiborg, Marie

    2015-01-01

    The metalloproteinase ADAM17 activates ErbB signalling by releasing ligands from the cell surface, a key step underlying epithelial development, growth, and tumour progression. However, mechanisms acutely controlling ADAM17 cell-surface availability to modulate the extent of ErbB ligand release are poorly understood. Here, through a functional genome-wide siRNA screen, we identify the sorting protein PACS-2 as a regulator of ADAM17 trafficking and ErbB signalling. PACS-2 loss reduces ADAM17 cell-surface levels and ADAM17-dependent ErbB ligand shedding, without apparent effects on related proteases. PACS-2 co-localizes with ADAM17 on early endosomes and PACS-2 knockdown decreases the recycling and stability of internalized ADAM17. Hence, PACS-2 sustains ADAM17 cell-surface activity by diverting ADAM17 away from degradative pathways. Interestingly, Pacs2-deficient mice display significantly reduced levels of phosphorylated EGFR and intestinal proliferation. We suggest that this mechanism controlling ADAM17 cell-surface availability and EGFR signalling may play a role in intestinal homeostasis, with potential implications for cancer biology. PMID:26108729

  14. A novel peptide ADAM8 inhibitor attenuates bronchial hyperresponsiveness and Th2 cytokine mediated inflammation of murine asthmatic models

    PubMed Central

    Chen, Jun; Deng, Linhong; Dreymüller, Daniela; Jiang, Xuemei; Long, Jiaoyue; Duan, Yiyuan; Wang, Yue; Luo, Mingzhi; Lin, Feng; Mao, Lizhen; Müller, Bernd; Koller, Garrit; Bartsch, Jörg W.

    2016-01-01

    A disintegrin and metalloproteinase 8 (ADAM8) has been identified as a signature gene associated with moderate and severe asthma. Studies in mice have demonstrated that the severity of asthma can be reduced by either transgenic knock-out or by antibodies blocking ADAM8 function, highlighting ADAM8 as potential drug target for asthma therapy. Here, we examined the therapeutic effect of an ADAM8 inhibitor peptide (BK-1361) that specifically blocks cellular ADAM8 activity in ovalbumin-sensitized and challenged Balb/c mice. We found that BK-1361 (25 μg/g body weight) attenuated airway responsiveness to methacholine stimulation by up to 42%, concomitantly reduced tissue remodeling by 50%, and decreased inflammatory cells (e.g. eosinophils down by 54%)/inflammatory factors (e.g. sCD23 down by 50%)/TH2 cytokines (e.g. IL-5 down by 70%)/ADAM8-positive eosinophils (down by 60%) in the lung. We further verified that BK-1361 specifically targets ADAM8 in vivo as the peptide caused significantly reduced levels of soluble CD23 in wild-type but not in ADAM8-deficient mice. These findings suggest that BK-1361 blocks ADAM8-dependent asthma effects in vivo by inhibiting infiltration of eosinophils and TH2 lymphocytes, thus leading to reduction of TH2-mediated inflammation, tissue remodeling and bronchial hyperresponsiveness. Taken together, pharmacological ADAM8 inhibition appears as promising novel therapeutic strategy for the treatment of asthma. PMID:27458083

  15. A-Disintegrin-And-Metalloproteinase (ADAM) 10 Activity on Resting and Activated Platelets.

    PubMed

    Facey, Adam; Pinar, Isaac; Arthur, Jane F; Qiao, Jianlin; Jing, Jing; Mado, Belden; Carberry, Josie; Andrews, Robert K; Gardiner, Elizabeth E

    2016-03-01

    The primary platelet collagen receptor, glycoprotein VI (GPVI), plays an important role in platelet activation and thrombosis. The ectodomain of human GPVI (sGPVI) is proteolytically shed from human platelets by a-disintegrin-and-metalloproteinase 10 (ADAM10). In this study, we used a novel ADAM10-sensitive fluorescence resonance energy transfer sensor to analyze ADAM10-mediated shedding of GPVI from human platelets in response to the exposure of GPVI ligands collagen-related peptide (10 μg/mL), collagen (10 μg/mL), and convulxin (0.1 μg/mL) to shear stress (1000-10000 s(-1), 5 min), or a generic activator of metalloproteinases, N-ethylmaleimide (NEM, 5 mM). Elevated shear, NEM, or ligand engagement of GPVI all induced shedding of GPVI, as detected by release of sGPVI; however, only shear or NEM significantly increased ADAM10 enzyme activity. ADAM10 activity was also detectable on the surface of thrombi formed on a collagen-coated surface under flow conditions. Our findings indicate different mechanisms regulate shear- and ligand-induced shedding and shear forces found within the vasculature can regulate ADAM10 activity. PMID:26840909

  16. Lrig2 Negatively Regulates Ectodomain Shedding of Axon Guidance Receptors by ADAM Proteases.

    PubMed

    van Erp, Susan; van den Heuvel, Dianne M A; Fujita, Yuki; Robinson, Ross A; Hellemons, Anita J C G M; Adolfs, Youri; Van Battum, Eljo Y; Blokhuis, Anna M; Kuijpers, Marijn; Demmers, Jeroen A A; Hedman, Håkan; Hoogenraad, Casper C; Siebold, Christian; Yamashita, Toshihide; Pasterkamp, R Jeroen

    2015-12-01

    Many guidance receptors are proteolytically cleaved by membrane-associated metalloproteases of the ADAM family, leading to the shedding of their ectodomains. Ectodomain shedding is crucial for receptor signaling and function, but how this process is controlled in neurons remains poorly understood. Here, we show that the transmembrane protein Lrig2 negatively regulates ADAM-mediated guidance receptor proteolysis in neurons. Lrig2 binds Neogenin, a receptor for repulsive guidance molecules (RGMs), and prevents premature Neogenin shedding by ADAM17 (TACE). RGMa reduces Lrig2-Neogenin interactions, providing ADAM17 access to Neogenin and allowing this protease to induce ectodomain shedding. Regulation of ADAM17-mediated Neogenin cleavage by Lrig2 is required for neurite growth inhibition by RGMa in vitro and for cortical neuron migration in vivo. Furthermore, knockdown of Lrig2 significantly improves CNS axon regeneration. Together, our data identify a unique ligand-gated mechanism to control receptor shedding by ADAMs and reveal functions for Lrigs in neuron migration and regenerative failure. PMID:26651291

  17. In silico investigation of ADAM12 effect on TGF-β receptors trafficking

    PubMed Central

    Gruel, Jérémy; LeBorgne, Michel; LeMeur, Nolwenn; Théret, Nathalie

    2009-01-01

    Background The transforming growth factor beta is known to have pleiotropic effects, including differentiation, proliferation and apoptosis. However the underlying mechanisms remain poorly understood. The regulation and effect of TGF-β signaling is complex and highly depends on specific protein context. In liver, we have recently showed that the disintegrin and metalloproteinase ADAM12 interacts with TGF-β receptors and modulates their trafficking among membranes, a crucial point in TGF-β signaling and development of fibrosis. The present study aims to better understand how ADAM12 impacts on TGF-β receptors trafficking and TGF-β signaling. Findings We extracted qualitative biological observations from experimental data and defined a family of models producing a behavior compatible with the presence of ADAM12. We computationally explored the properties of this family of models which allowed us to make novel predictions. We predict that ADAM12 increases TGF-β receptors internalization rate between the cell surface and the endosomal membrane. It also appears that ADAM12 modifies TGF-β signaling shape favoring a permanent response by removing the transient component observed under physiological conditions. Conclusion In this work, confronting differential models with qualitative biological observations, we obtained predictions giving new insights into the role of ADAM12 in TGF-β signaling and hepatic fibrosis process. PMID:19778441

  18. ADAMS/WT advanced development - version 1.4 and beyond

    SciTech Connect

    Elliott, A.S.; Depauw, T.R.

    1996-12-31

    ADAMS/WT is an wind-turbine-specific shell for the general-purpose mechanical system simulation package ADAMS5. It was developed under the guidance of the National Renewable Energy Laboratory to give engineers and analysts in the wind turbine community access to the analytical power of ADAMS, without having to become expert in its particular technology. The 1.4 version of ADAMS/WT is the most recent upgrade to the package, incorporating the most up-to-date version of the AeroDyn aerodynamic forcing subroutines from the University of Utah. It is also the first version to be made available on the Windows/NT platform. In version 1.4, ADAMS/WT has been significantly improved throughout and runs much faster. Automatic generation of standardized output has been added. The documentation has been extensively augmented with more detailed descriptions, more figures and more examples. ADAMS/WT remains the most powerful analytical tool available for horizontal-axis wind turbine development. 10 figs.

  19. ADAM and ADAMTS Family Proteins and Snake Venom Metalloproteinases: A Structural Overview

    PubMed Central

    Takeda, Soichi

    2016-01-01

    A disintegrin and metalloproteinase (ADAM) family proteins constitute a major class of membrane-anchored multidomain proteinases that are responsible for the shedding of cell-surface protein ectodomains, including the latent forms of growth factors, cytokines, receptors and other molecules. Snake venom metalloproteinases (SVMPs) are major components in most viper venoms. SVMPs are primarily responsible for hemorrhagic activity and may also interfere with the hemostatic system in envenomed animals. SVMPs are phylogenetically most closely related to ADAMs and, together with ADAMs and related ADAM with thrombospondin motifs (ADAMTS) family proteinases, constitute adamalysins/reprolysins or the M12B clan (MEROPS database) of metalloproteinases. Although the catalytic domain structure is topologically similar to that of other metalloproteinases such as matrix metalloproteinases, the M12B proteinases have a modular structure with multiple non-catalytic ancillary domains that are not found in other proteinases. Notably, crystallographic studies revealed that, in addition to the conserved metalloproteinase domain, M12B members share a hallmark cysteine-rich domain designated as the “ADAM_CR” domain. Despite their name, ADAMTSs lack disintegrin-like structures and instead comprise two ADAM_CR domains. This review highlights the current state of our knowledge on the three-dimensional structures of M12B proteinases, focusing on their unique domains that may collaboratively participate in directing these proteinases to specific substrates. PMID:27196928

  20. ADAM and ADAMTS Family Proteins and Snake Venom Metalloproteinases: A Structural Overview.

    PubMed

    Takeda, Soichi

    2016-01-01

    A disintegrin and metalloproteinase (ADAM) family proteins constitute a major class of membrane-anchored multidomain proteinases that are responsible for the shedding of cell-surface protein ectodomains, including the latent forms of growth factors, cytokines, receptors and other molecules. Snake venom metalloproteinases (SVMPs) are major components in most viper venoms. SVMPs are primarily responsible for hemorrhagic activity and may also interfere with the hemostatic system in envenomed animals. SVMPs are phylogenetically most closely related to ADAMs and, together with ADAMs and related ADAM with thrombospondin motifs (ADAMTS) family proteinases, constitute adamalysins/reprolysins or the M12B clan (MEROPS database) of metalloproteinases. Although the catalytic domain structure is topologically similar to that of other metalloproteinases such as matrix metalloproteinases, the M12B proteinases have a modular structure with multiple non-catalytic ancillary domains that are not found in other proteinases. Notably, crystallographic studies revealed that, in addition to the conserved metalloproteinase domain, M12B members share a hallmark cysteine-rich domain designated as the "ADAM_CR" domain. Despite their name, ADAMTSs lack disintegrin-like structures and instead comprise two ADAM_CR domains. This review highlights the current state of our knowledge on the three-dimensional structures of M12B proteinases, focusing on their unique domains that may collaboratively participate in directing these proteinases to specific substrates. PMID:27196928

  1. ADAM17 promotes breast cancer cell malignant phenotype through EGFR-PI3K-AKT activation

    PubMed Central

    Zheng, Xuguang; Jiang, Feng; Katakowski, Mark; Zhang, Zheng Gang; Lu, Qing-e; Chopp, Michael

    2009-01-01

    A disintegrin and metalloproteinase-17 (ADAM17) is involved in proteolytic ectodomain shedding of several membrane-bound growth factors and cytokines. The expression and activity of ADAM17 increase under some pathological conditions such as stroke and glioma. ADAM17 promotes neural progenitor cell migration and contributes to stroke-induced neurogenesis after stroke and brain tumor growth and invasion. In the present study, we sought to elucidate whether ADAM17 contributes to breast cancer progression and its mechanisms. To this end, we examined the role of ADAM17 in the proliferation, invasion, and tube formation of MDA-MB-231 breast cancer cells in vitro. Stable transfection of the MDA-MB-231 cell line with either a plasmid for over-expression of human ADAM17, or a siRNA to ADAM17 was employed in this study to establish high or low ADAM17 expression in breast cancer cells, respectively. For study of mechanism, the ADAM17 inhibitor TAPI-2 and the PI3K-AKT inhibitor LY294002 were used to counteract high ADAM17 expression or the activated PI3K-AKT pathway. Proliferation of MDA-MB-231 breast cancer cells were tested by MTT, Bromodeoxyuridine incorporation assay, growth curve, and sulforhodamine B assay. Matrigel invasion assays were used to assess the ability of MDA-MB-231 cells to penetrate the Extra Cellular Matrix. A Matrigel tube formation assay was performed to test capillary tube formation ability. EGFR-PI3K-Akt pathway activation in MDA-MB-231 cells under different ADAM17 expression levels were tested by Western blot and ELISA. Our data show that ADAM17 promotes the MDA-MB-231 malignant phenotype by increased proliferation, invasion and angiogenesis. TGF-α, VEGF secretion and VEGF expression was increasing by ADAM17 and counteracted by ADAM17 siRNA, TAPI-2, and LY294002 in MDA-MB-231 cells. ADAM17 activated, whereas ADAM17 siRNA, TAPI-2, and LY294002 deactivated the EGFR-PI3K-AKT signal pathway, which correlated with MDA-MB-231 cell malignant phenotype

  2. ADAM12 is a prognostic factor associated with an aggressive molecular subtype of high-grade serous ovarian carcinoma.

    PubMed

    Cheon, Dong-Joo; Li, Andrew J; Beach, Jessica A; Walts, Ann E; Tran, Hang; Lester, Jenny; Karlan, Beth Y; Orsulic, Sandra

    2015-07-01

    ADAM metallopeptidase domain 12 (ADAM12) is a promising biomarker because of its low expression in normal tissues and high expression in a variety of human cancers. However, ADAM12 levels in ovarian cancer have not been well characterized. We previously identified ADAM12 as one of the signature genes associated with poor survival in high-grade serous ovarian carcinoma (HGSOC). Here, we sought to determine if high levels of the ADAM12 protein and/or messenger RNA (mRNA) are associated with clinical variables in HGSOC. We show that high protein levels of ADAM12 in banked preoperative sera are associated with shorter progression-free and overall survival. Tumor levels of ADAM12 mRNA were also associated with shorter progression-free and overall survival as well as with lymphatic and vascular invasion, and residual tumor volume following cytoreductive surgery. The majority of genes co-expressed with ADAM12 in HGSOC were transforming growth factor (TGF)β signaling targets that function in collagen remodeling and cell-matrix adhesion. In tumor sections, the ADAM12 protein and mRNA were expressed in epithelial cancer cells and surrounding stromal cells. In vitro data showed that ADAM12 mRNA levels can be increased by TGFβ signaling and direct contact between epithelial and stromal cells. High tumor levels of ADAM12 mRNA were characteristic of the mesenchymal/desmoplastic molecular subtype of HGSOC, which is known to have the poorest prognosis. Thus, ADAM12 may be a useful biomarker of aggressive ovarian cancer for which standard treatment is not effective. PMID:25926422

  3. MT5-MMP, ADAM-10, and N-Cadherin Act in Concert To Facilitate Synapse Reorganization after Traumatic Brain Injury

    PubMed Central

    Warren, Kelly M.; Reeves, Thomas M.

    2012-01-01

    Abstract Matrix metalloproteinases (MMPs) influence synaptic recovery following traumatic brain injury (TBI). Membrane type 5-matrix metalloproteinase (MT5-MMP) and a distintegrin and metalloproteinase-10 (ADAM-10) are membrane-bound MMPs that cleave N-cadherin, a protein critical to synapse stabilization. This study examined protein and mRNA expression of MT5-MMP, ADAM-10, and N-cadherin after TBI, contrasting adaptive and maladaptive synaptogenesis. The effect of MMP inhibition on MT5-MMP, ADAM-10, and N-cadherin was assessed during maladaptive plasticity and correlated with synaptic function. Rats were subjected to adaptive unilateral entorhinal cortical lesion (UEC) or maladaptive fluid percussion TBI+bilateral entorhinal cortical lesion (TBI+BEC). Hippocampal MT5-MMP and ADAM-10 protein was significantly elevated 2 and 7 days post-injury. At 15 days after UEC, each MMP returned to control level, while TBI+BEC ADAM-10 remained elevated. At 2 and 7 days, N-cadherin protein was below control. By the 15-day synapse stabilization phase, UEC N-cadherin rose above control, a shift not seen for TBI+BEC. At 7 days, increased TBI+BEC ADAM-10 transcript correlated with protein elevation. UEC ADAM-10 mRNA did not change, and no differences in MT5-MMP or N-cadherin mRNA were detected. Confocal imaging showed MT5-MMP, ADAM-10, and N-cadherin localization within reactive astrocytes. MMP inhibition attenuated ADAM-10 protein 15 days after TBI+BEC and increased N-cadherin. This inhibition partially restored long-term potentiation induction, but did not affect paired-pulse facilitation. Our results confirm time- and injury-dependent expression of MT5-MMP, ADAM-10, and N-cadherin during reactive synaptogenesis. Persistent ADAM-10 expression was correlated with attenuated N-cadherin level and reduced functional recovery. MMP inhibition shifted ADAM-10 and N-cadherin toward adaptive expression and improved synaptic function. PMID:22489706

  4. "Mitochondrial Eve", "Y Chromosome Adam", testosterone, and human evolution.

    PubMed

    Howard, James Michael

    2002-01-01

    I suggest primate evolution began as a consequence of increased testosterone in males which increased aggression and sexuality, therefore, reproduction and success. With time, negative effects of excessive testosterone reduced spermatogenesis and started a decline of the group. Approximately 30-40 million years ago, the gene DAZ (Deleted in AZoospermia) appeared on the Y chromosome, increased spermatogenesis, and rescued the early primates from extinction. (Note: DAZ is considered by some to specifically, positively affect spermatogenesis; others suggest it has no effect on spermatogenesis.) Hominid evolution continued with increasing testosterone. The advent of increased testosterone in females of Homo erectus (or Homo ergaster) increased the female-to-male body size ratio, and eventually produced another era of excessive testosterone. Excessive testosterone caused a reduction in population size (bottleneck) that produced the "Mitochondrial Eve" (ME) mechanism. (Only certain females continued during the bottleneck to transmit their mitochondrial DNA.) That is, the ME mechanism culminated, again, in excessive testosterone and reduced spermatogenesis in the hominid line. Approximately 50,000 to 200,000 years ago, a "doubling" of the DAZ gene occurred on the Y chromosome in hominid males which rescued the hominid line with increased spermatogenesis in certain males. This produced the "Y Chromosome Adam" event. The doubling of DAZ allowed further increases in testosterone in hominids that resulted in the increased size and development of the brain. Modern humans periodically fluctuate between the positive and negative consequences of increased levels of testosterone, currently identifiable as the secular trend, increased infections, and reduced spermatogenesis. PMID:12449688

  5. Spiro K. Antiochos Receives 2013 John Adam Fleming Medal: Citation

    NASA Astrophysics Data System (ADS)

    Klimchuk, James A.

    2014-01-01

    The John Adam Fleming Medal is awarded for "original research and technical leadership in geomagnetism, atmospheric electricity, aeronomy, space physics, and related sciences." Originality and technical leadership are exactly the characteristics that distinguish the research of Spiro K. Antiochos. Spiro possesses a truly unique combination of physical insight, creativity, and mastery of the concepts and mathematical and numerical tools of space physics. These talents have allowed him to develop completely original theories for major observational problems and to test and refine those theories using sophisticated numerical simulation codes that he himself helped to develop. Spiro's physical insight is especially impressive. He has an uncanny ability to identify the fundamental aspects of complex problems and to see physical connections where others do not. This can sometimes involve ideas that may initially seem counterintuitive to those with less creativity. Many of Spiro's revolutionary advances have opened up whole new areas of study and shaped the course of space physics. Examples include the breakout model for coronal mass ejections (CMEs), the S-web model for the slow solar wind, and the thermal nonequilibrium model for solar prominences. The breakout model is of special significance to AGU as it strives to promote science for the betterment of humanity. CMEs are enormous explosions on the Sun that can have major "space weather" impacts here on Earth. They affect technologies ranging from communication and navigation systems to electrical power grids. Breakout is the leading theory for why CMEs occur and may one day be the foundation for more accurate space weather forecasting.

  6. Mutations in NOTCH1 cause Adams-Oliver syndrome.

    PubMed

    Stittrich, Anna-Barbara; Lehman, Anna; Bodian, Dale L; Ashworth, Justin; Zong, Zheyuan; Li, Hong; Lam, Patricia; Khromykh, Alina; Iyer, Ramaswamy K; Vockley, Joseph G; Baveja, Rajiv; Silva, Ermelinda Santos; Dixon, Joanne; Leon, Eyby L; Solomon, Benjamin D; Glusman, Gustavo; Niederhuber, John E; Roach, Jared C; Patel, Millan S

    2014-09-01

    Notch signaling determines and reinforces cell fate in bilaterally symmetric multicellular eukaryotes. Despite the involvement of Notch in many key developmental systems, human mutations in Notch signaling components have mainly been described in disorders with vascular and bone effects. Here, we report five heterozygous NOTCH1 variants in unrelated individuals with Adams-Oliver syndrome (AOS), a rare disease with major features of aplasia cutis of the scalp and terminal transverse limb defects. Using whole-genome sequencing in a cohort of 11 families lacking mutations in the four genes with known roles in AOS pathology (ARHGAP31, RBPJ, DOCK6, and EOGT), we found a heterozygous de novo 85 kb deletion spanning the NOTCH1 5' region and three coding variants (c.1285T>C [p.Cys429Arg], c.4487G>A [p.Cys1496Tyr], and c.5965G>A [p.Asp1989Asn]), two of which are de novo, in four unrelated probands. In a fifth family, we identified a heterozygous canonical splice-site variant (c.743-1 G>T) in an affected father and daughter. These variants were not present in 5,077 in-house control genomes or in public databases. In keeping with the prominent developmental role described for Notch1 in mouse vasculature, we observed cardiac and multiple vascular defects in four of the five families. We propose that the limb and scalp defects might also be due to a vasculopathy in NOTCH1-related AOS. Our results suggest that mutations in NOTCH1 are the most common cause of AOS and add to a growing list of human diseases that have a vascular and/or bony component and are caused by alterations in the Notch signaling pathway. PMID:25132448

  7. Fendiline inhibits proliferation and invasion of pancreatic cancer cells by interfering with ADAM10 activation and β-catenin signaling

    PubMed Central

    Woods, Neha; Trevino, Jose; Coppola, Domenico; Chellappan, Srikumar; Yang, Shengyu; Padmanabhan, Jaya

    2015-01-01

    ADAM10 (A Disintegrin and Metalloprotease Domain 10) affects the pathophysiology of various cancers, and we had shown that inhibition of ADAM10 sensitizes pancreatic cancer cells to gemcitabine. ADAM10 is activated in response to calcium influx, and here we examined if calcium channel blockers (CCB) would impede ADAM10 activation and affect biology of pancreatic cancer cells. We find that the CCB, fendiline, significantly reduces proliferation, migration, invasion, and anchorage independent growth of pancreatic cancer cells. This was associated with ADAM10 inhibition and its localization at the actin-rich membrane protrusions. Further, fendiline-treated cells formed cadherin-catenin positive tight adherens junctions and elicited defective protein trafficking and recycling. Furthermore, the expression of β-catenin target genes, cyclinD1, c-Myc and CD44, were significantly decreased, suggesting that fendiline might prevent cell proliferation and migration by inhibiting ADAM10 function, cadherin proteolysis and stabilization of cadherin-catenin interaction at the plasma membrane. This will subsequently diminish β-catenin intracellular signaling and repress TCF/LEF target gene expression. Supporting this notion, RNAi-directed downregulation of ADAM10 in cancer cells decreased the expression of cyclinD1, c-Myc and CD44. Furthermore, analysis of human pancreatic tumor tissue microarrays and lysates showed elevated levels of ADAM10, suggesting that aberrant activation of ADAM10 plays a fundamental role in growth and metastasis of PDACs and inhibiting this pathway might be a viable strategy to combat PDACs. PMID:26440150

  8. Expression of a disintegrin and metalloprotease (ADAM and ADAMTS) enzymes in human non-small-cell lung carcinomas (NSCLC)

    PubMed Central

    Rocks, N; Paulissen, G; Quesada Calvo, F; Polette, M; Gueders, M; Munaut, C; Foidart, J-M; Noel, A; Birembaut, P; Cataldo, D

    2006-01-01

    A Disintegrin and Metalloprotease (ADAM) are transmembrane proteases displaying multiple functions. ADAM with ThromboSpondin-like motifs (ADAMTS) are secreted proteases characterised by thrombospondin (TS) motifs in their C-terminal domain. The aim of this work was to evaluate the expression pattern of ADAMs and ADAMTS in non small cell lung carcinomas (NSCLC) and to investigate the possible correlation between their expression and cancer progression. Reverse transcriptase–polymerase chain reaction (RT–PCR), Western blot and immunohistochemical analyses were performed on NSCLC samples and corresponding nondiseased tissue fragments. Among the ADAMs evaluated (ADAM-8, -9, -10, -12, -15, -17, ADAMTS-1, TS-2 and TS-12), a modulation of ADAM-12 and ADAMTS-1 mRNA expression was observed. Amounts of ADAM-12 mRNA transcripts were increased in tumour tissues as compared to the corresponding controls. In sharp contrast, ADAMTS-1 mRNA levels were significantly lower in tumour tissues when compared to corresponding nondiseased lung. These results were corroborated at the protein level by Western blot and immunohistochemistry. A positive correlation was observed between the mRNA levels of ADAM-12 and those of two vascular endothelial growth factor (VEGF)-A isoforms (VEGF-A165 and VEGF-A121). Taken together, these results providing evidence for an overexpression of ADAM-12 and a lower expression of ADAMTS-1 in non-small-cell lung cancer suggest that these proteases play different functions in cancer progression. PMID:16495931

  9. TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    SciTech Connect

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-11-19

    Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

  10. Pyrococcus Furiosus Genome Supplementary Data from the Adams Laboratory at the University of Georgia

    DOE Data Explorer

    Adams, Michael W.W.; Weinberg, Michael V.; Schut, Gerrit J.; Brehm, Scott; Datta, Susmitta; Zhou, J.

    The research in the Adams Laboratory focuses on the physiology of hyperthermophilic organisms with an emphasis on metal-containing enzymes in the hyperthermophilic marine archaeon Pyrococcus furiosus. Three of the many articles from this University of Georgia lab have supplementary materials that are available on the Adams Lab website. All three sets of data are Open Reading Frames (ORFs) used for DNA microarray experiments and the changes in signal intensities. The full citations for the three articles are: 1) Weinberg, M. V., Schut, G. J., Brehm, S., Datta, S. and Adams, M. W. W. (2005) Cold shock of a hyperthermophilic archaeon: Pyrococcus furiosus exhibits multiple responses to a suboptimal growth temperature with a key role for membrane-bound glycoproteins. J Bacteriol. 187, 336-348; 2) Schut, G. J., Brehm, S. D., Datta, S. and Adams, M. W. W. (2003) "Whole genome DNA microarray analysis of a hyperthermophile and an archaeon: Pyrococcus furiosus grown on carbohydrates or peptides" J. Bacteriol. 185, 3935-3947; Schut, G. J., Zhou, J. and Adams, M. W. W. (2001) "DNA microarray analysis of the hyperthermophilic archaeon Pyrococcus furiosus evidence for a new type of sulfur-reducing enzyme" J. Bacteriol. 183, 7027-7036. Note that these articles are copyrighted by the Journal of Bacteriology.

  11. The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice.

    PubMed

    Kitaoka, Kazuyoshi; Shimizu, Noriyuki; Ono, Koji; Chikahisa, Sachiko; Nakagomi, Madoka; Shudo, Koichi; Ishimura, Kazunori; Séi, Hiroyoshi; Yoshizaki, Kazuo

    2013-09-01

    The retinoic acid (RA, a vitamin A metabolite) receptor (RAR) is a transcription factor. Vitamin A/RA administration improves the Alzheimer's disease (AD)- and age-related attenuation of memory/learning in mouse models. Recently, a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) was identified as a key molecule in RA-mediated anti-AD mechanisms. We investigated the effect of chronic administration of the RAR agonist Am80 (tamibarotene) on ADAM10 expression in senescence-accelerated mice (SAMP8). Moreover, we estimated changes in the expression of the amyloid precursor protein (APP), amyloid beta (Aβ), and hairy/enhancer of split (Hes), which are mediated by ADAM10. Spatial working memory and the levels of a hippocampal proliferation marker (Ki67) were also assessed in these mice. ADAM10 mRNA and protein expression was significantly reduced in the hippocampus of 13-month-old SAMP8 mice; their expression improved significantly after Am80 administration. Further, after Am80 administration, the expression levels of Hes5 and Ki67 were restored and the deterioration of working memory was suppressed, whereas APP and Aβ levels remained unchanged. Our results suggest that Am80 administration effectively improves dementia by activating the hippocampal ADAM10-Notch-Hes5 proliferative pathway. PMID:23624141

  12. Inverse regulation of the ADAM-family members, decysin and MADDAM/ADAM19 during monocyte differentiation

    PubMed Central

    Fritsche, Jana; Müller, Alexandra; Hausmann, Martin; Rogler, Gerhard; Andreesen, Reinhard; Kreutz, Marina

    2003-01-01

    Two members of the ADAM (a disintegrin and metalloprotease)-family, MADDAM and decysin, were described as dendritic cell (DC) maturation markers. We are interested in monocyte differentiation and investigated in particular the expression pattern of both genes during the differentiation of human monocytes into DC and macrophages (MAC). Both genes are weakly expressed in freshly isolated monocytes. In immature DC decysin mRNA was absent, even after induction of the terminal differentiation of DC by CD40L or tumour necrosis factor-α (TNF-α). Only in DC maturated by lipopolysaccharide (LPS) strong signals of decysin mRNA were detected. However, MADDAM mRNA was expressed in immature DC and the expression was markedly increased after induction of the terminal DC differentiation by various stimuli. In contrast, MAC showed a high constitutive decysin mRNA expression, but expressed no MADDAM mRNA. On protein level similar results of MADDAM expression were obtained. Stimulation of MAC by LPS did not induce MADDAM mRNA expression, while decysin mRNA expression was strongly increased. Further investigations revealed that the well-known inducer of MAC differentiation, 1α,25-dihydroxyvitamin D3 up-regulated decysin mRNA expression during the differentiation of primary monocytes and myelomonocytic THP-1 cells into MAC. In vivo decysin mRNA expression was only detected in human colon, but not in other tissues we examined. Accordingly, isolated intestinal MAC expressed decysin mRNA. In conclusion, decysin and MADDAM mRNA expression were regulated in an opposite way during monocyte differentiation: MADDAM mRNA and protein was mainly detected in DC, whereas decysin mRNA expression was mainly found in MAC. Therefore only MADDAM, but not decysin is a suitable marker for human monocyte-derived DC. PMID:14632642

  13. Cytokine secretion and NK cell activity in human ADAM17 deficiency

    PubMed Central

    Chavkin, Maor; Schmiedel, Dominik; Wong, Eitan; Werner, Marion; Yaacov, Barak; Averbuch, Diana; Molho-Pessach, Vered; Stepensky, Polina; Kaynan, Noa; Bar-On, Yotam; Seidel, Einat; Yamin, Rachel; Sagi, Irit; Elpeleg, Orly; Mandelboim, Ofer

    2015-01-01

    Genetic deficiencies provide insights into gene function in humans. Here we describe a patient with a very rare genetic deficiency of ADAM17. We show that the patient's PBMCs had impaired cytokine secretion in response to LPS stimulation, correlating with the clinical picture of severe bacteremia from which the patient suffered. ADAM17 was shown to cleave CD16, a major NK killer receptor. Functional analysis of patient's NK cells demonstrated that his NK cells express normal levels of activating receptors and maintain high surface levels of CD16 following mAb stimulation. Activation of individual NK cell receptors showed that the patient's NK cells are more potent when activated directly by CD16, albeit no difference was observed in Antibody Depedent Cytotoxicity (ADCC) assays. Our data suggest that ADAM17 inhibitors currently considered for clinical use to boost CD16 activity should be cautiously applied, as they might have severe side effects resulting from impaired cytokine secretion. PMID:26683521

  14. ADAM and ADAMTS family proteins and their role in the colorectal cancer etiopathogenesis

    PubMed Central

    Przemyslaw, Leszczynski; Boguslaw, Hendrich Andrzej; Elzbieta, Szmida; Malgorzata, Sasiadek Maria

    2013-01-01

    The ADAM and ADAMTS families, also called adamalysins belong to an important group of extracellular matrix proteins. The ADAMs family belong to both the transmembrane and secreted proteins, while ADAMTS family only contains secreted forms. Adamalysins play an important role in the cell phenotype regulation via their activities in signaling pathways, cell adhesion and migration. The human proteome contains 21 ADAM, and 19 ADAMTS proteins, which are involved in extracellular matrix remodeling, shedding of various substrates such as: adhesion ligands, growth factors, their receptors and diverse cytokines. Recent studies provide evidence that adamalysins play a crucial role in colorectal cancer (CRC) etiopathogenesis. It seems possible that adamalysins might be used as CRC prediction markers or potential pharmaceutical targets. [BMB Reports 2013; 46(3): 139-150] PMID:23527857

  15. [An important son of Aub: the military surgeon and ophthalmologist Johann Adam Schmidt (1759-1809)].

    PubMed

    Krogmann, Frank; Vollmuth, Ralf

    2009-01-01

    The following article gives you a review to the life and work of the military surgeon and ophthalmologist Johann Adam Schmidt who was born in Aub/Lower Franconia on the 12th of October 1759. He had got his surgical education in Würzburg and had worked as an Unterchirurgus in the War of the Bavarian succession. Later on he completed his education in Vienna where he, by joining different work places, had been appointed to a professorship at the Medico-Surgical Joseph's Academy and became a leading figure of the Austrian military medical service. Also as an ophthalmologist Johann Adam Schmidt obtained high credit for his practical activity and his academic work. Johann Adam Schmidt died on the 19th of February 1809 and left a multiplicity of publications. He got not least publicity as the doctor of Beethoven, who dedicated the trio for piano, clarinet or violin and violoncello (Es-major) Opus 38 to Schmidt. PMID:20509447

  16. The disintegrin domain of ADAM9: a ligand for multiple β1 renal integrins

    PubMed Central

    2004-01-01

    Renal tubular epithelial cells in all nephron segments express a distinct member of the metalloprotease-disintegrin family, ADAM9 (a disintegrin and metalloprotease 9), in a punctate basolateral distribution co-localized to the β1 integrin chain [Mahimkar, Baricos, Visaya, Pollock and Lovett (2000) J. Am. Soc. Nephrol. 11, 595–603]. Discrete segments of the nephron express several defined β1 integrins, suggesting that ADAM9 interacts with multiple renal integrins and thereby regulates epithelial cell–matrix interactions. Intact ADAM9 and a series of deletion constructs sequentially lacking the metalloprotease domain and the disintegrin domain were assembled as chimaeras with a C-terminal GFP (green fluorescent protein) tag. Stable expression of the ADAM9/GFP protein on the surface of HEK-293 cells (human embryonic kidney 293 cells) significantly decreased adhesion to types I and IV collagen, vitronectin and laminin, but had little effect on adhesion to fibronectin. Expression of the disintegrin/cysteine-rich/GFP construct yielded a similar, but more marked pattern of decreased adhesion. Expression of the cysteine-rich/GFP construct had no effect on adhesion, indicating that the disintegrin domain was responsible for the competitive inhibition of cell–matrix binding. To define the specific renal tubular β1 integrins interacting with the ADAM9 disintegrin domain, a recombinant GST (glutathione S-transferase)-disintegrin protein was used as a substrate in adhesion assays in the presence or absence of specific integrin-blocking antibodies. Inclusion of antibodies to α1, α3, α6, αv and β1 blocked adhesion of HEK-293 cells to GST-disintegrin protein. Immobilized GST-disintegrin domain perfused with renal cortical lysates specifically recovered the α3, α6, αv and β1 integrin chains by Western analysis. It is concluded that ADAM9 is a polyvalent ligand, through its disintegrin domain, for multiple renal integrins of the β1 class. PMID:15361064

  17. ADAM2 promotes migration of neuroblasts in the rostral migratory stream to the olfactory bulb

    PubMed Central

    Murase, Shin-ichi; Cho, Chunghee; White, Judith M.; Horwitz, Alan F.

    2009-01-01

    Neuroblasts migrate from the subventricular zone along the rostral migratory stream (RMS) to the olfactory bulb (OB). While the migration occurs by movement over other cells, the molecular mechanisms are poorly understood. We have found that ADAM2 (a disintegrin and metalloprotease 2) is expressed in migrating RMS neuroblasts and functions in their migration. The brains from ADAM2 knockout (KO) mice showed a smaller OB than that seen in wild-type (WT) mice at postnatal day 0. In addition, the RMS in ADAM2 KO mice appeared thinner and less voluminous in its rostral part and thicker in its caudal part. Estimates of migration in vivo using bromodeoxyuridine labeling revealed that neuroblasts from KO mice show a decreased migration rate compared with those from WT mice. Direct assays of migration by imaging living slices also showed a decreased migration speed and loss of directionality in the KO mice. This phenotype was similar to that seen in RMS containing slices from WT mice exposed to a peptide that mimicked the disintegrin loop of ADAM2. Finally, RMS explants from KO or WT mice that were cultured in Matrigel also revealed striking differences. The cells migrating out of explants from WT mice showed robust cell—cell interactions. In contrast, fewer cells migrated out of explants from ADAM2 KO mice, and those that did were largely dispersed and their migration inhibited. These experiments suggest that ADAM2 contributes to RMS migration, possibly through cell—cell interactions that mediate the rapid migration of the neuroblasts to their endpoint. PMID:18380661

  18. PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells.

    PubMed

    Marchesi, Nicoletta; Amadio, Marialaura; Colombrita, Claudia; Govoni, Stefano; Ratti, Antonia; Pascale, Alessia

    2016-09-01

    Neuronal ELAV/Hu (nELAV) are RNA-binding proteins that mainly regulate gene expression by increasing the stability and/or translation rate of target mRNAs bearing ARE (adenine and uracil-rich elements) sequences. Among nELAV target transcripts there is ADAM10, an α-secretase involved in the non-amyloidogenic processing of the amyloid-β protein precursor (AβPP) which leads to the production of the neuroprotective sAβPPα peptide. The aim of this study was to evaluate if nELAV depletion affects ADAM10 expression in human SH-SY5Y neuroblastoma cells. We also studied the effects of Bryostatin-1, a molecule able to activate nELAV protein cascade. The specific HuD/nELAV gene silencing decreased both nELAV and ADAM10 protein contents; similar results were obtained by Aβ40 treatment in wild-type SH-SY5Y cells. In HuD-silenced cells, the exposure to Bryostatin-1 counteracted both nELAV and ADAM10 proteins downregulation, by restoring nELAV/ADAM10 basal levels. We also found that sAβPPα release, which seemed not to be compromised by Aβ40 challenge or HuD-silencing, was favored by Bryostatin-1. Overall, these findings strongly suggest that a deficiency in nELAV content negatively affects ADAM10 expression and may play a role in neurodegenerative diseases, which may benefit by molecules activating ELAV cascade. PMID:27472877

  19. Cardiac conduction abnormalities and Stokes-Adams attacks in myotonic dystrophy.

    PubMed Central

    Noel, C.; Gagnon, R. M.

    1978-01-01

    Myotonic dystrophy is a well known cause of cardiomyopathy. While various cardiac conduction abnormalities have been described in patients with myotonic dystrophy, so far only sporadic cases of Stokes-Adams attacks have been reported. Of 27 patients with this disease various conduction disturbances were detected in 17 (63%), 5 of whom presented with Stokes-Adams attacks and were found to have intracardiac conduction defects. The prognosis in four of the five patients was greatly improved with permanent pacemaker implantation. Images FIG. 1 FIG. 2 PMID:657033

  20. Adam M. Reid: APA/APAGS Award for Distinguished Graduate Student in Professional Psychology.

    PubMed

    2015-11-01

    The APA/APAGS Award for Distinguished Graduate Student in Professional Psychology is awarded on an annual basis by the APA Board of Professional Affairs (BPA) and the American Psychological Association of Graduate Students (APAGS) to a graduate student who has demonstrated outstanding practice and application of psychology. One of the 2015 award winners is Adam M. Reid, who received this award "for his community service, in which he has integrated the highest standards of professional psychological clinical practice and science." Adam's award citation, biography, and a selected bibliography are presented here. PMID:26618976

  1. A Reader Response to File and Adams's "The Reality, Robustness, and Possible Superiority of Incidental Vocabulary Acquisition"

    ERIC Educational Resources Information Center

    Mason, Beniko; Krashen, Stephen

    2010-01-01

    File and Adams (2010) conclude that their data confirm the superiority of form-focused vocabulary instruction over incidental acquisition. The authors of this response argue that File and Adams's data actually confirm the reality, robustness, and possible superiority of incidental acquisition. Their subjects heard two passages read to them that…

  2. Problems with McAdams and Pals's (2006) Proposal of a Framework for an Integrative Theory of Personality

    ERIC Educational Resources Information Center

    Epstein, Seymour

    2007-01-01

    Comments on the original article "A New Big Five: Fundamental Principles for an Integrative Science of Personality," by Dan P. McAdams and Jennifer L. Pals (see record 2006-03947-002). Here, the current author begins with a critique of McAdams and Pals's (April 2006) five principles for a framework for an integrative theory of personality. The…

  3. MiR-222 modulates multidrug resistance in human colorectal carcinoma by down-regulating ADAM-17.

    PubMed

    Xu, Ke; Liang, Xin; Shen, Ke; Sun, Liyun; Cui, Daling; Zhao, Yuxia; Tian, Jianhui; Ni, Lei; Liu, Jianwen

    2012-10-15

    Colorectal carcinoma is a frequent cause of cancer-related death in men and women throughout the world. MicroRNAs are endogenous small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level. We investigated the role of ADAM-17 (a desintegrin and metalloproteases 17) as a novel multidrug resistance (MDR) mechanism in multidrug-resistant colorectal carcinoma (CRC) and the role of miR-222 in the development of MDR in CRC cells. We found that the high expression of ADAM-17, which results in growth factor shedding and growth factor receptor activation could induce drug resistance in CRC. Pharmacological inhibition of ADAM-17, in conjunction with chemotherapy, may have therapeutic potential for the treatment of CRC. ADAM-17 is a predicted target of miR-222, which was downregulated in multidrug-resistant CRC cells. The presence of miR-222 was consistently inversely proportionate to the expression levels of ADAM-17. We found that elevated levels of miR-222 in the mimics-transfected HCT116/L-OHP and HCT-8/VCR cells reduced the ADAM-17 protein level and the luciferase activity of an ADAM-17 3' untranslated region-based reporter and sensitized these cells' apoptosis to some anticancer drugs. Our findings suggest that miR-222 could play a role in the development of MDR by modulation of ADAM-17, the new MDR treatment target in colorectal carcinoma cells. PMID:22677042

  4. ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation.

    PubMed

    Meng, Xiangchao; Hu, Baoshan; Hossain, Mohammad Monir; Chen, Guofu; Sun, Ying; Zhang, Xuepeng

    2016-08-01

    A disintegrin and metalloproteinase-17 (ADAM17) can cut and release a wide variety of epidermal growth factor receptor (EGFR) ligands to promote survival, invasion and proliferation of cancer cell, and therefore, is considered to be a potential therapeutic target for cancer. The main goal of the present study was to observe the effects of ADAM17 small interfering RNA (ADAM17-siRNA) on human MCF-7 breast cancer and investigate its activation pathway. In vitro, MCF-7 cells were divided into ADAM17-siRNA groups, nonsense siRNA groups, AG1478 (selective EGFR blocker) groups, LY294002 [phosphatidylinositol 3-kinase (PI3K) phosphorylation inhibitor] groups, PD0325901 [mitogen extracellular kinase (MEK) inhibitor] groups and control groups. In vivo, MCF-7 cells were implanted subcutaneously into nude mice and then these mice were randomly divided into ADAM17-siRNA groups, vector groups and control groups. Our data showed that compared with the control groups, ADAM17-siRNA, AG1478 and LY294002 could inhibit the migration and proliferation of MCF-7 cells, but PD0325901 and nonsense siRNA did not show this effect. Except that specific ADAM17-siRNA could inhibit the expression of ADAM17 mRNA, others did not change it. Western blot analysis further confirmed that EGFR-PI3K-AKT signaling pathway is involved in ADAM17-siRNA inhibiting migration and proliferation of MCF-7 cells. Similarly to the former, the growth of MCF-7 breast cancer in nude mice was significantly inhibited by ADAM17-siRNA. Compared with the control group and the vector group, the tumor volume was smaller in the ADAM17-siRNA group, the tissues developed large areas of necrosis, immunohistochemistry showed low expressions of ADAM17 and Ki-67 and western blot analysis proved that the expression of ADAM17 protein in the tissue was also reduced. The present study suggests that ADAM17-siRNA inhibits MCF-7 breast cancer and is activated through the EGFR-PI3K-AKT signaling pathway. PMID:27221510

  5. Expression of ADAM15 in rheumatoid synovium: up-regulation by vascular endothelial growth factor and possible implications for angiogenesis

    PubMed Central

    Komiya, Koichiro; Enomoto, Hiroyuki; Inoki, Isao; Okazaki, Satoko; Fujita, Yoshinari; Ikeda, Eiji; Ohuchi, Eiko; Matsumoto, Hideo; Toyama, Yoshiaki; Okada, Yasunori

    2005-01-01

    ADAMs (a disintegrin and metalloproteinases) comprise a new gene family of metalloproteinases, and may play roles in cell-cell interaction, cell migration, signal transduction, shedding of membrane-anchored proteins and degradation of extracellular matrix. We screened the mRNA expression of 10 different ADAMs with a putative metalloproteinase motif in synovial tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Reverse transcription PCR and real-time quantitative PCR analyses indicated that among the ADAMs, ADAM15 mRNA was more frequently expressed in the RA samples and its expression level was significantly 3.8-fold higher in RA than in OA (p < 0.01). In situ hybridization, immunohistochemistry and immunoblotting demonstrated that ADAM15 is expressed in active and precursor forms in the synovial lining cells, endothelial cells of blood vessels and macrophage-like cells in the sublining layer of RA synovium. There was a direct correlation between ADAM15 mRNA expression levels and vascular density in the synovial tissues (r = 0.907, p < 0.001; n = 20). ADAM15 was constitutively expressed in RA synovial fibroblasts and human umbilical vein endothelial cells (HUVECs), and the expression level was increased in HUVECs by treatment with vascular endothelial growth factor (VEGF)165. On the other hand, ADAM15 expression in RA synovial fibroblasts was enhanced with VEGF165 only if vascular endothelial growth factor receptor (VEGFR)-2 expression was induced by treatment with tumor necrosis factor-α, and the expression was blocked with SU1498, a specific inhibitor of VEGFR-2. These data demonstrate that ADAM15 is overexpressed in RA synovium and its expression is up-regulated by the action of VEGF165 through VEGFR-2, and suggest the possibility that ADAM15 is involved in angiogenesis in RA synovium. PMID:16277668

  6. ADAM17 is critical for multipolar exit and radial migration of neuronal intermediate progenitor cells in mice cerebral cortex.

    PubMed

    Li, Qingyu; Zhang, Zhengyu; Li, Zengmin; Zhou, Mei; Liu, Bin; Pan, Le; Ma, Zhixing; Zheng, Yufang

    2013-01-01

    The radial migration of neuronal progenitor cells is critical for the development of cerebral cortex layers. They go through a critical step transforming from multipolar to bipolar before outward migration. A Disintegrin and Metalloprotease 17 (ADAM17) is a transmembrane protease which can process many substrates involved in cell-cell interaction, including Notch, ligands of EGFR, and some cell adhesion molecules. In this study, we used in utero electroporation to knock down or overexpress ADAM17 at embryonic day 14.5 (E14.5) in neuronal progenitor cells to examine the role of ADAM17 in cortical embryonic neurogenesis. Our results showed that the radial migration of ADAM17-knocked down cells were normal till E16.5 and reached the intermediate zone (IZ). Then most transfected cells stopped migration and stayed at the IZ to inner cortical plate (CP) layer at E18.5, and there was higher percentage of multipolar cells at IZ layer in the ADAM17-knocked down group compared to the cells in control group. Marker staining revealed that those ADAM17-knocked down cells differentiated normally from neural stem cells (NSCs) to neuronal intermediate progenitor cells (nIPCs) but did not differentiate into mature neurons. The migration and multipolar exit defects caused by ADAM17 knockdown could be partially rescued by over-expressing an shRNA resistant ADAM17, while overexpressing ADAM17 alone did not affect the radial migration. Taken together, our results showed for the first time that, ADAM17 is critical in regulating the multipolar-stage exit and radial migration of the nIPCs during telencephalon cortex development in mice. PMID:23755270

  7. The sheddase ADAM10 is a potent modulator of prion disease

    PubMed Central

    Altmeppen, Hermann C; Prox, Johannes; Krasemann, Susanne; Puig, Berta; Kruszewski, Katharina; Dohler, Frank; Bernreuther, Christian; Hoxha, Ana; Linsenmeier, Luise; Sikorska, Beata; Liberski, Pawel P; Bartsch, Udo; Saftig, Paul; Glatzel, Markus

    2015-01-01

    The prion protein (PrPC) is highly expressed in the nervous system and critically involved in prion diseases where it misfolds into pathogenic PrPSc. Moreover, it has been suggested as a receptor mediating neurotoxicity in common neurodegenerative proteinopathies such as Alzheimer's disease. PrPC is shed at the plasma membrane by the metalloprotease ADAM10, yet the impact of this on prion disease remains enigmatic. Employing conditional knockout mice, we show that depletion of ADAM10 in forebrain neurons leads to posttranslational increase of PrPC levels. Upon prion infection of these mice, clinical, biochemical, and morphological data reveal that lack of ADAM10 significantly reduces incubation times and increases PrPSc formation. In contrast, spatiotemporal analysis indicates that absence of shedding impairs spread of prion pathology. Our data support a dual role for ADAM10-mediated shedding and highlight the role of proteolytic processing in prion disease. DOI: http://dx.doi.org/10.7554/eLife.04260.001 PMID:25654651

  8. Higher Education Financing in the Fifty States: Significance for the 'Adams' States.

    ERIC Educational Resources Information Center

    Budig, Jeanne E.; Khan, Anwar

    Findings of a study on higher education financing in the states are summarized with specific reference for the states covered by the 1977 Adams versus Richardson decision. The study, "Higher Education Financing in the Fifty States: Interstate Comparisons" (Marilyn McCoy, D. Kent Halstead), was jointly issued by the National Center for Higher…

  9. Fractional Adams-Bashforth/Moulton methods: An application to the fractional Keller-Segel chemotaxis system

    NASA Astrophysics Data System (ADS)

    Zayernouri, Mohsen; Matzavinos, Anastasios

    2016-07-01

    We first formulate a fractional class of explicit Adams-Bashforth (A-B) and implicit Adams-Moulton (A-M) methods of first- and second-order accuracy for the time-integration of τ 0 CDt u (x , t) = g (t ; u), τ ∈ (0 , 1 ], where τ 0 CDt denotes the fractional derivative in the Caputo sense. In this fractional setting and in contrast to the standard Adams methods, an extra history load term emerges and the associated weight coefficients are τ-dependent. However when τ = 1, the developed schemes reduce to the well-known A-B and A-M methods with standard coefficients. Hence, in terms of scientific computing, our approach constitutes a minimal modification of the existing Adams libraries. Next, we develop an implicit-explicit (IMEX) splitting scheme for linear and nonlinear fractional PDEs of a general advection-reaction-diffusion type, and we apply our scheme to the time-space fractional Keller-Segel chemotaxis system. In this context, we evaluate the nonlinear advection term explicitly, employing the fractional A-B method in the prediction step, and we treat the corresponding diffusion term implicitly in the correction step using the fractional A-M scheme. Moreover, we perform the corresponding spatial discretization by employing an efficient and spectrally-accurate fractional spectral collocation method. Our numerical experiments exhibit the efficiency of the proposed IMEX scheme in solving nonlinear fractional PDEs.

  10. How To Survive in Postindustrial Environments: Adam Smith's Advice for Today's Colleges and Universities.

    ERIC Educational Resources Information Center

    Ortmann, Andreas

    1997-01-01

    Adam Smith's discussion of the payment modes of teachers and resulting consequences for the quality of teaching and process of curricular innovation are reviewed through the conceptual lens of modern agency theory. Smith's analysis of higher education in his day (eighteenth century) sheds light on faculty incentive and assessment problems that…

  11. Implementation of Distributed ADAMS Over Legion Using a Component DBMS Design. Final Report

    SciTech Connect

    Pfaltz, John L.; Orlandic, Ratko

    2002-11-26

    There were four primary research areas reported in the final report for the original funding period They are: implementation of high dimensional data spaces; knowledge discovery in scientific databases; and mismatch between implementing components; demonstrate the utility of ADAMS in a specific domain science.

  12. Serendipity in the Theater: Maude Adams as James M. Barrie's American Muse.

    ERIC Educational Resources Information Center

    Diaz de Chumaceiro, Cora L.

    2003-01-01

    This essay discusses how Maude Adams influenced James M. Barrie's creative process and became his inspiration. Set change theory is underscored as a cognitive explanation for Barrie's illumination. The psychoanalytic theory of transference is proposed as an underlying mechanism for facilitating the change of mental set during the incubation stage.…

  13. Black Employees in Traditionally White Institutions in the "Adams" States, 1975 to 1977.

    ERIC Educational Resources Information Center

    Pruitt, Anne S.

    Annual reports submitted to the federal government by eight states for 1975 and 1977 in compliance with criteria established by the Adams case were examined. Employment data from 232 formerly all-white institutions in the 8 states were evaluated, with emphasis on the public institutions in Arkansas, Georgia, Florida, and Maryland. The other states…

  14. Highlighting High Performance Buildings: Adam Joseph Lewis Center for Environmental Studies

    SciTech Connect

    2002-11-01

    Oberlin College's Adam Joseph Lewis Center for Environmental Studies is a high-performance building featuring an expansive photovoltaic system and a closed-loop groundwater heat pump system. Designers incorporated energy-efficient components and materials that are local, non-toxic, and durable.

  15. Comparing Adam Smith's Wealth of Nations to James Madison's Federalist #10.

    ERIC Educational Resources Information Center

    Mundell, Jean

    1987-01-01

    Presents a lesson which calls upon students to compare Adam Smith's WEALTH OF NATIONS to James Madison's FEDERALIST #10 to see how the ancient concept of individual rights and liberties was used to describe both economic and governmental systems. Presents questions to provide the basis for comparison. (GEA)

  16. Rhetorical Studies: A Reassessment of Adam Smith's Lectures on Rhetoric and Belles Lettres.

    ERIC Educational Resources Information Center

    Purcell, William M.

    1986-01-01

    Offers a dissenting interpretation of Adam Smith's Lectures on Rhetoric and Belles Lettres and a more conservative perspective on Smith's significance to the history of rhetorical theory. Views the lectures as an historical commentary on literature and rhetoric from the perspective of an eighteenth-century lecturer. (JD)

  17. Back to Beginnings: Credentialism, Productivity, and Adam Smith's Division of Labour.

    ERIC Educational Resources Information Center

    Davis, Denis J.

    1981-01-01

    The foundation of factional pressures for upgrading educational credentials in the labor market is examined through a review of human capital and screening theories. The writings of Adam Smith are referenced to show that the claims of the beneficial effects of educational upgrading have been questioned for 200 years. (Author/MLW)

  18. Two Rival Conceptions of Vocational Education: Adam Smith and Friedrich List.

    ERIC Educational Resources Information Center

    Winch, Christopher

    1998-01-01

    Examines and discusses two views of political economy: (1) the classical model of Adam Smith; and (2) the social capitalist model associated with Friedrich List. Explores two varieties of vocational education and training that emerge from a comparison of Smith's and List's ideas. (CMK)

  19. Boundary Value Technique for Initial Value Problems Based on Adams-Type Second Derivative Methods

    ERIC Educational Resources Information Center

    Jator, S. N.; Sahi, R. K.

    2010-01-01

    In this article, we propose a family of second derivative Adams-type methods (SDAMs) of order up to 2k + 2 ("k" is the step number) for initial value problems. The methods are constructed through a continuous approximation of the SDAM which is obtained by multistep collocation. The continuous approximation is used to obtain initial value methods,…

  20. Rethinking Equality of Opportunity: Comment on Adam Swift's "How Not to Be a Hypocrite"

    ERIC Educational Resources Information Center

    Anderson, Elizabeth

    2004-01-01

    Adam Swift objects to private schools on the grounds of equal opportunity and efficiency, and to both private and selective public schools on the grounds of solidarity and improving the academic achievement of less advantaged students. I argue that private schools are not inefficient, and that a meritocratic ideal of equality of opportunity in…

  1. Every Day Is Earth Day: A Resource List from the James P. Adams Library.

    ERIC Educational Resources Information Center

    Brennan, Patricia B. M.; And Others

    This is an extensive interdisciplinary bibliography of environmentally-related resources from the shelves of the James P. Adams Library at Rhode Island College. It is noted that the list is selective rather than comprehensive, and that the regional (United States, New England, or Rhode Island) has been emphasized when possible. The bibliography…

  2. Adam Smith and the Educative Critique: A Response to My Commentators

    ERIC Educational Resources Information Center

    Weinstein, Jack Russell

    2015-01-01

    This paper is both a response to the four reviewers in a special symposium on my book Adam Smith's Pluralism and a substantive discussion of philosophy of education. In it, I introduce what I call "the educative critique," a mode of analysis similar to Marxist, feminist, or postcolonial critiques, but focusing on the educative role of a…

  3. Music for Elementary Teachers; Self-Help Guide (MUS 370). Adams State College.

    ERIC Educational Resources Information Center

    Stokes, Cloyce

    This self-help guide for the music teacher is one of a series of eight Teacher Education Modules developed by Adams State College Teacher Corps Program. The guide itself consists of 11 modules, the first five of which focus on the mathematical and scientific aspects of music--pitch, tempo, furation, time, and key. These five modules are…

  4. miR-449a inhibits proliferation and invasion by regulating ADAM10 in hepatocellular carcinoma

    PubMed Central

    Liu, Songyang; Liu, Kai; Zhang, Wei; Wang, Yingchao; Jin, Zhe; Jia, Baoxing; Liu, Yahui

    2016-01-01

    MicroRNAs (miRNAs) are a class of small, non-coding RNAs that play a crucial role in tumor procession. It has been demonstrated that miR-449a expression was downregulated and served as tumor suppressor in many types of tumor. However, the biological function and molecular mechanism of miR-449a in hepatocellular carcinoma (HCC) still remains largely unknown. Therefore, the aims of this study were to investigate biological role and molecular mechanism of miR-449a in HCC by a serial of molecular experiments. Here, we demonstrated that miR-449a expression was downregulated in HCC tissues and cell lines compared with the adjacent nontumor tissues and normal hepatic cell line. Ectopic expression of miR-449a suppressed HCC cell proliferation, colony formation, migration and invasion. Moreover, A Disintegrin And Metalloproteinases 10 (ADAM10) was identified as a direct target gene of miR-449a in HCC cell. ADAM10 expression was upregulated in HCC tissues and cell lines, and was negatively correlated with the expression level of miR-449a in HCC tissues. Interesting, overexpression of ADAM10 attenuated the inhibition effect of miR-449a-mediated HCC cell proliferation, colony formation, migration and invasion. These results suggested that miR-449a might function as a tumor suppressor miRNA, at least in part, through regulating ADAM10 expression in HCC.

  5. Fractional Adams-Bashforth/Moulton methods: An application to the fractional Keller-Segel chemotaxis system

    NASA Astrophysics Data System (ADS)

    Zayernouri, Mohsen; Matzavinos, Anastasios

    2016-07-01

    We first formulate a fractional class of explicit Adams-Bashforth (A-B) and implicit Adams-Moulton (A-M) methods of first- and second-order accuracy for the time-integration of 0 CD t τ u (x , t) = g (t ; u), τ ∈ (0 , 1 ], where 0 CD t τ denotes the fractional derivative in the Caputo sense. In this fractional setting and in contrast to the standard Adams methods, an extra history load term emerges and the associated weight coefficients are τ-dependent. However when τ = 1, the developed schemes reduce to the well-known A-B and A-M methods with standard coefficients. Hence, in terms of scientific computing, our approach constitutes a minimal modification of the existing Adams libraries. Next, we develop an implicit-explicit (IMEX) splitting scheme for linear and nonlinear fractional PDEs of a general advection-reaction-diffusion type, and we apply our scheme to the time-space fractional Keller-Segel chemotaxis system. In this context, we evaluate the nonlinear advection term explicitly, employing the fractional A-B method in the prediction step, and we treat the corresponding diffusion term implicitly in the correction step using the fractional A-M scheme. Moreover, we perform the corresponding spatial discretization by employing an efficient and spectrally-accurate fractional spectral collocation method. Our numerical experiments exhibit the efficiency of the proposed IMEX scheme in solving nonlinear fractional PDEs.

  6. The Life and Times of John Couch Adams, from 1819 to 1847

    NASA Astrophysics Data System (ADS)

    Sheen, Brian M.

    2011-01-01

    John Couch Adams was born in 1819 in the middle of Cornwall, the most remote and isolated county in England. How he progressed from there to Cambridge University to become one of the finest mathematicians of the nineteenth century fills everyone who studies him with awe. Tragically what should have been his greatest triumph - the discovery of a new planet - was marred by mishap, controversy and unanswered questions. This presentation examines one of the first of these questions and provides new answers based on recently revealed evidence. The Astronomer Royal of the day was attempting to support Adams and as part of that support asked if his analysis took into account changes in radius vector of Uranus. Adams did not reply and the rest as they say is history. However there is far more to the question than a non-existent letter - this in itself turns out to be not exactly true. Further analysis of the orbits and a letter in French - not been translated before reveals Adams had a more profound understanding of the situation than some later authors have given him credit.

  7. THE E.O.A. BASIC EDUCATION COMMUNITY IN JOHN ADAMS ADULT SCHOOL, 1965-1966.

    ERIC Educational Resources Information Center

    EDMINSTER, HOWARD

    DATA FROM THE DEPARTMENT OF SOCIAL SERVICES AND SCHOOL FILES ARE PRESENTED ON 99 STUDENTS (90 PERCENT) REFERRED BY THE AGENCY TO THE BASIC EDUCATION PROGRAM AT THE JOHN ADAMS ADULT SCHOOL. OVER 60 PERCENT WERE NEGROES, WITH WHITES, MEXICANS, AND AMERICAN INDIANS ALSO REPRESENTED. THE MAJORITY WERE FROM SOUTHERN STATES, 37 PERCENT WERE DIVORCED OR…

  8. Making Socialists: Mary Bridges Adams and the Fight for Knowledge and Power, 1855-1939

    ERIC Educational Resources Information Center

    Weiler, Kathleen

    2012-01-01

    This article presents a review of "Making socialists: Mary Bridges Adams and the fight for knowledge and power, 1855-1939," by Jane Martin. Jane Martin has explored the history of late-nineteenth-century and early-twentieth century-British women educational activists in numerous publications over the past two decades. Her first book, "Women and…

  9. Development of a High Fidelity Dynamic Module of the Advanced Resistive Exercise Device (ARED) Using Adams

    NASA Technical Reports Server (NTRS)

    Humphreys, B. T.; Thompson, W. K.; Lewandowski, B. E.; Cadwell, E. E.; Newby, N. J.; Fincke, R. S.; Sheehan, C.; Mulugeta, L.

    2012-01-01

    NASA's Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and enhance countermeasure development. DAP provides expertise and computation tools to its research customers for model development, integration, or analysis. DAP is currently supporting the NASA Exercise Physiology and Countermeasures (ExPC) project by integrating their biomechanical models of specific exercise movements with dynamic models of the devices on which the exercises were performed. This presentation focuses on the development of a high fidelity dynamic module of the Advanced Resistive Exercise Device (ARED) on board the ISS. The ARED module, illustrated in the figure below, was developed using the Adams (MSC Santa Ana, California) simulation package. The Adams package provides the capabilities to perform multi rigid body, flexible body, and mixed dynamic analyses of complex mechanisms. These capabilities were applied to accurately simulate: Inertial and mass properties of the device such as the vibration isolation system (VIS) effects and other ARED components, Non-linear joint friction effects, The gas law dynamics of the vacuum cylinders and VIS components using custom written differential state equations, The ARED flywheel dynamics, including torque limiting clutch. Design data from the JSC ARED Engineering team was utilized in developing the model. This included solid modeling geometry files, component/system specifications, engineering reports and available data sets. The Adams ARED module is importable into LifeMOD (Life Modeler, Inc., San Clemente, CA) for biomechanical analyses of different resistive exercises such as squat and dead-lift. Using motion capture data from ground test subjects, the ExPC developed biomechanical exercise models in LifeMOD. The Adams ARED device module was then integrated with the exercise subject model into one integrated dynamic model. This presentation will describe the

  10. The Disintegrin-like and Cysteine-rich domains of ADAM-9 Mediate Interactions between Melanoma Cells and Fibroblasts*

    PubMed Central

    Zigrino, Paola; Nischt, Roswitha; Mauch, Cornelia

    2011-01-01

    A characteristic of malignant cells is their capacity to invade their surrounding and to metastasize to distant organs. During these processes, proteolytic activities of tumor and stromal cells modify the extracellular matrix to produce a microenvironment suitable for their growth and migration. In recent years the family of ADAM proteases has been ascribed important roles in these processes. ADAM-9 is expressed in human melanoma at the tumor-stroma border where direct or indirect interactions between tumor cells and fibroblasts occur. To analyze the role of ADAM-9 for the interaction between melanoma cells and stromal fibroblasts, we produced the recombinant disintegrin-like and cysteine-rich domain of ADAM-9 (DC-9). Melanoma cells and human fibroblasts adhered to immobilized DC-9 in a Mn2+-dependent fashion suggesting an integrin-mediated process. Inhibition studies showed that adhesion of fibroblasts was mediated by several β1 integrin receptors independent of the RGD and ECD recognition motif. Furthermore, interaction of fibroblasts and high invasive melanoma cells with soluble recombinant DC-9 resulted in enhanced expression of MMP-1 and MMP-2. Silencing of ADAM-9 in melanoma cells significantly reduced cell adhesion to fibroblasts. Ablation of ADAM-9 in fibroblasts almost completely abolished these cellular interactions and melanoma cell invasion in vitro. In summary, these results suggest that ADAM-9 expression plays an important role in mediating cell-cell contacts between fibroblasts and melanoma cells and that these interactions contribute to proteolytic activities required during invasion of melanoma cells. PMID:21135106

  11. Src plays a key role in ADAM28 expression in v-src-transformed epithelial cells and human carcinoma cells.

    PubMed

    Abe, Hitoshi; Mochizuki, Satsuki; Ohara, Kentaro; Ueno, Mari; Ochiai, Hiroki; Kitagawa, Yuko; Hino, Okio; Sato, Hiroshi; Okada, Yasunori

    2013-11-01

    ADAM28, a disintegrin and metalloproteinase 28, is overexpressed by carcinoma cells with direct correlations with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, the molecular mechanisms of ADAM28 gene expression in carcinoma cells remain elusive. Herein, we investigated the expression of ADAM28 in Madin-Darby canine kidney epithelial cells transformed by oncogenes, including v-src, LMP1, ErbB2, Ha-Ras, and c-Fos, and found that v-src transformants selectively induce ADAM28. Implantation of the v-src transformants showed a progressively growing tumor, which was significantly suppressed by local injections of anti-ADAM28 antibody. ADAM28 expression in v-src transformants was partially inhibited by treatment with inhibitors to Src kinase, mitogen-activated protein kinase kinase (MEK), phosphatidylinositol 3-kinase (PI3K), or mammalian target of rapamycin, and abrogated by v-Src kinase inhibitor, radicicol, or a mixture of MEK and PI3K inhibitors. Human carcinoma cell lines of the lung, breast, ovary, kidney, and colon showed ADAM28 expression, which was correlated with phosphorylation of c-Src and suppressed by the inhibitors in a similar way to v-src transformants. IHC of the human tumor tissues demonstrated co-expression of ADAM28 and phosphorylated Src in neoplastic cells of the breast, lung, and colon carcinomas and some adenomas of the colon, but not in nonneoplastic colon mucosa. Our data provide, to the best of our knowledge, the first evidence that Src is an inducer of ADAM28 gene expression through the MEK/extracellular signal-regulated kinase and PI3K/mammalian target of rapamycin pathways. PMID:24007880

  12. MiR-153 inhibits migration and invasion of human non-small-cell lung cancer by targeting ADAM19

    SciTech Connect

    Shan, Nianxi; Shen, Liangfang; Wang, Jun; He, Dan; Duan, Chaojun

    2015-01-02

    Highlights: • Decreased miR-153 and up-regulated ADAM19 are correlated with NSCLC pathology. • MiR-153 inhibits the proliferation and migration and invasion of NSCLC cells in vitro. • ADAM19 is a direct target of miR-153. • ADAM19 is involved in miR-153-suppressed migration and invasion of NSCLC cells. - Abstract: MiR-153 was reported to be dysregulated in some human cancers. However, the function and mechanism of miR-153 in lung cancer cells remains unknown. In this study, we investigated the role of miR-153 in human non-small-cell lung cancer (NSCLC). Using qRT-PCR, we demonstrated that miR-153 was significantly decreased in clinical NSCLC tissues and cell lines, and downregulation of miR-153 was significantly correlated with lymph node status. We further found that ectopic expression of miR-153 significantly inhibited the proliferation and migration and invasion of NSCLC cells in vitro, suggesting that miR-153 may be a novel tumor suppressor in NSCLC. Further integrated analysis revealed that ADAM19 is as a direct and functional target of miR-153. Luciferase reporter assay demonstrated that miR-153 directly targeted 3′UTR of ADAM19, and correlation analysis revealed an inverse correlation between miR-153 and ADAM19 mRNA levels in clinical NSCLC tissues. Knockdown of ADAM19 inhibited migration and invasion of NSCLC cells which was similar with effects of overexpression of miR-153, while overexpression of ADAM19 attenuated the function of miR-153 in NSCLC cells. Taken together, our results highlight the significance of miR-153 and ADAM19 in the development and progression of NSCLC.

  13. Extraction and Separation Modeling of Orion Test Vehicles with ADAMS Simulation

    NASA Technical Reports Server (NTRS)

    Fraire, Usbaldo, Jr.; Anderson, Keith; Cuthbert, Peter A.

    2013-01-01

    The Capsule Parachute Assembly System (CPAS) project has increased efforts to demonstrate the performance of fully integrated parachute systems at both higher dynamic pressures and in the presence of wake fields using a Parachute Compartment Drop Test Vehicle (PCDTV) and a Parachute Test Vehicle (PTV), respectively. Modeling the extraction and separation events has proven challenging and an understanding of the physics is required to reduce the risk of separation malfunctions. The need for extraction and separation modeling is critical to a successful CPAS test campaign. Current PTV-alone simulations, such as Decelerator System Simulation (DSS), require accurate initial conditions (ICs) drawn from a separation model. Automatic Dynamic Analysis of Mechanical Systems (ADAMS), a Commercial off the Shelf (COTS) tool, was employed to provide insight into the multi-body six degree of freedom (DOF) interaction between parachute test hardware and external and internal forces. Components of the model include a composite extraction parachute, primary vehicle (PTV or PCDTV), platform cradle, a release mechanism, aircraft ramp, and a programmer parachute with attach points. Independent aerodynamic forces were applied to the mated test vehicle/platform cradle and the separated test vehicle and platform cradle. The aero coefficients were determined from real time lookup tables which were functions of both angle of attack ( ) and sideslip ( ). The atmospheric properties were also determined from a real time lookup table characteristic of the Yuma Proving Grounds (YPG) atmosphere relative to the planned test month. Representative geometries were constructed in ADAMS with measured mass properties generated for each independent vehicle. Derived smart separation parameters were included in ADAMS as sensors with defined pitch and pitch rate criteria used to refine inputs to analogous avionics systems for optimal separation conditions. Key design variables were dispersed in a Monte

  14. A disintegrin and metalloproteinase 12 (ADAM12) localizes to invasive trophoblast, promotes cell invasion and directs column outgrowth in early placental development.

    PubMed

    Aghababaei, M; Perdu, S; Irvine, K; Beristain, A G

    2014-03-01

    During pregnancy, stromal- and vascular-remodeling trophoblasts serve critical roles in directing placental development acquiring pro-invasive characteristics. The A Disintegrin and Metalloproteinase (ADAM) family of multifunctional proteins direct cellular processes across multiple organ systems via their intrinsic catalytic, cell adhesive and intracellular signaling properties. ADAM12, existing as two distinct splice variants (ADAM12L and ADAM12S), is highly expressed in the human placenta and promotes cell migration and invasion in several tumor cell lines; however, its role in trophoblast biology is unknown. In this study, ADAM12 was localized to anchoring trophoblast columns in first trimester placentas and to highly invasive extracellular matrix-degrading trophoblasts in placental villous explants. The importance of ADAM12 in directing trophoblast invasion was tested using loss-of and gain-of-function strategies, where siRNA-directed knockdown of ADAM12 inhibited trophoblast cell invasion while over-expression promoted migration and invasion in two trophoblastic cell models. In placental villous explant cultures, siRNA-directed loss of ADAM12 significantly dampened trophoblast column outgrowth. Additionally, we provide functional evidence for the ADAM12S variant in promoting trophoblast invasion and column outgrowth through a mechanism requiring its catalytic activity. This is the first study to assign a function for ADAM12 in trophoblast biology, where ADAM12 may play a central role regulating the behavior of invasive trophoblast subsets in early pregnancy. This study also underlines the importance of ADAM12L and ADAM12S in directing cell motility in normal developmental processes outside of cancer, specifically highlighting a potentially important function of ADAM12S in directing early placental development. PMID:24243624

  15. Fibronectin fragments and the cleaving enzyme ADAM-8 in the degenerative human intervertebral disc

    PubMed Central

    Ruel, Nancy; Markova, Dessislava Z.; Adams, Sherrill L.; Scanzello, Carla; Cs-Szabo, Gabriella; Gerard, David; Shi, Peng; Anderson, D. Greg; Zack, Marc; An, Howard S.; Chen, Di; Zhang, Yejia

    2014-01-01

    Study Design The presence fibronectin fragments (FN-fs) and the cleaving enzyme, A disintegrin and metalloproteinase domain-containing protein (ADAM)-8 were examined in human intervertebral disc (IVD) tissue in vitro. Objective To investigate the presence and pathophysiological concentration of FN-fs and their cleaving enzyme, ADAM-8, in the human IVD tissue. Summary of Background Data The 29kDa FN-f has been shown to result in extracellular matrix loss in rabbit IVDs. However, the concentration of this biologically active fragment in the degenerative human IVD tissue has previously not been determined. Further, it is critical to identify the enzyme(s) responsible for FN cleavage in the IVD. Methods Human degenerative IVD tissues were removed during spinal surgery. A normal appearing young adult and an infant human cadaveric sample were obtained as controls. Soluble proteins were extracted, and analyzed by Western blotting utilizing antibodies specific for the human FN neoepitope VRAA271. A purified 29 kDa FN-f was used to allow estimation of the concentration of FN-fs in the tissues. ADAM-8, a FN-cleaving enzyme, was analyzed by Western blotting and immunostaining. Results All adult IVD tissues contain many FN-f species, but these species were absent from the infant disc tissue. Moderately degenerative discs contained the highest amount of FN-fs; the concentration was estimated to be in the nanomolar range per gram of tissue. ADAM-8, known to cleave FN resulting in the VRAA271 neoepitope, was present in the human disc. ADAM-8 primarily localized in the pericellular matrix of the nucleus pulposus (NP) tissue, as determined by immunostaining. Conclusion This is the first report that N-terminal FN-fs are consistently present in IVD tissues from adult subjects. The pathophysiological concentration of these fragments is estimated to be at nanomolar range per gram of IVD tissue. Further, ADAM-8, known to cleave FN, is present at the pericellular matrix of disc cells

  16. ADaM: augmenting existing approximate fast matching algorithms with efficient and exact range queries

    PubMed Central

    2014-01-01

    Background Drug discovery, disease detection, and personalized medicine are fast-growing areas of genomic research. With the advancement of next-generation sequencing techniques, researchers can obtain an abundance of data for many different biological assays in a short period of time. When this data is error-free, the result is a high-quality base-pair resolution picture of the genome. However, when the data is lossy the heuristic algorithms currently used when aligning next-generation sequences causes the corresponding accuracy to drop. Results This paper describes a program, ADaM (APF DNA Mapper) which significantly increases final alignment accuracy. ADaM works by first using an existing program to align "easy" sequences, and then using an algorithm with accuracy guarantees (the APF) to align the remaining sequences. The final result is a technique that increases the mapping accuracy from only 60% to over 90% for harder-to-align sequences. PMID:25079667

  17. Adams Oliver syndrome: Description of a new phenotype with cerebellar abnormalities in a family

    PubMed Central

    D’Amico, Alessandra; Melis, Daniela; D’Arco, Felice; Di Paolo, Nilde; Carotenuto, Barbara; D’Anna, Gennaro; Russo, Carmela; Boemio, Pasquale; Brunetti, Arturo

    2013-01-01

    Summary Background To describe cerebellar abnormalities in a family composed by a father and two affected sibs with Adams Oliver syndrome (AOS) (OMIM 100300). Material/Methods Brain MRI and MR angiography were performed at 1.5T. Results The siblings presented cerebellar cortex dysplasia characterized by the presence of cysts. Conclusions Abnormalities of CNS are an unusual manifestation of AOS. To our knowledge, this is the first report of cerebellar cortical dysplasia in a family with AOS. PMID:24505229

  18. Cleavage of neuregulin-1 by BACE1 or ADAM10 protein produces differential effects on myelination.

    PubMed

    Luo, Xiaoyang; Prior, Marguerite; He, Wanxia; Hu, Xiangyou; Tang, Xiaoying; Shen, Weizhen; Yadav, Satya; Kiryu-Seo, Sumiko; Miller, Robert; Trapp, Bruce D; Yan, Riqiang

    2011-07-01

    Neuregulin-1 (Nrg1) is encoded by a single gene and exists in naturally secreted and transmembrane isoforms. Nrg1 exerts its signaling activity through interaction with its cognate ErbB receptors. Multiple membrane-anchored Nrg1 isoforms, present in six different membrane topologies, must be processed by a protease to initiate a signaling cascade. Here, we demonstrate that BACE1 and ADAM10 can process type I and III Nrg1 at two adjacent sites. Our cleavage site mapping experiments showed that the BACE1 cleavage site is located eight amino acids downstream of the ADAM10 cleavage site, and this order of cleavage is the opposite of amyloid precursor protein cleavage by these two enzymes. Cleavages were further confirmed via optimized electrophoresis. Cleavage of type I or III Nrg1 by ADAM10 and BACE1 released a signaling-capable N-terminal fragment (ntf), either Nrg1-ntfα or Nrg1-ntfβ, which could similarly activate an ErbB receptor as evidenced by increased phosphorylation of Akt and ERK, two downstream signaling molecules. Although both Nrg1-ntfα and Nrg1-ntfβ could initiate a common signaling cascade, inhibition or down-regulation of ADAM10 alone in a co-culture system did not affect normal myelination, whereas specific inhibition of BACE1 impaired normal myelination. Thus, processing of Nrg1 by BACE1 appears to be more critical for regulating myelination. Our results imply that a significant inhibition of BACE1 could potentially impair Nrg1 signaling activity in vivo. PMID:21576249

  19. Promoter Variants of the ADAM10 Gene and Their Roles in Temporal Lobe Epilepsy

    PubMed Central

    Tao, Hua; Zhao, Jianghao; Zhou, Xu; Ma, Zhonghua; Chen, Ying; Sun, Fuhai; Cui, Lili; Zhou, Haihong; Cai, Yujie; Chen, Yanyan; Zhao, Shu; Yao, Lifen; Zhao, Bin; Li, Keshen

    2016-01-01

    Previous evidence has indicated that downregulated ADAM10 gives rise to epileptic seizures in Alzheimer’s disease, and this study investigated the association of ADAM10 with temporal lobe epilepsy (TLE) from a genetic perspective. A total of 496 TLE patients and 528 healthy individuals were enrolled and genotyped for ADAM10 promoter variants (rs653765 G > A and rs514049 A > C). The alleles, genotypes, and haplotypes were then compared with clarify the association of these variants with TLE and their impacts upon age at onset, initial seizure types before treatments, and responses to drug treatments. In cohorts I, II, and I + II, the frequencies of the A allele and AA genotype at rs514049 were consistently increased in the cases compared with the controls (p = 0.020 and p = 0.009; p = 0.008 and p = 0.009; p = 0.000 and p = 0.000; q = 0.003 and q = 0.002, respectively). In contrast, the frequency of the AC haplotype (rs653765–rs514049) decreased in cohorts I + II (p = 0.013). Further analyses of the TLE patients indicated that the AA genotype functioned as a predisposing factor to drug-resistant TLE and the AC haplotype as a protective factor against generalized tonic–clonic seizures (GTCS) and drug-resistant TLE. This study is the first to demonstrate an association of the ADAM10 promoter variants with TLE. In particular, the AA genotype and AC haplotype showed their effects upon GTCS and drug-resistant TLE. PMID:27445971

  20. Museum Quality: A New Museum and Recharged College Bring Creative Energy to North Adams, Massachusetts

    ERIC Educational Resources Information Center

    Grant, Mary

    2005-01-01

    Nestled in the valley between the Berkshire hills and the Taconic range, North Adams, Massachusetts, in many ways is typical of old New England mill towns working hard to create a new identity in the global economy. When Sprague Electric left town in 1985, the city of 16,000 reeled from the loss of 4,000 blue-collar jobs. This article describes…

  1. Tetraspanin CD9 modulates ADAM17-mediated shedding of LR11 in leukocytes.

    PubMed

    Tsukamoto, Shokichi; Takeuchi, Masahiro; Kawaguchi, Takeharu; Togasaki, Emi; Yamazaki, Atsuko; Sugita, Yasumasa; Muto, Tomoya; Sakai, Shio; Takeda, Yusuke; Ohwada, Chikako; Sakaida, Emiko; Shimizu, Naomi; Nishii, Keigo; Jiang, Meizi; Yokote, Koutaro; Bujo, Hideaki; Nakaseko, Chiaki

    2014-01-01

    LR11, also known as SorLA or SORL1, is a type-I membrane protein from which a large extracellular part, soluble LR11 (sLR11), is released by proteolytic shedding on cleavage with a disintegrin and metalloproteinase 17 (ADAM17). A shedding mechanism is presumed to have a key role in the functions of LR11, but the evidence for this has not yet been demonstrated. Tetraspanin CD9 has been recently shown to regulate the ADAM17-mediated shedding of tumor necrosis factor-α and intercellular adhesion molecule-1 on the cell surface. Here, we investigated the role of CD9 on the shedding of LR11 in leukocytes. LR11 was not expressed in THP-1 monocytes, but it was expressed and released in phorbol 12-myristate 13-acetate (PMA)-induced THP-1 macrophages (PMA/THP-1). Confocal microscopy showed colocalization of LR11 and CD9 proteins on the cell surface of PMA/THP-1. Ectopic neo-expression of CD9 in CCRF-SB cells, which are LR11-positive and CD9-negative, reduced the amount of sLR11 released from the cells. In contrast, incubation of LR11-transfected THP-1 cells with neutralizing anti-CD9 monoclonal antibodies increased the amount of sLR11 released from the cells. Likewise, the PMA-stimulated release of sLR11 increased in THP-1 cells transfected with CD9-targeted shRNAs, which was negated by treatment with the metalloproteinase inhibitor GM6001. These results suggest that the tetraspanin CD9 modulates the ADAM17-mediated shedding of LR11 in various leukemia cell lines and that the association between LR11 and CD9 on the cell surface has an important role in the ADAM17-mediated shedding mechanism. PMID:24699135

  2. INSULIN INDUCED EPIDERMAL GROWTH FACTOR ACTIVATION IN VASCULAR SMOOTH MUSCLE CELLS IS ADAM-DEPENDENT

    PubMed Central

    Roztocil, Elisa; Nicholl, Suzanne M.; Davies, Mark G.

    2008-01-01

    Background With the rise in metabolic syndrome, understanding the role of insulin signaling within the cells of vasculature has become more important but yet remains poorly defined. The study examines the role of insulin actions on a pivotal cross-talk receptor, Epidermal Growth Factor Receptor (EGFR). EGFR is transactivated by both G-protein-coupled receptors and receptor linked tyrosine kinases and is key to many of their responses. Objective To determine the pathway of EGFR transactivation by insulin in human coronary smooth muscle cells (VSMC) Methods VSMC were cultured in vitro. Assays of EGFR phosphorylation were examined in response to insulin in the presence and absence of the plasmin inhibitors (e-aminocaproic acid and aprotinin) matrix metalloprotease (MMP) inhibitor GM6001, the ADAM (A Disintegrin And Metalloproteinase Domain) inhibitors TAPI-0 and TAPI-1, Heparin binding epidermal growth factor (HB-EGF) inhibitor, CRM197, HB-EGF inhibitory antibodies, EGF inhibitory antibodies and the EGFR inhibitor AG1478. Results Insulin induced time-dependent EGFR phosphorylation, which was inhibited by AG1478 in a concentration dependent manner. Application of the plasmin inhibitors did not block the response. EGFR phosphorylation by insulin was blocked by inhibition of MMP activity and the ligand HB-EGF. The presence of the ADAM inhibitors, TAPI-0 and TAPI-1 significantly decreased EGFR activation. EGFR phosphorylation by EGF was not interrupted by inhibition of plasmin, MMPs TAPIs, or HB-EGF. Direct blockade of the EGFR prevented activation by both insulin and EGF. Conclusion Insulin can induce transactivation of EGFR by an ADAM-mediated, HB-EGF dependent process. This is the first description of crosstalk via ADAM between insulin and EGFR in vascular SMC. Targeting a pivotal cross-talk receptor such as EGFR, which can be transactivated by both G-protein-coupled receptors and receptor tyrosine kinases is an attractive molecular target. PMID:18656632

  3. ADAM13 function is required in the 3 dimensional context of the embryo during cranial neural crest cell migration in Xenopus laevis

    PubMed Central

    Cousin, Hélène; Abbruzzese, Genevieve; McCusker, Catherine; Alfandari, Dominique

    2012-01-01

    The cranial neural crest (CNC) is a population of cells that arises from the lateral part of the developing brain, migrates ventrally and coordinates the entire craniofacial development of vertebrates. Many molecules are involved in CNC migration including the transmembrane metalloproteases ADAM13 and 19. We have previously shown that these ADAMs cleave a number of extracellular proteins and modify the transcription of a number of genes, and that both of these activities are important for cell migration. Here we show that the knock down of ADAM13 inhibits CNC migration in vivo but not in vitro, indicating that ADAM13 function is required in the 3-dimentional context of the embryo. We further show that the migration of CNC that do not express ADAM13 and ADAM19 can be rescued in vivo by co-grafting wild type CNC. Furthermore, the migration of CNC lacking ADAM13 can be rescued by mechanically separating the CNC from the surrounding ectoderm and mesoderm. Finally, we show that ADAM13 function is autonomous to CNC tissue, as the migration of morphant CNC can only be rescued by ADAM13 expression in the CNC and not the surrounding tissues. Together our results suggest that ADAM13 changes CNC interaction with the extracellular environment and that this change is necessary for their migration in vivo. PMID:22683825

  4. Metalloprotease-disintegrin ADAM 12 binds to the SH3 domain of Src and activates Src tyrosine kinase in C2C12 cells.

    PubMed Central

    Kang, Q; Cao, Y; Zolkiewska, A

    2000-01-01

    ADAM 12, a member of the ADAM (protein containing a disintegrin and metalloprotease) family of metalloprotease-disintegrins, has been implicated in the differentiation and fusion of skeletal myoblasts, and its expression is dramatically up-regulated in many cancer cells. While the extracellular portion of ADAM 12 contains an active metalloprotease and a cell-adhesion domain, the function of the cytoplasmic portion is much less clear. In this paper, we show that the cytoplasmic tail of ADAM 12 mediates interactions with the non-receptor protein tyrosine kinase Src. The interaction is direct, specific, and involves the N-terminal proline-rich region in the cytoplasmic tail of ADAM 12 and the Src homology 3 (SH3) domain of Src. ADAM 12 and Src co-immunoprecipitate from transfected C2C12 cells, suggesting that the two proteins form a complex in vivo. Co-expression of Src and ADAM 12, but not ADAM 9, in C2C12 cells results in activation of the recombinant Src. Moreover, endogenous ADAM 12 associates with and activates endogenous Src in differentiating C2C12 cells. These results indicate that ADAM 12 may mediate adhesion-induced signalling during myoblast differentiation. PMID:11104699

  5. IL-1β and ADAM17 are central regulators of β-defensin expression in Candida esophagitis.

    PubMed

    Pahl, Rene; Brunke, Gabriele; Steubesand, Nadine; Schubert, Sabine; Böttner, Martina; Wedel, Thilo; Jürgensen, Christian; Hampe, Jochen; Schäfer, Heiner; Zeissig, Sebastian; Schreiber, Stefan; Rosenstiel, Philip; Reiss, Karina; Arlt, Alexander

    2011-04-01

    Candida albicans resides on epithelial surfaces as part of the physiological microflora. However, under certain conditions, it may cause life-threatening infections, including Candida sepsis. We have recently shown that human β-defensins (hBDs) hBD-2 and hBD-3 are upregulated in Candida esophagitis and that this antifungal host response is distinctly regulated by NF-κB and MAPK/activator protein-1 (AP-1) pathways. Here, we show that C. albicans induces hBD-2 through an autocrine IL-1β loop and that activation of the epidermal growth factor receptor (EGFR) by endogenous transforming growth factor-α (TGF-α) is a crucial event in the induction of hBD-3. To further dissect upstream signaling events, we investigated expression of the central sheddases for EGFR ligands ADAM10 and ADAM17 in the healthy and infected esophagus. Next, we used pharmaceutical inhibitors and small-interfering RNA-mediated knock down of ADAM10 and ADAM17 to reveal that ADAM17-induced shedding of TGF-α is a crucial step in the induction of hBD-3 expression in response to Candida infection. In conclusion, we describe for the first time an autocrine IL-1β loop responsible for the induction of hBD-2 expression and an ADAM17-TGF-α-EGFR-MAPK/AP-1 pathway leading to hBD-3 upregulation in the course of a Candida infection of the esophagus. PMID:21233274

  6. An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin.

    PubMed

    Lo Sardo, Valentina; Zuccato, Chiara; Gaudenzi, Germano; Vitali, Barbara; Ramos, Catarina; Tartari, Marzia; Myre, Michael A; Walker, James A; Pistocchi, Anna; Conti, Luciano; Valenza, Marta; Drung, Binia; Schmidt, Boris; Gusella, James; Zeitlin, Scott; Cotelli, Franco; Cattaneo, Elena

    2012-05-01

    The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role is obscure. We studied neurulation in htt-null embryonic stem cells and htt-morpholino zebrafish embryos and found a previously unknown, evolutionarily recent function for this ancient protein. We found that htt was essential for homotypic interactions between neuroepithelial cells; it permitted neurulation and rosette formation by regulating metalloprotease ADAM10 activity and Ncadherin cleavage. This function was embedded in the N terminus of htt and was phenocopied by treatment of htt knockdown zebrafish with an ADAM10 inhibitor. Notably, in htt-null cells, reversion of the rosetteless phenotype occurred only with expression of evolutionarily recent htt heterologues from deuterostome organisms. Conversely, all of the heterologues that we tested, including htt from Drosophila melanogaster and Dictyostelium discoideum, exhibited anti-apoptotic activity. Thus, anti-apoptosis may have been one of htt’s ancestral function(s), but, in deuterostomes, htt evolved to acquire a unique regulatory activity for controlling neural adhesion via ADAM10-Ncadherin, with implications for brain evolution and development. PMID:22466506

  7. Cytoplasmic Relaxation of Active Eph Controls Ephrin Shedding by ADAM10

    PubMed Central

    Frangakis, Achilleas S.; Treble, Kane; Griesshaber, Bettina; Sabet, Ola; Grabenbauer, Markus; Ting, Alice Y.; Saftig, Paul; Bastiaens, Philippe I.; Lackmann, Martin

    2009-01-01

    Release of cell surface-bound ligands by A-Disintegrin-And-Metalloprotease (ADAM) transmembrane metalloproteases is essential for signalling by cytokine, cell adhesion, and tyrosine kinase receptors. For Eph receptor ligands, it provides the switch between cell-cell adhesion and repulsion. Ligand shedding is tightly controlled by intrinsic tyrosine kinase activity, which for Eph receptors relies on the release of an inhibitory interaction of the cytoplasmic juxtamembrane segment with the kinase domain. However, a mechanism linking kinase and sheddase activities had remained elusive. We demonstrate that it is a membrane-proximal localisation of the latent kinase domain that prevents ephrin ligand shedding in trans. Fluorescence lifetime imaging microscopy and electron tomography reveal that activation extends the Eph receptor tyrosine kinase intracellular domain away from the cell membrane into a conformation that facilitates productive association with ADAM10. Accordingly, EphA3 mutants with constitutively-released kinase domains efficiently support shedding, even when their kinase is disabled. Our data suggest that this phosphorylation-activated conformational switch of EphA3 directly controls ADAM-mediated shedding. PMID:19823572

  8. Human NOTCH2 Is Resistant to Ligand-independent Activation by Metalloprotease Adam17*

    PubMed Central

    Habets, Roger A. J.; Groot, Arjan J.; Yahyanejad, Sanaz; Tiyanont, Kittichoat; Blacklow, Stephen C.; Vooijs, Marc

    2015-01-01

    Cell surface receptors of the NOTCH family of proteins are activated by ligand induced intramembrane proteolysis. Unfolding of the extracellular negative regulatory region (NRR), enabling successive proteolysis by the enzymes Adam10 and γ-secretase, is rate-limiting in NOTCH activation. Mutations in the NOTCH1 NRR are associated with ligand-independent activation and frequently found in human T-cell malignancies. In mammals four NOTCH receptors and five Delta/Jagged ligands exist, but mutations in the NRR are only rarely reported for receptors other than NOTCH1. Using biochemical and functional assays, we compared the molecular mechanisms of ligand-independent signaling in NOTCH1 and the highly related NOTCH2 receptor. Both murine Notch1 and Notch2 require the metalloprotease protease Adam17, but not Adam10 during ligand-independent activation. Interestingly, the human NOTCH2 receptor is resistant to ligand-independent activation compared with its human homologs or murine orthologs. Taken together, our data reveal subtle but functionally important differences for the NRR among NOTCH paralogs and homologs. PMID:25918160

  9. Endostatin and irradiation modifies the activity of ADAM10 and neprilysin in breast cancer cells.

    PubMed

    Aydemir, Esra Arslan; Şimşek, Ece; Korcum, Aylin Fidan; Fişkin, Kayahan

    2016-09-01

    Angiogenesis, the formation of new blood vessels, is regarded as a key cancer cell property. Endostatin (ES) is a potential antiangiogenic agent and it may be useful when implemented in combination with other cancer therapeutic strategies. The present study investigated the in vitro effects of ES, radiotherapy (RT) or combination therapy (ES + RT) on two important proteases, a disintegrin and metalloproteinase domain‑containing protein 10 (ADAM10) and neprilysin (NEP) in 4T1 mouse breast cancer cells and the more metastatic phenotype of 4THMpc breast cancer cells. 4T1 and 4THMpc cells were treated with recombinant murine ES (4 µg/ml) alone, RT (45 Gy) alone or with ES + RT. ADAM10 enzyme activity was determined using a tumor necrosis factor‑α converting enzyme (α‑secretase) activity assay kit, and NEP enzyme activity was measured with a fluorometric assay based on the generation of free dansyl‑D‑Ala‑Gly from N-dansyl-Ala-Gly-D-nitro-Phe-Gly, the substrate of NEP. Western blotting analysis was performed to determine whether the altered enzyme activity levels of the two cell lines occurred due to changes in expression level. These data indicate that ES independently potentiates the activity of ADAM10 and NEP enzymes in 4T1 and 4THMpc breast cancer cells. PMID:27430992

  10. iRHOM2-dependent regulation of ADAM17 in cutaneous disease and epidermal barrier function.

    PubMed

    Brooke, Matthew A; Etheridge, Sarah L; Kaplan, Nihal; Simpson, Charlotte; O'Toole, Edel A; Ishida-Yamamoto, Akemi; Marches, Olivier; Getsios, Spiro; Kelsell, David P

    2014-08-01

    iRHOM2 is a highly conserved, catalytically inactive member of the Rhomboid family, which has recently been shown to regulate the maturation of the multi-substrate ectodomain sheddase enzyme ADAM17 (TACE) in macrophages. Dominant iRHOM2 mutations are the cause of the inherited cutaneous and oesophageal cancer-susceptibility syndrome tylosis with oesophageal cancer (TOC), suggesting a role for this protein in epithelial cells. Here, using tissues derived from TOC patients, we demonstrate that TOC-associated mutations in iRHOM2 cause an increase in the maturation and activity of ADAM17 in epidermal keratinocytes, resulting in significantly upregulated shedding of ADAM17 substrates, including EGF-family growth factors and pro-inflammatory cytokines. This activity is accompanied by increased EGFR activity, increased desmosome processing and the presence of immature epidermal desmosomes, upregulated epidermal transglutaminase activity and heightened resistance to Staphylococcal infection in TOC keratinocytes. Many of these features are consistent with the presence of a constitutive wound-healing-like phenotype in TOC epidermis, which may shed light on a novel pathway in skin repair, regeneration and inflammation. PMID:24643277

  11. ADAM: a general method for using various data types in asteroid reconstruction

    NASA Astrophysics Data System (ADS)

    Viikinkoski, Matti; Kaasalainen, Mikko; Durech, Josef

    2015-04-01

    We introduce ADAM, the All-Data Asteroid Modelling algorithm. ADAM is simple and universal since it handles all disk-resolved data types (adaptive optics or other images, interferometry, and range-Doppler radar data) in a uniform manner via the 2D Fourier transform, enabling fast convergence in model optimization. The resolved data can be combined with disk-integrated data (photometry). In the reconstruction process, the difference between each data type is only a few code lines defining the particular generalized projection from 3D onto a 2D image plane. Occultation timings can be included as sparse silhouettes, and thermal infrared data are efficiently handled with an approximate algorithm that is sufficient in practice because of the dominance of the high-contrast (boundary) pixels over the low-contrast (interior) pixels. This is of particular importance to the raw ALMA data that can be directly handled by ADAM without having to construct the standard image. We study the reliability of the inversion, using the independent shape supports of function series and control-point surfaces. When other data are lacking, one can carry out fast non-convex lightcurve-only inversions, but any shape models resulting from it should only be taken as illustrative large-scale models. The code is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/576/A8

  12. ADAM10 new selective inhibitors reduce NKG2D ligand release sensitizing Hodgkin lymphoma cells to NKG2D-mediated killing

    PubMed Central

    Zocchi, Maria Raffaella; Camodeca, Caterina; Nuti, Elisa; Rossello, Armando; Venè, Roberta; Tosetti, Francesca; Dapino, Irene; Costa, Delfina; Musso, Alessandra; Poggi, Alessandro

    2016-01-01

    ABSTRACT Hodgkin lymphoma (HL) resistant to conventional therapies is increasing, making of interest the search for new schemes of treatment. Members of the “A Disintegrin And Metalloproteases” (ADAMs) family, mainly ADAM10 or ADAM17, have been proposed as therapeutic targets in solid tumors and some ADAMs inhibitors have been shown to exert antitumor effects. We have previously described an overexpression of ADAM10 in HL, together with increased release of NKG2D ligands (NKG2D-L) and reduced activation of effector T lymphocytes with anti-lymphoma capacity. Aim of the present work was to verify whether inhibition of ADAM10 in HL cells could restore the triggering of NKG2D-dependent anti-lymphoma T cell response. As no selective ADAM10 blockers have been reported so far, we synthesized the two hydroxamate compounds LT4 and MN8 with selectivity for ADAM10 over metalloproteases (MMPs), LT4 showing higher specificity for ADAM10 over ADAM17. We show that (i) HL lymph nodes (LN) and cultured HL cells express high levels of the mature active membrane form of ADAM10; (ii) ADAM10 is the major sheddase for the NKG2D-L in HL cells; (iii) the new LT4 and MN8 compounds strongly reduce the shedding of NKG2D-L by HL cell lines and enhance the binding of NKG2D receptor; (iv) of note, these new ADAM10 inhibitors increase the sensitivity of HL cell lines to NKG2D-dependent cell killing exerted by natural killer and γδ T cells. Overall, the biologic activity of LT4 and MN8 appears to be more potent than that of the commercial inhibitor GI254023X. PMID:27467923

  13. ADAM10 new selective inhibitors reduce NKG2D ligand release sensitizing Hodgkin lymphoma cells to NKG2D-mediated killing.

    PubMed

    Zocchi, Maria Raffaella; Camodeca, Caterina; Nuti, Elisa; Rossello, Armando; Venè, Roberta; Tosetti, Francesca; Dapino, Irene; Costa, Delfina; Musso, Alessandra; Poggi, Alessandro

    2016-05-01

    Hodgkin lymphoma (HL) resistant to conventional therapies is increasing, making of interest the search for new schemes of treatment. Members of the "A Disintegrin And Metalloproteases" (ADAMs) family, mainly ADAM10 or ADAM17, have been proposed as therapeutic targets in solid tumors and some ADAMs inhibitors have been shown to exert antitumor effects. We have previously described an overexpression of ADAM10 in HL, together with increased release of NKG2D ligands (NKG2D-L) and reduced activation of effector T lymphocytes with anti-lymphoma capacity. Aim of the present work was to verify whether inhibition of ADAM10 in HL cells could restore the triggering of NKG2D-dependent anti-lymphoma T cell response. As no selective ADAM10 blockers have been reported so far, we synthesized the two hydroxamate compounds LT4 and MN8 with selectivity for ADAM10 over metalloproteases (MMPs), LT4 showing higher specificity for ADAM10 over ADAM17. We show that (i) HL lymph nodes (LN) and cultured HL cells express high levels of the mature active membrane form of ADAM10; (ii) ADAM10 is the major sheddase for the NKG2D-L in HL cells; (iii) the new LT4 and MN8 compounds strongly reduce the shedding of NKG2D-L by HL cell lines and enhance the binding of NKG2D receptor; (iv) of note, these new ADAM10 inhibitors increase the sensitivity of HL cell lines to NKG2D-dependent cell killing exerted by natural killer and γδ T cells. Overall, the biologic activity of LT4 and MN8 appears to be more potent than that of the commercial inhibitor GI254023X. PMID:27467923

  14. Reliability evaluation of I-123 ADAM SPECT imaging using SPM software and AAL ROI methods

    NASA Astrophysics Data System (ADS)

    Yang, Bang-Hung; Tsai, Sung-Yi; Wang, Shyh-Jen; Su, Tung-Ping; Chou, Yuan-Hwa; Chen, Chia-Chieh; Chen, Jyh-Cheng

    2011-08-01

    The level of serotonin was regulated by serotonin transporter (SERT), which is a decisive protein in regulation of serotonin neurotransmission system. Many psychiatric disorders and therapies were also related to concentration of cerebral serotonin. I-123 ADAM was the novel radiopharmaceutical to image SERT in brain. The aim of this study was to measure reliability of SERT densities of healthy volunteers by automated anatomical labeling (AAL) method. Furthermore, we also used statistic parametric mapping (SPM) on a voxel by voxel analysis to find difference of cortex between test and retest of I-123 ADAM single photon emission computed tomography (SPECT) images.Twenty-one healthy volunteers were scanned twice with SPECT at 4 h after intravenous administration of 185 MBq of 123I-ADAM. The image matrix size was 128×128 and pixel size was 3.9 mm. All images were obtained through filtered back-projection (FBP) reconstruction algorithm. Region of interest (ROI) definition was performed based on the AAL brain template in PMOD version 2.95 software package. ROI demarcations were placed on midbrain, pons, striatum, and cerebellum. All images were spatially normalized to the SPECT MNI (Montreal Neurological Institute) templates supplied with SPM2. And each image was transformed into standard stereotactic space, which was matched to the Talairach and Tournoux atlas. Then differences across scans were statistically estimated on a voxel by voxel analysis using paired t-test (population main effect: 2 cond's, 1 scan/cond.), which was applied to compare concentration of SERT between the test and retest cerebral scans.The average of specific uptake ratio (SUR: target/cerebellum-1) of 123I-ADAM binding to SERT in midbrain was 1.78±0.27, pons was 1.21±0.53, and striatum was 0.79±0.13. The cronbach's α of intra-class correlation coefficient (ICC) was 0.92. Besides, there was also no significant statistical finding in cerebral area using SPM2 analysis. This finding might help us

  15. The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining.

    PubMed

    Guo, Zhi-Bao; Su, Ying-Ying; Wang, Yi-Hui; Wang, Wei; Guo, Da-Zhi

    2016-09-01

    ADAM10 (a disintegrin and metalloprotease 10) is a member of the ADAMs family, which is key in the development of the nervous system, by regulating proliferation, migration, differentiation and survival of various cells, including axonal growth and myelination. Previous studies have investigated the embryonic or postnatal expression of ADAM10, however, detailed information regarding its cellular distribution in the adult stage, to the best of our knowledge, is not available. The present study investigated the expression pattern of the ADAM10 gene in the adult mouse central nervous system (CNS) using an ADAM10 complementary RNA probe for in situ hybridization (ISH). Immunohistochemical staining was used to identify the type of the ISH staining‑positive cells with neuron‑ or astrocyte‑specific antibodies. The results of the current study demonstrated that the ADAM10 gene was predominantly expressed in the neurons of the cerebral cortex, hippocampus, thalamus and cerebellar granular cells in adult mouse CNS. PMID:27431484

  16. The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining

    PubMed Central

    Guo, Zhi-Bao; Su, Ying-Ying; Wang, Yi-Hui; Wang, Wei; Guo, Da-Zhi

    2016-01-01

    ADAM10 (a disintegrin and metalloprotease 10) is a member of the ADAMs family, which is key in the development of the nervous system, by regulating proliferation, migration, differentiation and survival of various cells, including axonal growth and myelination. Previous studies have investigated the embryonic or postnatal expression of ADAM10, however, detailed information regarding its cellular distribution in the adult stage, to the best of our knowledge, is not available. The present study investigated the expression pattern of the ADAM10 gene in the adult mouse central nervous system (CNS) using an ADAM10 complementary RNA probe for in situ hybridization (ISH). Immunohistochemical staining was used to identify the type of the ISH staining-positive cells with neuron- or astrocyte-specific antibodies. The results of the current study demonstrated that the ADAM10 gene was predominantly expressed in the neurons of the cerebral cortex, hippocampus, thalamus and cerebellar granular cells in adult mouse CNS. PMID:27431484

  17. Endothelial deletion of ADAM17 in mice results in defective remodeling of the semilunar valves and cardiac dysfunction in adults

    PubMed Central

    Wilson, Carole L.; Gough, Peter J.; Chang, Cindy A.; Chan, Christina K.; Frey, Jeremy M.; Liu, Yonggang; Braun, Kathleen R.; Chin, Michael T.; Wight, Thomas N.; Raines, Elaine W.

    2013-01-01

    Global inactivation of the metalloproteinase ADAM17 during mouse development results in perinatal lethality and abnormalities of the heart, including late embryonic cardiomegaly and thickened semilunar and atrioventricular valves. These defects have been attributed in part to a lack of ADAM17-mediated processing of HB-EGF, as absence of soluble HB-EGF results in similar phenotypes. Because valvular mesenchymal cells are largely derived from cardiac endothelial cells, we generated mice with a floxed Adam17 allele and crossed these animals with Tie2-Cre transgenics to focus on the role of endothelial ADAM17 in valvulogenesis. We find that although hearts from late-stage embryos with ablation of endothelial ADAM17 appear normal, an increase in valve size and cell number is evident, but only in the semilunar cusps. Unlike Hbegf−/− valves, ADAM17-null semilunar valves do not differ from controls in acute cell proliferation at embryonic day 14.5 (E14.5), suggesting compensatory processing of HB-EGF. However, levels of the proteoglycan versican are significantly reduced in mutant hearts early in valve remodeling (E12.5). After birth, aortic valve cusps from mutants are not only hyperplastic but also show expansion of the glycosaminoglycan-rich component, with the majority of adults exhibiting aberrant compartmentalization of versican and increased deposition of collagen. The inability of mutant outflow valve precursors to transition into fully mature cusps is associated with decreased postnatal viability, progressive cardiomegaly, and systolic dysfunction. Together, our data indicate that ADAM17 is required in valvular endothelial cells for regulating cell content as well as extracellular matrix composition and organization in semilunar valve remodeling and homeostasis. PMID:23354118

  18. Genetic variants of Adam17 differentially regulate TGFβ signaling to modify vascular pathology in mice and humans

    PubMed Central

    Kawasaki, Kyoko; Freimuth, Julia; Meyer, Dominique S.; Lee, Marie M.; Tochimoto-Okamoto, Akiko; Benzinou, Michael; Clermont, Frederic F.; Wu, Gloria; Roy, Ritu; Letteboer, Tom G. W.; Ploos van Amstel, Johannes Kristian; Giraud, Sophie; Dupuis-Girod, Sophie; Lesca, Gaeten; Westermann, Cornelius J. J.; Coffey, Robert J.; Akhurst, Rosemary J.

    2014-01-01

    Outcome of TGFβ1 signaling is context dependent and differs between individuals due to germ-line genetic variation. To explore innate genetic variants that determine differential outcome of reduced TGFβ1 signaling, we dissected the modifier locus Tgfbm3, on mouse chromosome 12. On a NIH/OlaHsd genetic background, the Tgfbm3bC57 haplotype suppresses prenatal lethality of Tgfb1−/− embryos and enhances nuclear accumulation of mothers against decapentaplegic homolog 2 (Smad2) in embryonic cells. Amino acid polymorphisms within a disintegrin and metalloprotease 17 (Adam17) can account, at least in part, for this Tgfbm3b effect. ADAM17 is known to down-regulate Smad2 signaling by shedding the extracellular domain of TGFβRI, and we show that the C57 variant is hypomorphic for down-regulation of Smad2/3-driven transcription. Genetic variation at Tgfbm3 or pharmacological inhibition of ADAM17, modulates postnatal circulating endothelial progenitor cell (CEPC) numbers via effects on TGFβRI activity. Because CEPC numbers correlate with angiogenic potential, this suggests that variant Adam17 is an innate modifier of adult angiogenesis, acting through TGFβR1. To determine whether human ADAM17 is also polymorphic and interacts with TGFβ signaling in human vascular disease, we investigated hereditary hemorrhagic telangiectasia (HHT), which is caused by mutations in TGFβ/bone morphogenetic protein receptor genes, ENG, encoding endoglin (HHT1), or ACVRL1 encoding ALK1 (HHT2), and considered a disease of excessive abnormal angiogenesis. HHT manifests highly variable incidence and severity of clinical features, ranging from small mucocutaneous telangiectases to life-threatening visceral and cerebral arteriovenous malformations (AVMs). We show that ADAM17 SNPs associate with the presence of pulmonary AVM in HHT1 but not HHT2, indicating genetic variation in ADAM17 can potentiate a TGFβ-regulated vascular disease. PMID:24812125

  19. Role of ADAM17 in invasion and migration of CD133-expressing liver cancer stem cells after irradiation.

    PubMed

    Hong, Sung Woo; Hur, Wonhee; Choi, Jung Eun; Kim, Jung-Hee; Hwang, Daehee; Yoon, Seung Kew

    2016-04-26

    We investigated the biological role of CD133-expressing liver cancer stem cells (CSCs) enriched after irradiation of Huh7 cells in cell invasion and migration. We also explored whether a disintegrin and metalloproteinase-17 (ADAM17) influences the metastatic potential of CSC-enriched hepatocellular carcinoma (HCC) cells after irradiation. A CD133-expressing Huh7 cell subpopulation showed greater resistance to sublethal irradiation and specifically enhanced cell invasion and migration capabilities. We also demonstrated that the radiation-induced MMP-2 and MMP-9 enzyme activities as well as the secretion of vascular endothelial growth factor were increased more predominantly in Huh7CD133+ cell subpopulations than Huh7CD133- cell subpopulations. Furthermore, we showed that silencing ADAM17 significantly inhibited the migration and invasiveness of enriched Huh7CD133+ cells after irradiation; moreover, Notch signaling was significantly reduced in irradiated CD133-expressing liver CSCs following stable knockdown of the ADAM17 gene. In conclusion, our findings indicate that CD133-expressing liver CSCs have considerable metastatic capabilities after irradiation of HCC cells, and their metastatic capabilities might be maintained by ADAM17. Therefore, suppression of ADAM17 shows promise for improving the efficiency of current radiotherapies and reducing the metastatic potential of liver CSCs during HCC treatment. PMID:26993601

  20. Targeting ADAM-17 with an inhibitory monoclonal antibody has antitumour effects in triple-negative breast cancer cells

    PubMed Central

    Caiazza, F; McGowan, P M; Mullooly, M; Murray, A; Synnott, N; O'Donovan, N; Flanagan, L; Tape, C J; Murphy, G; Crown, J; Duffy, M J

    2015-01-01

    Background: Identification and validation of a targeted therapy for triple-negative breast cancer (TNBC), that is, breast cancers negative for oestrogen receptors, progesterone receptors and HER2 amplification, is currently one of the most urgent problems in breast cancer treatment. EGFR is one of the best-validated driver genes for TNBC. EGFR is normally activated following the release of ligands such as TGFα, mediated by the two MMP-like proteases ADAM (a disintegrin and metalloproteinase)-10 and ADAM-17. The aim of this study was to investigate the antitumour effects of a monoclonal antibody against ADAM-17 on an in vitro model of TNBC. Methods: We investigated an inhibitory cross-domain humanised monoclonal antibody targeting both the catalytic domain and the cysteine-rich domain of ADAM17-D1(A12) in the HCC1937 and HCC1143 cell lines. Results: D1(A12) was found to significantly inhibit the release of TGFα, and to decrease downstream EGFR-dependent cell signalling. D1(A12) treatment reduced proliferation in two-dimensional clonogenic assays, as well as growth in three-dimensional culture. Furthermore, D1(A12) reduced invasion of HCC1937 cells and decreased migration of HCC1143 cells. Finally, D1(A12) enhanced cell death in HCC1143 cells. Conclusion: Our in vitro findings suggest that targeting ADAM-17 with D1(A12) may have anticancer activity in TNBC cells. PMID:26010411

  1. ADAM12 and PAPP-A: Candidate regulators of trophoblast invasion and first trimester markers of healthy trophoblasts.

    PubMed

    Christians, Julian K; Beristain, Alexander G

    2016-03-01

    Proper placental development and function is crucial for a healthy pregnancy, and there has been substantial research to identify markers of placental dysfunction for the early detection of pregnancy complications. Low first-trimester levels of a disintegrin and metalloproteinase 12 (ADAM12) and pregnancy-associated plasma protein-A (PAPP-A) have been consistently associated with the subsequent development of preeclampsia and fetal growth restriction. These molecules are both metalloproteinases secreted by the placenta that cleave insulin-like growth factor binding proteins (IGFBPs), although ADAM12 also has numerous other substrates. Recent work has identified ADAM12, and particularly its shorter variant, ADAM12S, as a regulator of the migration and invasion of trophoblasts into the lining of the uterus, a critical step in normal placental development. While the mechanisms underlying this regulation are not yet clear, they may involve the liberation of heparin-binding EGF-like growth factor (HB-EGF) and/or IGFs from IGFBPs. In contrast, there has been relatively little functional work examining PAPP-A or the IGFBP substrates of ADAM12 and PAPP-A. Understanding the functions of these markers and the mechanisms underlying their association with disease could improve screening strategies and enable the development of new therapeutic interventions. PMID:26417939

  2. Helicopter magnetic and electromagnetic surveys at Mounts Adams, Baker and Rainier, Washington: implications for debris flow hazards and volcano hydrology

    USGS Publications Warehouse

    Finn, Carol A.; Deszcz-Pan, Maria

    2011-01-01

    High‐resolution helicopter magnetic and electromagnetic (HEM) data flown over the rugged, ice‐covered Mt. Adams, Mt. Baker and Mt. Rainier volcanoes (Washington), reveal the distribution of alteration, water and ice thickness essential to evaluating volcanic landslide hazards. These data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses (>500 m) of water‐saturated hydrothermally altered rock west of the modern summit of Mount Rainier in the Sunset Amphitheater region and in the central core of Mount Adams north of the summit. Alteration at Mount Baker is restricted to thinner (<300 m) zones beneath Sherman Crater and the Dorr Fumarole Fields. The EM data identified water‐saturated rocks from the surface to the detection limit (100–200 m) in discreet zones at Mt. Rainier and Mt Adams and over the entire summit region at Mt. Baker. The best estimates for ice thickness are obtained over relatively low resistivity (<800 ohm‐m) ground for the main ice cap on Mt. Adams and over most of the summit of Mt. Baker. The modeled distribution of alteration, pore fluids and partial ice volumes on the volcanoes helps identify likely sources for future alteration‐related debris flows, including the Sunset Amphitheater region at Mt. Rainier, steep cliffs at the western edge of the central altered zone at Mount Adams and eastern flanks of Mt. Baker.

  3. Poor interoperability of the Adams-Harbertson method for analysis of anthocyanins: comparison with AOAC pH differential method.

    PubMed

    Brooks, Larry M; Kuhlman, Benjamin J; McKesson, Doug W; McCloskey, Leo

    2013-01-01

    The poor interoperability of anthocyanin glycosides measurements by two pH differential methods is documented. Adams-Harbertson, which was proposed for commercial winemaking, was compared to AOAC Official Method 2005.02 for wine. California bottled wines (Pinot Noir, Merlot, and Cabernet Sauvignon) were assayed in a collaborative study (n=105), which found mean precision of Adams-Harbertson winery versus reference measurements to be 77 +/- 20%. Maximum error is expected to be 48% for Pinot Noir, 42% for Merlot, and 34% for Cabernet Sauvignon from reproducibility RSD. Range of measurements was actually 30 to 91% for Pinot Noir. An interoperability study (n=30) found Adams-Harbertson produces measurements that are nominally 150% of the AOAC pH differential method. Large analytical chemistry differences are: AOAC method uses Beer-Lambert equation and measures absorbance at pH 1.0 and 4.5, proposed a priori by Flueki and Francis; whereas Adams-Harbertson uses "universal" standard curve and measures absorbance ad hoc at pH 1.8 and 4.9 to reduce the effects of so-called co-pigmentation. Errors relative to AOAC are produced by Adams-Harbertson standard curve over Beer-Lambert and pH 1.8 over pH 1.0. The study recommends using AOAC Official Method 2005.02 for analysis of wine anthocyanin glycosides. PMID:23513962

  4. Mary Adams and the producer's role in early BBC science broadcasts.

    PubMed

    Jones, Allan

    2012-11-01

    Mary Adams was a science producer at the BBC from 1930-6. She is shown to have played a crucial role in shaping science broadcasts, in particular devising formats and styles of presentation. However, her approach is shown to have been primarily motivated by broadcasting considerations rather than by the popularisation of science. Through her interaction with scientists she helped to construct a new professional domain, that of the science-broadcasting professional, at a time when other producers were creating analogous roles in other areas of broadcasting. This paper is based largely on unpublished archival documents. PMID:23832748

  5. The Co-simulation of Humanoid Robot Based on Solidworks, ADAMS and Simulink

    NASA Astrophysics Data System (ADS)

    Song, Dalei; Zheng, Lidan; Wang, Li; Qi, Weiwei; Li, Yanli

    A simulation method of adaptive controller is proposed for the humanoid robot system based on co-simulation of Solidworks, ADAMS and Simulink. A complex mathematical modeling process is avoided by this method, and the real time dynamic simulating function of Simulink would be exerted adequately. This method could be generalized to other complicated control system. This method is adopted to build and analyse the model of humanoid robot. The trajectory tracking and adaptive controller design also proceed based on it. The effect of trajectory tracking is evaluated by fitting-curve theory of least squares method. The anti-interference capability of the robot is improved a lot through comparative analysis.

  6. The Cysteine-Rich Domain of Human Adam 12 Supports Cell Adhesion through Syndecans and Triggers Signaling Events That Lead to β1 Integrin–Dependent Cell Spreading

    PubMed Central

    Iba, Kousuke; Albrechtsen, Reidar; Gilpin, Brent; Fröhlich, Camilla; Loechel, Frosty; Zolkiewska, Anna; Ishiguro, Kazuhiro; Kojima, Tetsuhito; Liu, Wei; Langford, J. Kevin; Sanderson, Ralph D.; Brakebusch, Cord; Fässler, Reinhard; Wewer, Ulla M.

    2000-01-01

    The ADAMs (a disintegrin and metalloprotease) family of proteins is involved in a variety of cellular interactions, including cell adhesion and ecto- domain shedding. Here we show that ADAM 12 binds to cell surface syndecans. Three forms of recombinant ADAM 12 were used in these experiments: the cys-teine-rich domain made in Escherichia coli (rADAM 12-cys), the disintegrin-like and cysteine-rich domain made in insect cells (rADAM 12-DC), and full-length human ADAM 12-S tagged with green fluorescent protein made in mammalian cells (rADAM 12-GFP). Mesenchymal cells specifically and in a dose-dependent manner attach to ADAM 12 via members of the syndecan family. After binding to syndecans, mesenchymal cells spread and form focal adhesions and actin stress fibers. Integrin β1 was responsible for cell spreading because function-blocking monoclonal antibodies completely inhibited cell spreading, and chondroblasts lacking β1 integrin attached but did not spread. These data suggest that mesenchymal cells use syndecans as the initial receptor for the ADAM 12 cysteine-rich domain–mediated cell adhesion, and then the β1 integrin to induce cell spreading. Interestingly, carcinoma cells attached but did not spread on ADAM 12. However, spreading could be efficiently induced by the addition of either 1 mM Mn2+ or the β1 integrin–activating monoclonal antibody 12G10, suggesting that in these carcinoma cells, the ADAM 12–syndecan complex fails to modulate the function of β1 integrin. PMID:10831617

  7. A Mechanism of Male Germ Cell Apoptosis Induced by Bisphenol-A and Nonylphenol Involving ADAM17 and p38 MAPK Activation

    PubMed Central

    Moreno, Ricardo D.

    2014-01-01

    Germ cell apoptosis regulation is pivotal in order to maintain proper daily sperm production. Several reports have shown that endocrine disruptors such as Bisphenol-A (BPA) and Nonylphenol (NP) induce germ cell apoptosis along with a decrease in sperm production. Given their ubiquitous distribution in plastic products used by humans it is important to clarify their mechanism of action. TACE/ADAM17 is a widely distributed extracellular metalloprotease and participates in the physiological apoptosis of germ cells during spermatogenesis. The aims of this work were: 1) to determine whether BPA and NP induce ADAM17 activation; and 2) to study whether ADAM17 and/or ADAM10 are involved in germ cell apoptosis induced by BPA and NP in the pubertal rat testis. A single dose of BPA or NP (50 mg/kg) induces germ cell apoptosis in 21-day-old male rats, which was prevented by a pharmacological inhibitor of ADAM17, but not by an inhibitor of ADAM10. In vitro, we showed that BPA and NP, at similar concentrations to those found in human samples, induce the shedding of exogenous and endogenous (TNF-α) ADAM17 substrates in primary rat Sertoli cell cultures and TM4 cell line. In addition, pharmacological inhibitors of metalloproteases and genetic silencing of ADAM17 prevent the shedding induced in vitro by BPA and NP. Finally, we showed that in vivo BPA and NP induced early activation (phosphorylation) of p38 MAPK and translocation of ADAM17 to the cell surface. Interestingly, the inhibition of p38 MAPK prevents germ cell apoptosis and translocation of ADAM17 to the cell surface. These results show for the first time that xenoestrogens can induce activation of ADAM17 at concentrations similar to those found in human samples, suggesting a mechanism by which they could imbalance para/juxtacrine cell-to-cell-communication and induce germ cell apoptosis. PMID:25474107

  8. Analysis of a two-bladed, teetering-hub turbine using the ADAMS{reg_sign} software

    SciTech Connect

    Wright, A D; Osgood, R O; Malcolm, D J

    1994-05-01

    A major goal of the federal wind energy program is the rapid development and validation of structural models to determine loads and response for a wide variety of different wind turbine configurations operating under extreme conditions. Such codes are crucial to the successful design of future advanced wind turbines. In cooperation with R. Lynette & Associates the Wind Technology Division at NREL has developed a full system dynamics model of the AWT-26 Pl machine, using the Automatic Dynamic analysis of Mechanical Systems (ADAMS) software from Mechanical Dynamics, Inc. In this paper, we show validation of sub-models by comparisons with modal test data. We describe the most important system modes involved in this structure and demonstrate how the ADAMS model can be used to tune the structure to avoid interactions. We also identify questions that remain unanswered by ADAMS in modeling this turbine and recommend future directions that DOE code development activities should take.

  9. Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer

    PubMed Central

    Zhou, Bin-Bing S.; Peyton, Michael; He, Biao; Liu, Changnian; Girard, Luc; Caudler, Eian; Lo, Yvonne; Baribaud, Frederic; Mikami, Iwao; Reguart, Noemi; Yang, Gengjie; Li, Yanlong; Yao, Wenqing; Vaddi, Kris; Gazdar, Adi F.; Friedman, Steven M.; Jablons, David M.; Newton, Robert C.; Fridman, Jordan S.; Minna, John D.; Scherle, Peggy A.

    2015-01-01

    Summary We describe here the existence of a heregulin-HER3 autocrine loop, and the contribution of heregulin-dependent, HER2-mediated HER3 activation to gefitinib insensitivity in non-small cell lung cancer (NSCLC). ADAM17 protein, a major ErbB ligand sheddase, is upregulated in NSCLC and is required not only for heregulin-dependent HER3 signaling, but also for EGFR ligand-dependent signaling in NSCLC cell lines. A selective ADAM inhibitor, INCB3619, prevents the processing and activation of multiple ErbB ligands, including heregulin. In addition, INCB3619 inhibits gefitinib-resistant HER3 signaling and enhances gefitinib inhibition of EGFR signaling in NSCLC. These results show that ADAM inhibition affects multiple ErbB pathways in NSCLC and thus offers an excellent opportunity for pharmacological intervention, either alone or in combination with other drugs. PMID:16843264

  10. Neptune: towards understanding how Adams's upbringing enabled him to predict, then miss the discovery of the century

    NASA Astrophysics Data System (ADS)

    Sheen, B.

    2013-03-01

    The story of John Couch Adams the great Cornish astronomer of the nineteenth century is well known and this paper will not revisit old ground. However, many questions remain unanswered and in this paper I propose to indicate some of them as section headings, and seek to address them. In this way Adams's early life is examined, and its effect on his academic life during the time of the Neptune discovery. The row that followed discovery is high-lighted together with the equally contentious issue of the new planet's name. Although it is usually believed that Adams graciously accepted the failure of the Cambridge University Observatory to find his planet, examination of his later work which is often highly critical of French astronomers sheds a different light on that theory.

  11. Neutralization of ADAM8 ameliorates liver injury and accelerates liver repair in carbon tetrachloride-induced acute liver injury.

    PubMed

    Li, San-Qiang; Zhu, Sha; Wan, Xue-Dong; Xu, Zheng-Shun; Ma, Zhao

    2014-04-01

    Although some studies have described the function of ADAM8 (a disintegrin and metalloprotease 8) related with rheumatoid arthritis, cancer and asthma, etc., the concrete role of ADAM8 in acute liver injury is still unknown. So mice respectively received anti-ADAM8 monoclonal antibody (mAb) of 100 μg/100 μl, 200 μg/100 μl or 300 μg/100 μl in PBS or PBS pre-injection. Then acute liver injury was induced in the mice by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl₄). Serum AST and ALT level, Haematoxylin-eosin (H&E) staining, the expression level of vascular endothelial growth factor (VEGF), cytochrome P450 1A2 (CYP1A2) and proliferating cell nuclear antigen (PCNA) were detected in the mice after CCl4 administration. Our results showed that anti-ADAM8 mAb pre-injection could effectively lower AST and ALT levels (P < 0.05 or P < 0.01) and reduce liver injury (P < 0.05 or P <0.01), induce the expression of VEGF, CYP1A2 and PCNA (P <0.05 or P < 0.01) in dose-dependent manner compared with the control mice which received PBS pre-injection. In summary, our study suggested that ADAM8 might promote liver injury by inhibiting the proliferation of hepatocytes, angiogenesis and affecting the metabolism function of liver during acute liver injury induced by CCl₄. Anti-ADAM8 mAb injection might be suitable as a potential method for acute liver injury therapy. PMID:24646716

  12. Adam's Dream

    ERIC Educational Resources Information Center

    Piacenti, Alexandria

    2011-01-01

    Growing up as a young girl, summer camp was a typical affair. Packed lunches kept cold with frozen freezer packs, seemingly endless slip n' slides, activities, games, contests. Every morning, the author was eager to wake up and head off to hours and hours of fun with friends and counselors. However, one may think the camping experience could not…

  13. Long-Term Electrical Stimulation of the Heart in Stokes-Adams Disease

    PubMed Central

    Johnson, A. L.; Klassen, G. A.; McGregor, M.; Dobell, A. R. C.

    1963-01-01

    Ten patients, between the ages of 39 and 75 years, underwent subcutaneous implantation of an electrode pacemaker for relief of recurrent syncopal episodes of Stokes-Adams disease. Their prolonged course of severe disability on medical therapy is in marked contrast to their new life, free of syncopal attacks, on pacemaker therapy. Experience in the management of these patients has shown that the electrode catheter, introduced intravenously to stimulate the right ventricular endocardium, is the best temporary therapy in a patient with uncontrollable syncopal attacks, and it should be used in all patients undergoing the surgical procedure of implantation. Pacemaker therapy is applicable to patients in sinus rhythm as well as to those in complete heart block. Observations on the effect of heart rate on cardiac output have shown the need of a faster rate in the presence of congestive failure for the maintenance of an adequate cardiac output. The favourable course of patients after implantation of a pacemaker indicates that this is the treatment of choice in Stokes-Adams disease. ImagesFig. 2 PMID:14055828

  14. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.

    PubMed

    Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique

    2016-07-15

    The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. PMID:26206614

  15. ADAM10-mediated release of heregulin confers resistance to trastuzumab by activating HER3

    PubMed Central

    Ebbing, Eva A.; Medema, Jan Paul; Damhofer, Helene; Meijer, Sybren L.; Krishnadath, Kausilia K.; van Berge Henegouwen, Mark I.

    2016-01-01

    Receptor tyrosine kinases of the HER-family are involved in the development and progression of multiple epithelial tumors, and have consequently become widely used targets for new anti-cancer therapies. Trastuzumab, an antibody against HER2, has shown potent growth inhibitory effects on HER2 overexpressing tumors, including gastro-esophageal cancer, however, resistance to this therapy is inevitable. Unfortunately, a paucity of data on the cellular mechanisms of resistance to targeted therapeutic agents exists in esophageal adenocarcinoma. Using primary established HER2-overexpressing cultures and patient-derived xenograft models, we now reveal a novel resistance mechanism to trastuzumab in esophageal cancer: In response to trastuzumab, both HER3 and the metalloprotease ADAM10 are simultaneously upregulated. The proteolytic activity of the latter then releases the HER3 ligand heregulin from the cell surface to activate HER3 and confer resistance to trastuzumab by inducing compensatory growth factor receptor signaling. Blocking either HER3 or ADAM10 effectively reverts the acquired resistance to trastuzumab. Our data thus provide strategies to inhibit this signaling and circumvent resistance to trastuzumab. PMID:26863569

  16. Sharp Adams type inequalities in Sobolev spaces W(Rn) for arbitrary integer m

    NASA Astrophysics Data System (ADS)

    Lam, Nguyen; Lu, Guozhen

    The main purpose of our paper is to prove sharp Adams type inequalities in unbounded domains of Rn for the Sobolev space W(Rn) for any positive integer m less than n. Our results complement those of Ruf and Sani (in press) [35] where such inequalities have been established for even integer m. We extend the main techniques of Ruf and Sani (in press) [35], which are the combinations of the comparison principle of Talenti (1976) [36] and Trombetti and Vázquez (1985) [38] for polyharmonic operators and a symmetrization argument together with constructions of radial auxiliary functions, to the case when m is odd. Moreover, we offer a completely different but much simpler approach to prove the comparison principle using the power of Bessel potentials and the Riesz rearrangement (see Remarks 3.2 and 3.3). This approach is of independent interest and works for any differential operators with appropriate radial kernels. As corollaries of our main theorems, we will derive the Adams type inequalities in the case when n=2m for all positive integer m by using different Sobolev norms.

  17. John G.C. Adams: father of Dental Public Health in Canada.

    PubMed

    Kenny, David J; Dale, Anne C; Wencer, David G

    2014-01-01

    John Gennings Curtis Adams (1839-1922), Canada's first resident dental missionary, was the father of Dental Public Health in Canada. He established, personally funded and operated the first free dental hospital in North America for poor children and their mothers in Toronto from 1872, three years before the founding of The Hospital for Sick Children; he later became their first dentist of record. He was a visionary zealot for prevention of decay, dental education, and treatment over extraction. Dr. Adams understood that neither parents (rich or poor) nor physicians were aware of the extent of pathosis present in children's mouths. He petitioned individuals, lobbied politicians and unions and pressured dental organizations on the importance of twice-annual school inspections to demonstrate disease so that parents would seek care for their children. He wanted government-funded dental hospitals like his own to treat those who could not afford care. He realized his objectives and his reforms to prevent suffering, as Toronto school inspections began in 1911 and Toronto's first publicly-funded free dental clinic opened in 1913. He was Canada's first dental philanthropist and a visionary for preventive dentistry. PMID:25549402

  18. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

    PubMed Central

    Kashef, Jubin; Alfandari, Dominique

    2015-01-01

    The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell–cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. PMID:26206614

  19. Isotopic and trace element constraints on the petrogenesis of lavas from the Mount Adams volcanic field, Washington

    USGS Publications Warehouse

    Jicha, B.R.; Hart, G.L.; Johnson, C.M.; Hildreth, W.; Beard, B.L.; Shirey, S.B.; Valley, J.W.

    2009-01-01

    Strontium, Nd, Pb, Hf, Os, and O isotope compositions for 30 Quaternary lava flows from the Mount Adams stratovolcano and its basaltic periphery in the Cascade arc, southern Washington, USA indicate a major component from intraplate mantle sources, a relatively small subduction component, and interaction with young mafic crust at depth. Major- and trace-element patterns for Mount Adams lavas are distinct from the rear-arc Simcoe volcanic field and other nearby volcanic centers in the Cascade arc such as Mount St. Helens. Radiogenic isotope (Sr, Nd, Pb, and Hf) compositions do not correlate with geochemical indicators of slab-fluids such as (Sr/P)n and Ba/Nb. Mass-balance modeling calculations, coupled with trace-element and isotopic data, indicate that although the mantle source for the calc-alkaline Adams basalts has been modified with a fluid derived from subducted sediment, the extent of modification is significantly less than what is documented in the southern Cascades. The isotopic and trace-element compositions of most Mount Adams lavas require the presence of enriched and depleted mantle sources, and based on volume-weighted chemical and isotopic compositions for Mount Adams lavas through time, an intraplate mantle source contributed the major magmatic mass of the system. Generation of basaltic andesites to dacites at Mount Adams occurred by assimilation and fractional crystallization in the lower crust, but wholesale crustal melting did not occur. Most lavas have Tb/Yb ratios that are significantly higher than those of MORB, which is consistent with partial melting of the mantle in the presence of residual garnet. ??18O values for olivine phenocrysts in Mount Adams lavas are within the range of typical upper mantle peridotites, precluding involvement of upper crustal sedimentary material or accreted terrane during magma ascent. The restricted Nd and Hf isotope compositions of Mount Adams lavas indicate that these isotope systems are insensitive to crustal

  20. Channel Catfish (Ictalurus punctatus Rafinesque, 1818) CD156a (ADAM Metallopeptidase Domain 8): cDNA Clone, Characterization and Expression in Tissues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CD156a, also known as a disintegrin and metalloprotease domain 8 (ADAM-8), is a type 1 transmembrane glycoprotein of the ADAM family. This protein plays important roles in immune and other physiological functions. In this communication, the channel catfish CD156a cDNA was characterized and its exp...

  1. Towards the "Informed Use" of Information and Communication Technology in Education: A Response to Adams' "Powerpoint, Habits of Mind, and Classroom Culture"

    ERIC Educational Resources Information Center

    Vallance, Michael; Towndrow, Phillip A.

    2007-01-01

    PowerPoint, the widely-used slide-show software package, is finding increasing currency in lecture halls and classrooms as the preferred method of communicating and presenting information. But, as Adams [Adams, C. (2006) "PowerPoint, habits of mind, and classroom culture." "Journal of Curriculum Studies," 38(4), 389-411] attempts to show, users…

  2. ADAM10 Cell Surface Expression but Not Activity Is Critical for Staphylococcus aureus α-Hemolysin-Mediated Activation of the NLRP3 Inflammasome in Human Monocytes

    PubMed Central

    Ezekwe, Ejiofor A.D.; Weng, Chengyu; Duncan, Joseph A.

    2016-01-01

    The Staphylococcus aureus toxin, α-hemolysin, is an important and well-studied virulence factor in staphylococcal infection. It is a soluble monomeric protein that, once secreted by the bacterium, forms a heptameric pore in the membrane of a broad range of host cell types. Hemolysin was recently discovered to bind and activate a disintegrin and metalloprotease 10 (ADAM10). In epithelial and endothelial cells, ADAM10 activation is required for the toxin’s activity against these cells. In host monocytic cells, α-hemolysin activates the nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 (NLRP3) inflammasome leading to production of pro-inflammatory cytokines and cell death. We now show that ADAM10 is critical for α-hemolysin-mediated activation of the NLRP3 inflammasome in human monocytes as siRNA knockdown or chemical blockade of ADAM10-α-hemolysin interaction leads to diminished inflammasome activation and cell death by reducing the available ADAM10 on the cell surface. Unlike epithelial cell and endothelial cell damage, which requires α-hemolysin induced ADAM10 activation, ADAM10 protease activity was not required for NLRP3 inflammasome activation. This work confirms the importance of ADAM10 in immune activation by α-hemolysin, but indicates that host cell signal induction by the toxin is different between host cell types. PMID:27043625

  3. ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

    PubMed

    Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

    2016-05-01

    ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. PMID:26918856

  4. ADAM8 is selectively up-regulated in endothelial cells and is associated with angiogenesis after spinal cord injury in adult mice.

    PubMed

    Mahoney, Edward T; Benton, Richard L; Maddie, Melissa A; Whittemore, Scott R; Hagg, Theo

    2009-01-10

    Endothelial cell (EC) loss and subsequent angiogenesis occur over the first week after spinal cord injury (SCI). To identify molecular mechanisms that could be targeted with intravenous (i.v.) treatments, we determined whether transmembrane "a disintegrin and metalloprotease" (ADAM) proteins are expressed in ECs of the injured spinal cord. ADAMs bind to integrins, which are important for EC survival and angiogenesis. Female adult C57Bl/6 mice with a spinal cord contusion had progressively more ADAM8 (CD156) immunostaining in blood vessels and individual ECs between 1 and 28 days following injury. Uninjured spinal cords had little ADAM8 staining. The increase in ADAM8 mRNA and protein was confirmed in spinal cord lysates, and ADAM8 mRNA was present in FACS-enriched ECs. ADAM8 colocalized extensively and exclusively with the EC marker PECAM and also with i.v.-injected lectins. Intravenous isolectin B4 (IB4) labels a subpopulation of blood vessels at and within the injury epicenter 3-7 days after injury, coincident with angiogenesis. Both ADAM8 and the proliferation marker Ki-67 were present in IB4-positive microvessels. ADAM8-positive proliferating cells were seen at the leading end of IB4-positive blood vessels. Angiogenesis was confirmed by BrdU incorporation, binding of i.v.-injected nucleolin antibodies, and MT1-MMP immunostaining in a subset of blood vessels. These data suggest that ADAM8 is vascular selective and plays a role in proliferation and/or migration of ECs during angiogenesis following SCI. PMID:19003792

  5. Human colonic myocytes are involved in postischemic inflammation through ADAM17-dependent TNFα production

    PubMed Central

    Jarry, Anne; Bach-Ngohou, Kalyane; Masson, Damien; Dejoie, Thomas; Lehur, Paul-Antoine; Mosnier, Jean-François; Denis, Marc G; Laboisse, Christian L

    2005-01-01

    The aim of this study was to identify human colonic resident cells able to initiate an inflammatory response in postischemic injury. Postischemic colonic injury, a condition relevant to various clinical settings, involves an inflammatory cascade in intestinal tissues through the recruitment of circulating inflammatory cells. However, there is no information on the nature of resident cells of the different intestinal layers able to initiate a postischemic inflammatory response. It is however an important issue in the context of a pharmacological approach of the early phase of intestinal ischemia. We reasoned that maintaining the different colonic layers as explant cultures in an oxygenated medium immediately after colonic resection, that is, after an ischemic period, would allow one to identify the resident cells able to initiate an inflammatory cascade, without interference of recruited inflammatory/immune cells. To this end, we designed an explant culture system that operationally defines three compartments in surgical specimens of the human colon, based on the microdissected layers, that is, mucosa, submucosa (containing muscularis mucosae) and muscularis propria. To validate the results obtained in explant cultures in the clinical setting of ischemic colitis, eight cases of sigmoid volvulus were examined. Only the myocytes-containing explants produced tumor necrosis factor alpha (TNFα), via an ADAM17 (a disintegrin and metalloproteinase-17)-dependent pathway, as shown by the abrogation of TNFα production by the inhibitor Tapi-2. Immunofluorescence studies identified nonvascular and vascular myocytes as resident cells coexpressing TNFα and ADAM17, both in our postischemic explant system and in surgical specimens from ischemic colitis patients. Finally, time-course experiments on explanted tissues showed that TNFα production by myocytes was an early event triggered by a postischemic oxidative stress involving nuclear factor kappa B (NF-κB). In conclusion

  6. Dysregulated ADAM10-Mediated Processing of APP during a Critical Time Window Leads to Synaptic Deficits in Fragile X Syndrome.

    PubMed

    Pasciuto, Emanuela; Ahmed, Tariq; Wahle, Tina; Gardoni, Fabrizio; D'Andrea, Laura; Pacini, Laura; Jacquemont, Sébastien; Tassone, Flora; Balschun, Detlef; Dotti, Carlos G; Callaerts-Vegh, Zsuzsanna; D'Hooge, Rudi; Müller, Ulrike C; Di Luca, Monica; De Strooper, Bart; Bagni, Claudia

    2015-07-15

    The Fragile X mental retardation protein (FMRP) regulates neuronal RNA metabolism, and its absence or mutations leads to the Fragile X syndrome (FXS). The β-amyloid precursor protein (APP) is involved in Alzheimer's disease, plays a role in synapse formation, and is upregulated in intellectual disabilities. Here, we show that during mouse synaptogenesis and in human FXS fibroblasts, a dual dysregulation of APP and the α-secretase ADAM10 leads to the production of an excess of soluble APPα (sAPPα). In FXS, sAPPα signals through the metabotropic receptor that, activating the MAP kinase pathway, leads to synaptic and behavioral deficits. Modulation of ADAM10 activity in FXS reduces sAPPα levels, restoring translational control, synaptic morphology, and behavioral plasticity. Thus, proper control of ADAM10-mediated APP processing during a specific developmental postnatal stage is crucial for healthy spine formation and function(s). Downregulation of ADAM10 activity at synapses may be an effective strategy for ameliorating FXS phenotypes. PMID:26182420

  7. Lightweight robotic mobility: template-based modeling for dynamics and controls using ADAMS/car and MATLAB

    NASA Astrophysics Data System (ADS)

    Adamczyk, Peter G.; Gorsich, David J.; Hudas, Greg R.; Overholt, James

    2003-09-01

    The U.S. Army is seeking to develop autonomous off-road mobile robots to perform tasks in the field such as supply delivery and reconnaissance in dangerous territory. A key problem to be solved with these robots is off-road mobility, to ensure that the robots can accomplish their tasks without loss or damage. We have developed a computer model of one such concept robot, the small-scale "T-1" omnidirectional vehicle (ODV), to study the effects of different control strategies on the robot's mobility in off-road settings. We built the dynamic model in ADAMS/Car and the control system in Matlab/Simulink. This paper presents the template-based method used to construct the ADAMS model of the T-1 ODV. It discusses the strengths and weaknesses of ADAMS/Car software in such an application, and describes the benefits and challenges of the approach as a whole. The paper also addresses effective linking of ADAMS/Car and Matlab for complete control system development. Finally, this paper includes a section describing the extension of the T-1 templates to other similar ODV concepts for rapid development.

  8. The Feasibility of Consolidating the Schools of Mount Joy Township, Adams County, Pennsylvania. Bulletin, 1920, No. 9

    ERIC Educational Resources Information Center

    Cook, Katherine M.; Deffenbaugh, W. S.

    1920-01-01

    Mount Joy Township is located in southeastern Pennsylvania, in Adams County. It is immediately adjacent to the historic battlefield and town of Gettysburg. Though irregular in shape, it averages about 5 miles from north to south and 41 miles from east to west, and contains approximately 36 square miles. The population of the township in 1910 was…

  9. 77 FR 25229 - Adams-Warnock Railway, Inc.-Lease and Operation Exemption-Norfolk Southern Railway Company

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... Surface Transportation Board Adams-Warnock Railway, Inc.--Lease and Operation Exemption-- Norfolk Southern... exemption under ] 49 CFR 1150.31 to lease from Norfolk Southern Railway Company (NSR), and to operate, a... the lease agreement that is expected to be completed prior to the effective date of the...

  10. A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease

    PubMed Central

    Hao, Jingcan; Wang, Wenyu; Wen, Yan; Xiao, Xiao; He, Awen; Guo, Xiong; Yang, Tielin; Liu, Xiaogang; Shen, Hui; Chen, Xiangding; Tian, Qing; Deng, Hong-Wen; Zhang, Feng

    2016-01-01

    Kashin-Beck disease (KBD) is a chronic osteoarthropathy, which manifests as joint deformities and growth retardation. Only a few genetic studies of growth retardation associated with the KBD have been carried out by now. In this study, we conducted a two-stage bivariate genome-wide association study (BGWAS) of the KBD using joint deformities and body height as study phenotypes, totally involving 2,417 study subjects. Articular cartilage specimens from 8 subjects were collected for immunohistochemistry. In the BGWAS, ADAM12 gene achieved the most significant association (rs1278300 p-value = 9.25 × 10−9) with the KBD. Replication study observed significant association signal at rs1278300 (p-value = 0.007) and rs1710287 (p-value = 0.002) of ADAM12 after Bonferroni correction. Immunohistochemistry revealed significantly decreased expression level of ADAM12 protein in the KBD articular cartilage (average positive chondrocyte rate = 47.59 ± 7.79%) compared to healthy articular cartilage (average positive chondrocyte rate = 64.73 ± 5.05%). Our results suggest that ADAM12 gene is a novel susceptibility gene underlying both joint destruction and growth retardation of the KBD. PMID:27545300

  11. A new approach to sharp Moser-Trudinger and Adams type inequalities: A rearrangement-free argument

    NASA Astrophysics Data System (ADS)

    Lam, Nguyen; Lu, Guozhen

    The main purpose of this paper is two-fold. On the one hand, we will develop a new approach to establish sharp singular Moser-Trudinger and Adams type inequalities in unbounded domains of Euclidean spaces without using the standard symmetrization. On the other hand, we will prove the sharp singular Adams type inequality on high order Sobolev spaces W(Rn) of arbitrary integer order m (Theorem 1.1) which improves the results of Ruf and Sani (2013) [48] where sharp Adams inequalities were established for even m and those of the authors (Lam and Lu, 2012 [28,29]) for odd m but with different and more restricted norms. We first establish the sharp local singular Adams inequality on domains Ω in Rn of finite measure (Theorem 1.4). We take a perspective that any function in the high order Sobolev spaces W(Rn) can be represented as a Bessel potential. Thus, we can fully use the tools from harmonic analysis and the kernel properties of the polyharmonic operators (. Once we have established this sharp local Adams inequality, then we can adapt the rearrangement-free method we will develop in this paper to derive a global sharp Adams inequality from a local one. Our argument substantially simplifies those in Ruf and Sani (2013) [48] and Lam and Lu (2012) [28,29] and avoids the use of rather deep and complicated comparison principle of solutions to polyharmonic operators used in Ruf and Sani (2013) [48], Lam and Lu (2012) [28,29]. Moreover, our theorem holds on Sobolev spaces W(Rn) of any positive fractional order αAdams inequalities with less restrictions on the Sobolev norms (see Theorems 1.2, 1.3 and 1.5). Our approach is surprisingly simple and general and can be easily applied to scenarios such as Riemannian and sub-Riemannian manifolds where symmetrization argument does not work (see, e.g., on the Heisenberg group Lam and Lu (2012) [30]).

  12. Adam Smith's invisible hand is unstable: physics and dynamics reasoning applied to economic theorizing

    NASA Astrophysics Data System (ADS)

    McCauley, Joseph L.

    2002-11-01

    Neo-classical economic theory is based on the postulated, nonempiric notion of utility. Neo-classical economists assume that prices, dynamics, and market equilibria are supposed to be derived from utility. The results are supposed to represent mathematically the stabilizing action of Adam Smith's invisible hand. In deterministic excess demand dynamics, however, a utility function generally does not exist mathematically due to nonintegrability. Price as a function of demand does not exist and all equilibria are unstable. Qualitatively, and empirically, the neo-classical prediction of price as a function of demand describes neither consumer nor trader demand. We also discuss five inconsistent definitions of equilibrium used in economics and finance, only one of which is correct, and then explain the fallacy in the economists’ notion of ‘temporary price equilibria’.

  13. [Spontaneus ductal closure in a fetus postnatally diagnosed as Adams-Olivier syndrome].

    PubMed

    Włoch, Agata; Borowski, Dariusz; Czuba, Bartosz; Włoch, Stanisław; Sodowski, Krzysztof

    2006-08-01

    In utero isolated ductal closure is uncommon and can lead to congestive heart failure, fetal hydrops and death if not recognized. A case report of premature spontaneus ductal closure in the third trimester of pregnancy in a fetus postnatally diagnosed as Adams-Olivier Syndrome is presented. On ultrasound examination an intrauterine growth restriction, defects of bones of hands and feet as well as ventriculomegaly were found. No nonsteroid drug treatment during pregnancy was applied. Fetal echocardiography was performed following an abnormal four-chamber view. Premature ductal closure was diagnosed. Fetal echocardiogram showed absent flow in the ductus arteriosus, dilated right ventricle with decreased function, and moderate tricuspid and pulmonary valve insufficiency with no signs of fetal hydrops. An elective cesarean section was performed. All abnormalities observed on former echocardiogram exam withdrew within 3 months of infant's life. The infant stays in the tertiary care centre due to the extracardiac malformations. PMID:17076195

  14. ADAM17 promotes proliferation of collecting duct kidney epithelial cells through ERK activation and increased glycolysis in polycystic kidney disease.

    PubMed

    Beck Gooz, Monika; Maldonado, Eduardo N; Dang, Yujing; Amria, May Y; Higashiyama, Shigeki; Abboud, Hanna E; Lemasters, John J; Bell, P Darwin

    2014-09-01

    Polycystic kidney disease (PKD) is a common genetic disorder leading to cyst formation in the kidneys and other organs that ultimately results in kidney failure and death. Currently, there is no therapy for slowing down or stopping the progression of PKD. In this study, we identified the disintegrin metalloenzyme 17 (ADAM17) as a key regulator of cell proliferation in kidney tissues of conditional knockout Ift88(-/-) mice and collecting duct epithelial cells from Ift88°(rpk) mice, animal models of autosomal recessive polycystic kidney disease (ARPKD). Using Western blotting, an enzyme activity assay, and a growth factor-shedding assay in the presence or absence of the specific ADAM17 inhibitor TMI-005, we show that increased expression and activation of ADAM17 in the cystic kidney and in collecting duct epithelial cells originating from the Ift88°(rpk) mice (designated as PKD cells) lead to constitutive shedding of several growth factors, including heparin-binding EGF-like growth factor (HB-EGF), amphiregulin, and transforming growth factor-α (TGF-α). Increased growth factor shedding induces activation of the EGFR/MAPK/ERK pathway and maintains higher cell proliferation rate in PKD cells compared with control cells. PKD cells also displayed increased lactate formation and extracellular acidification indicative of aerobic glycolysis (Warburg effect), which was blocked by ADAM17 inhibition. We propose that ADAM17 is a key promoter of cellular proliferation in PKD cells by activating the EGFR/ERK axis and a proproliferative glycolytic phenotype. PMID:24899059

  15. Heightened cleavage of Axl receptor tyrosine kinase by ADAM metalloproteases may contribute to disease pathogenesis in SLE.

    PubMed

    Orme, Jacob J; Du, Yong; Vanarsa, Kamala; Mayeux, Jessica; Li, Li; Mutwally, Azza; Arriens, Cristina; Min, Soyoun; Hutcheson, Jack; Davis, Laurie S; Chong, Benjamin F; Satterthwaite, Anne B; Wu, Tianfu; Mohan, Chandra

    2016-08-01

    Systemic lupus erythematosus (SLE) is characterized by antibody-mediated chronic inflammation in the kidney, lung, skin, and other organs to cause inflammation and damage. Several inflammatory pathways are dysregulated in SLE, and understanding these pathways may improve diagnosis and treatment. In one such pathway, Axl tyrosine kinase receptor responds to Gas6 ligand to block inflammation in leukocytes. A soluble form of the Axl receptor ectodomain (sAxl) is elevated in serum from patients with SLE and lupus-prone mice. We hypothesized that sAxl in SLE serum originates from the surface of leukocytes and that the loss of leukocyte Axl contributes to the disease. We determined that macrophages and B cells are a source of sAxl in SLE and in lupus-prone mice. Shedding of the Axl ectodomain from the leukocytes of lupus-prone mice is mediated by the matrix metalloproteases ADAM10 and TACE (ADAM17). Loss of Axl from lupus-prone macrophages renders them unresponsive to Gas6-induced anti-inflammatory signaling in vitro. This phenotype is rescued by combined ADAM10/TACE inhibition. Mice with Axl-deficient macrophages develop worse disease than controls when challenged with anti-glomerular basement membrane (anti-GBM) sera in an induced model of nephritis. ADAM10 and TACE also mediate human SLE PBMC Axl cleavage. Collectively, these studies indicate that increased metalloprotease-mediated cleavage of leukocyte Axl may contribute to end organ disease in lupus. They further suggest dual ADAM10/TACE inhibition as a potential therapeutic modality in SLE. PMID:27237127

  16. Further Genetic Evidence for Three Psoriasis-Risk Genes: ADAM33, CDKAL1, and PTPN22

    PubMed Central

    Li, Yonghong; Liao, Wilson; Chang, Monica; Schrodi, Steven J.; Bui, Nam; Catanese, Joseph J.; Poon, Annie; Matsunami, Nori; Callis-Duffin, Kristina P.; Leppert, Mark F.; Bowcock, Anne M.; Kwok, Pui-Yan; Krueger, Gerald G.; Begovich, Ann B.

    2014-01-01

    Predisposition to psoriasis is known to be affected by genetic variation in HLA-C, IL12B, and IL23R, and although other psoriasis-associated variants have been identified, incontrovertible statistical evidence for these markers has not yet been obtained. To help resolve this issue, we tested 15 single-nucleotide polymorphisms (SNPs) from 7 putative psoriasis-risk genes in 1,448 psoriasis patients and 1,385 control subjects; 3 SNPs, rs597980 in ADAM33, rs6908425 in CDKAL1 and rs3789604 in PTPN22, were significant with the same risk allele as in prior reports (one-sided P<0.05, false discovery rate<0.15). These three markers were tested in a fourth sample set (599 cases and 299 controls); one marker, rs597980, replicated (one-sided P<0.05) and the other two had odds ratios with the same directionality as in the original sample sets. Mantel–Haenszel meta-analyses of all available case–control data, including those published by other groups, showed that these three markers were highly significant (rs597980: P =0.0057 (2,025 cases and 1,597 controls), rs6908425: P =1.57×10−5 (3,206 cases and 4,529 controls), and rs3789604: P =3.45×10−5 (2,823 cases and 4,066 controls)). These data increase the likelihood that ADAM33, CDKAL1, and PTPN22 are true psoriasis-risk genes. PMID:18923449

  17. Adams-Harbertson protein precipitation-based wine tannin method found invalid.

    PubMed

    Brooks, Larry; McCloskey, Leo; McKesson, Doug; Sylvan, Marshall

    2008-01-01

    The poor precision of the Adams-Harbertson wine tannin assay which was proposed for commercial winemaking, thereby creating the real possibility of quality control problems, is documented. The method is a version of the Hagerman and Butler protein precipitation-based tannin method. An extensive invalidation of the assay results with luxury wine data shows that the assay cannot distinguish bottled wine with reasonable accuracy. Five laboratories used Adams-Harbertson to assay 9 replicates each, of 3 bottled wines (n = 135) found in California supermarkets, with tannin concentrations of nominally 500 and 1000 ppm by high-performance liquid chromatography (HPLC). Reliability exceeded the +/-5% industry requirement by nominally 5 times (z-score based on 5% distribution). Coefficient of variation was +/-27%, making the standard deviation range 54% for Pinot Noir, 34% for Merlot, and 44% for Cabernet Sauvignon. Validity exceeded the 100% requirement. Intralaboratory validity recovery was 55-63%. Interwinery validity was 71-178% of the mean for Pinot Noir, 81-144% for Merlot, and 83-164% for Cabernet Sauvignon. Range as a function of the mean was 89% for Pinot Noir, 55% for Merlot, and 67% for Cabernet Sauvignon. Expect intermethod validity to be nominally 50%, i.e., percent recovery to HPLC. These statistically significant errors were predicted by the literature. First-order error is related to the tannin-protein equilibrium constant (Ka), as suggested by the original author, Hagerman, and the protein equivalence point error as suggested by Silber. This does not obviate second-order errors for tannin-protein analytical chemistry. Winemakers using the measurements risk making wines that are relatively more tannic than the measurements report. PMID:18980123

  18. Enthalpies of Mixing in Sodium Silicate Glasses and Relevance to Adam-Gibbs Theory

    NASA Astrophysics Data System (ADS)

    Hovis, G.; Jarry, P.; Toplis, M.; Richet, P.

    2003-12-01

    Solution calorimetric measurements have been made in 20.1 wt % hydrofluoric acid at 50° C on binary Na2O-SiO2 glasses ranging in composition from 0 to 50 mol % Na2O. The initial calorimetric data for compositions between 20 and 50 mol % Na2O were highly variable, determined later to be due to the development of Na carbonate on the glass surfaces. However, additional measurements using minimally-ground specimens that had been remelted shortly before the calorimetric dissolutions produced highly reproducible results. After adjustment of the data for glass transition temperature (Richet et al., 1984, J. Amer. Ceram. Soc.), the results show nearly linear ("ideal") behavior of the heats of solution between 50 % Na2O and 30-35 % Na2O. However, positive enthalpies of mixing (Hex) are evident in the compositional region between 0 and 30-35 mol % Na2O, with maximum magnitudes of Hex on the order of 5 kJ/mol relative to 0 and 35 % Na2O end members. Within the framework of the Adam-Gibbs theory of structural relaxation, viscosity and heat capacity data may be combined to determine configurational entropies of silicate glasses. When applied to sodium silicate glasses (Toplis, 2001, Chemical Geology), positive entropies of mixing (Sex) are calculated for compositions between 0 and 30 mole % Na2O, a compositional region where liquid immiscibility also is known to occur (Haller et al., 1974, J. Amer. Ceram. Soc.) and where Gibbs free energies of mixing (Gex) therefore must be positive. Because positive entropies of mixing contribute negatively (-TSex) to Gex, the observed immiscibility requires positive enthalpies of mixing (Hex) in the silicic part of the compositional range. The present study confirms such positive enthalpies of mixing and supports the usefulness of Adam-Gibbs theory for the prediction of viscosity/entropy behavior of silicate glasses and liquids.

  19. [Adam hammer (1818 - 1878) - remarks on a forgotten pioneer of ether anaesthesia in obstetrics].

    PubMed

    Goerig, M; Streckfuss, W

    2004-05-01

    Adam Hammer, born in 1818, and working as a doctor for the poor since 1847 in Mannheim, was the first person in the German speaking world to use ether for pain relief during labor on February 18th 1847. He took part in the abortive April 1848 Revolution in Mannheim - a pinnacle of German liberalism and later of political radicalism, which attented to abolish the Monarchy and introduce a democratic Republic. After the revolution was put down, Hammer emigrated to the United States and settled down in St. Louis, Missouri. Remaining politically active, he joined the Republican Party, founded in 1854 and served as a military surgeon in the Union Army during the American Civil War. Even before the war, he was engaged in efforts to improve the level of medical training in America and was involved with the foundation of High Schools which offered training courses along the lines of German universities. His ideas and innovations were not introduced immediately, but had a significant impact on medical training methology later on in the US. During a visit in Europe in 1876, he was the first to diagnose a coronary thombosis as the cause of a heart attack on a live patient. The diagnosis was later confirmed by post-morten autopsy on the patient. In 1877 he returned to Germany and died one year later. The biography of Adam Hammer mirrows that of many other German-Americans whose emigration proved to be a gain for America but a loss for Germany. This story was destinated to be repeated in terrible circumstances some decades later. PMID:15156417

  20. Computational identification and experimental validation of microRNAs binding to the Alzheimer-related gene ADAM10

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) are post-transcriptional regulators involved in numerous biological processes including the pathogenesis of Alzheimer’s disease (AD). A key gene of AD, ADAM10, controls the proteolytic processing of APP and the formation of the amyloid plaques and is known to be regulated by miRNA in hepatic cancer cell lines. To predict miRNAs regulating ADAM10 expression concerning AD, we developed a computational approach. Methods MiRNA binding sites in the human ADAM10 3' untranslated region were predicted using the RNA22, RNAhybrid and miRanda programs and ranked by specific selection criteria with respect to AD such as differential regulation in AD patients and tissue-specific expression. Furthermore, target genes of miR-103, miR-107 and miR-1306 were derived from six publicly available miRNA target site prediction databases. Only target genes predicted in at least four out of six databases in the case of miR-103 and miR-107 were compared to genes listed in the AlzGene database including genes possibly involved in AD. In addition, the target genes were used for Gene Ontology analysis and literature mining. Finally, we used a luciferase assay to verify the potential effect of these three miRNAs on ADAM10 3'UTR in SH-SY5Y cells. Results Eleven miRNAs were selected, which have evolutionary conserved binding sites. Three of them (miR-103, miR-107, miR-1306) were further analysed as they are linked to AD and most strictly conserved between different species. Predicted target genes of miR-103 (p-value = 0.0065) and miR-107 (p-value = 0.0009) showed significant overlap with the AlzGene database except for miR-1306. Interactions between miR-103 and miR-107 to genes were revealed playing a role in processes leading to AD. ADAM10 expression in the reporter assay was reduced by miR-1306 (28%), miR-103 (45%) and miR-107 (52%). Conclusions Our approach shows the requirement of incorporating specific, disease-associated selection criteria into the prediction

  1. An organized approach to trauma care: legacy of R Adams Cowley.

    PubMed

    Edlich, Richard F; Wish, John R; Britt, L D; Long, William B

    2004-01-01

    The organized approach to caring for trauma patients was introduced into the civilian setting by the innovative pioneer, R Adams Cowley. His system in Maryland has the following 11 components: (1) a State Police Aviation Division that transports patients throughout the State; (2) trained paramedics at the scene of the accident as well as on the helicopter, who will stabilize the patients en route to the Shock Trauma Center; (3) one central dispatch communication center in Baltimore that coordinates information between paramedics and the Trauma Center; (4) a Shock Trauma Center with a helicopter landing zone near the building; (5) trained trauma nurses and trauma technicians to transfer the patient from the helicopter by stretcher to the resuscitation area; if there is a special complication, such as an airway problem, the anesthesiologist and or trauma surgeon may meet the helicopter on the roof as well; (6) trauma surgeons, board-certified in surgery, with a certificate of added qualification in surgical critical care, to treat the critically ill trauma patients in the resuscitation area; (7) a CT scan and portable X-ray units in the admission area that aid in the diagnosis of the injury; (8) operating rooms adjacent to the admission area for repair of trauma injuries; (9) a surgical intensive unit to care for the trauma patient; (10) a team of specialty physicians trained in a wide variety of specialties who work as a multidisciplinary unit caring for the hospitalized patient; and (11) an ambulatory outpatient unit that allows the patient to be followed in the center after discharge. Dr. R Adams Cowley incorporated each of these 11 components for an organized trauma center into Maryland. In recognition of his landmark contributions to trauma, the eight-story Shock Trauma Center was named the R Adams Cowley Shock Trauma Center. There is growing evidence that this organized system in trauma care seen in Maryland must be replicated in every state in our nation. The

  2. ADAM10 controls collagen signaling and cell migration on collagen by shedding the ectodomain of discoidin domain receptor 1 (DDR1)

    PubMed Central

    Shitomi, Yasuyuki; Thøgersen, Ida B.; Ito, Noriko; Leitinger, Birgit; Enghild, Jan J.; Itoh, Yoshifumi

    2015-01-01

    Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and transmits signals from various collagens in epithelial cells. However, how DDR1–dependent signaling is regulated has not been understood. Here we report that collagen binding induces ADAM10-dependent ectodomain shedding of DDR1. DDR1 shedding is not a result of an activation of its signaling pathway, since DDR1 mutants defective in signaling were shed in an efficient manner. DDR1 and ADAM10 were found to be in a complex on the cell surface, but shedding did not occur unless collagen bound to DDR1. Using a shedding-resistant DDR1 mutant, we found that ADAM10-dependent DDR1 shedding regulates the half-life of collagen-induced phosphorylation of the receptor. Our data also revealed that ADAM10 plays an important role in regulating DDR1-mediated cell adhesion to achieve efficient cell migration on collagen matrices. PMID:25540428

  3. Production of porcine TNFα by ADAM17-mediated cleavage negatively regulates porcine reproductive and respiratory syndrome virus infection.

    PubMed

    Li, Ren; Guo, Longjun; Gu, Weihong; Luo, Xiaolei; Zhang, Jian; Xu, Yunfei; Tian, Zhijun; Feng, Li; Wang, Yue

    2016-06-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) causes a series of inflammatory reactions in sites of infection, companied by the upregulation of key inflammatory factor TNFα. TNFα, which serves as a "master regulator" of inflammatory cytokine production, is mainly produced by macrophages at the early infection stage. Here, we showed that porcine alveolar macrophages produced a great amount of soluble TNFα upon PRRSV infection. Furthermore, we found that TNFα had great anti-PRRSV effect. Next, by using inhibitor and genetic modification methods, we addressed that porcine TNFα production was mediated by ADAM17. Lastly, we proved that the (78)Arg-Ser-Ser motif of porcine TNFα contained the essential information for efficient cleavage. Taken together, our findings provide the direct evidence that ADAM17 cleaves porcine TNFα, which represents a new view for identifying potential therapeutic targets in anti-PRRSV therapy. PMID:26724939

  4. EphrinB2 affects apical constriction in Xenopus embryos and is regulated by ADAM10 and flotillin-1

    NASA Astrophysics Data System (ADS)

    Ji, Yon Ju; Hwang, Yoo-Seok; Mood, Kathleen; Cho, Hee-Jun; Lee, Hyun-Shik; Winterbottom, Emily; Cousin, Hélène; Daar, Ira O.

    2014-03-01

    The Eph/ephrin signalling pathways have a critical function in cell adhesion and repulsion, and thus play key roles in various morphogenetic events during development. Here we show that a decrease in ephrinB2 protein causes neural tube closure defects during Xenopus laevis embryogenesis. Such a decrease in ephrinB2 protein levels is observed on the loss of flotillin-1 scaffold protein, a newly identified ephrinB2-binding partner. This dramatic decline in ephrinB2 protein levels on the absence of flotillin-1 expression is specific, and is partly the result of an increased susceptibility to cleavage by the metalloprotease ADAM10. These findings indicate that flotillin-1 regulates ephrinB2 protein levels through ADAM10, and is required for appropriate neural tube morphogenesis in the Xenopus embryo.

  5. ADAM9 Expression Is Associate with Glioma Tumor Grade and Histological Type, and Acts as a Prognostic Factor in Lower-Grade Gliomas.

    PubMed

    Fan, Xing; Wang, Yongheng; Zhang, Chuanbao; Liu, Li; Yang, Sen; Wang, Yinyan; Liu, Xing; Qian, Zenghui; Fang, Shengyu; Qiao, Hui; Jiang, Tao

    2016-01-01

    The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas. The ADAM9 expression between lower-grade glioma (LGG) and glioblastoma (GBM) patients was compared and its association with progression-free survival (PFS) and overall survival (OS) was assessed to evaluate its prognostic value. Our data suggested that GBM patients had significantly higher expression of ADAM9 in comparison to LGG patients (p < 0.001, t-test). In addition, among the LGG patients, aggressive astrocytic tumors displayed significantly higher ADAM9 expression than oligodendroglial tumors (p < 0.001, t-test). Moreover, high ADAM9 expression also correlated with poor clinical outcome (p < 0.001 and p < 0.001, log-rank test, for PFS and OS, respectively) in LGG patients. Further, multivariate analysis suggested ADAM9 expression to be an independent marker of poor survival (p = 0.002 and p = 0.003, for PFS and OS, respectively). These results suggest that ADAM9 mRNA expression is associated with tumor grade and histological type in gliomas and can serve as an independent prognostic factor, specifically in LGG patients. PMID:27571068

  6. Formulation of adaptive Adam-Bashforth method for solving ordinary differential equations: modeling of highly doped waveguide amplifiers

    NASA Astrophysics Data System (ADS)

    Bekal, Anish; Srinivasan, Balaji

    2012-06-01

    Accurate modeling of dynamic optical interactions such as saturation and re-absorption in highly doped waveguide amplifiers requires solving a stiff system of ordinary differential equations (ODEs). Traditional ODE solvers including Range-Kutta methods are computationally ill-suited for such applications. In this paper, we derive and apply predictor - corrector adaptive Adam-Bashforth scheme for modeling the population dynamics in Erbium - Doped Fiber Amplifiers (EDFA). Predictor and corrector equations for adaptive Adam-Bashforth have been derived by using Lagrange polynomial as basis rather than the Newton polynomials used in constant stepsize Adam-Bashforth scheme. Convergence and stability analysis conducted on the scheme shows that the method has similar characteristics as that of constant step-size conventional Adam-Bashforth methods for small changes in step sizes. Solutions have been validated by re-generating the absorption and emission coefficients for doped fibers with two different doping concentrations, which is found to match with the manufacturer datasheet. This method is compared with other method like Euler and the optimum order of predictor and corrector is estimated. The result show that this modified form of the scheme results in 75% reduction in step-size to maintain an relative accuracy level of 10-3 as compared to adaptive Euler method. Finally, different orders were compared by using ratio of step-size and number of operations per step as a metric for Figure of Merit (FOM). FOM analysis shows that use of higher order methods are not efficient in reducing the number of steps required to obtain accurate results. It is found that the scheme with both second order predictor and corrector is the most efficient computationally. However, in terms of accuracy second order predictor and third order corrector is more suitable with only a marginal degradation of FOM.

  7. Detrital zircon geochronology of the Adams Argillite and Nation River Formation, east-central Alaska, U.S.A

    USGS Publications Warehouse

    Gehrels, G.E.; Johnsson, M.J.; Howell, D.G.

    1999-01-01

    The Cambrian Adams Argillite and the Devonian Nation River Formation are two sandstone-bearing units within a remarkably complete Paleozoic stratigraphic section in east-central Alaska. These strata, now foreshortened and fault-bounded, were originally contiguous with miogeoclinal strata to the east that formed as a passive-margin sequence along the northwestern margin of the North American continent. Seventy-five detrital zircon grains from the Adams Argillite and the Nation River Formation were analyzed in an effort to provide constraints on the original sources of the grains, and to generate a detrital zircon reference for miogeoclinal strata in the northern Cordillera. Thirty-five single zircon grains from a quartzite in the Adams Argillite yield dominant age clusters of 1047-1094 (n = 6), 1801-1868 (n = 10), and 2564-2687 (n = 5) Ma. Forty zircons extracted from a sandstone in the Nation River Formation yield clusters primarily of 424-434 (n = 6), 1815-1838 (n = 6), 1874-1921 (n = 7), and 2653-2771 (n = 4) Ma. The Early Proterozoic and Archean grains in both units probably originated in basement rocks in a broad region of the Canadian Shield. In contrast, the original igneous sources for mid-Protcrozoic grains in the Adams Argillite and ??? 430 Ma grains in the Nation River Formation are more difficult to identify. Possible original sources for the mid-Proterozoic grains include: (1) the Grenville Province of eastern Laurentia, (2) the Pearya terrane along the Arctic margin, and (3) mid-Proterozoic igneous rocks that may have been widespread along or outboard of the Cordilleran margin. The ??? 430 Ma grains may have originated in: (1) arc-type sources along the Cordilleran margin, (2) the Caledonian orogen, or (3) a landmass, such as Pearya, Siberia, or crustal fragments now in northern Asia, that resided outboard of the Innuitian orogen during mid-Paleozoic time. Copyright ?? 1999, SEPM (Society for Sedimentary Geology).

  8. A disintegrin and metalloprotease 33 (ADAM33) gene polymorphisms and the risk of asthma: a meta-analysis.

    PubMed

    Liang, Siqiao; Wei, Xuan; Gong, Chen; Wei, Jinmei; Chen, Zhangrong; Deng, Jingmin

    2013-05-01

    Polymorphisms in the ADAM33 gene have been associated with asthma, but the data are controversial. Therefore, we reviewed the related studies and quantitatively summarized the associations between ADAM33 polymorphisms and asthma risk using meta-analysis. A dominant model (AA+Aa vs. aa), recessive model (AA vs. Aa+aa), additive model (AA vs. aa) and allelic model (A vs. a) were used to estimate the association between ADAM33 polymorphism and asthma risk. A total of 29 case-control studies referring to 14 SNPs were identified: rs2280091(T1), rs2787094(V4), rs528557(S2), rs2280090(T2), rs511898(F+1), rs44707(ST+4), rs3918396(S1), rs543749(V-1), rs574174(ST+7), rs597980(ST+5), rs2853209(S+1), rs2280089(T+1), rs612709(Q-1), and rs3746631(V5). The results indicated that S1, V-1, V5, S+1, S2, ST+4, ST+7, ST+5, and Q-1 were not associated with asthma. Significant associations were found with the T1, V4, F+1 and T+1 polymorphisms in the overall population. In the subgroup analysis by ethnicity, a positive result was only found for the T1, V4, F+1 and T2 polymorphisms in Asia but not in Europe or Latin America. This meta-analysis provides evidence that the T1, V4, F+1, T2, and T+1 polymorphisms in the ADAM33 gene are risk factors for asthma, especially in the Asian population. PMID:23380143

  9. Mid-trimester maternal ADAM12 levels differ according to fetal gender in pregnancies complicated by preeclampsia.

    PubMed

    Myers, Jenny E; Thomas, Grégoire; Tuytten, Robin; Van Herrewege, Yven; Djiokep, Raoul O; Roberts, Claire T; Kenny, Louise C; Simpson, Nigel A B; North, Robyn A; Baker, Philip N

    2015-02-01

    An overrepresentation of adverse pregnancy outcomes has been observed in pregnancies associated with a male fetus. We investigated the association between fetal gender and candidate biomarkers for preeclampsia. Proteins were quantified in samples taken at 20 weeks from women recruited to the SCreening fOr Pregnancy Endpoints (SCOPE) study (preeclampsia n = 150; no preeclampsia n = 450). In contrast to placental growth factor, soluble endoglin, and insulin-like growth factor acid labile subunit, levels of metallopeptidase domain 12 (ADAM12) at 20 weeks were dependent on fetal gender in pregnancies complicated by preeclampsia, for male (n = 73) fetuses the multiples of the median (MoM; interquartile range [IQR] 1.1-1.5) was 1.3, whereas for female fetuses (n = 75) MoM was 1.1 (1.0-1.3); P < .01. Prediction of preeclampsia using ADAM12 levels was improved for pregnancies associated with a male fetus (area under receiver-operator curve [AUC] 0.73 [95% confidence interval [CI] 0.67-0.80]) than that of a female fetus (AUC 0.62 [0.55-0.70]); P = .03. The data presented here fit a contemporary hypothesis that there is a difference between the genders in response to an adverse maternal environment and suggest that an alteration in ADAM12 may reflect an altered placental response in pregnancies subsequently complicated by preeclampsia. PMID:24899472

  10. Transcriptional control of PAX4-regulated miR-144/451 modulates metastasis by suppressing ADAMs expression.

    PubMed

    Zhang, J; Qin, X; Sun, Q; Guo, H; Wu, X; Xie, F; Xu, Q; Yan, M; Liu, J; Han, Z; Chen, W

    2015-06-01

    Paired box gene 4 (PAX4) is a transcriptional modulator located on chromosome 7q32, and its expression is dysregulated in a variety of human cancers, suggesting that PAX4 may be important in multiple tumors as a driver gene. Here, we show that PAX4 promoted migration and invasion in human epithelial cancers by decreasing miR-144 and miR-451 (miR-144/451) expression levels. Accordingly, miR-144/451 suppressed the migratory and invasive phenotypes, even in PAX4-expressing cells. Mechanistically, miR-144/451 inhibits cancer metastasis by targeting the A disintegrin and metalloproteinase (ADAM) protein family members ADAMTS5 and ADAM10. Their dysregulation is associated with increased tumor invasiveness and metastasis, then reduced patient prognosis in certain epithelial cancers. This discovery suggests that a PAX4-miR-144/451-ADAMs axis regulates human epithelial cancer metastasis, thus opening up therapeutic possibilities and predicting prognosis for those cancer types. PMID:25151965

  11. Cleavage of E-cadherin by ADAM10 mediates epithelial cell sorting downstream of EphB signalling.

    PubMed

    Solanas, Guiomar; Cortina, Carme; Sevillano, Marta; Batlle, Eduard

    2011-09-01

    The formation and maintenance of complex organs requires segregation of distinct cell populations into defined territories (that is, cell sorting) and the establishment of boundaries between them. Here we have investigated the mechanism by which Eph/ephrin signalling controls the compartmentalization of cells in epithelial tissues. We show that EphB/ephrin-B signalling in epithelial cells regulates the formation of E-cadherin-based adhesions. EphB receptors interact with E-cadherin and with the metalloproteinase ADAM10 at sites of adhesion and their activation induces shedding of E-cadherin by ADAM10 at interfaces with ephrin-B1-expressing cells. This process results in asymmetric localization of E-cadherin and, as a consequence, in differences in cell affinity between EphB-positive and ephrin-B-positive cells. Furthermore, genetic inhibition of ADAM10 activity in the intestine of mice results in a lack of compartmentalization of Paneth cells within the crypt stem cell niche, a defect that phenocopies that of EphB3-null mice. These results provide important insights into the regulation of cell migration in the intestinal epithelium and may help in the understanding of the nature of the cell sorting process in other epithelial tissues where Eph-ephrin interactions play a central role. PMID:21804545

  12. Posttranslational proteolytic processing of Leda-1/Pianp involves cleavage by MMPs, ADAM10/17 and gamma-secretase.

    PubMed

    Biswas, Siladitta; Adrian, Monica; Weber, Jochen; Evdokimov, Konstantin; Winkler, Manuel; Géraud, Cyrill

    2016-09-01

    Leda-1/Pianp is a type I transmembrane protein expressed by CNS cells, murine melanoma cell line B16F10 and rat liver sinusoidal endothelial cells. The early steps of posttranslational modifications of Leda-1/Pianp have been described to include glycosylation and processing by proprotein convertases. Here, we comprehensively characterized the subsequent steps of proteolytic processing of Leda-1/Pianp. For this purpose specific protease inhibitors and cell lines deficient in PS1, PS2, PS1/PS2 and ADAM10/17 were deployed. Leda-1/Pianp was cleaved at numerous cleavage sites within the N-terminal extracellular domain. The sheddases involved included MMPs and ADAM10/17. Ectodomain shedding yielded C-terminal fragments (CTF) of ∼15 kDa. The CTF was further processed by the γ (gamma)-secretase complex to generate the intracellular domain (ICD) of ∼10 kDa. Although PS1 was the dominant intramembrane protease, PS2 was also able to cleave Leda-1/Pianp in the absence of PS1. Thus, Leda-1/Pianp is constitutively processed by proprotein convertases, sheddases including MMPs and ADAM10/17 and intramembrane protease γ-secretase. PMID:27349870

  13. Differentiation-induced skin cancer suppression by FOS, p53, and TACE/ADAM17

    PubMed Central

    Guinea-Viniegra, Juan; Zenz, Rainer; Scheuch, Harald; Jiménez, María; Bakiri, Latifa; Petzelbauer, Peter; Wagner, Erwin F.

    2012-01-01

    Squamous cell carcinomas (SCCs) are heterogeneous and aggressive skin tumors for which innovative, targeted therapies are needed. Here, we identify a p53/TACE pathway that is negatively regulated by FOS and show that the FOS/p53/TACE axis suppresses SCC by inducing differentiation. We found that epidermal Fos deletion in mouse tumor models or pharmacological FOS/AP-1 inhibition in human SCC cell lines induced p53 expression. Epidermal cell differentiation and skin tumor suppression were caused by a p53-dependent transcriptional activation of the metalloprotease TACE/ADAM17 (TNF-α–converting enzyme), a previously unknown p53 target gene that was required for NOTCH1 activation. Although half of cutaneous human SCCs display p53-inactivating mutations, restoring p53/TACE activity in mouse and human skin SCCs induced tumor cell differentiation independently of the p53 status. We propose FOS/AP-1 inhibition or p53/TACE reactivating strategies as differentiation-inducing therapies for SCCs. PMID:22772468

  14. Distribution of melt beneath Mount St Helens and Mount Adams inferred from magnetotelluric data

    USGS Publications Warehouse

    Hill, G.J.; Caldwell, T.G.; Heise, W.; Chertkoff, D.G.; Bibby, H.M.; Burgess, M.K.; Cull, J.P.; Cas, Ray A.F.

    2009-01-01

    Three prominent volcanoes that form part of the Cascade mountain range in Washington State (USA)Mounts StHelens, Adams and Rainierare located on the margins of a mid-crustal zone of high electrical conductivity1,5. Interconnected melt can increase the bulk conductivity of the region containing the melt6,7, which leads us to propose that the anomalous conductivity in this region is due to partial melt associated with the volcanism. Here we test this hypothesis by using magnetotelluric data recorded at a network of 85 locations in the area of the high-conductivity anomaly. Our data reveal that a localized zone of high conductivity beneath thisvolcano extends downwards to join the mid-crustal conductor. As our measurements were made during the recent period of lava extrusion at Mount St Helens, we infer that the conductivity anomaly associated with the localized zone, and by extension with the mid-crustal conductor, is caused by the presence of partial melt. Our interpretation is consistent with the crustal origin of silicic magmas erupting from Mount St Helens8, and explains the distribution of seismicity observed at the time of the catastrophic eruption in 1980 (refs9, 10). ?? 2009 Macmillan Publishers Limited. All rights reserved.

  15. SIVA/DIVA- INITIAL VALUE ORDINARY DIFFERENTIAL EQUATION SOLUTION VIA A VARIABLE ORDER ADAMS METHOD

    NASA Technical Reports Server (NTRS)

    Krogh, F. T.

    1994-01-01

    The SIVA/DIVA package is a collection of subroutines for the solution of ordinary differential equations. There are versions for single precision and double precision arithmetic. These solutions are applicable to stiff or nonstiff differential equations of first or second order. SIVA/DIVA requires fewer evaluations of derivatives than other variable order Adams predictor-corrector methods. There is an option for the direct integration of second order equations which can make integration of trajectory problems significantly more efficient. Other capabilities of SIVA/DIVA include: monitoring a user supplied function which can be separate from the derivative; dynamically controlling the step size; displaying or not displaying output at initial, final, and step size change points; saving the estimated local error; and reverse communication where subroutines return to the user for output or computation of derivatives instead of automatically performing calculations. The user must supply SIVA/DIVA with: 1) the number of equations; 2) initial values for the dependent and independent variables, integration stepsize, error tolerance, etc.; and 3) the driver program and operational parameters necessary for subroutine execution. SIVA/DIVA contains an extensive diagnostic message library should errors occur during execution. SIVA/DIVA is written in FORTRAN 77 for batch execution and is machine independent. It has a central memory requirement of approximately 120K of 8 bit bytes. This program was developed in 1983 and last updated in 1987.

  16. Desperately seeking social approval: Adam Smith, Thorstein Veblen and the moral limits of capitalist culture.

    PubMed

    Watson, Matthew

    2012-09-01

    Adam Smith and Thorstein Veblen shared much in matters of economic ontology. Both dismissed the very notion of an autonomous economic self and instead investigated the processes through which self and other are mutually constituted under changing cultural traditions of individual aspiration. Their strikingly similar critiques of status-oriented consumption and concern for the moral basis of the market economy are established in this manner. However, the political implications of their analyses point in different directions, with Veblen being the more radical. The Smithian individual can always use spectatorial insights to assert through genuinely praiseworthy behaviour personal moral distance from social norms of status-oriented consumption. The Veblenian individual, by contrast, has no such capacity for elevating abstract moral principles above socially-situated conduct, as mind and environment co-evolve in line with changing material circumstances of life. For Veblen, the rise of status-oriented consumption itself acted as a form of moral self-education that more deeply entrenched the social norms of ownership out of which it arose, thus the impossibility of an autonomous economic self was matched by the impossibility of an autonomous moral self. To his way of thinking, moral degradation in conspicuous consumption was irredeemably inscribed into the whole cultural structure of capitalism. PMID:22950465

  17. TLR ligand–induced podosome disassembly in dendritic cells is ADAM17 dependent

    PubMed Central

    West, Michele A.; Prescott, Alan R.; Chan, Kui Ming; Zhou, Zhongjun; Rose-John, Stefan; Scheller, Jürgen; Watts, Colin

    2008-01-01

    Toll-like receptor (TLR) signaling induces a rapid reorganization of the actin cytoskeleton in cultured mouse dendritic cells (DC), leading to enhanced antigen endocytosis and a concomitant loss of filamentous actin–rich podosomes. We show that as podosomes are lost, TLR signaling induces prominent focal contacts and a transient reduction in DC migratory capacity in vitro. We further show that podosomes in mouse DC are foci of pronounced gelatinase activity, dependent on the enzyme membrane type I matrix metalloprotease (MT1-MMP), and that DC transiently lose the ability to degrade the extracellular matrix after TLR signaling. Surprisingly, MMP inhibitors block TLR signaling–induced podosome disassembly, although stimulated endocytosis is unaffected, which demonstrates that the two phenomena are not obligatorily coupled. Podosome disassembly caused by TLR signaling occurs normally in DC lacking MT1-MMP, and instead requires the tumor necrosis factor α–converting enzyme ADAM17 (a disintegrin and metalloprotease 17), which demonstrates a novel role for this “sheddase” in regulating an actin-based structure. PMID:18762577

  18. Differentiation-induced skin cancer suppression by FOS, p53, and TACE/ADAM17.

    PubMed

    Guinea-Viniegra, Juan; Zenz, Rainer; Scheuch, Harald; Jiménez, María; Bakiri, Latifa; Petzelbauer, Peter; Wagner, Erwin F

    2012-08-01

    Squamous cell carcinomas (SCCs) are heterogeneous and aggressive skin tumors for which innovative, targeted therapies are needed. Here, we identify a p53/TACE pathway that is negatively regulated by FOS and show that the FOS/p53/TACE axis suppresses SCC by inducing differentiation. We found that epidermal Fos deletion in mouse tumor models or pharmacological FOS/AP-1 inhibition in human SCC cell lines induced p53 expression. Epidermal cell differentiation and skin tumor suppression were caused by a p53-dependent transcriptional activation of the metalloprotease TACE/ADAM17 (TNF-α-converting enzyme), a previously unknown p53 target gene that was required for NOTCH1 activation. Although half of cutaneous human SCCs display p53-inactivating mutations, restoring p53/TACE activity in mouse and human skin SCCs induced tumor cell differentiation independently of the p53 status. We propose FOS/AP-1 inhibition or p53/TACE reactivating strategies as differentiation-inducing therapies for SCCs. PMID:22772468

  19. A colorimetric-based amplification system for proteinases including MMP2 and ADAM8.

    PubMed

    Moss, Marcia L; Koller, Garrit; Bartsch, Jörg W; Rakow, Sinja; Schlomann, Uwe; Rasmussen, Fred H

    2015-09-01

    We have developed a new amplification system for proteinases that is sensitive, simple, and inexpensive to run, exemplified by a horseradish peroxidase (HRP)-conjugated, dual MMP2 (matrix metalloproteinase 2) and ADAM8 (a disintegrin and metalloproteinase 8) peptide substrate assay presented herein. The HRP-conjugated substrate is attached to beads through a 6× histidine tag and then incubated with the target enzyme, cleaving the HRP reporter. This product is subsequently removed from the unreacted bound portions of the substrate by magnetic deposition of the beads. The amount of product is then quantified using a standard HRP color development assay employing 3,3',5,5'-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2). This HRP amplification system represents a new approach to proteinase assays and could be applied to other enzymes, such as lipases, esterases, and kinases, as long as the unreacted substrate can be physically separated from the product and catalysis by the enzyme to be quantified is not impaired dramatically by steric hindrance from the HRP entity. PMID:26026386

  20. Radiological Survey Results for the R.P. Adams Company Property, Tonawanda, New York (TNY003)

    SciTech Connect

    Carrier, R.F.; McKenzie, S.P.; Uziel, M.S.

    1998-11-01

    At the request of the U.S. Department of Energy (DOE), a team horn Oak Ridge National Laboratory conducted a radiological survey of property belonging to the R P. Adarns Company, Inc., Tonawanda, New York. The survqy was performed in November 1995 and May and July 1996. The P-e of tie SUIWY was to determine if radioactive residuals had migrated, or been re&stribu@ from the former Linde property to the south onto the R P. Adams property. The Linde Air Products Division of Union Carbide Corporation, Toni~w~da, New York, had used radioactive materials at that location for work performed under government contract born 1942 through 1948. The survey was performed in response to Formerly Utilized Sites Remedial Action Program (FUSRAP) requirements. These requirements dictate that the radiological status of certain vicinity properties shall be assessed and docw.nented according to prescribed procedures prior to certification of the property for release for unrestricted use. Such release can only be granted if the property is found to be within current applicable authorized limits. The survey included a gamma scan of accessible areas in both the developed and the undeveloped portions of the property and the collection and radionuclide analysis of soil samples. A comparison of these data to the current DOE guidelines shows that all radionuclide concentrations and radioactivity levels found on the property are below the current guidelines. Therefore, this property should not be included in the FUSRAP program for remediation. xi

  1. Evaluation of ADAM/1 model for advanced coal-extraction concepts

    SciTech Connect

    Deshpande, G. K.; Gangal, M. D.

    1982-01-15

    The Advanced Coal Extraction Project is sponsored by the Department of Energy at the Jet Propulsion Laboratory to define and develop advanced underground coal extraction systems which: (1) are suitable for significant remaining resources after the year 2000, and (2) promise a significant improvement in production cost and miner safety, with no degradation in miner health, environmental quality and resource recovery. System requirements in the five performance areas have been defined by Goldsmith and Lavin (1980). Several existing computer programs for estimating life-cycle cost of mining systems have been evaluated. A commercially available program ADAM/1 was found to be satisfactory in relation to the needs of the Advanced Coal Extraction Project. Two test cases were run to confirm the ability of the program to handle non-conventional mining equipment and procedures. The results were satisfactory. The model, therefore, is recommended to the project team for evaluation of their conceptual designs. Since the model is commercially available, data preparation instructions are not reproduced in this document; instead the reader is referred to the original documents for this information.

  2. ADAM19 and HTR4 Variants and Pulmonary Function: The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Targeted Sequencing Study

    PubMed Central

    London, Stephanie J.; Gao, Wei; Gharib, Sina A.; Hancock, Dana B.; Wilk, Jemma B.; House, John S.; Gibbs, Richard A.; Muzny, Donna M.; Lumley, Thomas; Franceschini, Nora; North, Kari E.; Psaty, Bruce M.; Kovar, Christie L.; Coresh, Josef; Zhou, Yanhua; Heckbert, Susan R.; Brody, Jennifer A.; Morrison, Alanna C.; Dupuis, Josée

    2014-01-01

    Background The pulmonary function measures of forced expiratory volume in one second (FEV1) and its ratio to forced vital capacity (FVC) are used in the diagnosis and monitoring of lung diseases and predict cardiovascular mortality in the general population. Genome wide association studies (GWAS) have identified numerous loci associated with FEV1 and FEV1/FVC but the causal variants remain uncertain. We hypothesized that novel or rare variants poorly tagged by GWAS may explain the significant associations between FEV1/FVC and two genes: ADAM19 and HTR4. Methods and Results We sequenced ADAM19 and its promoter region along with the approximately 21 kb portion of HTR4 harboring GWAS SNPs for pulmonary function and analyzed associations with FEV1/FVC among 3,983 participants of European ancestry from Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). Meta-analysis of common variants in each region identified statistically significant associations (316 tests, P < 1.58×10−4) with FEV1/FVC for 14 ADAM19 SNPs and 24 HTR4 SNPs. After conditioning on the sentinel GWAS hit in each gene [ADAM19 rs1422795, minor allele frequency (MAF)=0.33 and HTR4 rs11168048, MAF=0.40] one SNP remained statistically significant (ADAM19 rs13155908, MAF = 0.12, P = 1.56×10−4). Analysis of rare variants (MAF < 1%) using Sequence Kernel Association Test did not identify associations with either region. Conclusions Sequencing identified one common variant associated with FEV1/FVC independently of the sentinel ADAM19 GWAS hit and supports the original HTR4 GWAS findings. Rare variants do not appear to underlie GWAS associations with pulmonary function for common variants in ADAM19 and HTR4. PMID:24951661

  3. The role of polymorphisms in ADAM33, a disintegrin and metalloprotease 33, in childhood asthma and lung function in two German populations

    PubMed Central

    Schedel, Michaela; Depner, Martin; Schoen, Carola; Weiland, Stephan K; Vogelberg, Christian; Niggemann, Bodo; Lau, Susanne; Illig, Thomas; Klopp, Norman; Wahn, Ulrich; von Mutius, Erika; Nickel, Renate; Kabesch, Michael

    2006-01-01

    Background ADAM33, the first asthma candidate gene identified by positional cloning, may be associated with childhood asthma, lung function decline and bronchial hyperresponsiveness. However, replication results have been inconclusive in smaller previous study populations probably due to inconsistencies in asthma phenotypes or yet unknown environmental influences. Thus, we tried to further elucidate the role of ADAM33 polymorphisms (SNPs) in a genetic analysis of German case control and longitudinal populations. Methods Using MALDI-TOF, ten ADAM33 SNPs were genotyped in 1,872 children from the International Study of Asthma and Allergy in Childhood (ISAAC II) in a case control setting and further 824 children from the longitudinal cohort Multicentre Study of Allergy (MAS). In both populations the effects of single SNPs and haplotypes were studied and a gene environment analysis with passive smoke exposure was performed using SAS/Genetics. Results No single SNP showed a significant association with doctor's diagnosis of asthma. A trend for somewhat more profound effects of ADAM33 SNPs was observed in individuals with asthma and BHR. Haplotype analyses suggested a minor effect of the ADAM33 haplotype H4 on asthma (p = 0.033) but not on BHR. Associations with non atopic asthma and baseline lung function were identified but no interaction with passive smoke exposure could be detected. Conclusion The originally reported association between ADAM33 polymorphisms and asthma and BHR could not be confirmed. However, our data may suggest a complex role of ADAM33 polymorphisms in asthma ethiology, especially in non atopic asthma. PMID:16784537

  4. Heterozygous Loss-of-Function Mutations in DLL4 Cause Adams-Oliver Syndrome

    PubMed Central

    Meester, Josephina A.N.; Southgate, Laura; Stittrich, Anna-Barbara; Venselaar, Hanka; Beekmans, Sander J.A.; den Hollander, Nicolette; Bijlsma, Emilia K.; Helderman-van den Enden, Appolonia; Verheij, Joke B.G.M.; Glusman, Gustavo; Roach, Jared C.; Lehman, Anna; Patel, Millan S.; de Vries, Bert B.A.; Ruivenkamp, Claudia; Itin, Peter; Prescott, Katrina; Clarke, Sheila; Trembath, Richard; Zenker, Martin; Sukalo, Maja; Van Laer, Lut; Loeys, Bart; Wuyts, Wim

    2015-01-01

    Adams-Oliver syndrome (AOS) is a rare developmental disorder characterized by the presence of aplasia cutis congenita (ACC) of the scalp vertex and terminal limb-reduction defects. Cardiovascular anomalies are also frequently observed. Mutations in five genes have been identified as a cause for AOS prior to this report. Mutations in EOGT and DOCK6 cause autosomal-recessive AOS, whereas mutations in ARHGAP31, RBPJ, and NOTCH1 lead to autosomal-dominant AOS. Because RBPJ, NOTCH1, and EOGT are involved in NOTCH signaling, we hypothesized that mutations in other genes involved in this pathway might also be implicated in AOS pathogenesis. Using a candidate-gene-based approach, we prioritized DLL4, a critical NOTCH ligand, due to its essential role in vascular development in the context of cardiovascular features in AOS-affected individuals. Targeted resequencing of the DLL4 gene with a custom enrichment panel in 89 independent families resulted in the identification of seven mutations. A defect in DLL4 was also detected in two families via whole-exome or genome sequencing. In total, nine heterozygous mutations in DLL4 were identified, including two nonsense and seven missense variants, the latter encompassing four mutations that replace or create cysteine residues, which are most likely critical for maintaining structural integrity of the protein. Affected individuals with DLL4 mutations present with variable clinical expression with no emerging genotype-phenotype correlations. Our findings demonstrate that DLL4 mutations are an additional cause of autosomal-dominant AOS or isolated ACC and provide further evidence for a key role of NOTCH signaling in the etiology of this disorder. PMID:26299364

  5. Atmospheric Deposition And MediterraneAN sea water productiviTy (Thales - ADAMANT) An overview

    NASA Astrophysics Data System (ADS)

    Christodoulaki, Sylvia; Petihakis, George; Triantafyllou, George; Pitta, Paraskevi; Papadimitriou, Vassileios; Tsiaras, Konstantinos; Mihalopoulos, Nikolaos; Kanakidou, Maria

    2015-04-01

    In the marine environment the salinity and biological pumps sequester atmospheric carbon dioxide. The biological pump is directly related to marine primary production which is controlled by nutrient availability mainly of iron, nitrogen and phosphorus. The Mediterranean Sea, especially the eastern basin is one of the most oligotrophic seas. The nitrogen (N) to phosphorus (P) ratio is unusually high, especially in the eastern basin (28:1) and primary production is limited by phosphorus availability. ADAMANT project contributes to new knowledge into how nutrients enter the marine environment through atmospheric deposition, how they are assimilated by organisms and how this influences carbon and nutrient fluxes. Experimental work has been combined with atmospheric and marine models. Important knowledge is obtained on nutrients deposition through mesocosm experiments on their uptake by the marine systems and their effects on the marine carbon cycle and food chain. Kinetic parameters of adsorption of acidic and organic volatile compounds in atmospheric samples of dust and marine salts are estimated in conjunction with solubility of N and P in mixtures contained in dust. Atmospheric and oceanographic models are coupled to create a system that is able to holistically simulate the effects of atmospheric deposition on the marine environment over time, beginning from the pre-industrial era until the future years (hind cast, present and forecast simulations). This research has been co-financed by the European Union (European Social Fund) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework - Research Funding Program: THALES, Investing in knowledge society through European Social Fund.

  6. Estimates of Asian dust deposition over the Asian region by using ADAM2 in 2007.

    PubMed

    Park, Soon-Ung; Choe, Anna; Park, Moon-Soo

    2010-05-01

    The Asian Dust Aerosol Model 2 (ADAM2) with the MM5 meteorological model has been employed to estimate the dust concentration, and wet and dry depositions of dust in the Asian region for the year of 2007. It is found that the model simulates quite reasonably the dust (PM(10)) concentrations both in the dust source region (100-110 degrees E and 37-43 degrees N) and the downstream region of Korea. The starting and ending times of most of dust events and their peak concentration occurring times are well simulated. The annual average dust (PM(10)) concentration near the surface is found to be 171microgm(-3) over the dust source area, 39microgm(-3) over the Yellow Sea, 25microgm(-3) over the Korean peninsula and 17microgm(-3) over the East Sea. It is also found that the annual total deposition of dust is about 118.1tkm(-2) (dry deposition, 101.4tkm(-2); wet deposition, 16.7tkm(-2)) in the dust source region, 19.0tkm(-2) (dry deposition, 7.8tkm(-2); wet deposition, 11.2tkm(-2)) in the Yellow Sea, 12.6tkm(-2) (dry deposition, 6.5tkm(-2); wet deposition, 6.1tkm(-2)) in the Korean peninsula and 10.7tkm(-2) (dry deposition, 2.1tkm(-2); wet deposition, 8.6tkm(-2)) in the East Sea. Their ratios of wet deposition to total deposition of dust in the respective regions are 14%, 59%, 48% and 80%. This clearly indicates that the main dust removal mechanism from the atmosphere is dry deposition over the source region whereas wet deposition predominates in the downstream region of the sea. The estimated dust deposition could adversely impact the eco-environmental system in the downstream regions of the dust source region significantly. PMID:20227107

  7. Genome Wide Analysis of Chromosomal Alterations in Oral Squamous Cell Carcinomas Revealed over Expression of MGAM and ADAM9

    PubMed Central

    Vincent-Chong, Vui King; Anwar, Arif; Karen-Ng, Lee Peng; Cheong, Sok Ching; Yang, Yi-Hsin; Pradeep, Padmaja Jayaprasad; Rahman, Zainal Ariff Abdul; Ismail, Siti Mazlipah; Zaini, Zuraiza Mohamad; Prepageran, Narayanan; Kallarakkal, Thomas George; Ramanathan, Anand; Mohayadi, Nur Aaina Binti Mohd; Rosli, Nurul Shielawati Binti Mohamed; Mustafa, Wan Mahadzir Wan; Abraham, Mannil Thomas; Tay, Keng Kiong; Zain, Rosnah Binti

    2013-01-01

    Despite the advances in diagnosis and treatment of oral squamous cell carcinoma (OSCC), mortality and morbidity rates have not improved over the past decade. A major drawback in diagnosis and treatment of OSCC is the lack of knowledge relating to how genetic instability in oral cancer genomes affects oral carcinogenesis. Hence, the key aim of this study was to identify copy number alterations (CNAs) that may be cancer associated in OSCC using high-resolution array comparative genomic hybridization (aCGH). To our knowledge this is the first study to use ultra-high density aCGH microarrays to profile a large number of OSCC genomes (n = 46). The most frequently amplified CNAs were located on chromosome 11q11(52%), 2p22.3(52%), 1q21.3–q22(54%), 6p21.32(59%), 20p13(61%), 7q34(52% and 72%),8p11.23–p11.22(80%), 8q11.1–q24.4(54%), 9q13–q34.3(54%), 11q23.3–q25(57%); 14q21.3–q31.1(54%); 14q31.3–q32.33(57%), 20p13–p12.3(54%) and 20q11.21–q13.33(52%). The most frequently deleted chromosome region was located on 3q26.1 (54%). In order to verify the CNAs from aCGH using quantitative polymerase chain reaction (qPCR), the three top most amplified regions and their associated genes, namely ADAM5P (8p11.23–p11.22), MGAM (7q34) and SIRPB1 (20p13.1), were selected in this study. The ADAM5P locus was found to be amplified in 39 samples and deleted in one; MGAM (24 amplifications and 3 deletions); and SIRPB1 (12 amplifications, others undetermined). On the basis of putative cancer-related annotations, two genes, namely ADAM metallopeptidase domain 9 (ADAM9) and maltase-glucoamylase alpha-glucosidase (MGAM), that mapped to CNA regions were selected for further evaluation of their mRNA expression using reverse transcriptase qPCR. The over-expression of MGAM was confirmed with a 6.6 fold increase in expression at the mRNA level whereas the fold change in ADAM9 demonstrated a 1.6 fold increase. This study has identified significant regions in the OSCC genome that

  8. In Vivo Targeting of ADAM9 Gene Expression Using Lentivirus-Delivered shRNA Suppresses Prostate Cancer Growth by Regulating REG4 Dependent Cell Cycle Progression

    PubMed Central

    He, Yun-Chi; Lo, Sen-Jei; Liang, Ji-An; Hsieh, Teng-Fu; Josson, Sajni; Chung, Leland W. K.; Hung, Mien-Chie; Sung, Shian-Ying

    2013-01-01

    Cancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM) 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo evidence that therapeutic targeting of ADAM9 gene expression by lentivirus-delivered small hairpin RNA (shRNA) significantly inhibited proliferation of human prostate cancer cell lines and blocked tumor growth in a murine model of prostate cancer bone metastasis. Cell cycle studies confirmed an increase in the G1-phase and decrease in the S-phase population of cancer cells under starvation stress conditions, which correlated with elevated intracellular superoxide levels. Microarray data showed significantly decreased levels of regenerating islet-derived family member 4 (REG4) expression in prostate cancer cells with knockdown of ADAM9 gene expression. This REG4 downregulation also resulted in induction of expression of p21Cip1/WAF1, which negatively regulates cyclin D1 and blocks the G1/S transition. Our data reveal a novel molecular mechanism of ADAM9 in the regulation of prostate cancer cell proliferation, and suggests a combined modality of ADAM9 shRNA gene therapy and cytotoxic agents for hormone refractory and bone metastatic prostate cancer. PMID:23342005

  9. Genetic Variants in IL6R and ADAM19 are Associated with COPD Severity in a Mexican Mestizo Population.

    PubMed

    Pérez-Rubio, Gloria; Silva-Zolezzi, Irma; Fernández-López, Juan Carlos; Camarena, Ángel; Velázquez-Uncal, Mónica; Morales-Mandujano, Fabiola; Hernández-Zenteno, Rafael De Jesús; Flores-Trujillo, Fernando; Sánchez-Romero, Candelaria; Velázquez-Montero, Alejandra; Espinosa de Los Monteros, Carlos; Sansores, Raúl H; Ramírez-Venegas, Alejandra; Falfán-Valencia, Ramcés

    2016-10-01

    Chronic obstructive pulmonary disease (COPD) is a complex and multifactorial disease with a strong genetic component. Our objective is to identify the genetic variants associated with COPD risk and its severity in Mexican Mestizo population. We evaluated 1285 single-nucleotide polymorphisms (SNPs) of candidate genes in 299 smokers with COPD (COPD-S) and 531 smokers without COPD (SWOC) using an Illumina GoldenGate genotyping microarray. In addition, 251 ancestry informative markers were included. Allele A of rs2545771 in CYP2F2P is associated with a lower risk of COPD (p = 4.02E-10, odds ratio [OR] = 0.104, confidence interval [CI] 95% 0.05-0.18). When the COPD group was stratified by severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD; levels III + IV vs. I + II), 3 SNPs (rs4329505 and rs4845626 in interleukin 6 receptor [IL6R] and rs1422794 in a disintegrin and metalloproteinase domain 19 [ADAM19]) were associated with a lower risk of suffering the most severe stages of the disease. rs2819096 in the surfactant protein D (SFTPD) gene was associated with a higher risk of COPD GOLD III + IV (p = 7.79E-03, OR = 1.80, CI 95% 1.16-2.79). Finally, the haplotype in IL6R was associated with a lower risk of suffering from more severe COPD, whereas the haplotype in ADAM19 was associated with a higher risk (p = 7.40E-03, OR = 2.83, CI 95% 1.20-6.86) of suffering from the severe stages of the disease. Our data suggest that there are alleles and haplotypes in the IL6R, ADAM19, and SFTPD genes associated with different severity stages of COPD; in CYP2F2P, rs25455771 is associated with a lower risk of COPD. PMID:27078193

  10. Adrenergic Regulation of IgE Involves Modulation of CD23 and ADAM10 Expression on Exosomes1

    PubMed Central

    Padro, Caroline J.; Shawler, Todd M.; Gormley, Matthew G.; Sanders, Virginia M.

    2013-01-01

    Soluble CD23 (sCD23) plays a role in the positive regulation of an IgE response. Engagement of the beta-2 adrenergic receptor (β2AR) on a B cell is known to enhance the level of both sCD23 and IgE, although the mechanism by which this occurs is not completely understood. We report herein that, in comparison to a CD40L/IL-4-primed murine B cell alone, β2AR engagement on a primed B cell increased gene expression of ADAM10, which is the primary sheddase of CD23, and protein expression of both CD23 and ADAM10, in a PKA- and p38 MAPK-dependent manner, and promoted the localization of these proteins to exosomes as early as two days after priming, as determined by both Western blot and flow cytometry, and confirmed by electron microscopy. In comparison to isolated exosomes released from primed B cells alone, the transfer of exosomes released from β2AR agonist-exposed primed B cells to cultures of recipient primed B cells resulted in an increase in the level of IgE produced per cell, without affecting the number of cells producing IgE, as determined by ELISPOT. These effects still occurred when a β2AR antagonist was added along with the transfer to block residual agonist, and failed to occur when exosomes were isolated from β2AR-deficient B cells. These findings suggest that the mechanism responsible for mediating the β2AR-induced increase in IgE involves a shuttling of the β2AR-induced increase in CD23 and ADAM10 proteins to exosomes that subsequently mediate an increase in IgE. PMID:24140643

  11. The Development of Airborne Data for Assessing Models (ADAM) - A central repository of airborne field campaign data archives

    NASA Astrophysics Data System (ADS)

    Chen, G.; Kleb, M. M.; Aknan, A. A.; Brown, C. C.; Mangosing, D. C.; Thornhill, A.; Rinsland, P. L.

    2010-12-01

    NASA, NOAA, and NSF have conducted over 30 airborne campaigns during the past three decades aimed at gaining an understanding of the tropospheric chemical and physical processes related to climate change and air-quality issues. In recent years, the scientific value of this accumulated airborne data has been increasingly recognized for use in satellite validation and model assessment and evaluation activities. In addition to the high spatial-temporal resolutions, the airborne data, especially from the more recent studies, offers a comprehensive view of the atmosphere through a large suite of the simultaneously observed atmospheric species/parameters, ranging from photochemical precursors to products as well as particle chemical, microphysical, and optical properties. To better facilitate the model assessment and evaluation activities, we are actively engaged in the development of a web-based central airborne data archive: ADAM (Airborne Data for Assessing Models). This effort is sponsored by the NASA MEaSUREs program and is intended to archive data from tropospheric chemistry airborne field campaign since the 1980s. The principal design philosophy of the ADAM web site is to provide an intuitive user interface that allows users to browse, visualize, subset (both spatially and temporally), merge, and download the airborne data, as well as providing adequate metadata associated with the data archive. A working version of the web site which shows the ADAM user interface and functionalities will be presented. Also presented are conventions to establish common names for the atmospheric variables which are often observed during airborne campaigns as well as the approaches to handle missing data and limit of detections. This presentation is intended to serve the purpose of getting feedback from the broad atmospheric community, including both modelers and measurement experts.

  12. Association of ADAM33 gene polymorphism and arginase activity with susceptibility to ventilatory impairment in wood dust-exposed workers.

    PubMed

    Saad-Hussein, A; Thabet, E H; Taha, M M; Shahy, E M; Mahdy-Abdallah, H

    2016-09-01

    ADAM33 represents an important gene of susceptibility for lung function impairment. This work aimed to evaluate the association between genetic polymorphism of ADAM33 at four single nucleotide polymorphisms (T1, T2, S1, and Q1) and arginase activity with respiratory functions impairment in wood workers. The study was done to compare ventilatory functions and arginase activity of 82 wood workers and 81 controls. Genotyping was determined by using the polymerase chain restriction fragment length polymorphism method. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEF) of the workers were significantly reduced compared with the controls. T1 single nucleotide polymorphism (SNP) was associated with obvious decline in the FEV1, FVC, and PEF in wood workers, while T2 SNP was associated with decline in FEV1 and PEF. A significant increase in arginase activity was found in T2 and S1 SNPs of the exposed workers. Increase in duration of exposure was correlated with the decline in ventilatory functions. This inverse correlation was significant for pulmonary function indices in AA and GG genotypes of T1 and T2, respectively. Moreover, significance was detected for FVC and FEV1 in AA and GA genotypes of S1 and Q1. A positive correlation between arginase activity and duration of exposure was found to be significant in GG genotype of S1 SNP. An association between ADAM33 gene polymorphism and impaired lung functions was detected in wood dust-exposed workers. Arginase activity may play an associated important role in increasing this impairment in wood workers. PMID:26500222

  13. Water-level records for Adams, Larimer, Logan, Morgan, Sedgwick, Washington, and Weld Counties, Colorado, 1973-77

    USGS Publications Warehouse

    Major, Thomas J.; Vaught, Kenneth D.

    1977-01-01

    Water levels measured during March 1977 in 350 wells tapping alluvial aquifers in Adams, Larimer, Logan, Morgan, Sedgwick, Washington, and Weld Counties, Colo., are presented. Water-level records for the 4 preceding years are included to serve as references illustrating declining or rising water levels. These data can be used by well owners for planning their irrigation schedules for the next irrigation season and can be used by water managers for developing plans to manage the ground-water resources. (Woodard-USGS)

  14. Analyses of geochemical samples and descriptions of rock samples, Adams Gap and Shinbone Creek Roadless Areas, Clay County, Alabama

    USGS Publications Warehouse

    Erickson, M.S.; Hanley, J.T.; Kelley, D.L.; Sherlock, L.J.

    1983-01-01

    Semiquantitative spectrographic analyses for 31 elements on 105 rocks, 47 stream-sediment, and 70 soil samples from the Adams Gap and Shinbone Creek Roadless Areas and vicinity, Talladega National Forest, Clay County, Alabama are reported here in detail. Atomic-absorption analyses for zinc in all samples and for gold in 5 selected rock samples are also reported. Localities for all sables are given in Universal Transverse Mercator (UTM) coordinates. A brief description of each rock sample is included. Rocks analyzed include quartzite, phyllite, vein quartz, and schist.

  15. Digitization Procedures of Analogue Seismograms from the Adam Dziewonski Observatory (HRV) at Harvard, MA

    NASA Astrophysics Data System (ADS)

    Torpey, M.; Ishii, M.

    2010-12-01

    This project explores methods of digitization of analogue seismic recordings for better preservation and to facilitate data distribution to the community. Different techniques are investigated using seismograms from one particular station, the Adam Dziewonski Observatory (HRV) at Harvard, Massachusetts. This seismological station, still in operation as a part of the Global Seismographic Network today, is one of the oldest stations in the United States. The station was built in 1933, and since its installation, the station has produced approximately 16,000 analogue seismograms. The majority of these recordings were taken between 1933 and 1953, with some intermittent recordings between 1962 and 1998 after digital seismometers had become a standard. These analogue seismograms have the potential of expanding the database for seismological research such as identification of events previously not catalogued. Due to poor storage environment at the station, some of the records, especially those on regular type of paper, are damaged beyond repair. Nevertheless, many of the records on photographic paper are in better condition, and we have focused on a subset of these recordings that are least damaged. Even these seismograms require cleaning and, in consultation with the Weissman Preservation Center of Harvard Library, preparation techniques for the photographic records are examined. After the seismograms are cleaned and flattened, three different equipments are investigated for digitization, i.e., a copy machine, scanner, and camera. These instruments allow different imaging resolutions, ranging from 200 dots per inch (dpi) to 800 dpi. The image resolution and the bit depth have a wide range of implications that are closely linked to the digitization program one chooses to convert the image to time series. We explore three different software for this conversion, SeisDig (Bromirski and Chuang, 2003), Teseo2 (Pintore and Quintiliani, 2008), and NeuraLog (www

  16. Yakama Nation Housing Authority, Adams View: System Retrofit Research Report and Case Study Summary; 23 February 2004--15 January 2005

    SciTech Connect

    CARB

    2005-11-01

    The Yakama Nation is the largest tribe in the Pacific Northwest. The Yakama Nation Housing Authority (YNHA) is working to rehabilitate single family homes (two to four bedrooms) in its Adams View project using public and tax credit financing. It is in need of a major rehabilitation as a result of wear and tear after many years of use and overcrowding. The scope for the current CARB ''gut rehab'' project is 25 of the 40 homes in the Adams View development, but the proposed strategies could be replicated for the remaining 15 homes as well as for several other similar developments of the YNHA. On a larger scale, the system rehabilitation strategy developed for the Adam's View project should be replicable for most of the more than 4,300 housing units that were constructed in the Northwest (Washington, Oregon, and Idaho) under the US Department of Housing and Urban Development (HUD) Housing Act of 1937.

  17. Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors.

    PubMed

    Ohkawa, Toshika; Fukata, Yuko; Yamasaki, Miwako; Miyazaki, Taisuke; Yokoi, Norihiko; Takashima, Hiroshi; Watanabe, Masahiko; Watanabe, Osamu; Fukata, Masaki

    2013-11-13

    More than 30 mutations in LGI1, a secreted neuronal protein, have been reported with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although LGI1 haploinsufficiency is thought to cause ADLTE, the underlying molecular mechanism that results in abnormal brain excitability remains mysterious. Here, we focused on a mode of action of LGI1 autoantibodies associated with limbic encephalitis (LE), which is one of acquired epileptic disorders characterized by subacute onset of amnesia and seizures. We comprehensively screened human sera from patients with immune-mediated neurological disorders for LGI1 autoantibodies, which also uncovered novel autoantibodies against six cell surface antigens including DCC, DPP10, and ADAM23. Our developed ELISA arrays revealed a specific role for LGI1 antibodies in LE and concomitant involvement of multiple antibodies, including LGI1 antibodies in neuromyotonia, a peripheral nerve disorder. LGI1 antibodies associated with LE specifically inhibited the ligand-receptor interaction between LGI1 and ADAM22/23 by targeting the EPTP repeat domain of LGI1 and reversibly reduced synaptic AMPA receptor clusters in rat hippocampal neurons. Furthermore, we found that disruption of LGI1-ADAM22 interaction by soluble extracellular domain of ADAM22 was sufficient to reduce synaptic AMPA receptors in rat hippocampal neurons and that levels of AMPA receptor were greatly reduced in the hippocampal dentate gyrus in the epileptic LGI1 knock-out mouse. Therefore, either genetic or acquired loss of the LGI1-ADAM22 interaction reduces the AMPA receptor function, causing epileptic disorders. These results suggest that by finely regulating the synaptic AMPA receptors, the LGI1-ADAM22 interaction maintains physiological brain excitability throughout life. PMID:24227725

  18. Autoantibodies to Epilepsy-Related LGI1 in Limbic Encephalitis Neutralize LGI1-ADAM22 Interaction and Reduce Synaptic AMPA Receptors

    PubMed Central

    Ohkawa, Toshika; Fukata, Yuko; Yamasaki, Miwako; Miyazaki, Taisuke; Yokoi, Norihiko; Takashima, Hiroshi; Watanabe, Masahiko; Watanabe, Osamu

    2013-01-01

    More than 30 mutations in LGI1, a secreted neuronal protein, have been reported with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although LGI1 haploinsufficiency is thought to cause ADLTE, the underlying molecular mechanism that results in abnormal brain excitability remains mysterious. Here, we focused on a mode of action of LGI1 autoantibodies associated with limbic encephalitis (LE), which is one of acquired epileptic disorders characterized by subacute onset of amnesia and seizures. We comprehensively screened human sera from patients with immune-mediated neurological disorders for LGI1 autoantibodies, which also uncovered novel autoantibodies against six cell surface antigens including DCC, DPP10, and ADAM23. Our developed ELISA arrays revealed a specific role for LGI1 antibodies in LE and concomitant involvement of multiple antibodies, including LGI1 antibodies in neuromyotonia, a peripheral nerve disorder. LGI1 antibodies associated with LE specifically inhibited the ligand-receptor interaction between LGI1 and ADAM22/23 by targeting the EPTP repeat domain of LGI1 and reversibly reduced synaptic AMPA receptor clusters in rat hippocampal neurons. Furthermore, we found that disruption of LGI1-ADAM22 interaction by soluble extracellular domain of ADAM22 was sufficient to reduce synaptic AMPA receptors in rat hippocampal neurons and that levels of AMPA receptor were greatly reduced in the hippocampal dentate gyrus in the epileptic LGI1 knock-out mouse. Therefore, either genetic or acquired loss of the LGI1-ADAM22 interaction reduces the AMPA receptor function, causing epileptic disorders. These results suggest that by finely regulating the synaptic AMPA receptors, the LGI1-ADAM22 interaction maintains physiological brain excitability throughout life. PMID:24227725

  19. Deletions in the cytoplasmic domain of iRhom1 and iRhom2 promote shedding of the TNF receptor by the protease ADAM17.

    PubMed

    Maney, Sathish K; McIlwain, David R; Polz, Robin; Pandyra, Aleksandra A; Sundaram, Balamurugan; Wolff, Dorit; Ohishi, Kazuhito; Maretzky, Thorsten; Brooke, Matthew A; Evers, Astrid; Vasudevan, Ananda A Jaguva; Aghaeepour, Nima; Scheller, Jürgen; Münk, Carsten; Häussinger, Dieter; Mak, Tak W; Nolan, Garry P; Kelsell, David P; Blobel, Carl P; Lang, Karl S; Lang, Philipp A

    2015-11-01

    The protease ADAM17 (a disintegrin and metalloproteinase 17) catalyzes the shedding of various transmembrane proteins from the surface of cells, including tumor necrosis factor (TNF) and its receptors. Liberation of TNF receptors (TNFRs) from cell surfaces can dampen the cellular response to TNF, a cytokine that is critical in the innate immune response and promotes programmed cell death but can also promote sepsis. Catalytically inactive members of the rhomboid family of proteases, iRhom1 and iRhom2, mediate the intracellular transport and maturation of ADAM17. Using a genetic screen, we found that the presence of either iRhom1 or iRhom2 lacking part of their extended amino-terminal cytoplasmic domain (herein referred to as ΔN) increases ADAM17 activity, TNFR shedding, and resistance to TNF-induced cell death in fibrosarcoma cells. Inhibitors of ADAM17, but not of other ADAM family members, prevented the effects of iRhom-ΔN expression. iRhom1 and iRhom2 were functionally redundant, suggesting a conserved role for the iRhom amino termini. Cells from patients with a dominantly inherited cancer susceptibility syndrome called tylosis with esophageal cancer (TOC) have amino-terminal mutations in iRhom2. Keratinocytes from TOC patients exhibited increased TNFR1 shedding compared with cells from healthy donors. Our results explain how loss of the amino terminus in iRhom1 and iRhom2 impairs TNF signaling, despite enhancing ADAM17 activity, and may explain how mutations in the amino-terminal region contribute to the cancer predisposition syndrome TOC. PMID:26535007

  20. HIV-Nef and ADAM17-Containing Plasma Extracellular Vesicles Induce and Correlate with Immune Pathogenesis in Chronic HIV Infection

    PubMed Central

    Lee, Jung-Hyun; Schierer, Stephan; Blume, Katja; Dindorf, Jochen; Wittki, Sebastian; Xiang, Wei; Ostalecki, Christian; Koliha, Nina; Wild, Stefan; Schuler, Gerold; Fackler, Oliver T.; Saksela, Kalle; Harrer, Thomas; Baur, Andreas S.

    2016-01-01

    Antiretroviral therapy (ART) efficiently suppresses HIV replication but immune activation and low CD4 T cell counts often persist. The underlying mechanism of this ART-resistant pathogenesis is not clear. We observed that levels of plasma extracellular vesicles (pEV) are strongly elevated in HIV infection and do not decline during ART. Surprisingly, these vesicles contained the viral accessory proteins Nef and Vpu, which are assumed to be not expressed under efficient ART, as well as pro-inflammatory effectors, including activated ADAM17. HIV pEV were characterized by the presence of activated αvβ3 and absence of CD81 and Tsg101. Correlating with immune activation, peripheral monocytes ingested large amounts of pEV, giving rise to an increased population of CD1c+ CD14+ cells that secreted inflammatory cytokines. Importantly, the pro-inflammatory content, particularly ADAM17 activity, correlated with low T cell counts. Preliminary evidence suggested that HIV pEV derived from peripheral mononuclear cells and from an unknown myeloid cell population. In summary we propose an important role of pro-inflammatory pEV in chronic HIV infection due to ongoing viral Nef activity. PMID:27211553

  1. The Adam and Eve story as exemplar of an early-life variant of the oedipus complex.

    PubMed

    Osman, M P

    2000-01-01

    The Adam and Eve story is construed as having an organizing function that facilitates the analytic understanding of certain patients. In this interpretation, the story epitomizes a psychodynamic in which progressive growth, with separation and individuation, of the young is experienced as perilous--not only to them, but also correspondingly to their procreators. In the myth, the increasing psychic and physical maturation of Adam and Eve produced a crisis. Not only was divine authority flouted, but also apprehensions were aroused that God might be humbled or diminished. This threatened him, evoking his wrath and leading to the punishment by abandonment of his youthful wards. It is suggested that the story depicts an emotional complex of widespread application and is an archaic version of the oedipus complex, continuous with the oedipus complex proper, but from an earlier stage of development. This archaic complex is delineated with clinical vignettes, and a clinical explication of its various components is provided. Clinical management is considered, particularly with reference to the challenge that a closed-system perspective (Fairbairn 1958) presents to a patient's development. PMID:11212191

  2. Association of ADAM10 and CAMK2A polymorphisms with conduct disorder: evidence from family-based studies.

    PubMed

    Jian, Xue-Qiu; Wang, Ke-Sheng; Wu, Tie-Jian; Hillhouse, Joel J; Mullersman, Jerald E

    2011-08-01

    Twin and family studies have shown that genetic factors play a role in the development of conduct disorder (CD). The purpose of this study was to identify genetic variants associated with CD using a family-based association study. We used 4,720 single nucleotide polymorphisms (SNPs) from the Illumina Panel and 11,120 SNPs from the Affymetrix 10K GeneChips genotyped in 155 Caucasian nuclear families from Genetic Analysis Workshop (GAW) 14, a subset from the Collaborative Study on the Genetics of Alcoholism (COGA). 20 SNPs had suggestive associations with CD (p<10(-3)), nine of which were located in known genes, including ADAM10 (rs383902, p=0.00036) and CAMK2A (rs2053053, p=0.00098). Our results were verified using the International Multi-Center ADHD Genetics Project (IMAGE) dataset. In conclusion, we identified several loci associated with CD. Especially, the two genes (ADAM10 and CAMK2A) have been reported to be associated with Alzheimer's disease, bipolar disorder and depression. These findings may serve as a resource for replication in other populations. PMID:21611732

  3. Adam-Gibbs model in the density scaling regime and its implications for the configurational entropy scaling

    PubMed Central

    Masiewicz, Elżbieta; Grzybowski, Andrzej; Grzybowska, Katarzyna; Pawlus, Sebastian; Pionteck, Jürgen; Paluch, Marian

    2015-01-01

    To solve a long-standing problem of condensed matter physics with determining a proper description of the thermodynamic evolution of the time scale of molecular dynamics near the glass transition, we have extended the well-known Adam-Gibbs model to describe the temperature-volume dependence of structural relaxation times, τα(T, V). We also employ the thermodynamic scaling idea reflected in the density scaling power law, τα = f(T−1V−γ), recently acknowledged as a valid unifying concept in the glass transition physics, to differentiate between physically relevant and irrelevant attempts at formulating the temperature-volume representations of the Adam-Gibbs model. As a consequence, we determine a straightforward relation between the structural relaxation time τα and the configurational entropy SC, giving evidence that also SC(T, V) = g(T−1V−γ) with the exponent γ that enables to scale τα(T, V). This important findings have meaningful implications for the connection between thermodynamics and molecular dynamics near the glass transition, because it implies that τα can be scaled with SC. PMID:26365623

  4. ADAM9 enhances CDCP1 protein expression by suppressing miR-218 for lung tumor metastasis.

    PubMed

    Chiu, Kuo-Liang; Kuo, Ting-Ting; Kuok, Qian-Yu; Lin, Yu-Sen; Hua, Chung-Hung; Lin, Chen-Yuan; Su, Pei-Yuan; Lai, Liang-Chuan; Sher, Yuh-Pyng

    2015-01-01

    Metastasis is the leading cause of death in cancer patients due to the difficulty of controlling this complex process. MicroRNAs (miRNA), endogenous noncoding short RNAs with important biological and pathological functions, may play a regulatory role during cancer metastasis, but this role has yet to be fully defined. We previously demonstrated that ADAM9 enhanced the expression of the pro-migratory protein CDCP1 to promote lung metastasis; however, the regulatory process remains unknown. Here we demonstrate that endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 was associated with high migration ability in lung cancer cells. Direct interaction between miR-218 and the 3'-UTR of CDCP1 mRNAs was detected in luciferase-based transcription reporter assays. CDCP1 protein levels decreased as expression levels of miR-218 increased, and increased in cells treated with miR-218 antagomirs. Induction of miR-218 inhibited tumor cell mobility, anchorage-free survival, and tumor-initiating cell formation in vitro and delayed tumor metastases in mice. Our findings revealed an integrative tumor suppressor function of miR-218 in lung carcinogenesis and metastasis. PMID:26553452

  5. Tumor necrosis factor α-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163.

    PubMed

    Etzerodt, Anders; Maniecki, Maciej Bogdan; Møller, Kirsten; Møller, Holger Jon; Moestrup, Søren Kragh

    2010-12-01

    CD163 is expressed specifically in the monocyte/macrophage lineage, where it mediates uptake of haptoglobin-hemoglobin complexes, leading to metabolism of the oxidative heme molecule. Shedding of the CD163 ectodomain from the cell surface produces a sCD163 plasma protein, and a positive correlation is seen between the sCD163 plasma level and the severity of various infectious and inflammatory diseases. In the present analysis of the phorbol ester-induced shedding of sCD163 in CD163 cDNA-transfected HEK293 cells, we used metalloproteinase inhibitors and siRNA-mediated inhibition of metalloproteinases to identify TACE/ADAM17 as an enzyme responsible for PMA-induced cleavage of the membrane-proximal region of CD163. As TACE/ADAM17-mediated shedding of TNF-α is up-regulated in macrophages subjected to inflammatory stimuli, the present results now provide a likely explanation for the strong empirical relationship between the sCD163 plasma level and infectious/inflammatory diseases relating to macrophage activity. PMID:20807704

  6. ADAM9 enhances CDCP1 protein expression by suppressing miR-218 for lung tumor metastasis

    PubMed Central

    Chiu, Kuo-Liang; Kuo, Ting-Ting; Kuok, Qian-Yu; Lin, Yu-Sen; Hua, Chung-Hung; Lin, Chen-Yuan; Su, Pei-Yuan; Lai, Liang-Chuan; Sher, Yuh-Pyng

    2015-01-01

    Metastasis is the leading cause of death in cancer patients due to the difficulty of controlling this complex process. MicroRNAs (miRNA), endogenous noncoding short RNAs with important biological and pathological functions, may play a regulatory role during cancer metastasis, but this role has yet to be fully defined. We previously demonstrated that ADAM9 enhanced the expression of the pro-migratory protein CDCP1 to promote lung metastasis; however, the regulatory process remains unknown. Here we demonstrate that endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 was associated with high migration ability in lung cancer cells. Direct interaction between miR-218 and the 3′-UTR of CDCP1 mRNAs was detected in luciferase-based transcription reporter assays. CDCP1 protein levels decreased as expression levels of miR-218 increased, and increased in cells treated with miR-218 antagomirs. Induction of miR-218 inhibited tumor cell mobility, anchorage-free survival, and tumor-initiating cell formation in vitro and delayed tumor metastases in mice. Our findings revealed an integrative tumor suppressor function of miR-218 in lung carcinogenesis and metastasis. PMID:26553452

  7. Adam-Gibbs model in the density scaling regime and its implications for the configurational entropy scaling.

    PubMed

    Masiewicz, Elżbieta; Grzybowski, Andrzej; Grzybowska, Katarzyna; Pawlus, Sebastian; Pionteck, Jürgen; Paluch, Marian

    2015-01-01

    To solve a long-standing problem of condensed matter physics with determining a proper description of the thermodynamic evolution of the time scale of molecular dynamics near the glass transition, we have extended the well-known Adam-Gibbs model to describe the temperature-volume dependence of structural relaxation times, τα(T, V). We also employ the thermodynamic scaling idea reflected in the density scaling power law, τα = f(T(-1)V(-γ)), recently acknowledged as a valid unifying concept in the glass transition physics, to differentiate between physically relevant and irrelevant attempts at formulating the temperature-volume representations of the Adam-Gibbs model. As a consequence, we determine a straightforward relation between the structural relaxation time τα and the configurational entropy SC, giving evidence that also SC(T, V) = g(T(-1)V(-γ)) with the exponent γ that enables to scale τα(T, V). This important findings have meaningful implications for the connection between thermodynamics and molecular dynamics near the glass transition, because it implies that τα can be scaled with SC. PMID:26365623

  8. ADAM17_i33780A>G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the genetics of lipid lowering drugs and diet network study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes, and elevated levels of expression have been linked to obesity and insulin resistance. This study evaluated the association of six ADAM17 single nucleotide polymorphi...

  9. INTERNATIONAL UNION OF OPERATING ENGINEERS NATIONAL HAZMAT PROGRAM - ADAMANT CIRCULAR SAW OENHP{number_sign}: 2001-05, VERSION A

    SciTech Connect

    Unknown

    2002-01-01

    Florida International University's (FIU) Hemispheric Center for Environmental Technology (HCET) evaluated five saws for their effectiveness in cutting up specially prepared fiberglass-reinforced plywood crates. These crates were built as surrogates for crates that presently hold radioactive contaminated glove boxes at the Department of Energy's (DOE) Los Alamos facility. The Adamant circular saw was assessed on August 14, 2001. During the FIU test of efficacy, a team from the Operating Engineers National Hazmat Program (OENHP) evaluated the occupational safety and health issues associated with this technology. The Adamant was only used during a limited ''test'' on a regular plywood crate due to safety considerations of the tool for this application. The Adamant circular saw, a counter-rotating twin-cutter, constructed with blades that work differently than conventional cutting wheels with twin blades, each rotating in opposite directions. It is used to cut wood and metals. Each blade is approximately 8 3/4 inches in diameter with a maximum cutting depth of 2 1/2 inches. The machine has two rotation speeds: 1,900 and 2,900 rotations per minute (rpm). The saw is operated with an interlocked, guarded trigger switch located at the end of the saw opposite the cutting blades. To operate the saw, the safety interlock must be depressed prior to powering the saw with the trigger control. The saw is supported by a handle at the front of the saw near the cutting blades. The top part of the blades is guarded near the handle, with approximately three-fourths of the face of the blades exposed. The Adamant circular saw is an innovative technology used to cut metals and wood. Its safety features include: interlocking switch for powering the saw, overload indicator and shutoff, and an electronic brake that stops the engine immediately when the start button is released. The top part of the blades is guarded near the motor. With approximately three-fourths of the face of the blades

  10. The Earliest Reference to ADHD in the Medical Literature? Melchior Adam Weikard's Description in 1775 of "Attention Deficit" (Mangel der Aufmerksamkeit, Attentio Volubilis)

    ERIC Educational Resources Information Center

    Barkley, Russell A.; Peters, Helmut

    2012-01-01

    Objective: The present article reports on the discovery and translation of a chapter in a 1775 medical textbook by the German physician, Melchior Adam Weikard, which describes attention disorders. This article is believed to be the earliest reference to the syndrome that today is known as attention deficit hyperactivity disorder, or ADHD. Method:…

  11. Testimony of Gina Adams, Senior Fellow, Urban Institute. Before the Early Childhood, Elementary, and Secondary Education Subcommittee Hearing on "Improving Early Childhood Development Policies and Practices"

    ERIC Educational Resources Information Center

    Adams, Gina

    2009-01-01

    This paper presents the testimony of Gina Adams before the Early Childhood, Elementary, and Secondary Education Subcommittee Hearing on "Improving Early Childhood Development Policies and Practices." This testimony was presented to the House Committee on Education and Labor, U.S. House of Representatives last March 19, 2009. She talks about how…

  12. Superfund record of decision (EPA Region 3), Westinghouse Elevator Company Plant, Operable Unit 2, Cumberland Township, Adams County, Gettysburg, PA, March 31, 1995

    SciTech Connect

    1995-04-01

    This Record of Decision (ROD) presents the selected remedial action for Operable Unit 2 (Soils) at the Westinghouse Elevator Company Plant Site in Adams County, Pennsylvania. The selected remedy for the soils at the Westinghouse Elevator Plant is No Additional Action for this Operable Unit. The other alternatives evaluated would produce little or no environmental benefit at substantial cost.

  13. What Is Essential in Standard Setting and Construct Maps? Commentary on Adam E. Wyse's "Construct Maps as a Foundation for Standard Setting"

    ERIC Educational Resources Information Center

    Schulz, E. Matthew

    2013-01-01

    In this article, E. Matthew Schulz responds to Adam Wyse's article, "Construct Maps as a Foundation for Standard Setting." In doing so, he asserts that one of the most important ideas in Wyse's work is that information used in standard setting needs to be better represented through the use of graphics. However, he's not…

  14. Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling

    PubMed Central

    Chang, Mei-Chi; Chan, Chiu-Po; Chen, Yi-Jane; Hsien, Hsiang-Chi; Chang, Ya-Ching; Yeung, Sin-Yuet; Jeng, Po-Yuan; Cheng, Ru-Hsiu; Hahn, Liang-Jiunn; Jeng, Jiiang-Huei

    2016-01-01

    Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production. ANE-induced EGF production was inhibited by catalase. Addition of anti-EGF neutralizing antibody attenuated ANE-induced cyclooxygenase-2 (COX-2), mature ADAM9 expression and PGE2 and 8-isoprostane production. ANE-induced IL-1α production was inhibited by catalase, anti-EGF antibody, PD153035 (EGF receptor antagonist) and U0126 (MEK inhibitor) but not by α-naphthoflavone (cytochrome p450-1A1 inhibitor). ANE-induced ADAM17 production was inhibited by pp2 (Src inhibitor), U0126, α-naphthoflavone and aspirin. AG490 (JAK inhibitor) prevented ANE-stimulated ADAM17, IL-1α, PGE2 production, COX-2 expression, ADAM9 maturation, and the ANE-induced decline in keratin 5 and 14, but showed little effect on cdc2 expression and EGF production. Moreover, ANE-induced 8-isoprostane production by GKs was inhibited by catalase, anti-EGF antibody, AG490, pp2, U0126, α-naphthoflavone, Zinc protoporphyrin (ZnPP) and aspirin. These results indicate that AN components may involve in BQ-induced oral cancer by induction of reactive oxygen species, EGF/EGFR, IL-1α, ADAMs, JAK, Src, MEK/ERK, CYP1A1, and COX signaling pathways, and the aberration of cell cycle and differentiation. Various blockers against ROS, EGF, IL-1α, ADAM, JAK, Src, MEK, CYP1A1, and COX can be used for prevention or treatment of BQ chewing-related diseases. PMID:26919242

  15. Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling.

    PubMed

    Chang, Mei-Chi; Chan, Chiu-Po; Chen, Yi-Jane; Hsien, Hsiang-Chi; Chang, Ya-Ching; Yeung, Sin-Yuet; Jeng, Po-Yuan; Cheng, Ru-Hsiu; Hahn, Liang-Jiunn; Jeng, Jiiang-Huei

    2016-03-29

    Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production. ANE-induced EGF production was inhibited by catalase. Addition of anti-EGF neutralizing antibody attenuated ANE-induced cyclooxygenase-2 (COX-2), mature ADAM9 expression and PGE2 and 8-isoprostane production. ANE-induced IL-1α production was inhibited by catalase, anti-EGF antibody, PD153035 (EGF receptor antagonist) and U0126 (MEK inhibitor) but not by α-naphthoflavone (cytochrome p450-1A1 inhibitor). ANE-induced ADAM17 production was inhibited by pp2 (Src inhibitor), U0126, α-naphthoflavone and aspirin. AG490 (JAK inhibitor) prevented ANE-stimulated ADAM17, IL-1α, PGE2 production, COX-2 expression, ADAM9 maturation, and the ANE-induced decline in keratin 5 and 14, but showed little effect on cdc2 expression and EGF production. Moreover, ANE-induced 8-isoprostane production by GKs was inhibited by catalase, anti-EGF antibody, AG490, pp2, U0126, α-naphthoflavone, Zinc protoporphyrin (ZnPP) and aspirin. These results indicate that AN components may involve in BQ-induced oral cancer by induction of reactive oxygen species, EGF/EGFR, IL-1α, ADAMs, JAK, Src, MEK/ERK, CYP1A1, and COX signaling pathways, and the aberration of cell cycle and differentiation. Various blockers against ROS, EGF, IL-1α, ADAM, JAK, Src, MEK, CYP1A1, and COX can be used for prevention or treatment of BQ chewing-related diseases. PMID:26919242

  16. Understanding Influence within the Context of Nursing: Development of the Adams Influence Model Using Practice, Research, and Theory.

    PubMed

    Adams, Jeffrey M; Natarajan, Sudha

    2016-01-01

    Acquiring influence, and knowing how to use it, is a required competency for nurse leaders, yet the concept of influence and how it works is not well described in the nursing literature. In this article, the authors examine what is known about influence and present an influence model specific to nurse leaders. The Adams Influence Model was developed through an iterative process and is based on a comprehensive review of the influence literature, expert commentary, multiple pilot studies, evaluation of nursing theories, and validation by an external data source. Rather than defining "how to" influence, the model serves as a guide for personal reflection, helping nurse leaders understand and reflect on the influence process and factors, tactics, and strategies they can use when seeking to influence others. PMID:27490886

  17. 123I-ADAM SPECT imaging of serotonin transporter binding in patients with night eating syndrome: a preliminary report.

    PubMed

    Lundgren, Jennifer D; Newberg, Andrew B; Allison, Kelly C; Wintering, Nancy A; Ploessl, Karl; Stunkard, Albert J

    2008-04-15

    Night eating syndrome (NES) represents a delay in the circadian pattern of food intake, manifested by evening hyperphagia and/or nocturnal awakenings accompanied by ingestions of food. A neurobiological marker of NES has been implicated with the recently discovered therapeutic response to the selective serotonin reuptake inhibitor (SSRI) sertraline. This pilot SPECT (single photon emission computed tomography) study compared the serotonin transporter (SERT) uptake ratios of night eaters with those of healthy controls. Six night eaters underwent SPECT imaging using the radiopharmaceutical (123)I-ADAM. Uptake, compared with that of the cerebellum, was obtained for the midbrain, basal ganglia, and temporal lobes; uptake ratios in night eaters were compared with those of six healthy controls. Night eaters had significantly greater SERT uptake ratios in the midbrain than healthy controls. These findings, in conjunction with the therapeutic response of NES to sertraline, indicate that the serotonin system is involved in the pathophysiology of NES. PMID:18281200

  18. Notch1 Autoactivation via Transcriptional Regulation of Furin, Which Sustains Notch1 Signaling by Processing Notch1-Activating Proteases ADAM10 and Membrane Type 1 Matrix Metalloproteinase

    PubMed Central

    Qiu, Hong; Tang, Xiaoying; Ma, Jun; Shaverdashvili, Khvaramze; Zhang, Keman

    2015-01-01

    Notch1 is an evolutionarily conserved transmembrane receptor involved in melanoma growth. Notch1 is first cleaved by furin in the Golgi apparatus to produce the biologically active heterodimer. Following ligand binding, Notch1 is cleaved at the cell membrane by proteases such as ADAM10 and -17 and membrane type 1 matrix metalloproteinase (MT1-MMP), the latter of which we recently identified as a novel protease involved in Notch1 processing. The final cleavage is γ-secretase dependent and releases the active Notch intracellular domain (NIC). We now demonstrate that Notch1 directly regulates furin expression. Aside from activating Notch1, furin cleaves and activates several proteases, including MT1-MMP, ADAM10, and ADAM17. By chromatin immunoprecipitation and a reporter assay, we demonstrate that Notch1 binds at position −1236 of the furin promoter and drives furin expression. The Notch1-dependent enhancement of furin expression increases the activities of MT1-MMP and ADAM10 but not that of ADAM17, as demonstrated by short hairpin RNA (shRNA) knockdown of furin, and promotes the cleavage of Notch1 itself. These data highlight a novel positive-feedback loop whereby Notch1-dependent furin expression can induce Notch1 signaling by increasing Notch1 processing and by potentiating the activity of the proteases responsible for Notch1 activation. This leads to Notch1 signal amplification, which can promote melanoma tumor growth and progression, as demonstrated by the inhibition of cell migration and invasion upon furin inhibition downstream of Notch1. Disruption of such feedback signaling might represent an avenue for the treatment of melanoma. PMID:26283728

  19. Functional and molecular evidence for expression of the renin angiotensin system and ADAM17-mediated ACE2 shedding in COS7 cells

    PubMed Central

    Grobe, Nadja; Di Fulvio, Mauricio; Kashkari, Nada; Chodavarapu, Harshita; Somineni, Hari K.; Singh, Richa

    2015-01-01

    The renin angiotensin system (RAS) plays a vital role in the regulation of the cardiovascular and renal functions. COS7 is a robust and easily transfectable cell line derived from the kidney of the African green monkey, Cercopithecus aethiops. The aims of this study were to 1) demonstrate the presence of an endogenous and functional RAS in COS7, and 2) investigate the role of a disintegrin and metalloproteinase-17 (ADAM17) in the ectodomain shedding of angiotensin converting enzyme-2 (ACE2). Reverse transcription coupled to gene-specific polymerase chain reaction demonstrated expression of ACE, ACE2, angiotensin II type 1 receptor (AT1R), and renin at the transcript levels in total RNA cell extracts. Western blot and immunohistochemistry identified ACE (60 kDa), ACE2 (75 kDa), AT1R (43 kDa), renin (41 kDa), and ADAM17 (130 kDa) in COS7. At the functional level, a sensitive and selective mass spectrometric approach detected endogenous renin, ACE, and ACE2 activities. ANG-(1–7) formation (m/z 899) from the natural substrate ANG II (m/z 1,046) was detected in lysates and media. COS7 cells stably expressing shRNA constructs directed against endogenous ADAM17 showed reduced ACE2 shedding into the media. This is the first study demonstrating endogenous expression of the RAS and ADAM17 in the widely used COS7 cell line and its utility to study ectodomain shedding of ACE2 mediated by ADAM17 in vitro. The transfectable nature of this cell line makes it an attractive cell model for studying the molecular, functional, and pharmacological properties of the renal RAS. PMID:25740155

  20. Extraction-Separation Performance and Dynamic Modeling of Orion Test Vehicles with Adams Simulation: 2nd Edition

    NASA Technical Reports Server (NTRS)

    Fraire, Usbaldo, Jr.; Anderson, Keith; Varela, Jose G.; Bernatovich, Michael A.

    2015-01-01

    NASA's Orion Capsule Parachute Assembly System (CPAS) project has advanced into the third generation of its parachute test campaign and requires technically comprehensive modeling capabilities to simulate multi-body dynamics (MBD) of test articles released from a C-17. Safely extracting a 30,000 lbm mated test article from a C-17 and performing stable mid-air separation maneuvers requires an understanding of the interaction between elements in the test configuration and how they are influenced by extraction parachute performance, aircraft dynamics, aerodynamics, separation dynamics, and kinetic energy experienced by the system. During the real-time extraction and deployment sequences, these influences can be highly unsteady and difficult to bound. An avionics logic window based on time, pitch, and pitch rate is used to account for these effects and target a favorable separation state in real time. The Adams simulation has been employed to fine-tune this window, as well as predict and reconstruct the coupled dynamics of the Parachute Test Vehicle (PTV) and Cradle Platform Separation System (CPSS) from aircraft extraction through the mid-air separation event. The test-technique for the extraction of CPAS test articles has evolved with increased complexity and requires new modeling concepts to ensure the test article is delivered to a stable test condition for the programmer phase. Prompted by unexpected dynamics and hardware malfunctions in drop tests, these modeling improvements provide a more accurate loads prediction by incorporating a spring-damper line-model derived from the material properties. The qualification phase of CPAS testing is on the horizon and modeling increasingly complex test-techniques with Adams is vital to successfully qualify the Orion parachute system for human spaceflight.

  1. Three-dimensional geophysical mapping of rock alteration and water content at Mount Adams, Washington: Implications for lahar hazards

    USGS Publications Warehouse

    Finn, C.A.; Deszcz-Pan, M.; Anderson, E.D.; John, D.A.

    2007-01-01

    Hydrothermally altered rocks, particularly if water saturated, can weaken stratovolcanoes, thereby increasing the potential for catastrophic sector collapses that can lead to far-traveled, destructive debris flows. Evaluating the hazards associated with such alteration is difficult because alteration has been mapped on few active volcanoes and the distribution and intensity of subsurface alteration are largely unknown on any active volcano. At Mount Adams, some Holocene debris flows contain abundant hydrothermal minerals derived from collapse of the altered, edifice. Intense hydrothermal alteration significantly reduces the resistivity and magnetization of volcanic rock, and therefore hydrothermally altered rocks can be identified with helicopter electromagnetic and magnetic measurements. Electromagnetic and magnetic data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses of hydrothermally altered rock in the central core of Mount Adams north of the summit. We identify steep cliffs at the western edge of this zone as the likely source for future large debris flows. In addition, the electromagnetic data identified water in the brecciated core of the upper 100-200 m of the volcano. Water helps alter the rocks, reduces the effective stress, thereby increasing the potential for slope failure, and acts, with entrained melting ice, as a lubricant to transform debris avalanches into lahars. Therefore knowing the distribution of water is also important for hazard assessments. Our results demonstrate that high-resolution geophysical and geological observations can yield unprecedented views of the three-dimensional distribution of altered rock and shallow pore water aiding evaluation of the debris avalanche hazard.

  2. More than a neuroanatomical representation in The Creation of Adam by Michelangelo Buonarroti, a representation of the Golden Ratio.

    PubMed

    de Campos, Deivis; Malysz, Tais; Bonatto-Costa, João Antonio; Jotz, Geraldo Pereira; de Oliveira Junior, Lino Pinto; da Rocha, Andrea Oxley

    2015-09-01

    Michelangelo Buonarroti (1475-1564) was a master anatomist as well as an artistic genius. He dissected numerous cadavers and developed a profound understanding of human anatomy. Among his best-known artworks are the frescoes painted on the ceiling of the Sistine Chapel (1508-1512), in Rome. Currently, there is some debate over whether the frescoes merely represent the teachings of the Catholic Church at the time or if there are other meanings hidden in the images. In addition, there is speculation regarding the image of the brain embedded in the fresco known as "The Creation of Adam," which contains anatomic features of the midsagittal and lateral surfaces of the brain. Within this context, we report our use of Image Pro Plus Software 6.0 to demonstrate mathematical evidence that Michelangelo painted "The Creation of Adam" using the Divine Proportion/Golden Ratio (GR) (1.6). The GR is classically associated with greater structural efficiency and is found in biological structures and works of art by renowned artists. Thus, according to the evidence shown in this article, we can suppose that the beauty and harmony recognized in all Michelangelo's works may not be based solely on his knowledge of human anatomical proportions, but that the artist also probably knew anatomical structures that conform to the GR display greater structural efficiency. It is hoped that this report will at least stimulate further scientific and scholarly contributions to this fascinating topic, as the study of these works of art is essential for the knowledge of the history of Anatomy. PMID:26182895

  3. Mapping Weak, Altered Zones and Perched Water With Aerogeophysical Measurements at Mount Adams, Washington: Implications for Volcanic Instability

    NASA Astrophysics Data System (ADS)

    Finn, C. A.; Deszcz-Pan, M.; Anderson, E. D.; Horton, R.

    2006-12-01

    Hydrothermally altered rocks, particularly if water saturated, can weaken stratovolcanoes. This increases the potential for catastrophic sector collapses that can lead to destructive debris flows. Evaluating the hazards associated with such alteration is difficult, because alteration has been mapped on few active volcanoes and the distribution and intensity of subsurface alteration and location of perched water tables are largely unknown on any active volcano. At Mount Adams, some Holocene debris flows contain abundant hydrothermal minerals derived from collapse of an altered edifice. Intense hydrothermal alteration can significantly reduce the resistivity (from hundreds to tens ohm-m) and magnetization of volcanic rocks. These changes can be identified with helicopter electromagnetic and magnetic measurements and visualized in 3D. 100 m is the greatest depth that the lowest frequency electromagnetic data could penetrate into the low resistivity, altered zones; outside the altered zones, the depth of penetration was up to 300 m. Total-field magnetic data can detect magnetization variations to several thousand meters depth. Electromagnetic and magnetic data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses of hydrothermally altered rock in the central core of Mount Adams north of the summit. We identify steep cliffs at the western edge of this zone as the likely source for future large debris flows. Water, and perhaps melted ice, is needed as a lubricant to transform debris avalanches into lahars. Therefore, knowing the distribution of both is important for hazard assessments. Over the low resistivity summit, the electromagnetic data detected ice with a thickness of 0 to about 80 m and an estimated volume of up to 0.1 km3. Over resistive ridges ice thicknesses could not be determined. The electromagnetic data also identified perched water tables in the brecciated core of the upper 300 m of the volcano

  4. N-Cadherin, ADAM-10 and Aquaporin 1 expression in lung tissue exposed to fluoro-edenite fibers: an immunohistochemical study.

    PubMed

    Musumeci, Giuseppe; Loreto, Carla; Szychlinska, Marta Anna; Imbesi, Rosa; Rapisarda, Venerando; Aiello, Flavia Concetta; Castorina, Sergio; Castrogiovanni, Paola

    2015-08-01

    Fluoro-edenite (FE) fibers are similar to other amphibole asbestos fibers. The scientific relevance of FE is due to its ability to lead to chronic inflammation and carcinogenesis in lung tissue shown after its inhalation. These fibers stimulate aberrant host cell proliferation and induce the release of cytokines, growth factors, reactive oxygen and nitrite species, which results in DNA damage. In previous studies, we showed that FE induces functional modifications in sheep and human lung fibroblasts and alveolar epithelial cells, where the overexpression of several molecules probably involved in pathological cellular mechanisms induced by FE exposition have been detected. However, the mechanisms of cellular and molecular toxicity and the cellular response to FE fibers are still not well known. N-cadherin, ADAM-10 and AQP1 are molecules involved in carcinogenesis and in inflammatory process. In this study we analyzed, through immunohistochemistry, their expression in the lung tissue of sheep exposed to FE. Our results showed different patterns of immunolabeling for N-cadherin, ADAM-10 and AQP1. N-cadherin and ADAM-10 were more expressed in FE exposed lung tissue, when compared with the control. On the contrary, AQP1 was more expressed in non exposed lung tissue. These results suggest that N-Cadherin, ADAM-10 and AQP1 are probably involved in different pathological processes induced by FE fiber exposition. The aim of the study was to better understand the mechanisms of cellular and molecular toxicity and of cellular response to FE fibers in order to identify, in the future, a possible therapeutic intervention in cases of FE-associated pathogenesis. PMID:25757887

  5. Loss of ADAM17-Mediated Tumor Necrosis Factor Alpha Signaling in Intestinal Cells Attenuates Mucosal Atrophy in a Mouse Model of Parenteral Nutrition

    PubMed Central

    Feng, Yongjia; Tsai, Yu-Hwai; Xiao, Weidong; Ralls, Matthew W.; Stoeck, Alex; Wilson, Carole L.; Raines, Elaine W.

    2015-01-01

    Total parenteral nutrition (TPN) is commonly used clinically to sustain patients; however, TPN is associated with profound mucosal atrophy, which may adversely affect clinical outcomes. Using a mouse TPN model, removing enteral nutrition leads to decreased crypt proliferation, increased intestinal epithelial cell (IEC) apoptosis and increased mucosal tumor necrosis factor alpha (TNF-α) expression that ultimately produces mucosal atrophy. Upregulation of TNF-α signaling plays a central role in mediating TPN-induced mucosal atrophy without intact epidermal growth factor receptor (EGFR) signaling. Currently, the mechanism and the tissue-specific contributions of TNF-α signaling to TPN-induced mucosal atrophy remain unclear. ADAM17 is an ectodomain sheddase that can modulate the signaling activity of several cytokine/growth factor receptor families, including the TNF-α/TNF receptor and ErbB ligand/EGFR pathways. Using TPN-treated IEC-specific ADAM17-deficient mice, the present study demonstrates that a loss of soluble TNF-α signaling from IECs attenuates TPN-induced mucosal atrophy. Importantly, this response remains dependent on the maintenance of functional EGFR signaling in IECs. TNF-α blockade in wild-type mice receiving TPN confirmed that soluble TNF-α signaling is responsible for downregulation of EGFR signaling in IECs. These results demonstrate that ADAM17-mediated TNF-α signaling from IECs has a significant role in the development of the proinflammatory state and mucosal atrophy observed in TPN-treated mice. PMID:26283731

  6. The Elsevier Trophoblast Research Award Lecture: Importance of metzincin proteases in trophoblast biology and placental development: a focus on ADAM12.

    PubMed

    Aghababaei, Mahroo; Beristain, Alexander G

    2015-04-01

    Placental development is a highly regulated process requiring signals from both fetal and maternal uterine compartments. Within this complex system, trophoblasts, placental cells of epithelial lineage, form the maternal-fetal interface controlling nutrient, gas and waste exchange. The commitment of progenitor villous cytotrophoblasts to differentiate into diverse trophoblast subsets is a fundamental process in placental development. Differentiation of trophoblasts into invasive stromal- and vascular-remodeling subtypes is essential for uterine arterial remodeling and placental function. Inadequate placentation, characterized by defects in trophoblast differentiation, may underlie the earliest cellular events driving pregnancy disorders such as preeclampsia and fetal growth restriction. Molecularly, invasive trophoblasts acquire characteristics defined by profound alterations in cell-cell and cell-matrix adhesion, cytoskeletal reorganization and production of proteolytic factors. To date, most studies have investigated the importance of the matrix metalloproteinases (MMPs) and their ability to efficiently remodel components of the extracellular matrix (ECM). However, it is now becoming clear that besides MMPs, other related proteases regulate trophoblast invasion via mechanisms other than ECM turnover. In this review, we will summarize the current knowledge on the regulation of trophoblast invasion by members of the metzincin family of metalloproteinases. Specifically, we will discuss the emerging roles that A Disintegrin and Metalloproteinases (ADAMs) play in placental development, with a particular focus on the ADAM subtype, ADAM12. PMID:25589360

  7. Systematic evaluation of methyl ester bioisosteres in the context of developing alkenyldiarylmethanes (ADAMs) as non-nucleoside reverse transcriptase inhibitors (NNRTIs) for anti-HIV-1 chemotherapy.

    PubMed

    Hoshi, Ayako; Sakamoto, Takeshi; Takayama, Jun; Xuan, Meiyan; Okazaki, Mari; Hartman, Tracy L; Buckheit, Robert W; Pannecouque, Christophe; Cushman, Mark

    2016-07-01

    The alkenyldiarylmethanes (ADAMs) are a class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) targeting HIV-1. Four chemically and metabolically stabilized ADAMs incorporating N-methoxyimidoyl halide replacements of the methyl esters of the lead compound were previously reported. In this study, twenty-five new ADAMs were synthesized in order to investigate the biological consequences of installing nine different methyl ester bioisosteres at three different locations. Attempts to define a universal rank order of methyl ester bioisosteres and discover the 'best' one in terms of inhibitory activity versus HIV-1 reverse transcriptase (RT) led to the realization that the potencies are critically dependent on the surrounding structure at each location, and therefore the definition of universal rank order is impossible. This investigation produced several new non-nucleoside reverse transcriptase inhibitors in which all three of the three methyl esters of the lead compound were replaced by methyl ester bioisosteres, resulting in compounds that are more potent as HIV-1 RT inhibitors and antiviral agents than the lead compound itself and are expected to also be more metabolically stable than the lead compound. PMID:27234889

  8. Three-dimensional viscoelastic time-domain finite-difference seismic modelling using the staggered Adams-Bashforth time integrator

    NASA Astrophysics Data System (ADS)

    Bohlen, Thomas; Wittkamp, Florian

    2016-03-01

    We analyse the performance of a higher order accurate staggered viscoelastic time-domain finite-difference method, in which the staggered Adams-Bashforth (ABS) third-order and fourth-order accurate time integrators are used for temporal discretization. ABS is a multistep method that uses previously calculated wavefields to increase the order of accuracy in time. The analysis shows that the numerical dispersion is much lower than that of the widely used second-order leapfrog method. Numerical dissipation is introduced by the ABS method which is significantly smaller for fourth-order than third-order accuracy. In 1-D and 3-D simulation experiments, we verify the convincing improvements of simulation accuracy of the fourth-order ABS method. In a realistic elastic 3-D scenario, the computing time reduces by a factor of approximately 2.4, whereas the memory requirements increase by approximately a factor of 2.2. The ABS method thus provides an alternative strategy to increase the simulation accuracy in time by investing computer memory instead of computing time.

  9. The Moral Dignity of Inductive Method and the Reconciliation of Science and Faith in Adam Sedgwick's Discourse

    NASA Astrophysics Data System (ADS)

    Bellon, Richard

    2012-07-01

    Science's inductive method required patient, humble and self-controlled behavior; Christian revelation demanded the same virtues. The discoveries of science and the truths of scripture would always harmonize as long as both men of science and men of faith conducted themselves in scrupulous accordance with their duty. So ran a central argument in A Discourse on the studies of the university (1833; 5th ed, 1850) by Adam Sedgwick (1785-1873), the longtime professor of geology at the University of Cambridge. This sanctification of the inductive method provided the foundation for a theistic science which (in theory) did not subordinate scientific theory to religious doctrine. This vision provided the foundation for Sedgwick's lifelong crusade against all forms of evolutionary theory. Evolution's impiety, he insisted, resulted from (and exacerbated) a failure to behave inductively. The fact that Sedgwick (in principle if not always in practice) elevated norms of behavior above systems of belief had an important and paradoxical consequence. Even though his personal hatred of evolution never cooled, his Discourse nonetheless provided a dominant model for younger theists to reconcile faith with Charles Darwin's evolutionary theory.

  10. PET Imaging of Serotonin Transporters With 4-[(18)F]-ADAM in a Parkinsonian Rat Model With Porcine Neural Xenografts.

    PubMed

    Chiu, Chuang-Hsin; Li, I-Hsun; Weng, Shao-Ju; Huang, Yuahn-Sieh; Wu, Shinn-Chih; Chou, Ta-Kai; Huang, Wen-Sheng; Liao, Mei-Hsiu; Shiue, Chyng-Yann; Cheng, Cheng-Yi; Ma, Kuo-Hsing

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disease characterized by a loss of dopaminergic neurons in the nigrostriatal pathway. Apart from effective strategies to halt the underlying neuronal degeneration, cell replacement now offers novel prospects for PD therapy. Porcine embryonic neural tissue has been considered an alternative source to human fetal grafts in neurodegenerative disorders because its use avoids major practical and ethical issues. This study was undertaken to evaluate the effects of embryonic day 27 (E27) porcine mesencephalic tissue transplantation in a PD rat model using animal positron emission tomography (PET) coupled with 4-[(18)F]-ADAM, a serotonin transporter (SERT) imaging agent. The parkinsonian rat was induced by injecting 6-hydroxydopamine into the medial forebrain bundle (MFB) of the right nigrostriatal pathway. The apomorphine-induced rotation behavioral test and 4-[(18)F]-ADAM/animal PET scanning were carried out following 6-OHDA lesioning. At the second week following 6-OHDA lesioning, the parkinsonian rat rotates substantially on apomorphine-induced contralateral turning. In addition, the mean striatal-specific uptake ratio (SUR) of 4-[(18)F]-ADAM decreased by 44%. After transplantation, the number of drug-induced rotations decreased markedly, and the mean SUR of 4-[(18)F]-ADAM and the level of SERT immunoreactivity (SERT-ir) in striatum were partially restored. The mean SUR level was restored to 71% compared to that for the contralateral intact side, which together with the abundant survival of tyrosine hydroxylase (TH) neurons accounted for functional recovery at the fourth week postgraft. In regard to the extent of donor-derived cells, we found the neurons of the xenografts from E27 transgenic pigs harboring red fluorescent protein (RFP) localized with TH-ir cells and SERT-ir in the grafted area. Thus, transplanted E27 porcine mesencephalic tissue may restore dopaminergic and serotonergic systems in the parkinsonian rat

  11. Sequence-Specific Interaction between the Disintegrin Domain of Mouse ADAM 3 and Murine Eggs: Role of β1 Integrin-associated Proteins CD9, CD81, and CD98

    PubMed Central

    Takahashi, Yuji; Bigler, Dora; Ito, Yasuhiko; White, Judith M.

    2001-01-01

    ADAM 3 is a sperm surface glycoprotein that has been implicated in sperm-egg adhesion. Because little is known about the adhesive activity of ADAMs, we investigated the interaction of ADAM 3 disintegrin domains, made in bacteria and in insect cells, with murine eggs. Both recombinant proteins inhibited sperm-egg binding and fusion with potencies similar to that which we recently reported for the ADAM 2 disintegrin domain. Alanine scanning mutagenesis revealed a critical importance for the glutamine at position 7 of the disintegrin loop. Fluorescent beads coated with the ADAM 3 disintegrin domain bound to the egg surface. Bead binding was inhibited by an authentic, but not by a scrambled, peptide analog of the disintegrin loop. Bead binding was also inhibited by the function-blocking anti-α6 monoclonal antibody (mAb) GoH3, but not by a nonfunction blocking anti-α6 mAb, or by mAbs against either the αv or β3 integrin subunits. We also present evidence that in addition to the tetraspanin CD9, two other β1-integrin-associated proteins, the tetraspanin CD81 as well as the single pass transmembrane protein CD98 are expressed on murine eggs. Antibodies to CD9 and CD98 inhibited in vitro fertilization and binding of the ADAM 3 disintegrin domain. Our findings are discussed in terms of the involvement of multiple sperm ADAMs and multiple egg β1 integrin-associated proteins in sperm-egg binding and fusion. We propose that an egg surface “tetraspan web” facilitates fertilization and that it may do so by fostering ADAM–integrin interactions. PMID:11294888

  12. Molecular structure, configurational entropy and viscosity of silicate melts: link through the Adam and Gibbs theory of viscous flow

    NASA Astrophysics Data System (ADS)

    Le Losq, Charles; Neuville, Daniel R.

    2016-04-01

    The rheological and thermodynamic properties of silicate melts played a crucial role in the formation and the evolution of the Earth. For instance, they influenced the evolution of a plausible primordial magma ocean, and, as a result, the differentiation of the Earth mantle and crust. Further, they control the dynamic of volcanic eruptions. Because of that, modelling the viscosity or the heat capacity of silicate melts is crucial in order to model the physical processes they are involved in. The Adam and Gibbs theory of viscous flow offers a thermodynamic framework that assumes that the viscosity η (Pa s) at a temperature T (K) of a melt can be expressed as: log(η) = A + ----Be--- e T Sconf(T) (1) with Ae a pre-exponential constant related to the viscosity at infinite temperature, Be (J mol‑1) a constant proportional to the potential energy barrier opposed to the cooperative rearrangement of the liquid structure and Sconf(T) (J mol‑1 K‑1) the melt configurational entropy. With expressing Sconf(T) as the sum of the residual entropy of the glass and of the variation in melt configurational heat capacity, it is possible to link existing thermodynamic and viscosity data for melts with various chemical composition, e.g., SiO2, NaAlSi3O8 or CaAl2Si2O8. Further, it also is possible to describe the viscosity variation induced by mixing Ca and Mg or Na and K in silicate melts, under the assumption that such mixing produces an ideal excess entropy of mixing. An interesting point in the Adam and Gibbs framework is that it assumes that viscous flow occurs through the cooperative re-arrangement of molecular sub-regions in the melt. From high temperature 29Si NMR and Raman spectroscopy data, it actually is known that viscous flow occurs because of the cooperative exchange of oxygen atoms between tetrahedral SiO2 units, allowing their motions. Therefore, it is tempting to link such structural knowledge to heat capacity and viscosity data through the use of equation 1. In

  13. Rock property measurements guide interpretation of electromagnetic, magnetic and gravity models at Mts. Adams, Baker, Rainier and St. Helens (Invited)

    NASA Astrophysics Data System (ADS)

    Finn, C.; Bedrosian, P. A.; Horton, R.; Polster, S.

    2010-12-01

    Mt. Adams north of the summit. Alteration at Mt. Baker is restricted to thinner (<300 m) zones beneath Sherman Crater and the Dorr Fumerole Fields. The presence of water not only helps form clay minerals that weaken the edifice but also can reduce the pore pressures, increasing the potential for slope failure. In addition, water with entrained melting ice acts as a lubricant to transform debris avalanches into lahars. The EM data identified water-saturated rocks from the surface to the detection limit (100 - 200 m) in discreet zones at Mt. Rainier and Mt Adams and over the entire summit region at Mt. Baker. At Mt. St. Helens, perched aquifers are identified in the 1980 avalanche deposits as well as in older, thick breccia or avalanche deposits. The modeled distribution of alteration and pore fluids helps identify likely sources for future alteration-related debris flows and clearly shows that debris flow hazard studies on altered volcanoes are greatly enhanced by magnetic, EM and gravity data.

  14. Haploinsufficiency of the NOTCH1 Receptor as a Cause of Adams-Oliver Syndrome with Variable Cardiac Anomalies

    PubMed Central

    Southgate, Laura; Sukalo, Maja; Karountzos, Anastasios S.V.; Taylor, Edward J.; Collinson, Claire S.; Ruddy, Deborah; Snape, Katie M.; Dallapiccola, Bruno; Joss, Shelagh; Brancati, Francesco; Digilio, M. Cristina; Graul-Neumann, Luitgard M.; Salviati, Leonardo; Coerdt, Wiltrud; Jacquemin, Emmanuel; Wuyts, Wim; Zenker, Martin

    2015-01-01

    Background Adams-Oliver syndrome (AOS) is a rare disorder characterized by congenital limb defects and scalp cutis aplasia. In a proportion of cases, notable cardiac involvement is also apparent. Despite recent advances in the understanding of the genetic basis of AOS, for the majority of affected subjects the underlying molecular defect remains unresolved. This study aimed to identify novel genetic determinants of AOS. Methods and Results Whole-exome sequencing was performed for 12 probands, each with a clinical diagnosis of AOS. Analyses led to the identification of novel heterozygous truncating NOTCH1 mutations (c.1649dupA and c.6049_6050delTC) in two kindreds in which AOS was segregating as an autosomal dominant trait. Screening a cohort of 52 unrelated AOS subjects, we detected 8 additional unique NOTCH1 mutations, including three de novo amino-acid substitutions, all within the ligand-binding domain. Congenital heart anomalies were noted in 47% (8/17) of NOTCH1-positive probands and affected family members. In leucocyte-derived RNA from subjects harboring NOTCH1 extracellular domain mutations, we observed significant reduction of NOTCH1 expression, suggesting instability and degradation of mutant mRNA transcripts by the cellular machinery. Transient transfection of mutagenized NOTCH1 missense constructs also revealed significant reduction in gene expression. Mutant NOTCH1 expression was associated with down-regulation of the Notch target genes HEY1 and HES1, indicating that NOTCH1-related AOS arises through dysregulation of the Notch signaling pathway. Conclusions These findings highlight a key role for NOTCH1 across a range of developmental anomalies that include cardiac defects, and implicate NOTCH1 haploinsufficiency as a likely molecular mechanism for this group of disorders. PMID:25963545

  15. 1,25-dihydroxyvitamin D3 causes ADAM10-dependent ectodomain shedding of tumor necrosis factor receptor 1 in vascular smooth muscle cells.

    PubMed

    Yang, Won Seok; Kim, Hyun Woo; Lee, Joo Mi; Han, Nam Jeong; Lee, Mee Jeong; Park, Su-Kil

    2015-01-01

    1,25-Dihydroxyvitamin D3 (1,25D3) has a potential antiatherosclerotic effect through anti-inflammatory actions. We investigated how 1,25D3 regulates tumor necrosis factor-α (TNF-α)-induced lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression in cultured human aortic smooth muscle cells. TNF-α activated Rac1/reactive oxygen species/spleen tyrosine kinase and transcriptional factors, activator protein-1, and nuclear factor κB, which led to LOX-1 expression. 1,25D3 inhibited TNF-α-induced LOX-1 expression by inhibiting Rac1 activation and thereby its downstream signals. 1,25D3 rapidly induced extracellular Ca(2+) influx. Verapamil, an inhibitor of L-type calcium channels, inhibited 1,25D3-induced Ca(2+) influx and counteracted the inhibitory effects of 1,25D3 on Rac1 activation, whereas Bay K8644 [1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid, methyl ester], an L-type calcium channel agonist, attenuated TNF-α-induced Rac1 activation, as 1,25D3 did. 1,25D3 induced the ectodomain shedding of TNF receptor 1 (TNFR1), which was abolished by verapamil and in Ca(2+)-free media. Like 1,25D3, Bay K8644 induced the ectodomain shedding of TNFR1. Both 1,25D3 and Bay K8644 caused the translocation of a disintegrin and metalloprotease (ADAM) 10 from the cytoplasm to the plasma membrane, which was dependent on extracellular Ca(2+) influx. In contrast, depletion of ADAM10 by transfection of ADAM10-small interfering RNA prevented 1,25D3- or Bay K8644-induced ectodomain shedding of TNFR1 and abolished the suppressive effect of 1,25D3 on TNF-α-induced Rac1 activation. Taken together, these findings suggest that 1,25D3 induces extracellular Ca(2+) influx via L-type calcium channel, triggering ADAM10-mediated ectodomain shedding of TNFR1, and it thereby decreases responsiveness to TNF-α. By shedding TNFR1 from the cell surface, 1,25D3 may regulate inflammation and atherogenesis, whereas this effect could be

  16. Elevated plasma-soluble CD16 levels in porcine reproductive and respiratory syndrome virus-infected pigs: correlation with ADAM17-mediated shedding.

    PubMed

    Gu, Weihong; Guo, Longjun; Li, Ren; Niu, Junwei; Luo, Xiaolei; Zhang, Jian; Xu, Yunfei; Tian, Zhijun; Feng, Li; Wang, Yue

    2016-03-01

    Soluble CD16 (sCD16) is closely correlated with chronic diseases in humans. Here, plasma sCD16 levels in pigs were increased by infection with porcine reproductive and respiratory syndrome virus (PRRSV) but not with porcine epidemic diarrhea virus, porcine circovirus type 2 and pseudorabies virus. Of interest, PRRSV attached to blood neutrophils and reduced surface CD16 expression on neutrophils. In vitro data confirmed that PRRSV caused CD16 shedding in neutrophils. Further analyses revealed that ADAM17 was involved in porcine CD16 shedding. Thus, our findings suggest that increase in sCD16 levels may be an indicator of PRRSV infection. PMID:26653711

  17. Sox2 functionally interacts with βAPP, the βAPP intracellular domain and ADAM10 at a transcriptional level in human cells.

    PubMed

    Sarlak, G; Htoo, H H; Hernandez, J-F; Iizasa, H; Checler, F; Konietzko, U; Song, W; Vincent, B

    2016-01-15

    Sox2 (SRY (Sex-determining region Y)-related high mobility group (HMG) box 2) is a transcription factor that serves key roles in controlling the balance between stem cells maintenance and commitment to differentiated lineages throughout the lifetime. Importantly, Sox2 deficiency results in early embryonic lethality whereas the down-regulation of Sox2 expression triggers neurodegeneration in the adult mouse brain. Moreover, Sox2 is decreased in the brain of Alzheimer's disease (AD) patients and co localizes with the β-amyloid precursor protein (βAPP) in stem cells. Here we report the existence of functional interactions between Sox2 and βAPP, the βAPP intracellular domain AICD50 and the α-secretase ADAM10 in human cells. We first show, as observed in embryonic stem cells, that βAPP overexpression in HEK293 cells results in an increase of Sox2 immunoreactivity and we further establish the transcriptional nature of this pathway. Moreover, overexpression of the pro-apoptotic C-terminal βAPP-derived AICD50 metabolite leads to the down-regulation of Sox2 transcription whereas the pharmacological inhibition of endogenous AICD production increases Sox2 expression in both HEK293 and SH-SY5Y cell lines. In addition, we demonstrate that Sox2 is a potent activator of the non amyloidogenic processing of βAPP as shown by the Sox2-dependent augmentation of ADAM10 catalytic activity, immunoreactivity, promoter transactivation and mRNA levels with no modification of the activity and the expression of the β-secretase BACE1. Finally, the fact that γ-secretase inhibition induces an increase of ADAM10 protein levels in SH-SY5Y cells further supports the occurrence of functional AICD/Sox2/ADAM10 interactions. Altogether, our study identifies and characterizes new functional cross-talks between Sox2 and proteins involved in AD, thereby adding support to the view that Sox2 likely behaves as a protective factor during the development of this neurodegenerative disease. PMID

  18. The relationship of dynamical heterogeneity to the Adam-Gibbs and random first-order transition theories of glass formation

    PubMed Central

    Starr, Francis W.; Douglas, Jack F.; Sastry, Srikanth

    2013-01-01

    We carefully examine common measures of dynamical heterogeneity for a model polymer melt and test how these scales compare with those hypothesized by the Adam and Gibbs (AG) and random first-order transition (RFOT) theories of relaxation in glass-forming liquids. To this end, we first analyze clusters of highly mobile particles, the string-like collective motion of these mobile particles, and clusters of relative low mobility. We show that the time scale of the high-mobility clusters and strings is associated with a diffusive time scale, while the low-mobility particles' time scale relates to a structural relaxation time. The difference of the characteristic times for the high- and low-mobility particles naturally explains the well-known decoupling of diffusion and structural relaxation time scales. Despite the inherent difference of dynamics between high- and low-mobility particles, we find a high degree of similarity in the geometrical structure of these particle clusters. In particular, we show that the fractal dimensions of these clusters are consistent with those of swollen branched polymers or branched polymers with screened excluded-volume interactions, corresponding to lattice animals and percolation clusters, respectively. In contrast, the fractal dimension of the strings crosses over from that of self-avoiding walks for small strings, to simple random walks for longer, more strongly interacting, strings, corresponding to flexible polymers with screened excluded-volume interactions. We examine the appropriateness of identifying the size scales of either mobile particle clusters or strings with the size of cooperatively rearranging regions (CRR) in the AG and RFOT theories. We find that the string size appears to be the most consistent measure of CRR for both the AG and RFOT models. Identifying strings or clusters with the “mosaic” length of the RFOT model relaxes the conventional assumption that the “entropic droplets” are compact. We also confirm

  19. The relationship of dynamical heterogeneity to the Adam-Gibbs and random first-order transition theories of glass formation.

    PubMed

    Starr, Francis W; Douglas, Jack F; Sastry, Srikanth

    2013-03-28

    We carefully examine common measures of dynamical heterogeneity for a model polymer melt and test how these scales compare with those hypothesized by the Adam and Gibbs (AG) and random first-order transition (RFOT) theories of relaxation in glass-forming liquids. To this end, we first analyze clusters of highly mobile particles, the string-like collective motion of these mobile particles, and clusters of relative low mobility. We show that the time scale of the high-mobility clusters and strings is associated with a diffusive time scale, while the low-mobility particles' time scale relates to a structural relaxation time. The difference of the characteristic times for the high- and low-mobility particles naturally explains the well-known decoupling of diffusion and structural relaxation time scales. Despite the inherent difference of dynamics between high- and low-mobility particles, we find a high degree of similarity in the geometrical structure of these particle clusters. In particular, we show that the fractal dimensions of these clusters are consistent with those of swollen branched polymers or branched polymers with screened excluded-volume interactions, corresponding to lattice animals and percolation clusters, respectively. In contrast, the fractal dimension of the strings crosses over from that of self-avoiding walks for small strings, to simple random walks for longer, more strongly interacting, strings, corresponding to flexible polymers with screened excluded-volume interactions. We examine the appropriateness of identifying the size scales of either mobile particle clusters or strings with the size of cooperatively rearranging regions (CRR) in the AG and RFOT theories. We find that the string size appears to be the most consistent measure of CRR for both the AG and RFOT models. Identifying strings or clusters with the "mosaic" length of the RFOT model relaxes the conventional assumption that the "entropic droplets" are compact. We also confirm the

  20. The relationship of dynamical heterogeneity to the Adam-Gibbs and random first-order transition theories of glass formation

    NASA Astrophysics Data System (ADS)

    Starr, Francis W.; Douglas, Jack F.; Sastry, Srikanth

    2013-03-01

    We carefully examine common measures of dynamical heterogeneity for a model polymer melt and test how these scales compare with those hypothesized by the Adam and Gibbs (AG) and random first-order transition (RFOT) theories of relaxation in glass-forming liquids. To this end, we first analyze clusters of highly mobile particles, the string-like collective motion of these mobile particles, and clusters of relative low mobility. We show that the time scale of the high-mobility clusters and strings is associated with a diffusive time scale, while the low-mobility particles' time scale relates to a structural relaxation time. The difference of the characteristic times for the high- and low-mobility particles naturally explains the well-known decoupling of diffusion and structural relaxation time scales. Despite the inherent difference of dynamics between high- and low-mobility particles, we find a high degree of similarity in the geometrical structure of these particle clusters. In particular, we show that the fractal dimensions of these clusters are consistent with those of swollen branched polymers or branched polymers with screened excluded-volume interactions, corresponding to lattice animals and percolation clusters, respectively. In contrast, the fractal dimension of the strings crosses over from that of self-avoiding walks for small strings, to simple random walks for longer, more strongly interacting, strings, corresponding to flexible polymers with screened excluded-volume interactions. We examine the appropriateness of identifying the size scales of either mobile particle clusters or strings with the size of cooperatively rearranging regions (CRR) in the AG and RFOT theories. We find that the string size appears to be the most consistent measure of CRR for both the AG and RFOT models. Identifying strings or clusters with the "mosaic" length of the RFOT model relaxes the conventional assumption that the "entropic droplets" are compact. We also confirm the

  1. ADAM17 and EGFR regulate IL-6 receptor and amphiregulin mRNA expression and release in cigarette smoke-exposed primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD).

    PubMed

    Stolarczyk, Marta; Amatngalim, Gimano D; Yu, Xiao; Veltman, Mieke; Hiemstra, Pieter S; Scholte, Bob J

    2016-08-01

    Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as TACE, and epidermal growth factor receptor (EGFR) has been suggested to contribute to chronic obstructive pulmonary disease (COPD) development and progression. The aim of this study was to investigate the role of these proteins in activation of primary bronchial epithelial cells differentiated at the air-liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing cells from COPD patients with non-COPD CS exposure of ALI-PBEC enhanced ADAM17-mediated shedding of the IL-6 receptor (IL6R) and the EGFR agonist amphiregulin (AREG) toward the basolateral compartment, which was more pronounced in cells from COPD patients than in non-COPD controls. CS transiently increased IL6R and AREG mRNA in ALI-PBEC to a similar extent in cultures from both groups, suggesting that posttranslational events determine differential shedding between COPD and non-COPD cultures. We show for the first time by in situ proximity ligation (PLA) that CS strongly enhances interactions of phosphorylated ADAM17 with AREG and IL-6R in an intracellular compartment, suggesting that CS-induced intracellular trafficking events precede shedding to the extracellular compartment. Both EGFR and ADAM17 activity contribute to CS-induced IL-6R and AREG protein shedding and to mRNA expression, as demonstrated using selective inhibitors (AG1478 and TMI-2). Our data are consistent with an autocrine-positive feedback mechanism in which CS triggers shedding of EGFR agonists evoking EGFR activation, in ADAM17-dependent manner, and subsequently transduce paracrine signaling toward myeloid cells and connective tissue. Reducing ADAM17 and EGFR activity could therefore be a therapeutic approach for the tissue remodeling and inflammation observed in COPD. PMID:27561911

  2. Learning C with Adam

    ERIC Educational Resources Information Center

    Gilbert, Juan; Wilson, Dale-Marie; Gupta, Priyanka

    2005-01-01

    Studies have shown that when learning occurs in an environment that uses animated pedagogical agents and personalized instruction, the learner learns the material more deeply and can recall it easier when compared to learning without an agent. Thus, an effective learning system creates personalized contexts for each learner. The "one size fits…

  3. Furin-, ADAM 10-, and γ-Secretase-Mediated Cleavage of a Receptor Tyrosine Phosphatase and Regulation of β-Catenin's Transcriptional Activity†

    PubMed Central

    Anders, Lars; Mertins, Philipp; Lammich, Sven; Murgia, Marta; Hartmann, Dieter; Saftig, Paul; Haass, Christian; Ullrich, Axel

    2006-01-01

    Several receptor protein tyrosine phosphatases (RPTPs) are cell adhesion molecules involved in homophilic interactions, suggesting that RPTP outside-in signaling is coupled to cell contact formation. However, little is known about the mechanisms by which cell density regulates RPTP function. We show that the MAM family prototype RPTPκ is cleaved by three proteases: furin, ADAM 10, and γ-secretase. Cell density promotes ADAM 10-mediated cleavage and shedding of RPTPκ. This is followed by γ-secretase-dependent intramembrane proteolysis of the remaining transmembrane part to release the phosphatase intracellular portion (PIC) from the membrane, thereby allowing its translocation to the nucleus. When cells were treated with leptomycin B, a nuclear export inhibitor, PIC accumulated in nuclear bodies. PIC is an active protein tyrosine phosphatase that binds to and dephosphorylates β-catenin, an RPTPκ substrate. The expression of RPTPκ suppresses β-catenin's transcriptional activity, whereas the expression of PIC increases it. Notably, this increase required the phosphatase activity of PIC. Thus, both isoforms have acquired opposing roles in the regulation of β-catenin signaling. We also found that RPTPμ, another MAM family member, undergoes γ-secretase-dependent processing. Our results identify intramembrane proteolysis as a regulatory switch in RPTPκ signaling and implicate PIC in the activation of β-catenin-mediated transcription. PMID:16648485

  4. Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity

    PubMed Central

    Misemer, Benjamin S; Skubitz, Amy P N; Carlos Manivel, J; Schmechel, Stephen C; Cheng, Edward Y; Henriksen, Jonathan C; Koopmeiners, Joseph S; Corless, Christopher L; Skubitz, Keith M

    2014-01-01

    Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy. PMID:24402778

  5. Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity.

    PubMed

    Misemer, Benjamin S; Skubitz, Amy P N; Carlos Manivel, J; Schmechel, Stephen C; Cheng, Edward Y; Henriksen, Jonathan C; Koopmeiners, Joseph S; Corless, Christopher L; Skubitz, Keith M

    2014-02-01

    Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy. PMID:24402778

  6. Essential-oil variability of Juniperus deltoides R.P.Adams along the east Adriatic coast - how many chemotypes are there?

    PubMed

    Rajčević, Nemanja; Janaćković, Peđa; Dodoš, Tanja; Tešević, Vele; Marin, Petar D

    2015-01-01

    The composition of the essential oils isolated from twigs of ten Juniperus deltoides R.P. Adams populations from the east Adriatic coast was determined by GC-FID and GC/MS analyses. Altogether, 169 compounds were identified, representing 95.6-98.4% of the total oil composition. The oils were dominated by monoterpenes (average content of 61.6%), which are characteristic oil components of species of the Juniperus section. Two monoterpenes, α-pinene and limonene, were the dominant constituents, comprising on average 46.78% of the essential oils. Statistical methods were deployed to determine the diversity of the terpene classes and the common terpenes between the investigated populations. These statistical analyses revealed the existence of three chemotypes within all populations, i.e., a α-pinene, limonene, and limonene/α-pinene type. PMID:25641838

  7. Association of a disintegrin and metalloprotease 33 (ADAM33) gene polymorphisms with the risk of COPD: an updated meta-analysis of 2,644 cases and 4,804 controls.

    PubMed

    Zhou, Deng-Chuan; Zhou, Cheng-Fan; Toloo, Sam; Shen, Tong; Tong, Shi-Lu; Zhu, Qi-Xing

    2015-02-01

    A series of observational studies have been made to investigate the association of the ADAM33 gene polymorphisms with the risk of COPD, but their results were conflicting. Therefore, we performed an updated meta-analysis to quantitatively summarize the associations of ADAM33 gene polymorphisms with the risk of COPD. Thirteen case-control studies referring to nine SNPs were identified: V4 (rs2787094), T+1 (rs2280089), T2 (rs2280090), T1 (rs2280091), S2 (rs528557), S1 (rs3918396), Q-1 (rs612709), F+1 (rs511898) and ST+5 (rs597980). A dominant model (AA+Aa vs. aa), recessive model (AA vs. Aa+aa), additive model (AA vs. aa) and allelic model (A vs. a) were used to evaluate the association of ADAM33 polymorphism with the risk of COPD. The results indicated that significant associations were found for ADAM33 T1, T2, S1, Q-1, F+1 and ST+5 polymorphisms associated with the risk of COPD in different populations. However, no significant associations were found for V4, T+1 and S2 polymorphisms with the risk of COPD in all genetic models, even in the subgroup analysis by ethnicity. This meta-analysis provided evidence that the ADAM33 T1, T2, S1, Q-1, F+1 and ST+5 six locus polymorphisms association with the risk of COPD. Furthermore, T2, Q-1 and ST+5 indicated an association with the risk of COPD in the European populations, whereas T1, T2, S1, F+1 and Q-1 indicated an association with the risk of COPD in the Asian populations. PMID:25280544

  8. Implication of TNF-alpha convertase (TACE/ADAM17) in inducible nitric oxide synthase expression and inflammation in an experimental model of colitis.

    PubMed

    Colón, A L; Menchén, L A; Hurtado, O; De Cristóbal, J; Lizasoain, I; Leza, J C; Lorenzo, P; Moro, M A

    2001-12-21

    Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine which is shed in its soluble form by a disintegrin and metalloproteinase (ADAM) called TNF-alpha convertase (TACE; ADAM17). TNF-alpha plays a role in inflammatory bowel disease (IBD) and is involved in the expression of inducible nitric oxide synthase (iNOS) which has also been implicated in IBD. The study was designed to investigate whether colitis induced by trinitrobenzene sulphonic acid (TNBS) in rats produces an increase in TACE activity and/or expression and whether its pharmacological inhibition reduces TNF-alpha levels, iNOS expression and colonic damage in this model. TNBS (30 mg in 0.4 ml of 50% ethanol) was instilled into the colon of female Wistar rats. Saline or TACE inhibitor BB1101 (10 mg/kg/day) was administered intraperitoneally 5 days after TNBS instillation. On day 10, colons were removed and assessed for pathological score, myeloperoxidase (MPO), NO synthase (NOS), TACE enzymatic activity and protein levels, colonic TNF-alpha and NOx- levels. Instillation of TNBS caused an increase in TACE activity and expression and the release of TNF-alpha. TNBS also resulted in iNOS expression and colonic damage. BB1101 blocked TNBS-induced increase in TACE activity, TNF-alpha release and iNOS expression. Concomitantly, BB1101 ameliorated TNBS-induced colonic damage and inflammation. TNBS causes TNF-alpha release by an increase in TACE activity and expression and this results in the expression of iNOS and subsequent inflammation, suggesting that TACE inhibition may prove useful as a therapeutic means in IBD. PMID:11884025

  9. Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹⁸F]-ADAM/small-animal PET study.

    PubMed

    Shih, Jui-Hu; Ma, Kuo-Hsing; Chen, Chien-Fu F; Cheng, Cheng-Yi; Pao, Li-Heng; Weng, Shao-Ju; Huang, Yuahn-Sieh; Shiue, Chyng-Yann; Yeh, Ming-Kung; Li, I-Hsun

    2016-01-01

    The misuse of 3,4-methylenedioxymethamphetamine (MDMA) has drawn a growing concern worldwide for its psychophysiological impacts on humans. MDMA abusers are often accompanied by long-term serotonergic neurotoxicity, which is associated with reduced density of cerebral serotonin transporters (SERT) and depressive disorders. Resveratrol (RSV) is a natural polyphenolic phytoalexin that has been known for its antidepressant and neuroprotective effects. However, biological targets of RSV as well as its neuroprotective effects against MDMA remained largely unknown. In this study, we examined binding potency of RSV and MDMA to SERT using small-animal positron emission tomography (PET) with the SERT radioligand, N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) and investigated the protection of RSV against the acute and long-term adverse effects of MDMA. We found that RSV exhibit binding potentials to SERT in vivo in a dose-dependent manner with variation among brain regions. When the MDMA-treated rats (10mg/kg, s.c.) were co-injected with RSV (20mg/kg, i.p.) twice daily for 4 consecutive days, MDMA-induced acute elevation in plasma corticosterone was significantly reduced. Further, 4-[(18)F]-ADAM PET imaging revealed that RSV protected against the MDMA-induced decrease in SERT availability in the midbrain and the thalamus 2 weeks following the co-treatment. The PET data were comparable to the observation from the forced swim test that RSV sufficiently ameliorated the depressive-like behaviors of the MDMA-treated rats. Together, these findings suggest that RSV is a potential antidepressant and may confer protection against neurobiological and behavioral changes induced by MDMA. PMID:26612383

  10. Morphology and phylogenetic analysis of two oxytrichid soil ciliates from China, Oxytricha paragranulifera n. sp. and Oxytricha granulifera Foissner and Adam, 1983 (Protista, Ciliophora, Hypotrichia).

    PubMed

    Shao, Chen; Lv, Zhao; Pan, Ying; Al-Rasheid, Khaled A S; Yi, Zhenzhen

    2014-09-01

    The morphology and infraciliature of two hypotrichous ciliates, Oxytricha paragranulifera n. sp. and Oxytricha granulifera Foissner and Adam, 1983, collected respectively from the surface of a sandy soil in the Huguang mangrove forest, Zhanjiang, China, and the surface of soil in a forest beside Ziwu Road, Xian, north-west China, were examined. O. paragranulifera n. sp. is characterized by an elongate body with slightly tapered anterior end, two macronuclear nodules and two micronuclei, paroral and endoral in Stylonychia-pattern, colourless cortical granules distributed in clusters or irregular short rows, adoral zone occupying 37 % of the body length, marginal rows almost confluent posteriorly, six dorsal kineties and three caudal cirri, caudal cirri and dorsal bristles almost indistinguishable when viewed in vivo. The well-known O. granulifera Foissner and Adam, 1983 was also redescribed and can be separated from the novel species by having cortical granules arranged along dorsal kineties and marginal rows on both sides (vs grouped in clusters as well as in short irregular rows), paroral and endoral in Oxytricha-pattern (vs in Stylonychia-pattern), macronuclear nodules obviously detached (vs adjacent) and a non-saline terrestrial habitat (vs saline terrestrial). The separation of these two taxa is also firmly supported by the molecular data, which show a significant difference between the two in their SSU rRNA gene sequences (similarity 97.1 %). Phylogenetic analyses based on SSU rRNA gene sequence data suggest a close relationship within the Oxytrichidae assemblage between O. paragranulifera n. sp. and O. granulifera. PMID:24928427

  11. Shedding of TNF receptor 2 by effector CD8+ T cells by ADAM17 is important for regulating TNF-α availability during influenza infection

    PubMed Central

    DeBerge, Matthew P.; Ely, Kenneth H.; Wright, Peter F.; Thorp, Edward B.; Enelow, Richard I.

    2015-01-01

    Elevated levels of solTNFR2 are observed in a variety of human pathophysiological conditions but regulation of TNFR2 levels during disease is not well understood. We found that solTNFR2 levels were increased following influenza infection or live-attenuated influenza virus challenge in mice and humans, respectively. As influenza-specific CD8+ T cells up-regulated expression of TNFR2 after infection in mice, we hypothesized that CD8+ T cells contributed, in part, to solTNFR2 production after influenza infection and were interested in the mechanisms by which CD8+ T cells regulate TNFR2 shedding. Activation of these cells by TCR stimulation resulted in enhanced shedding of TNFR2 that required actin remodeling and lipid raft formation and was dependent on MAPK/ERK signaling. Furthermore, we identified ADAM17 as the protease responsible for TNFR2 shedding by CD8+ T cells, with ADAM17 and TNFR2 required in "cis" for shedding to occur. We observed similar activation thresholds for TNF-α expression and TNFR2 shedding, suggesting that solTNFR2 functioned, in part, to regulate solTNF-α levels. Production of solTNFR2 by activated CD8+ T cells reduced the availability of solTNF-α released by these cells, and TNFR2 blockade during influenza infection in mice enhanced the levels of solTNF-α, supporting this hypothesis. Taken together, this study identifies critical cellular mechanisms regulating TNFR2 shedding on CD8+ T cells and demonstrates that TNFR2 contributes, in part, to the regulation of TNF-α levels during infection. PMID:26019295

  12. Ground-water resources of the South Platte River Basin in western Adams and southwestern Weld Counties, Colorado

    USGS Publications Warehouse

    Smith, Rex O.; Schneider, P.A.; Petri, Lester R.

    1964-01-01

    The area described in this report consists of about 970 square miles in western Adams and southwestern Weld Counties in northeastern Colorado. It includes that part of the South Platte River valley between Denver and Kuner, Colo., all of Beebe Draw, and the lower part of the valley of Box Elder Creek. The stream-valley lowlands are separated by rolling uplands. The climate is semiarid, the normal annual precipitation being about 13 inches; thus, irrigation is essential for stable agricultural development. The area contains about 220,000 acres of irrigated land in the stream valleys. Most of the remaining 400,000 acres of land is used for dry farming or grazing because it lacks irrigation water. Most of the lowlands were brought under irrigation with surface water during the early 1900's, and now nearly all the surface water in the area is appropriated for irrigation within and downstream from the area. Because the natural flow of the streams is sometimes less than the demand for water, ground water is used to supplement the surface-water supply. Wells, drilled chiefly since 1930, supply the supplemental water and in some places are the sole supply for irrigation use. Rocks exposed in the area are of sedimentary origin and range in age from Lato Cretaceous to Recent. Those that are consolidated, called 'bedrock' in this report, consist of the Fox Hills sandstone and the Laramie and Arapahoe formations, all of Late Cretaceous age, and the Denver formation and Dawson arkose of Late Cretaceous and Tertiary age. The surface of the bedrock was shaped by ancestral streams, the valleys of which are reflected by the present surface topography. Dune sand, slope wash, and thin upland deposits of Quaternary age mantle the bedrock in the divide areas, and stream deposits ranging in thickness from 0 to about 125 feet partly fill the ancestral valleys. The valley-fill deposits consist of beds and lenses of clay, silt, sand, gravel, cobbles, and boulders. Abundant supplies of

  13. Discriminating assimilants and decoupling deep- vs. shallow-level crystal records at Mount Adams using 238U-230Th disequilibria and Os isotopes

    USGS Publications Warehouse

    Jicha, B.R.; Johnson, C.M.; Hildreth, W.; Beard, B.L.; Hart, G.L.; Shirey, S.B.; Singer, B.S.

    2009-01-01

    A suite of 23 basaltic to dacitic lavas erupted over the last 350??kyr from the Mount Adams volcanic field has been analyzed for U-Th isotope compositions to evaluate the roles of mantle versus crustal components during magma genesis. All of the lavas have (230Th/238U) > 1 and span a large range in (230Th/232Th) ratios, and most basalts have higher (230Th/232Th) ratios than andesites and dacites. Several of the lavas contain antecrysts (crystals of pre-existing material), yet internal U-Th mineral isochrons from six of seven lavas are indistinguishable from their eruption ages. This indicates a relatively brief period of time between crystal growth and eruption for most of the phenocrysts (olivine, clinopyroxene, plagioclase, magnetite) prior to eruption. One isochron gave a crystallization age that is ~ 20-25??ka older than its corresponding eruptive age, and is interpreted to reflect mixing of older and juvenile crystals or a protracted period of magma storage in the crust. Much of the eruptive volume since 350??ka consists of lavas that have small to moderate 230Th excesses (2-16%), which are likely inherited from melting of a garnet-bearing intraplate ("OIB-like") mantle source. Following melt generation and subsequent migration through the upper mantle, most Mt. Adams magmas interacted with young, mafic lower crust, as indicated by 187Os/188Os ratios that are substantially more radiogenic than the mantle or those expected via mixing of subducted material and the mantle wedge. Moreover, Os-Th isotope variations suggest that unusually large 230Th excesses (25-48%) and high 187Os/188Os ratios in some peripheral lavas reflect assimilation of small degree partial melts of pre-Quaternary basement that had residual garnet or Al-rich clinopyroxene. Despite the isotopic evidence for lower crustal assimilation, these processes are not generally recorded in the erupted phenocrysts, indicating that the crystal record of the deep-level 'cryptic' processes has been

  14. Activation of microRNA-494-targeting Bmi1 and ADAM10 by silibinin ablates cancer stemness and predicts favourable prognostic value in head and neck squamous cell carcinomas.

    PubMed

    Chang, Yu-Chao; Jan, Chia-Ing; Peng, Chih-Yu; Lai, Yu-Chi; Hu, Fang-Wei; Yu, Cheng-Chia

    2015-09-15

    Tumor initiating cells (TICs) possessing cancer stemness were shown to be enriched after therapy, resulting in the relapse and metastasis of head and neck squamous cell carcinomas (HNC). An effective therapeutic approach suppressing the HNC-TICs would be a potential method to improve the treatments for HNC. We observed that the treatment of silibinin (SB) dose dependently down-regulated the ALDH1 activity, CD133 positivity, stemness signatures expression, self-renewal property, and chemoresistance in ALDH1+CD44+ HNC-TICs. Using miRNA-microarray and mechanistic studies, SB increased the expression of microRNA-494 (miR-494) and both Bmi1 and ADAM10 were identified as the novel targets of miR-494. Moreover, overexpression of miR-494 results in a reduction in cancer stemness. However, knockdown of miR-494 in CD44-ALDH1- non-HNC-TICs enhanced cancer stemness and oncogenicity, while co-knockdown of Bmi1 and ADAM10 effectively reversed these phenomena. Mice model showed that SB treatment by oral gavage to xenograft tumors reduced tumor growth and prolonged the survival time of tumor-bearing mice by activation of miR-494-inhibiting Bmi1/ADAM10 expression. Survival analysis indicated that a miR494highBmi1lowADAM10low phenotype predicted a favourable clinical outcome. We conclude that the inhibition of tumor aggressiveness in HNC-TICs by SB was mediated by up-regulation miR-494, suggesting that SB would be a valuable anti-cancer drug for treatment of HNC. PMID:26090866

  15. DigitSeis: A New Digitization Software and its Application to the Harvard-Adam Dziewoński Observatory Collection

    NASA Astrophysics Data System (ADS)

    Bogiatzis, P.; Altoé, I. L.; Karamitrou, A.; Ishii, M.; Ishii, H.

    2015-12-01

    DigitSeis is a new open-source, interactive digitization software written in MATLAB that converts digital, raster images of analog seismograms to readily usable, discretized time series using image processing algorithms. DigitSeis automatically identifies and corrects for various geometrical distortions of seismogram images that are acquired through the original recording, storage, and scanning procedures. With human supervision, the software further identifies and classifies important features such as time marks and notes, corrects time-mark offsets from the main trace, and digitizes the combined trace with an analysis to obtain as accurate timing as possible. Although a large effort has been made to minimize the human input, DigitSeis provides interactive tools for challenging situations such as trace crossings and stains in the paper. The effectiveness of the software is demonstrated with the digitization of seismograms that are over half a century old from the Harvard-Adam Dziewoński observatory that is still in operation as a part of the Global Seismographic Network (station code HRV and network code IU). The spectral analysis of the digitized time series shows no spurious features that may be related to the occurrence of minute and hour marks. They also display signals associated with significant earthquakes, and a comparison of the spectrograms with modern recordings reveals similarities in the background noise.

  16. Phase change alloy viscosities down to Tg using Adam-Gibbs-equation fittings to excess entropy data: A fragile-to-strong transition

    NASA Astrophysics Data System (ADS)

    Wei, Shuai; Lucas, Pierre; Angell, C. Austen

    2015-07-01

    A striking anomaly in the viscosity of Te85Ge15 alloys noted by Greer and coworkers from the work of Neumann et al. is reminiscent of the equally striking comparison of liquid tellurium and water anomalies documented long ago by Kanno et al. In view of the power laws that are used to fit the data on water, we analyze the data on Te85Ge15 using the Speedy-Angell power-law form, and find a good account with a singularity Ts only 25 K below the eutectic temperature. However, the heat capacity data in this case are not diverging, but instead exhibit a sharp maximum like that observed in fast cooling in the Molinero-Moore model of water. Applying the Adam-Gibbs viscosity equation to these calorimetric data, we find that there must be a fragile-to-strong liquid transition at the heat capacity peak temperature, and then predict the "strong" liquid course of the viscosity down to Tg at 406 K (403.6 K at 20 K min-1 in this study). Since crystallization can be avoided by moderately fast cooling in this case, we can check the validity of the extrapolation by making a direct measurement of fragility at Tg, using differential scanning calorimetric techniques, and then comparing with the value from the extrapolated viscosity at Tg. The agreement is encouraging, and prompts discussion of relations between water and phase change alloy anomalies.

  17. Phase change alloy viscosities down to T{sub g} using Adam-Gibbs-equation fittings to excess entropy data: A fragile-to-strong transition

    SciTech Connect

    Wei, Shuai; Lucas, Pierre; Angell, C. Austen

    2015-07-21

    A striking anomaly in the viscosity of Te{sub 85}Ge{sub 15} alloys noted by Greer and coworkers from the work of Neumann et al. is reminiscent of the equally striking comparison of liquid tellurium and water anomalies documented long ago by Kanno et al. In view of the power laws that are used to fit the data on water, we analyze the data on Te{sub 85}Ge{sub 15} using the Speedy-Angell power-law form, and find a good account with a singularity T{sub s} only 25 K below the eutectic temperature. However, the heat capacity data in this case are not diverging, but instead exhibit a sharp maximum like that observed in fast cooling in the Molinero-Moore model of water. Applying the Adam-Gibbs viscosity equation to these calorimetric data, we find that there must be a fragile-to-strong liquid transition at the heat capacity peak temperature, and then predict the 'strong' liquid course of the viscosity down to T{sub g} at 406 K (403.6 K at 20 K min{sup −1} in this study). Since crystallization can be avoided by moderately fast cooling in this case, we can check the validity of the extrapolation by making a direct measurement of fragility at T{sub g}, using differential scanning calorimetric techniques, and then comparing with the value from the extrapolated viscosity at T{sub g}. The agreement is encouraging, and prompts discussion of relations between water and phase change alloy anomalies.

  18. Incongruent Reduction of Serotonin Transporter Associated with Suicide Attempts in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM

    PubMed Central

    Yeh, Yi-Wei; Ho, Pei-Shen; Chen, Chun-Yen; Kuo, Shin-Chang; Liang, Chih-Sung; Ma, Kuo-Hsing; Shiue, Chyng-Yann; Huang, Wen-Sheng; Cheng, Cheng-Yi; Wang, Tzu-Yun; Lu, Ru-Band

    2015-01-01

    Background: Much evidence supports the role of the serotonin transporter (SERT) in the pathophysiology and pharmacotherapy of major depressive disorder (MDD) and suicidal behaviors. Methods: In this study, we recruited 17 antidepressant-naïve patients with MDD and 17 age- and gender-matched healthy controls. SERT availability was measured in vivo with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) positron emission tomography (PET) imaging. The 21-item Hamilton Depression Rating Scale (HDRS) and Beck Scale for Suicide Ideation were used to assess the severity of depression and the intent of suicide ideation prior to PET imaging. All subjects with MDD were in a current state of depression with HDRS scores ≧18. Subjects who attempted suicide within two weeks of the study onset were recruited in the depressed suicidal group (n = 8). Subjects with MDD who denied any prior suicide attempt were recruited into the depressed non-suicidal group (n = 9). Results: A significant reduction of SERT availability in the midbrain, thalamus, and striatum was noted in the MDD group relative to the control group (Bonferroni-adjusted p-value < 0.05). Moreover, this effect was more pronounced in the depressed suicidal group compared to the control group (Bonferroni-adjusted p-value < 0.01). Relative to both the depressed non-suicidal and control groups, the depressed suicidal group showed an increased prefrontal cortex (PFC)/midbrain SERT binding ratio (Bonferroni-adjusted p-value < 0.01). Conclusions: This study suggests an incongruent reduction of PFC SERT binding relative to the midbrain might discriminate between depressed suicide attempters and non-attempters in patients with MDD and may be involved in the pathophysiology of suicide behaviors. PMID:25522405

  19. Strain-induced Differentiation of Fetal Type II Epithelial Cells Is Mediated via the Integrin α6β1-ADAM17/Tumor Necrosis Factor-α-converting Enzyme (TACE) Signaling Pathway*

    PubMed Central

    Wang, Yulian; Huang, Zheping; Nayak, Pritha S.; Matthews, Benjamin D.; Warburton, David; Shi, Wei; Sanchez-Esteban, Juan

    2013-01-01

    Mechanical forces are critical for normal fetal lung development. However, the mechanisms regulating this process are not well-characterized. We hypothesized that strain-induced release of HB-EGF and TGF-α is mediated via integrin-ADAM17/TACE interactions. Employing an in vitro system to simulate mechanical forces in fetal lung development, we showed that mechanical strain of fetal epithelial cells actives TACE, releases HB-EGF and TGF-α, and promotes differentiation. In contrast, in samples incubated with the TACE inhibitor IC-3 or in cells isolated from TACE knock-out mice, mechanical strain did not release ligands or promote cell differentiation, which were both rescued after transfection of ADAM17. Cell adhesion assay and co-immunoprecipitation experiments in wild-type and TACE knock-out cells using several TACE constructs demonstrated not only that integrins α6 and β1 bind to TACE via the disintegrin domain but also that mechanical strain enhances these interactions. Furthermore, force applied to these integrin receptors by magnetic beads activated TACE and shed HB-EGF and TGF-α. The contribution of integrins α6 and β1 to differentiation of fetal epithelial cells by strain was demonstrated by blocking their binding site with specific antibodies and by culturing the cells on membranes coated with anti-integrin α6 and β1 antibodies. In conclusion, mechanical strain releases HB-EGF and TGF-α and promotes fetal type II cell differentiation via α6β1 integrin-ADAM17/TACE signaling pathway. These investigations provide novel mechanistic information on how mechanical forces promote fetal lung development and specifically differentiation of epithelial cells. This information could be also relevant to other tissues exposed to mechanical forces. PMID:23888051

  20. FOREWORD: Foreword from Peter Adams Foreword from Peter Adams

    NASA Astrophysics Data System (ADS)

    Adams, Peter D.

    2009-11-01

    As part of this twentieth anniversary special issue I was asked to write a few words about Richard Palmer, the one permanent fixture on the journal over its twenty year history. Richard and I go back a (very) long way! He began his career at IOP Publishing in Bristol in 1971 while my publishing career with the American Physical Society began a little earlier, located at Brookhaven National Laboratory on Long Island NY. Since then, and for nearly forty years we have met often, if irregularly, at many locations throughout the world. As members of two very strong physics organizations we were clearly in competition with each other to seek out and publish the best physics research. At the same time we frequently exchanged experiences and policy ideas for dealing with serious violations of scientific ethical standards and how academic society-run journals can best serve the general scientific community. Overall my relationship with Richard has been a most rewarding one and I shall miss his opinions and sage advice. Richard: Compatriot; competitor; collaborator; I salute you!

  1. Homozygous loss of ADAM3A revealed by genome-wide analysis of pediatric high-grade glioma and diffuse intrinsic pontine gliomas

    PubMed Central

    Barrow, Jennifer; Adamowicz-Brice, Martyna; Cartmill, Maria; MacArthur, Donald; Lowe, James; Robson, Keith; Brundler, Marie-Anne; Walker, David A.; Coyle, Beth; Grundy, Richard

    2011-01-01

    Overall, pediatric high-grade glioma (pHGG) has a poor prognosis, in part due to the lack of understanding of the underlying biology. High-resolution 244 K oligo array comparative genomic hybridization (CGH) was used to analyze DNA from 38 formalin-fixed paraffin-embedded predominantly pretreatment pHGG samples, including 13 diffuse intrinsic pontine gliomas (DIPGs). The patterns of gains and losses were distinct from those seen in HGG arising in adults. In particular, we found 1q gain in up to 27% of our cohort compared with 9% reported in adults. A total of 13% had a balanced genetic profile with no large-scale copy number alterations. Homozygous loss at 8p12 was seen in 6 of 38 (16%) cases of pHGG. This novel deletion, which includes the ADAM3A gene, was confirmed by quantitative real-time PCR (qPCR). Loss of CDKN2A/CDKN2B in 4 of 38 (10%) samples by oligo array CGH was confirmed by fluorescent in situ hybridization on tissue microarrays and was restricted to supratentorial tumors. Only ∼50% of supratentorial tumors were positive for CDKN2B expression by immunohistochemistry (IHC), while ∼75% of infratentorial tumors were positive for CDKN2B expression (P = 0.03). Amplification of the 4q11–13 region was detected in 8% of cases and included PDGFRA and KIT, and subsequent qPCR analysis was consistent with the amplification of PDGFRA. MYCN amplification was seen in 5% of samples being significantly associated with anaplastic astrocytomas (P= 0.03). Overall, DIPG shared similar spectrum of changes to supratentorial HGG with some notable differences, including high-frequency loss of 17p and 14q and lack of CDKN2A/CDKN2B deletion. Informative genetic data providing insight into the underlying biology and potential therapeutic possibilities can be generated from archival tissue and typically small biopsies from DIPG. Our findings highlight the importance of obtaining pretreatment samples. PMID:21138945

  2. Success, Succession, and Adam Smith

    ERIC Educational Resources Information Center

    Woodwell, G. M.

    1974-01-01

    Offers a contemporary analysis of the interaction of man and the rest of the biota. Suggests that the dependence of man on nature is, more than the crisis of energy and world economics, the emergent scientific and political issue of the next years. (JR)

  3. Advanced action manipulator system (ADAMS)

    NASA Technical Reports Server (NTRS)

    Kugath, D. A.; Dane, D. H.; Blaise, H. T.

    1973-01-01

    Manipulator offers improved performance over other models in its category. It features larger force and reach capabilities and is readily convertible for underwater use. Unique kinematic arrangement provides extremely large working envelope. System has six degrees of motion: azimuth joint, shoulder joint, upper arm rotating joint, elbow joint, wrist pitch, and wrist twist.

  4. Interplay of metabolism and transport in determining oral drug absorption and gut wall metabolism: a simulation assessment using the "Advanced Dissolution, Absorption, Metabolism (ADAM)" model.

    PubMed

    Darwich, A S; Neuhoff, S; Jamei, M; Rostami-Hodjegan, A

    2010-11-01

    systematic variation of drug characteristics, in accordance with the Biopharmaceutics Classification System (BCS) within one of the most physiological models of oral drug absorption currently available, respectively ADAM. Variables studied included the intrinsic clearance (CLint) and the Michaelis-Menten Constant (Km) for CYP3A4 and P-gp (C(Lint-CYP3A4) and K(m-CYP3A4), CL(int-P-gp) and K(m-P-gp)). The impact of CYP3A4 and P-gp intracellular topography were not investigated since a well-stirred enterocyte is assumed within ADAM. An increased CLint-CYP3A4 resulted in a reduced F(G) whereas an increase in C(Lint-P-gp) resulted in a reduced F(a), but interestingly decreased F(G) too. The reduction in FG was limited to certain conditions and was modest. Non-linear relationships between various parameters determining the permeability (e.g. P(app), C(Lint-P-gp,) and K(m-P-gp)) and gut wall metabolism (e.g. C(Lint-CYP3A4,) K(m-CYP3A4)) resulted in disproportionate changes in F(G) compared to the magnitude of singular effects. The results suggest that P-gp efflux decreases enterocytic drug concentration for drugs given at reasonably high dose which possess adequate passive permeability (high P(app)), by de-saturating CYP3A4 in the gut resulting in a lower F(G). However, these findings were observed only in a very limited area of the parameters space matching very few therapeutic drugs (a group with very high metabolism, high turn-over by efflux transporters and low F(a)). The systematic approach in this study enabled us to recognise the combination of parameters values where the potential interplay between metabolising enzymes and efflux transporters is expected to be highest, using a realistic range of parameter values taken from an intensive literature search. PMID:21189140

  5. Variants in SELL, MRPS36P2, TP63, DDB2, CACNA1H, ADAM19, GNAI1, CDH13 and GABRG2 interact to confer risk of acne in Chinese population.

    PubMed

    Wang, HongYan; Guo, MeiHua; Shen, SongKe; He, Li; Zhang, XueJun; Zuo, XianBo; Yang, Sen

    2015-04-01

    Acne vulgaris is a common skin disease characterized by chronic inflammation of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinization, inflammation and bacterial colonization of hair follicles by propionibacterium acnes. Our previous genome-wide association study on acne has identified two new susceptibility loci. To search for potential gene-gene interactions and investigate the best-fit association models for the single nucleotide polymorphisms (SNP) from these interacting genes, we implemented logistic regression analysis in the combined sample of 2916 cases with severe acne and 4716 controls. The most significant association evidence was observed under an additive model for rs6896064 and under a dominant model the rest of these SNP. Significant interactions between these SNP were observed in this study: the SELL × MRPS36P2 (Padjusted = 4.15 × 10(-10)), TP63 × DDB2 (Padjusted = 7.62 × 10(-08)), DDB2 × CACNA1H (Padjusted = 1.89 × 10(-07)), ADAM19 × GNAI1 × CDH13 (Padjusted = 1.22 × 10(-04)) and ADAM19 × GABRG2 × GNAI2 × CDH13 (Pad justed = 6.33 × 10(-05)). These results may contribute to our understanding of acne genetic etiology and account for the additional risk of certain patients. PMID:25573302

  6. Disproportionate Reduction of Serotonin Transporter May Predict the Response and Adherence to Antidepressants in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM

    PubMed Central

    Yeh, Yi-Wei; Ho, Pei-Shen; Kuo, Shin-Chang; Chen, Chun-Yen; Liang, Chih-Sung; Yen, Che-Hung; Huang, Chang-Chih; Ma, Kuo-Hsing; Shiue, Chyng-Yann; Huang, Wen-Sheng; Shyu, Jia-Fwu; Wan, Fang-Jung; Lu, Ru-Band

    2015-01-01

    Background: Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants. Methods: We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more. Results: Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders. Conclusions: The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD. PMID:25568284

  7. Geographic information system datasets of regolith-thickness data, regolith-thickness contours, raster-based regolith thickness, and aquifer-test and specific-capacity data for the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado

    USGS Publications Warehouse

    Arnold, L. Rick

    2010-01-01

    These datasets were compiled in support of U.S. Geological Survey Scientific-Investigations Report 2010-5082-Hydrogeology and Steady-State Numerical Simulation of Groundwater Flow in the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. The datasets were developed by the U.S. Geological Survey in cooperation with the Lost Creek Ground Water Management District and the Colorado Geological Survey. The four datasets are described as follows and methods used to develop the datasets are further described in Scientific-Investigations Report 2010-5082: (1) ds507_regolith_data: This point dataset contains geologic information concerning regolith (unconsolidated sediment) thickness and top-of-bedrock altitude at selected well and test-hole locations in and near the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. Data were compiled from published reports, consultant reports, and from lithologic logs of wells and test holes on file with the U.S. Geological Survey Colorado Water Science Center and the Colorado Division of Water Resources. (2) ds507_regthick_contours: This dataset consists of contours showing generalized lines of equal regolith thickness overlying bedrock in the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. Regolith thickness was contoured manually on the basis of information provided in the dataset ds507_regolith_data. (3) ds507_regthick_grid: This dataset consists of raster-based generalized thickness of regolith overlying bedrock in the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. Regolith thickness in this dataset was derived from contours presented in the dataset ds507_regthick_contours. (4) ds507_welltest_data: This point dataset contains estimates of aquifer transmissivity and hydraulic conductivity at selected well locations in the Lost Creek Designated Ground Water Basin, Weld, Adams, and

  8. Carnosic acid suppresses the production of amyloid-β 1-42 and 1-43 by inducing an α-secretase TACE/ADAM17 in U373MG human astrocytoma cells.

    PubMed

    Yoshida, Hidemi; Meng, Pengfei; Matsumiya, Tomoh; Tanji, Kunikazu; Hayakari, Ryo; Xing, Fei; Wang, Liang; Tsuruga, Kazushi; Tanaka, Hiroshi; Mimura, Junsei; Kosaka, Kunio; Itoh, Ken; Takahashi, Ippei; Imaizumi, Tadaatsu

    2014-02-01

    Amyloid beta (Aβ) peptides are key molecules in the pathogenesis of Alzheimer's disease (AD). The sequential cleavage of amyloid precursor protein (APP) by the β- and γ-secretases generates Aβ peptides; however, the alternate cleavage of APP by the α- and γ-secretases decreases Aβ production. We previously reported that carnosic acid (CA), a phenolic diterpene compound found in the labiate herbs rosemary and sage, suppresses Aβ (1-40 and 1-42) production by activating α-secretase in cultured SH-SY5Y human neuroblastoma cells (Neurosci. Res. 2013; 75: 94-102). Here, we investigated the effect of CA on the production of Aβ peptides (1-40, 1-42 and 1-43) in U373MG human astrocytoma cells. The treatment of cells with CA suppressed Aβ40/42/43 release (55-71% decrease at 50μM). CA treatment enhanced the mRNA expressions of an α-secretase TACE (tumor necrosis factor-α-converting enzyme, also called a disintegrin and metalloproteinase-17, ADAM17); however, the β-secretase BACE1 (β-site APP-cleaving enzyme-1) was not increased by CA. Knockdown of TACE by siRNA reduced soluble-APPα release enhanced by CA and partially recovered the CA-suppressed Aβ40/42/43 release. These results suggest that CA reduces Aβ production, at least partially, by activating TACE in human astroglial cells. The use of CA may have a potential in the prevention of Aβ-mediated diseases. PMID:24295810

  9. Adaptation of the South-West Wing of Collegium Chemicum of Adam Mickiewicz University in Poznań for Storage Facilities/ Adaptacja Południowo-Zachodniego Skrzydła Budynku Collegium Chemicum Uam W Poznaniu Na Cele Magazynowe

    NASA Astrophysics Data System (ADS)

    Ścigałło, Jacek

    2015-06-01

    The article refers to the problems of adaptation of Collegium Chemicum facilities belonging to Adam Mickiewicz Uniwersity in Poznań to its storage needs. The subject building is situated in Grunwaldzka Street in Poznań. In the introduction part, the building and its structural solutions are described. The results of the materials research and the measurements of the used reinforcement have been presented. The structure diagnostic analyses were performed basing on measurements and research. The analysis allowed the determination of the limit loads. The results of the performed analysis of the current state turned out to be unsatisfactory, not only in terms of the planned storage load but also in terms of the current load state, as was shown by the construction analysis. W pracy przedstawiono problemy związane z adaptacją budynku dydaktycznego Collegium Chemicum przy ul. Grunwaldzkiej w Poznaniu na cele magazynowe Biblioteki Głównej UAM. Na wstępie opisano badany budynek oraz scharakteryzowano zastosowane w nim rozwiązania konstrukcyjne. Przedstawiono wyniki wykonanych badań materiałowych oraz pomiarów inwentaryzacyjnych zastosowanego zbrojenia. Na podstawie wykonanych pomiarów i badań przeprowadzono analizę diagnostyczną konstrukcji, która pozwoliła na wyznaczenie dopuszczalnych wartości obciążeń powierzchni stropowych. Wyniki wykonanej analizy konstrukcji w stanie istniejącym okazały się dalece niezadowalające nie tylko z punktu widzenia planowanych, znacznych obciążeń magazynowych. Analiza wykazała bowiem, że konstrukcja jest już znacznie przeciążona w aktualnym stanie jej obciążenia

  10. Genetics Home Reference: Adams-Oliver syndrome

    MedlinePlus

    ... scalp, and skull AOS aplasia cutis congenita with terminal transverse limb defects congenital scalp defects with distal ... of clinical phenotypes in aplasia cutis congenita and terminal transverse limb defects. Am J Med Genet A. ...

  11. 'Helen Taft' and 'Abigail Adams' flowering cherries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The U.S. National Arboretum has an ongoing breeding program aimed at broadening the genetic base of ornamental cherry trees (Prunus species) by developing new cultivars with disease and pest resistance, tolerance to environmental stresses, and superior ornamental characteristics. This report documen...

  12. ADAM-M Data and Information

    Atmospheric Science Data Center

    2013-05-30

    ... Information Creating a Unified Airborne Database for Assessment and Validation of Global Models of Atmospheric ...  (3)  To generate a standardized in-situ observational database with best possible matching temporal and spatial scales to model ...

  13. Adam Walsh Reauthorization Act of 2012

    THOMAS, 112th Congress

    Rep. Sensenbrenner, F. James, Jr. [R-WI-5

    2012-01-19

    08/02/2012 Received in the Senate and Read twice and referred to the Committee on the Judiciary. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  14. Adam Smith in the Mathematics Classroom

    ERIC Educational Resources Information Center

    Lipsey, Sally I.

    1975-01-01

    The author describes a series of current economic ideas and situations which can be used in the mathematics classroom to illustrate the use of signed numbers, the coordinate system, univariate and multivariate functions, linear programing, and variation. (SD)

  15. Personnel Training at Adams High School.

    ERIC Educational Resources Information Center

    Parker, John L.

    A proposed clinical training program for secondary school personnel was based on the principles of job regeneration through curriculum study and research, interprofessional training, and individual career advancement. Early and increasing delegation of instructional tasks and close supervision of both peers and superordinates are provided to…

  16. Karl Marx vs. Adam Smith Revisited

    ERIC Educational Resources Information Center

    Manton, Edgar J.; English, Donald E.; Flanagan, Jennifer; Dubey, Anvit

    2013-01-01

    The purpose of this study was to determine whether the ability of freshman college students to identify the founding fathers of free enterprise and of communism has improved. This study is a follow-up to four previous studies. A questionnaire was developed and distributed to College of Business and College of Education & Human Services…

  17. Economic Heritage: Adam Smith vs. Karl Marx

    ERIC Educational Resources Information Center

    Manton, Edgar J.; English, Donald E.

    2008-01-01

    The problem of this study was to determine the number of first semester college freshmen who could correctly identify the individuals who are generally considered the "fathers" of communism and capitalism. A questionnaire was administered to 241 freshmen students enrolled in English 101, College Reading and Writing, at Texas A&M…

  18. Adams, John Couch (1819-92)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Born in Laneast, Cornwall, England, he became fellow and mathematical tutor at Cambridge. He developed a procedure for numerical integration of differential equations and, inspired by MARY SOMERVILLE, he deduced mathematically the existence and location of the planet Neptune from its perturbations on the planet Uranus. Neptune was discovered by JOHANN GALLE in Berlin, in September 1846, using URB...

  19. Mike Fuller Receives 2012 John Adam Fleming Medal: Response

    NASA Astrophysics Data System (ADS)

    Fuller, Mike

    2013-01-01

    Thank you, Chris and Subir, for nominating me for the Fleming Medal and for your very kind comments on my research. In looking back over the medalists since 1962, it is hard to believe that I could be lucky enough to join such distinguished company. Yet, I have been very lucky through life. First, I was lucky to go to Christ's Hospital and Cambridge University. Second, my Aunt Marjorie married a physicist, Johnnie Clegg, who was an excellent teacher and inspiration for me. Third, to be born in England in the mid-1930s was to be a member of a fortunate generation of scientists. Providing one safely negotiated World War II, one joined the academic world at a time of great excitement, of expansion, and support for science.

  20. World History: Need It Be from Adam to Atom?

    ERIC Educational Resources Information Center

    Monahan, Dan

    1976-01-01

    Upon rejecting traditional world history curricula, which include all chronological developments from cave dweller to 20th century, a course is suggested to study significant patterns of government, economics, revolution, war, major religions, geography, scientific advancement, education, and rise and fall of civilizations. (Author/AV)

  1. Spiro K. Antiochos Receives 2013 John Adam Fleming Medal: Response

    NASA Astrophysics Data System (ADS)

    Antiochos, Spiro K.

    2014-01-01

    Thank you, Jim Klimchuk, for this far too generous citation, and thank you very much, my AGU colleagues, for honoring me with the Fleming Medal. When I consider the list of excellent scientists who have been awarded the Fleming Medal, I am humbled that you have included me in their company. I am especially proud that this award is from AGU because only later in my career did I change my science focus and join AGU. This was the best professional decision I have ever made. As a result, I have met many wonderful colleagues. I've always loved doing research, but my colleagues in AGU have made it so much more enjoyable. Also, moving to AGU gave me the opportunity to participate in truly exciting science. My present position is that of senior scientist for space weather at NASA Goddard. It is interesting to note that the field of space weather science did not even exist when I started my career. I was very fortunate to be part of the beginning of a new field and, as a result, to be able to participate in the explosive advances of space weather science over the past 2 decades.

  2. The Marriage of Alma Mater to Adam Smith.

    ERIC Educational Resources Information Center

    Buescher, John B.

    1987-01-01

    Businesses and universities must be encouraged to act from their traditional positions of strength, based on the longest view and the broadest interests. They must examine carefully their potential sources of conflict as well as opportunities for benefit before engaging in alliances that may become complex and difficult to manage. (MSE)

  3. Adam's Escape: Children and the Discordant Nature of Colonial Conversions

    ERIC Educational Resources Information Center

    Vallgarda, Karen A. A.

    2011-01-01

    The article traces the fundamental incoherency that structured the Danish Missionary Society's work at a boarding school for low-caste "heathen" children in South India in the 1860s and 1870s. Through elaborate disciplinary methods, the missionaries set out to Christianize and civilize the Indian children's morality, social behaviour and bodily…

  4. Geologic map of the Mount Adams Quadrangle, Washington

    SciTech Connect

    Korosec, M.A.

    1987-01-01

    This report is comprised of a 1:100,000 scale geologic map and accompanying text. The text consists of unit descriptions, a table of age dates, a table of major element geochemistry, correlation diagram, and a source of mapping diagram. (ACR)

  5. DETECTION OF K-RAS AND P53 MUTATIONS IN SPUTUM SAMPLES OF LUNG CANCER PATIENTS USING LASER CAPTURE MICRODISSECTION MICROSCOPE AND MUTATION ANALYSIS

    EPA Science Inventory

    Detection of K-ras and p53 Mutations in Sputum Samples of Lung Cancer Patients Using Laser Capture Microdissection Microscope and Mutation Analysis

    Phouthone Keohavong a,*, Wei-Min Gao a, Kui-Cheng Zheng a, Hussam Mady b, Qing Lan c, Mona Melhem b, and Judy Mumford d.
    <...

  6. Evaluation of School Uniform Policy at John Adams and Truman Middle Schools for Albuquerque Public Schools.

    ERIC Educational Resources Information Center

    Elder, Deborah L.

    A uniform policy at two Albuquerque middle schools became a reality as a result of parent initiative. Parents provided input through attending meetings and a fashion show, serving on the uniform task force, completing surveys, voting, and revisiting the policy. Parents not only initiated the development of the policy, but were active participants…

  7. 75 FR 81641 - Odessa Subarea Special Study; Adams, Franklin, Grant, and Lincoln Counties, WA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-28

    ... was originally scheduled to end on December 31, 2010 (75 FR 65503). DATES: Written or e-mailed... Main Street, Warden WA 98857. Washington State Library, 6880 Capitol Boulevard South, Olympia, WA...

  8. Contradicting Mainstream Reform Rhetoric: Interview with Richard P. McAdams.

    ERIC Educational Resources Information Center

    English, Fenwick W.

    1993-01-01

    Compared to Germany, Japan, and Denmark, U.S. fails its students by neglecting basic health and welfare needs, permitting inequitable school funding system, and perpetuating cultural ethos that undermines serious academic achievement. Teachers are not to blame. Factors influencing underachievement are low parent expectations and standards, local…

  9. VizieR Online Data Catalog: Emission-line galaxies from HETDEX pilot survey (Adams+, 2011)

    NASA Astrophysics Data System (ADS)

    Adams, J. J.; Blanc, G. A.; Hill, G. J.; Gebhardt, K.; Drory, N.; Hao, L.; Bender, R.; Byun, J.; Ciardullo, R.; Cornell, M. E.; Finkelstein, S. L.; Fry, A.; Gawiser, E.; Gronwall, C.; Hopp, U.; Jeong, D.; Kelz, A.; Kelzenberg, R.; Komatsu, E.; MacQueen, P. J.; Murphy, J.; Odoms, P. S.; Roth, M.; Schneider, D. P.; Tufts, J. R.; Wilkinson, C. P.

    2011-03-01

    We obtained regular fall/winter/spring dark time observations from 2007 September to 2010 February on the McDonald 2.7m Harlan J. Smith telescope with the Visible Integral-field Replicable Unit Spectrograph Prototype (VIRUS-P). (3 data files).

  10. From Adam Smith to Ronald Reagan: Public Libraries as a Public Good.

    ERIC Educational Resources Information Center

    Braverman, Miriam

    1982-01-01

    Contrasts the arguments of economists who measure the value of library services to society by business standards with the criteria of "the public good" which predominated during the development of public libraries and argues that libraries must continue to serve the whole community. Twenty references are cited. (RAA)

  11. 77 FR 2992 - Columbia National Wildlife Refuge, Adams and Grant Counties, WA; Final Comprehensive Conservation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-20

    ... process for Columbia NWR. We started this process through a notice in the Federal Register (74 FR 25576... notice of availability in the Federal Register (76 FR 45600; July 29, 2011). We announce our CCP decision... solicited comments on the draft CCP/EA for the refuge from July 29, 2011, to August 29, 2011 (76 FR...

  12. Epidemiology and risk factors of amniotic band syndrome, or ADAM sequence

    PubMed Central

    Cignini, Pietro; Giorlandino, Claudio; Padula, Francesco; Dugo, Nella; Cafà, Ester Valentina; Spata, Anna

    2012-01-01

    Summary Amniotic band sequence (ABS) is the term applied to a wide range of congenital anomalies, most typically limb and digital amputations and constriction rings, that occur in association with fibrous bands (1). These alterations may be associated or not with cutaneous and visceral abnormalities. This work, which is a literature review, examines several studies that relate to cases of amniotic band syndrome (SBA). In particular, our attention was focused on the causes and pathogenesis of the SBA. These for the most part are still unknown, but from what we observe in different jobs, are due to a mechanism of vascular damage. Therefore in this paper we examine chemical risk factors, like smoking, drug use, maternal hyperglycemia, mechanical risk factors such as the puncture of the amniotic sac after amniocentesis. We also speak of the altitude as a risk factor related to blood pressure, of the increased incidence of disease in primigravid, in women with a low level of education, in which the pregnancy was not planned, and then we talk of a higher incidence in young fathers and of the role of familiarity. PMID:23272276

  13. Adam Smith's Pins, Sausage Making and the Funding of College Education

    ERIC Educational Resources Information Center

    Barrett, Ralph V.

    2005-01-01

    Using the language and concepts of economic markets for the purpose of describing and evaluating the function and performance of educational institutions has been a common and growing practice throughout Western industrial societies for many years. The critique of such market analysis also has a long history. Critical assessments of market theory…

  14. Post-KR Delay Intervals and Mental Practice: A Test of Adams' Closed Loop Theory

    ERIC Educational Resources Information Center

    Bole, Ronald

    1976-01-01

    The present study suggests that post-KR delay interval time or activity in the interval has little to do with learning on a self-paced positioning task, not ruling out that on ballistic tasks or more complex nonballistic tasks that a learner could make use of additional time or strategy. (MB)

  15. 75 FR 51519 - Regional Transportation District-Acquisition Exemption-Union Pacific Railroad Company in Adams...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-20

    ... Surface Transportation Board Regional Transportation District--Acquisition Exemption--Union Pacific... Denver, to milepost 6.50 in Jefferson County, Colo. (the Gold Line Segment).\\2\\ RTD states that, on both... Gold Line Segment, UP will retain the tracks on which it currently operates. RTD also states that...

  16. An Analysis of the Doctor-Patient Relationship Using "Patch Adams"

    ERIC Educational Resources Information Center

    Pettit, Michelle L.

    2008-01-01

    Navigating the contemporary health care system represents an arduous challenge for consumers. In response to this challenge, health educators should prepare informed and skilled consumers to assume active roles in their health care. Through active participation in health care decisions, consumers can maximize the quality and duration of…

  17. Some Reasons for Studying Gesture and Second Language Acquisition (Hommage a Adam Kendon)

    ERIC Educational Resources Information Center

    Gullberg, Marianne

    2006-01-01

    This paper outlines some reasons for why gestures are relevant to the study of SLA. First, given cross-cultural and cross-linguistic gestural repertoires, gestures can be treated as part of what learners can acquire in a target language. Gestures can therefore be studied as a developing system in their own right both in L2 production and…

  18. Neo-classical theory of competition or Adam Smith's hand as mathematized ideology

    NASA Astrophysics Data System (ADS)

    McCauley, Joseph L.

    2001-10-01

    Orthodox economic theory (utility maximization, rational agents, efficient markets in equilibrium) is based on arbitrarily postulated, nonempiric notions. The disagreement between economic reality and a key feature of neo-classical economic theory was criticized empirically by Osborne. I show that the orthodox theory is internally self-inconsistent for the very reason suggested by Osborne: lack of invertibility of demand and supply as functions of price to obtain price as functions of supply and demand. The reason for the noninvertibililty arises from nonintegrable excess demand dynamics, a feature of their theory completely ignored by economists.

  19. From the Adam Smith Institute to the Zapatistas: An Internet Gateway to all Development Knowledge.

    ERIC Educational Resources Information Center

    Wilks, Alex

    2002-01-01

    Examines the World Bank Internet initiative, the Development Gateway. Describes the importance of the Bank as a knowledge bank and the threats posed by the Internet to its near monopoly of development thinking. Argues that the initiative reveals biases and misunderstandings in the World Bank's approach to knowledge for development. (CAJ)

  20. Learner Control and Error Correction in ICALL: Browsers, Peekers, and Adamants.

    ERIC Educational Resources Information Center

    Heift, Trude

    2002-01-01

    Reports a study on the impact of learner control on the error correction process within a web-based Intelligent Language Tutoring System (ILTS). During three 1-hour grammar practice sessions, 33 students used an ILTS for German that provided error-specific and individualized feedback. Results indicate the majority of students (85%) sought to…

  1. 76 FR 45600 - Columbia National Wildlife Refuge, Adams and Grant Counties, WA; Draft Comprehensive Conservation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-29

    ... process by publishing a notice of intent in the Federal Register (74 FR 25576) on May 28, 2009. The Refuge... publishing a notice of intent in the Federal Register (74 FR 25576) on May 28, 2009, announcing our intention... Washington Department of Fish and Wildlife, develop volunteer opportunities, and make restoration of...

  2. Leaf surface chemicals fromNicotiana affecting germination ofPeronospora tabacina (adam) sporangia.

    PubMed

    Kennedy, B S; Nielsen, M T; Severson, R F; Sisson, V A; Stephenson, M K; Jackson, D M

    1992-09-01

    A bioassay was used to evaluate the effects of cuticular leaf components, isolated fromN. tabacum, N. glutinosa (accessions 24 and 24a), and 23other Nicotiana species, on germinationof P. tabacina (blue mold). The leaf surface compounds includedα- andβ-4,8,13,-duvatriene-l,3-diols (DVT-diols), (13-E)-labda-13-ene-8α-,15-diol (labdenediol), (12-Z)-labda-12,14-diene-8α-ol (cis-abienol), (13-R)-labda-8,14-diene-13-ol (manool), 2-hydroxymanool, a mixture of (13-R)-labda-14-ene-8α,13-diol (sclareol), and (13-S)-labda-14-ene-8α,13-diol (episclareol), and various glucose and/or sucrose ester isolates. The above in acetone were applied onto leaf disks of the blue moldsusceptibleN. tabacum cv. TI 1406, which was then inoculated with blue mold sporangia. Estimated IC50 values (inhibitory concentration) were 3.0μg/cm(2) forα-DVT-diol, 2.9μ/cm(2) forβ-DVT-diol, 0.4μg/cm(2) for labdenediol and 4.7μg/cm(2) for the sclareol mixture. Manool, 2-hydroxymanool, andcis-abienol at application rates up to 30μg/cm(2) had little or no effect on sporangium germination. Glucose and/or sucrose ester isolates from the cuticular leaf extracts of 23Nicotiana species and three different fractions fromN. bigelovii were also evaluated for antimicrobial activity at a concentration of 30μg/cm(2). Germination was inhibited by >20% when exposed to sugar esters isolated fromN. acuminata, N. benthamiana, N. attenuata, N. clevelandii, andN. miersii, and accessions 10 and 12 ofN. bigelovii. These results imply that a number of compounds may influence resistance to blue mold in tobacco. PMID:24254279

  3. "Adam Smith Meets Walt Disney": School Image on the World Wide Web

    ERIC Educational Resources Information Center

    Smith, Alison

    2007-01-01

    This article describes a small-scale research project undertaken as part of the coursework in a Doctor of Education programme. The project investigated the organisational images or identities portrayed by ten secondary schools in Auckland, New Zealand on their school websites. The recent proliferation of school websites has provided schools with a…

  4. 77 FR 75207 - The Adams Express Company and Petroleum & Resources Corporation; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    ... permit certain registered closed-end investment companies to make periodic distributions of long-term... permit a Fund to provide its common shareholders with periodic distributions as nearly equal as... to understand that their periodic distributions are not tied to the Fund's net investment...

  5. The Development of a Practical and Reliable Assessment Measure for Atopic Dermatitis (ADAM).

    ERIC Educational Resources Information Center

    Charman, Denise; Varigos, George; Horne, David J. de L.; Oberklaid, Frank

    1999-01-01

    A study was conducted in Australia to develop a reliable, valid, and practical measure of atopic dermatitis. The test development process and validity evaluation with two doctors and 51 patients are discussed. Results suggest that operational definitions of the scales need to be defined more clearly. The measure satisfies assumptions for a partial…

  6. Grades of Severity and the Validation of an Atopic Dermatitis Assessment Measure (ADAM).

    ERIC Educational Resources Information Center

    Charman, Denise P.; Varigos, George A.

    1999-01-01

    Studied the validity of the Atopic Dermatitis Assessment Measure (D. Charman and others, 1999) with 171 pediatric patients in Australia using partial credit analyses to produce clinically relevant "word pictures" of grades of severity for atopic dermatitis. Discusses implications for measurement in medicine. (SLD)

  7. Accelerators and Superconductivity: A Marriage of Convenience. Second John Adams Memorial Lecture

    NASA Astrophysics Data System (ADS)

    Wilson, Martin

    1987-06-01

    This lecture deals with the relationship between accelerator technology in high-energy-physics laboratories and the development of superconductors. It concentrates on synchrotron magnets, showing how their special requirements have brought about significant advances in the technology, particularly the development of filamentary superconducting composites. Such developments have made large superconducting accelerators an actuality: the Tevatron in routine operation, the Hadron Electron Ring Accelerator (HERA) under construction, and the Superconducting Super Collider (SSC) and Large Hadron Collider (LHC) at the conceptual design stage. Other applications of superconductivity have also been facilitated - for example medical imaging and small accelerators for industrial and medical use.

  8. A Beacon of Light: Tougaloo during the Presidency of Dr. Adam Daniel Beittel (1960-1964)

    ERIC Educational Resources Information Center

    Speed, John Gregory

    2014-01-01

    This study examines leadership efforts that supported the civil rights movements that came from administrators and professors, students and staff at Tougaloo College between 1960 and 1964. A review of literature reveals that little has been written about the college's role in the Civil Rights Movement during this time. Thus, one goal of this study…

  9. To extend the legislative authority of the Adams Memorial Foundation to establish a commemorative work in honor of former President John Adams and his legacy, and for other purposes.

    THOMAS, 113th Congress

    Rep. Lynch, Stephen F. [D-MA-8

    2013-12-19

    07/23/2014 Received in the Senate and Read twice and referred to the Committee on Energy and Natural Resources. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  10. A bill to provide for an extension of the legislative authority of the Adams Memorial Foundation to establish a commemorative work in honor of former President John Adams and his legacy.

    THOMAS, 113th Congress

    Sen. Markey, Edward J. [D-MA

    2013-12-19

    07/23/2014 Committee on Energy and Natural Resources Senate Subcommittee on National Parks. Hearings held. With printed Hearing: S.Hrg. 113-493. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  11. The influence of emerging administrative scientists: an interview with Dr Maja Djukic. Interview by Jeffrey M. Adams.

    PubMed

    Djukic, Maja

    2014-01-01

    This department highlights emerging nursing leaders and scientists who have demonstrated great promise and findings in advancing innovation and patient care leadership in practice, policy, research, education and theory. This interview profiles Maja Djukic, PhD, RN, assistant professor, New York University College of Nursing. PMID:24316612

  12. A cybertaxonomic revision of the micro-landsnail genus Plectostoma Adam (Mollusca, Caenogastropoda, Diplommatinidae), from Peninsular Malaysia, Sumatra and Indochina.

    PubMed

    Liew, Thor-Seng; Vermeulen, Jaap Jan; Marzuki, Mohammad Effendi Bin; Schilthuizen, Menno

    2014-01-01

    Plectostoma is a micro land snail restricted to limestone outcrops in Southeast Asia. Plectostoma was previously classified as a subgenus of Opisthostoma because of the deviation from regular coiling in many species in both taxa. This paper is the first of a two-part revision of the genus Plectostoma, and includes all non-Borneo species. In the present paper, we examined 214 collection samples of 31 species, and obtained 62 references, 290 pictures, and 155 3D-models of 29 Plectostoma species and 51 COI sequences of 19 species. To work with such a variety of taxonomic data, and then to represent it in an integrated, scaleable and accessible manner, we adopted up-to-date cybertaxonomic tools. All the taxonomic information, such as references, classification, species descriptions, specimen images, genetic data, and distribution data, were tagged and linked with cyber tools and web servers (e.g. Lifedesks, Google Earth, and Barcoding of Life Database). We elevated Plectostoma from subgenus to genus level based on morphological, ecological and genetic evidence. We revised the existing 21 Plectostoma species and described 10 new species, namely, P. dindingensis sp. n., P. mengaburensis sp. n., P. whitteni sp. n., P. kayiani sp. n., P. davisoni sp. n., P. relauensis sp. n., P. kubuensis sp. n., P. tohchinyawi sp. n., P. tenggekensis sp. n., and P. ikanensis sp. n. All the synthesised, semantic-tagged, and linked taxonomic information is made freely and publicly available online. PMID:24715783

  13. Coal geology of the Bowman-Gascoyne area, Adams, Billings, Bowman, Golden Valley, and Slope counties, North Dakota

    USGS Publications Warehouse

    Lewis, Robert C.

    1979-01-01

    The Bowrnan-Gascoyne area is located in southwestern North Dakota. It is situated on the southwestern edge of the Williston structural basin and the northeastern flank of the Cedar Creek anticline. Strata of the Fort Union Formation (Paleocene), consisting of nonmarine claystone, sandstone, and lignite, dip to the northeast 25-50 ft/mi. Seven correlatable coal beds of varying thicknesses and areal dimensions occur in the area. The thickest and most persistent of these beds is the Harmon bed which attains a maximum thickness of 38 ft in T. 134 N., Rs. 101 and 102 W. Analyses show a heating value of 5,915-6,680 Btu/lb and a sulfur content of 0.6-1.4 percent. Two areas of high-coal-development potential are located near Gascoyne and Amidon. The Harmon bed in these two areas contains a total of 740,000,000 and 650,000,000 tons, respectively, and is under less than 150 ft of overburden.

  14. 78 FR 37791 - In the Matter of: Jose Guadalupe Reyes-Martinez, Inmate Number #85993-279, CI Adams County...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ... by successive Presidential Notices, the most recent being that of August 15, 2012 (77 FR 49699... Bureau of Industry and Security In the Matter of: Jose Guadalupe Reyes-Martinez, Inmate Number 85993-279...-Martinez (``Reyes-Martinez'') was convicted of violating Section 38 of the Arms Export Control Act (22...

  15. 77 FR 64847 - Union Pacific Railroad Company-Abandonment Exemption-in Adams, Weld and Boulder Counties, Colo.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-23

    ... been sold and incorporated into the RTD mass transit system. Therefore, no such requests will be... District (RTD) in June 2009.\\2\\ UP states that the line has been incorporated into the master plan for RTD... operating easement over the entire Lead, and that RTD assumed no common carrier obligation with regard...

  16. What Would Adam Smith Have on His iPod? Uses of Music in Teaching the History of Economic Thought

    ERIC Educational Resources Information Center

    Van Horn, Robert; Van Horn, Monica

    2013-01-01

    In this article, the authors examine two ways that they use music (i.e., popular song lyrics) as an active learning technique in an undergraduate history of economic thought course. First, they use music to help students grasp the ideas of the great thinkers in economics and see their relevance today. Second, because they require students to read…

  17. Hydrogeology and simulation of ground-water flow at the Gettysburg Elevator Plant Superfund Site, Adams County, Pennsylvania

    USGS Publications Warehouse

    Low, Dennis J.; Goode, Daniel J.; Risser, Dennis W.

    2000-01-01

    Ground water in Triassic-age sedimentary fractured-rock aquifers in the area of Gettysburg, Pa., is used as drinking water and for industrial and commercial supply. In 1983, ground water at the Gettysburg Elevator Plant was found by the Pennsylvania Department of Environmental Resources to be contaminated with trichloroethene, 1,1,1-trichloroethane, and other synthetic organic compounds. As part of the U.S. Environmental Protection Agency?s Comprehensive Environmental Response, Compensation, and Liability Act, 1980 process, a Remedial Investigation was completed in July 1991, a method of site remediation was issued in the Record of Decision dated June 1992, and a Final Design Report was completed in May 1997. In cooperation with the U.S. Environmental Protection Agency in the hydrogeologic assessment of the site remediation, the U.S. Geological Survey began a study in 1997 to determine the effects of the onsite and offsite extraction wells on ground-water flow and contaminant migration from the Gettysburg Elevator Plant. This determination is based on hydrologic and geophysical data collected from 1991 to 1998 and on results of numerical model simulations of the local ground-water flow-system. The Gettysburg Elevator Site is underlain by red, green, gray, and black shales of the Heidlersburg Member of the Gettysburg Formation. Correlation of natural-gamma logs indicates the sedimentary rock strike about N. 23 degrees E. and dip about 23 degrees NW. Depth to bedrock onsite commonly is about 6 feet but offsite may be as deep as 40 feet. The ground-water system consists of two zones?a thin, shallow zone composed of soil, clay, and highly weathered bedrock and a thicker, nonweathered or fractured bedrock zone. The shallow zone overlies the bedrock zone and truncates the dipping beds parallel to land surface. Diabase dikes are barriers to ground-water flow in the bedrock zone. The ground-water system is generally confined or semi-confined, even at shallow depths. Depth to water can range from flowing at land surface to more than 71 feet below land surface. Potentiometric maps based on measured water levels at the Gettysburg Elevator Plant indicate ground water flows from west to east, towards Rock Creek. Multiple-well aquifer tests indicate the system is heterogeneous and flow is primarily in dipping beds that contain discrete secondary openings separated by less permeable beds. Water levels in wells open to the pumped bed, as projected along the dipping stratigraphy, are drawn down more than water levels in wells not open to the pumped bed. Ground-water flow was simulated for steady-state conditions prior to pumping and long-term average pumping conditions. The three-dimensional numerical flow model (MODFLOW) was calibrated by use of a parameter estimation program (MODFLOWP). Steady-state conditions were assumed for the calibration period of 1996. An effective areal recharge rate of 7 inches was used in model calibration. The calibrated flow model was used to evaluate the effectiveness of the current onsite and offsite extraction well system. The simulation results generally indicate that the extraction system effectively captures much of the ground-water recharge at the Gettysburg Elevator Plant and, hence, contaminated ground-water migrating from the site. Some of the extraction wells pump at low rates and have very small contributing areas. Results indicate some areal recharge onsite will move to offsite extraction wells.

  18. Computation and visualization of the MacAdam limits for any lightness, hue angle, and light source

    NASA Astrophysics Data System (ADS)

    Martínez-Verdú, Francisco; Perales, Esther; Chorro, Elisabet; de Fez, Dolores; Viqueira, Valentín; Gilabert, Eduardo

    2007-06-01

    We present a systematic algorithm capable of searching for optimal colors for any lightness L* (between 0 and 100), any illuminant (D65, F2, F7, F11, etc.), and any light source reported by CIE. Color solids are graphed in some color spaces (CIELAB, SVF, DIN99d, and CIECAM02) by horizontal (constant lightness) and transversal (constant hue angle) sections. Color solids plotted in DIN99d and CIECAM02 color spaces look more spherical or homogeneous than the ones plotted in CIELAB and SVF color spaces. Depending on the spectrum of the light source or illuminant, the shape of its color solid and its content (variety of distinguishable colors, with or without color correspondence) change drastically, particularly with sources whose spectrum is discontinuous and/or very peaked, with correlated color temperature lower than 5500 K. This could be used to propose an absolute colorimetric quality index for light sources comparing the volumes of their gamuts, in a uniform color space.

  19. Pathologic survey on the Manila clam Ruditapes philippinarum (Adams and Reeve 1850) from Haeju off the western coastal Yellow Sea

    NASA Astrophysics Data System (ADS)

    Yang, Hyun-Sung; Park, Kwang-Jae; Choi, Kwang-Sik

    2010-06-01

    Pathologic condition of Manila clam, Ruditapes philippinarum collected from Haeju off the west coast of North Korea in February and March 2007 was investigated in this study. The diagnostics included a protozoan parasite, Perkinsus olseni, the brown ring disease (BRD) caused by bacteria Vibrio tapetis and metazoan parasites Trematod and Cestod. P. olseni infection was examined using histology and Ray’s fluid thioglycollate medium (RFTM) assay along with Choi’s NaOH digestion technique. Trematode and cestode infection was also examined from the histology. A total of 140 clams with 35-45 mm in shell length (2-3 years old) were analyzed. Condition factor (CF), a ratio of the wet tissue weight to the shell dry weight, ranged from 0.445±0.074 (February) to 0.544±0.132 (March). Total body burden of P. olseni (i.e. infection intensity) ranged from 18,644±37,755 (February) to 26,933±80,611 cells/g wet tissue (March) with the prevalence of 76.7-43.3% (March) respectively. Prevalence of trematode and cestode infection in February and March varied 22.5-25.0 and 15.0-22.5% respectively. Infection intensity of V. tapetis ranged 1-2 and the prevalence was 1.4 (February) and 5.7% (March). Prevalence and infection intensity of P. olseni in clams from Haeju was comparatively lower than those of clams reported on the west coast of Korea. BRD and the other metazoan parasite infection were also relatively lower or similar to the condition of the clams reported previously. CF of Haeju clams was also relatively higher than the clams in Gyeonggi Bay and Taean, suggesting that Haeju clams had relatively better pathologic and health condition.

  20. A cybertaxonomic revision of the micro-landsnail genus Plectostoma Adam (Mollusca, Caenogastropoda, Diplommatinidae), from Peninsular Malaysia, Sumatra and Indochina

    PubMed Central

    Liew, Thor-Seng; Vermeulen, Jaap Jan; Marzuki, Mohammad Effendi bin; Schilthuizen, Menno

    2014-01-01

    Abstract Plectostoma is a micro land snail restricted to limestone outcrops in Southeast Asia. Plectostoma was previously classified as a subgenus of Opisthostoma because of the deviation from regular coiling in many species in both taxa. This paper is the first of a two-part revision of the genus Plectostoma, and includes all non-Borneo species. In the present paper, we examined 214 collection samples of 31 species, and obtained 62 references, 290 pictures, and 155 3D-models of 29 Plectostoma species and 51 COI sequences of 19 species. To work with such a variety of taxonomic data, and then to represent it in an integrated, scaleable and accessible manner, we adopted up-to-date cybertaxonomic tools. All the taxonomic information, such as references, classification, species descriptions, specimen images, genetic data, and distribution data, were tagged and linked with cyber tools and web servers (e.g. Lifedesks, Google Earth, and Barcoding of Life Database). We elevated Plectostoma from subgenus to genus level based on morphological, ecological and genetic evidence. We revised the existing 21 Plectostoma species and described 10 new species, namely, P. dindingensis sp. n., P. mengaburensis sp. n., P. whitteni sp. n., P. kayiani sp. n., P. davisoni sp. n., P. relauensis sp. n., P. kubuensis sp. n., P. tohchinyawi sp. n., P. tenggekensis sp. n., and P. ikanensis sp. n. All the synthesised, semantic-tagged, and linked taxonomic information is made freely and publicly available online. PMID:24715783

  1. Association of "ADAM10" and "CAMK2A" Polymorphisms with Conduct Disorder: Evidence from Family-Based Studies

    ERIC Educational Resources Information Center

    Jian, Xue-Qiu; Wang, Ke-Sheng; Wu, Tie-Jian; Hillhouse, Joel J.; Mullersman, Jerald E.

    2011-01-01

    Twin and family studies have shown that genetic factors play a role in the development of conduct disorder (CD). The purpose of this study was to identify genetic variants associated with CD using a family-based association study. We used 4,720 single nucleotide polymorphisms (SNPs) from the Illumina Panel and 11,120 SNPs from the Affymetrix 10K…

  2. Neoliberalism, Emotional Experience in Education and Adam Smith: Reading "The Theory of Moral Sentiments" Alongside "The Wealth of Nations"

    ERIC Educational Resources Information Center

    Hanley, Christopher

    2015-01-01

    This paper examines some critical accounts of emotional life shaped by neoliberalism. A range of literature concerned with neoliberalism and emotional experience in educational contexts is reviewed. I argue that neoliberal "reforms" in public institutions create an ever-increasing demand for emotional performance. Neoliberals often refer…

  3. Bringing Adam Smith's Pin Factory to Life: Field Trips and Discussions as Forms of Experiential Learning

    ERIC Educational Resources Information Center

    Galizzi, Monica

    2014-01-01

    Educators are often aware of the need to implement a variety of teaching techniques to reach out to students with different learning styles. I describe an attempt to target multimodal learners by bringing classical economic texts and concepts to life through discussions, field visits and role playing exercises. In my Labor Economics class I…

  4. 75 FR 65503 - Odessa Subarea Special Study; Adams, Franklin, Grant, and Lincoln Counties, Washington INT-DES 10-54

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-25

    ... Subarea Special Study. The Washington Department of Ecology (Ecology) is a joint lead with Reclamation in..., Congress has funded Reclamation to investigate this problem. Ecology has partnered with Reclamation by... legislature passed the Columbia River Water Resource Management Act (HB 2860) that directs Ecology...

  5. The Moral Dignity of Inductive Method and the Reconciliation of Science and Faith in Adam Sedgwick's "Discourse"

    ERIC Educational Resources Information Center

    Bellon, Richard

    2012-01-01

    Science's inductive method required patient, humble and self-controlled behavior; Christian revelation demanded the same virtues. The discoveries of science and the truths of scripture would always harmonize as long as both men of science and men of faith conducted themselves in scrupulous accordance with their duty. So ran a central argument in…

  6. Mineral Resources of the Hells Canyon Study Area, Wallowa County, Oregon, and Idaho and Adams Counties, Idaho

    USGS Publications Warehouse

    Simmons, George C.; Gualtieri, James L.; Close, Terry J.; Federspiel, Francis E.; Leszcykowski, Andrew M.

    2007-01-01

    Field studies supporting the evaluation of the mineral potential of the Hells Canyon study area were carried out by the U.S. Geological Survey and the U.S. Bureau of Mines in 1974-76 and 1979. The study area includes (1) the Hells Canyon Wilderness; (2) parts of the Snake River, Rapid River, and West Fork Rapid River Wild and Scenic Rivers; (3) lands included in the second Roadless Area Review and Evaluation (RARE II); and (4) part of the Hells Canyon National Recreation Area. The survey is one of a series of studies to appraise the suitability of the area for inclusion in the National Wilderness Preservation System as required by the Wilderness Act of 1964. The spectacular and mineralized area covers nearly 950 mi2 (2,460 km2) in northeast Oregon and west-central Idaho at the junction of the Northern Rocky Mountains and the Columbia Plateau.

  7. "Essential noise" - enhancing variability of informational constraints benefits movement control: a comment on Waddington and Adams (2003).

    PubMed

    Davids, K; Shuttleworth, R; Button, C; Renshaw, I; Glazier, P

    2004-10-01

    This commentary proposes a dynamical systems perspective to re-interpret data from a group of international soccer players demonstrating that wearing textured insoles in soccer boots enhanced tactile information from the sole of the foot and increased movement discrimination capacity in ankle inversion sensitivity tests to levels similar to those in barefoot conditions. Theoretical arguments on the functional role of variability induced in the sensorimotor system by textured insoles, acting as a form of "essential noise" to enhance the accuracy of foot positioning are presented. It seems that, far from interfering with motor performance, variability can actually enhance perception of information to support motor performance. The addition of intermittent, intermediate levels of noise in a perceptual motor context may benefit performers by helping them to pick up information signals from background structure. Movement system variability is conceived as noise induced resonance benefiting the pick up of information to regulate behaviour. Variability can be functional in practical programmes to offset negative effects of losses in sensory sensitivity through ageing, disease, illness, or injury. PMID:15388548

  8. North Adams State College Institutional Self-Evaluation Study Report, Vol. 2. Appendix 1: Agreement Between the Board of Trustees of State Colleges and North Adams State College Association, Massachusetts; Appendix 2: Agreement Between The Board of Trustees of State Colleges and the North Adams State College Mark Hopkins Faculty Association-MTA/NEA.

    ERIC Educational Resources Information Center

    Massachusetts State Coll. System, Boston.

    The two agreements included in this document are in effect until June 30, 1976 and June 30, 1977, respectively. Articles cover: recognition and definitions, relationship between the board and the association, use of college facilities, faculty fringe benefits, statement on academic freedom, responsibilities of department chairmen, participation in…

  9. 78 FR 75376 - Entergy Operations, Inc.; Combined License Application for River Bend Unit 3, Exemption From the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-11

    ... System (ADAMS): You may access publicly available documents online in the NRC Library at http://www.nrc.gov/reading-rm/adams.html . To begin the search, select ``ADAMS Public Documents'' and then select ``Begin Web- based ADAMS Search.'' For problems with ADAMS, please contact the NRC's Public Document...

  10. 78 FR 75379 - Entergy Operations, Inc.; Combined License Application for Grand Gulf Unit 3; Exemption From the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-11

    ... System (ADAMS): You may access publicly available documents online in the NRC Library at http://www.nrc.gov/reading-rm/adams.html . To begin the search, select ``ADAMS Public Documents'' and then select ``Begin Web- based ADAMS Search.'' For problems with ADAMS, please contact the NRC's Public Document...

  11. Effects of agricultural best-management practices on the Brush Run Creek headwaters, Adams County, Pennsylvania, prior to and during nutrient management

    USGS Publications Warehouse

    Langland, M.J.; Fishel, D.K.

    1996-01-01

    The U.S. Geological Survey, in cooperation with the Susquehanna River Basin Commission and the Pennsylvania Department of Environmental Resources, investigated the effects of agricultural best-management practices on surface-water quality as part of the U.S. Environmental Protection Agency's Chesapeake Bay Program. This report characterizes a 0.63-square- mile agricultural watershed underlain by shale, mudstone, and red arkosic sandstone in the Lower Susquehanna River Basin. The water quality of the Brush Run Creek site was studied from October 1985 through September 1991, prior to and during the implementation of nutrient management designed to reduce sediment and nutrient discharges into Conewago Creek, a tributary to the Chesapeake Bay. The original study area was 0.38 square mile and included an area immediately upstream from a manure lagoon. The study area was increased to 0.63 square mile in the fall of 1987 after an extensive tile-drain network was discovered upstream and downstream from the established streamflow gage, and the farm owner made plans to spray irrigate manure to the downstream fields. Land use for about 64 percent of the 0.63 square mile watershed is cropland, 14 percent is pasture, 7 percent is forest, and the remaining 15 percent is yards, buildings, water, or gardens. About 73 percent of the cropland was used to produce corn during the study. The average annual animal population consisted of 57,000 chickens, 1,530 hogs, and 15 sheep during the study. About 59,340 pounds of nitrogen and 13,710 pounds of phosphorus were applied as manure and commercial fertilizer to fields within the subbasin during the 3-year period prior to implementation of nutrient management. During nutrient management, about 14 percent less nitrogen and 57 percent less phosphorus were applied as commercial and manure fertilizer. Precipitation totaled 209 inches, or 13 percent less than the long-term normal, during the 6-year study. Concentrations of total ammonia in precipitation were as high as 2.7 mg/L (milligrams per liter); in dry deposition the concentrations were as high as 5.4 mg/L, probably because of the ammonia that had volatilized from the manure-storage lagoon. Nitrate nitrogen in the upper 4 feet of the soil ranged from 17 to 452 pounds per acre and soluble phosphorus content ranged from 0.29 to 65 pounds per acre. The maximum concentration of total nitrogen was 2,400 mg/L on September 10, 1986, in discharge from the tile drain near the streamflow gage. Median concentrations of total nitrogen and dissolved nitrite plus nitrate in base flow at the water-quality gage were 14 mg/L and 4.4 mg/L, respectively; prior to nutrient management and during nutrient management, median concentrations were 14 mg/L and 6.2 mg/L, respectively. Significant reductions in total phosphorus and suspended-sediment concentrations occurred at the water-quality gage. The maximum concentrations of total phosphorus (160 mg/L) and suspended sediment (3,530 mg/L) were measured at a tile line above the water-quality gage. Concentrations of total nitrogen, dissolved ammonia, and total phosphorus in base flow increased during dry periods when discharges from the tile drain were not diluted. During nutrient management, only base-flow loads of suspended sediment increased. Total streamflow was about 121.8 inches. About 81 percent was storm runoff. Loads of total nitrogen, total phosphorus in stormflow, and suspended sediment increased 14, 44, and 41 percent during nutrient management, respectively. A load of about 787,780 pounds of sediment, 22,418 pounds of nitrogen, and 5,479 pounds of phosphorus was measured during 214 sampled stormflow days that represented 84 percent of the stormflow. About 812,924 pounds of sediment, 38,421 pounds of nitrogen, and 6,377 pounds of phosphorus were discharged during the 6-year study.

  12. Healing the Wounds of War and More: An Integrative Approach to Peace--The Work of Adam Curle and Others with Mir i dobro in Zupanja, Croatia.

    ERIC Educational Resources Information Center

    Mitchels, Barbara

    2003-01-01

    Examines practical implications of Curle's approach to psychological aspects of conflict and peacemaking as evidenced in the Mir i dobro project in Zupanja, taking into consideration some of the current debates concerning treatment of psychological trauma, including validity of the diagnosis of posttraumatic stress disorder and use of so-called…

  13. Women as Members of Communities. Third Grade Social Studies: Abigail Adams, Sarah Winnemucca, Helen Keller, Shirley Chisholm, March Fong Eu, [and] Carmen Delgado Votaw.

    ERIC Educational Resources Information Center

    National Women's History Project, Santa Rosa, CA.

    Part of the National Women's History Project funded to promote the study of women in history, this unit will help third grade students learn about women's contributions to U.S. society. Equity cannot be achieved until equality is expected and until the contributions of all women are understood and accepted as a simple matter of fact. The unit…

  14. Ground-water availability in part of the Borough of Carroll Valley, Adams County, Pennsylvania, and the establishment of a drought-monitor well

    USGS Publications Warehouse

    Low, Dennis J.; Conger, Randall W.

    2002-01-01

    Continued population growth in the Borough of Carroll Valley (Borough) coupled with the drought of 2001 have increased the demand for ground water in the Borough. This demand has led Borough officials to undertake an effort to evaluate the capability of the crystalline-bedrock aquifers to meet future, projected growth and to establish a drought-monitor well within and for the use of the Borough. As part of this effort, this report summarizes ground-water data available from selected sections within the Borough and provides geohydrologic information needed to evaluate ground-water availability and recharge sources within part of the Borough. The availability of ground water in the Borough is limited by the physical characteristics of the underlying bedrock, and its upland topographic setting. The crystalline rocks (metabasalt, metarhyolite, greenstone schist) that underlie most of the study area are among the lowest yielding aquifers in the Commonwealth. More than 25 percent of the wells drilled in the metabasalt, the largest bedrock aquifer in the study area, have driller reported yields less than 1.25 gallons per minute. Driller reports indicate also that water-producing zones are shallow and few in number. In general, 50 percent of the water-producing zones reported by drillers are penetrated at depths of 200 feet or less and 90 percent at depths of 370 feet or less. Borehole geophysical data indicate that most of the water-producing zones are at lithologic contacts, but such contacts are penetrated infrequently and commonly do not intersect areas of ground-water recharge. Single-well aquifer tests and slug tests indicate that the bedrock aquifers also do not readily transmit large amounts of water. The median hydraulic conductivity and transmissivity of the bedrock aquifers are 0.01 foot per dayand 2.75 feet squared per day, respectively. The crystalline and siliciclastic (Weverton and Loudoun Formations) bedrock aquifers are moderately to highly resistant to weathering, resulting in topographic highs coupled with steep, narrow valleys. This rugged topography results in extensive surface runoff, which limits infiltration and hence recharge to the shallow and deep ground-water systems. Streams that flow through the study area generally are small and ephemeral. Where perennial, the streams represent areas of ground-water discharge. Thickness of the overlying mantle (regolith or depth to bedrock) varies from 0 to more than 65 feet over short distances. In general, a thick regolith will store and transmit large quantities of water to the underlying bedrock aquifers. In the study area, however, there is no correlation between thick regolith and greater reported yields. Thus, it appears that the hydraulic connection between water-bearing fractures at depth and ground water stored in the regolith is poor, which further limits ground-water availability. Recharge to the bedrock aquifers from the approximately 46 inches of annual precipitation aver-ages about 13 inches per year, or 975 gallons per day per acre. During drought years, however, this recharge rate may average only 9 inches per year [675 gallons per day per acre]. Decreased recharge to the bedrock aquifers results in declining water levels and possibly dry wells, as well as reduced flows to streams and other surface-water bodies. Although the consumptive use of ground water by homeowners is minor (about 14 percent), the pumping of a well will change the natural flow paths of ground water and reduce the amount of water stored (at least temporarily) in the bedrock aquifers.

  15. 77 FR 38126 - In the Matter of the Designation of Abubakar Adam Kambar, Also Known as Abu Yasir, Also Known as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-26

    ... the Order who might have a constitutional presence in the United States would render ineffectual the... determination who might have a constitutional presence in the United States, because to do so would...

  16. Identification of potential water-bearing zones by the use of borehole geophysics in the vicinity of Keystone Sanitation Superfund Site, Adams County, Pennsylvania and Carroll County, Maryland

    USGS Publications Warehouse

    Conger, Randall W.

    1997-01-01

    Between April 23, 1996, and June 21, 1996, the U.S. Environmental Protection Agency contracted Haliburton-NUS, Inc., to drill four clusters of three monitoring wells near the Keystone Sanitation Superfund Site. The purpose of the wells is to allow monitoring and sampling of shallow, intermediate, and deep waterbearing zones for the purpose of determining the horizontal and vertical distribution of any contaminated ground water migrating from the Keystone Site. Twelve monitoring wells, ranging in depth from 50 to 397.9 feet below land surface, were drilled in the vicinity of the Keystone Site. The U.S. Geological Survey conducted borehole-geophysical logging and determined, with geophysical logs and other available data, the ideal intervals to be screened in each well. Geophysical logs were run on four intermediate and four deep wells, and a caliper log only was run on shallow well CL-AD-173 (HN-1S). Interpretation of geophysical logs and existing data determined the placement of screens within each borehole.

  17. Hydrogeology and steady-state numerical simulation of groundwater flow in the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado

    USGS Publications Warehouse

    Arnold, L.R.

    2010-01-01

    The Lost Creek Designated Ground Water Basin (Lost Creek basin) is an important alluvial aquifer for irrigation, public supply, and domestic water uses in northeastern Colorado. Beginning in 2005, the U.S. Geological Survey, in cooperation with the Lost Creek Ground Water Management District and the Colorado Water Conservation Board, collected hydrologic data and constructed a steady-state numerical groundwater flow model of the Lost Creek basin. The model builds upon the work of previous investigators to provide an updated tool for simulating the potential effects of various hydrologic stresses on groundwater flow and evaluating possible aquifer-management strategies. As part of model development, the thickness and extent of regolith sediments in the basin were mapped, and data were collected concerning aquifer recharge beneath native grassland, nonirrigated agricultural fields, irrigated agricultural fields, and ephemeral stream channels. The thickness and extent of regolith in the Lost Creek basin indicate the presence of a 2- to 7-mile-wide buried paleovalley that extends along the Lost Creek basin from south to north, where it joins the alluvial valley of the South Platte River valley. Regolith that fills the paleovalley is as much as about 190 ft thick. Average annual recharge from infiltration of precipitation on native grassland and nonirrigated agricultural fields was estimated by using the chloride mass-balance method to range from 0.1 to 0.6 inch, which represents about 1-4 percent of long-term average precipitation. Average annual recharge from infiltration of ephemeral streamflow was estimated by using apparent downward velocities of chloride peaks to range from 5.7 to 8.2 inches. Average annual recharge beneath irrigated agricultural fields was estimated by using passive-wick lysimeters and a water-balance approach to range from 0 to 11.3 inches, depending on irrigation method, soil type, crop type, and the net quantity of irrigation water applied. Estimated average annual recharge beneath irrigated agricultural fields represents about 0-43 percent of net irrigation. The U.S. Geological Survey modular groundwater modeling program, MODFLOW-2000, was used to develop a steady-state groundwater flow model of the Lost Creek basin. Groundwater in the basin is simulated generally to flow from the basin margins toward the center of the basin and northward along the paleovalley. The largest source of inflow to the model occurs from recharge beneath flood- and sprinkler-irrigated agricultural fields (14,510 acre-feet per year [acre-ft/yr]), which represents 39.7 percent of total simulated inflow. Other substantial sources of inflow to the model are recharge from precipitation and stream-channel infiltration in nonirrigated areas (13,810 acre-ft/yr) seepage from Olds Reservoir (4,280 acre-ft/yr), and subsurface inflow from ditches and irrigated fields outside the model domain (2,490 acre-ft/yr), which contribute 37.7, 11.7, and 6.8 percent, respectively, of total inflow. The largest outflow from the model occurs from irrigation well withdrawals (26,760 acre-ft/yr), which represent 73.2 percent of total outflow. Groundwater discharge (6,640 acre-ft/yr) at the downgradient end of the Lost Creek basin represents 18.2 percent of total outflow, and evapotranspiration (3,140 acre-ft/yr) represents about 8.6 percent of total outflow.

  18. Water-supply assessment of the Laramie-Fox Hills aquifer in parts of Adams, Boulder, Jefferson, and Weld counties, Colorado

    USGS Publications Warehouse

    Schneider, Paul A.

    1980-01-01

    Groundwater in the Laramie-Fox Hills aquifer is a potential source of supplemental municipal water supplies for the communities of Erie, Lafayette, Louisville, and Superior in Colorado. The present water supplies for these communities are not always adequate to meet current demands. The U.S. Geological Survey made a water-supply assessment of the Laramie-Fox Hills aquifer for the U.S. Bureau of Reclamation, which is investigating and evaluating alternative sources of water for the communities. Recharge to the aquifer is mostly in the western and southwestern parts of the study area. Groundwater movement is generally from the southwest to northeast. Groundwater discharge in the study area is primarily by pumping wells. Since 1961, this pumping has caused water-level declines of about 250 to 300 feet from Broomfield to east of Erie, Colorado. Generally, water levels in other parts of the area have remained the same. The aggregate sand thickness determined from well logs ranges from 42 to 360 feet and the mean thickness is 229 feet. The volume of groundwater in storage in the study area is about 5 million acre-feet. Reported yields from 93 wells ranged from 1 to 90 gallons per minute and averaged 22 gallons per minute. Well yields tended to be larger in the areas where aggregate sand thickness is the greatest. The water generally changes from a sodium calcium bicarbonate type to a sodium calcium sulfate type as it moves through the aquifer away from the recharge areas. The maximum limit established by the U.S. Environmental Protection Agency for nitrite plus nitrate in public-water supplies was exceeded in water from three wells, the maximum limit for fluoride was exceeded in water from two wells, and the maximum limit for selenium was exceeded in water from three wells. (USGS)

  19. Acute and chronic toxicity of the herbicide benzofenap (Taipan 300) to Chironomus tepperi Skuse (Diptera: Chironomidae) and Isidorella newcombi (Adams and Angas) (Gastropoda: Planorbidae).

    PubMed

    Wilson, A L; Stevens, M M; Watts, R J

    2000-02-01

    Acute and chronic toxicity tests were conducted on the herbicide benzofenap (Taipan 300) using two Australian freshwater invertebrates. The commercial formulation of benzofenap and a blank formulation containing only the adjuvants of Taipan 300 were tested against final instar larvae of the midge Chironomus tepperi and adults of the aquatic snail Isidorella newcombi. In 24-h acute bioassays the midge larvae did not show significant mortality at a nominal concentration of 1.2 mg/L active ingredient (AI), double the maximum notional concentration expected in rice fields after application of Taipan 300 at the permit rate of 2 L/ha. No significant snail mortality was recorded in acute bioassays (24-h exposure, 48-h recovery) at nominal concentrations up to 76 mg/L AI, which is over 120 times the maximum notional field concentration. In chronic assays, the pupation and emergence of C. tepperi was monitored after a 4-h pulse exposure of final instar larvae to Taipan 300 (nominal concentrations 0.001 to 0.1 mg/L AI) and adjuvant-only (0.1 mg/L equivalent) treatments. No statistically significant effects were observed, although emergence appeared to be delayed by higher benzofenap concentrations and by the adjuvant-only treatment. During snail bioassays, egg and feces production were monitored for 21 days after 24-h exposure to Taipan 300 (nominal concentrations 1.2 mg/L to 60 mg/L AI) and adjuvant-only treatments (60 mg/L equivalent). No significant chronic effects were proven against I. newcombi, despite a decline in egg mass production following exposure to all treatments and a reduction in the total numbers of eggs produced at the highest nominal concentrations tested (60 mg/L AI and adjuvant-only treatments). Similarly, feces production by snail pairs exposed to the majority of treatments declined, but these differences were not statistically significant. It is concluded that Taipan 300 does not represent a significant risk to mature C. tepperi larvae or adult I. newcombi in downstream environments when applied to rice fields at the permit rate of 2 L/ha. PMID:10629279

  20. Potassium-argon geochronology of a basalt-andesite-dacite arc system: the Mount Adams volcanic field, Cascade Range of southern Washington

    USGS Publications Warehouse

    Hildreth, W.; Lanphere, M.A.

    1994-01-01

    High-precision K-Ar dating and detailed mapping have established an eruptive chronology for a Cascade stratovolcano and its surrounding array of coeval basaltic centers. The time-volume-composition data bear upon several fundamental questions concerning the long-term behavior of arc volcanoes. -from Authors

  1. Flood-inundation maps for the Hoosic River, North Adams and Williamstown, Massachusetts, from the confluence with the North Branch Hoosic River to the Vermont State line

    USGS Publications Warehouse

    Lombard, Pamela J.; Bent, Gardner C.

    2015-01-01

    The availability of the flood-inundation maps, combined with information regarding current (near real-time) stage from USGS streamgage Hoosic River near Williamstown, and forecasted flood stages from the National Weather Service Advanced Hydrologic Prediction Service will provide emergency management personnel and residents with information that is critical for flood response activities such as evacuations and road closures, and post-flood recovery efforts. The flood-inundation maps are nonregulatory, but provide Federal, State, and local agencies and the public with estimates of the potential extent of flooding during selected peak-flow events.

  2. Large-Scale Simulation of the Effects of Climate Change on Runoff Erosion Following Extreme Wildfire Events Authors: Gould, Adam, Warren, Barber, Wagenbrenner, Robichaud, Wang, Cherkauer

    NASA Astrophysics Data System (ADS)

    Gould, G.; Adam, J. C.; Barber, M. E.; Wagenbrenner, J. W.; Robichaud, P. R.; Wang, L.; Cherkauer, K. A.

    2012-12-01

    Across the western U.S., there is clear concern for increases in wildfire occurrence, severity, and post-fire runoff erosion due to projected climate changes. The aim of this study was to advance our capability to simulate post-fire runoff erosion at scales larger than a single hillslope to examine the relative contribution of sediment being released to larger streams and rivers in response to wildfire. We applied the Variable Capacity Infiltration-Water Erosion Prediction Project (VIC-WEPP), a newly-developed physically-based modeling framework that combines large-scale hydrology with hillslope-scale runoff erosion, over the Salmon River basin (SRB) in central Idaho. We selected the SRB for this study because of recent research that suggested that forest wildfires are likely contributing the majority of coarser sands that settle in downstream navigation channels and in reservoirs, causing adverse impacts to aquatic life, navigation, and flood storage. Using the Normalized Burn Ratio (NBR), burn intensity and severity maps show the regularity of wildfire occurrence in the SRB. These maps compare pre-fire images to next growing season images from the Landsat Thematic Mapper multispectral scanning sensor. Rather than implementing WEPP over all hillslopes within the SRB, we applied a representative hillslope approach. A monofractal scaling method downscales globally available 30 arc second digital elevation model (DEM) data to a 30 m resolution for simulations. This information determined the distribution of slope gradients within each VIC grid cell. This study applied VIC-WEPP over the 1979-2010 period and compared an ensemble of future climate simulations for the period of 2041-2070. For future scenarios, we only considered meteorological impacts on post-fire erosion and did not incorporate changes in future fire occurrence or severity. We ran scenarios for a variety of land cover and soil parameter sets, particularly those that relate to pre and post-fire characteristics, such as vegetative cover, interrill and rill erodibility factors, and saturated hydraulic conductivity. Evaluation of runoff erosion at experimental sites, observed by the U.S. Forest Service, involved using Disturbed WEPP which showed reasonable first post-fire year annual erosion predictions. We evaluated VIC-WEPP by comparing sediment observations downstream of the SRB with simulated yields for both pre and post-fire conditions. Generation of maps showing erosion over the SRB for each of the scenarios show specific areas within the SRB to be high, moderate, or low runoff-induced post-fire erosion regions. Our methodology will enable forest managers in the region to incorporate the impacts of changes in meteorological events on runoff erosion into their strategic management plans.

  3. Title VI and Title IX Compliance by the Office for Civil Rights in State-Operated Special Purpose and Vocational Schools Pursuant to Adams v. Mathews.

    ERIC Educational Resources Information Center

    McClure, Phyllis

    This paper examines the compliance activities of the Office for Civil Rights (OCR) undertaken to eliminate racial and sex discrimination in special purpose schools administered by State departments of education. After reviewing background to non-enforcement of Title VI, and briefly explaining Title IX, the activities of OCR with regard to special…

  4. ADMINISTRATION OF A SUBSTITUTED ADAMANTLY-UREA INHIBITOR OF THE SOLUBLE EPOXIDE HYDROLASE PROTECTS THE KIDNEY FROM DAMAGE IN HYPERTENSIVE GOTO-KAKIZAKI RATS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hypertension and type II diabetes are co-morbid diseases that lead to the development of nephropathy. Soluble epoxide hydrolase (sEH) inhibitors are reported to provide protection from renal injury. We hypothesized that the sEH inhibitor 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA) protects ...

  5. Correlation of Paleocene Harmon and Hansen lignite beds, Adams, Billings, Bowman, Golden Valley, Hettinger, and Slope Counties, Williston Basin, North Dakota

    SciTech Connect

    Keighin, C.W.; Flores, R.M.; Ochs, A.

    1998-12-31

    In southwestern North Dakota, minable lignite beds in the Paleocene Fort Union Formation include the Harmon and Hansen beds in the Bowman-Gascoyne area. Data from more than 700 drill holes penetrating these beds was used to construct stratigraphic cross sections. The Harmon and Hansen beds are the thickest and most laterally persistent lignites found under < 150 ft of overburden. The Harmon coal bed is as much as 34 ft thick, and is often split by claystone interbeds of variable thickness. The Hansen coal bed typically occurs 10--100 ft below the Harmon coal bed; it rarely attains a thickness of 15 ft, and averages 4 ft in thickness.

  6. Muscovite- and R1 illite/smectite-kaolinite intergrowths in the Eocene McAdams Sandstone: Non-existence of hydromuscovite and implications for illite metastability

    SciTech Connect

    Jiang, Weiteh; Peacor, D.R.; Essene, E.J. . Dept. of Geological Sciences)

    1992-01-01

    Illite-like grains in hydrothermally altered Eocene sandstones from Kettleman North Dome in the San Joaquin Valley, CA have been characterized by electron microscopy to investigate the cause of the low-K contents obtained in previous electron microprobe analyses that were inferred to represent true hydromuscovite-hydropyrophyllite solid solutions and to conclude that illite may be a stable phase. The illite-like grains are of two types: (1) curved, flaky grains that fill pore space in fractured K-feldspar and along grain boundaries between K-feldspar and quartz, and (2) aggregates of lath-like grains that fill cavities. EDS analyses show that the former has an illite-like composition of 0.7--0.8 K per O[sub 10](OH)[sub 2] and the latter is muscovite. Electron diffraction and lattice-fringe images show that the first type of grains is rectorite-like R1 illite/smectite (I/S). Both the R1 I/S and muscovite are interlayered with and/or irregularly embayed by kaolinite, implying that they may have been partially replaced by kaolinite or vice versa. Aggregates of randomly oriented, very fine-grained R1 I/S and kaolinite that formed as cements are abundant. It is not possible to define individual single-phase grains in any of these types of mixtures with optical microscopy. Analyses of such mixtures have low K contents and high Al/Si ratios. The data demonstrate that the previously-reported low-K, hydronium-rich phases that were implied to represent hydromuscovite-hydropyrophyllite solid solutions do not exist. There is no evidence for the presence of interlayer H[sub 2]O and H[sub 3]O[sup +] that were hypothesized to stabilize illite. Common illite is thus a K-deficient, Si-rich dioctahedral mica with composition that is approximately intermediate to those of pyrophyllite and muscovite and within the pyrophyllite-muscovite solvus. It is therefore metastable with respect to muscovite + pyrophyllite.

  7. Cellular alterations in Mytilus galloprovincialis (LMK) and Tapes philippinarum (Adams and Reeve, 1850) as biomarkers of environmental stress: field studies in the Lagoon of Venice (Italy).

    PubMed

    Da Ros, L; Nesto, N

    2005-09-01

    A long-term biomonitoring study was carried out in the Lagoon of Venice (North-East Italy) with the aim of evaluating variations in biological responses to environmental stress in estuarine bivalves. Two different species, the mussel Mytilus galloprovincialis and the clam Tapes philippinarum, both widespread in the Lagoon, were studied in several sites. Two cellular biomarkers: lysosomal membrane stability in digestive cells and thickness of digestive epithelia, were evaluated in native organisms (on a seasonal basis), and in organisms which have been transferred from a reference site to several differently influenced ones. Results indicate that, to some extent, both test and organisms were able to highlight site-specific differences, but the effects of pollution were generally more easily detected by reduction in lysosomal stability than by reduction in digestive tubule epithelium. Further findings show that the inherent variability of a number of natural parameters, particularly in the reference sites, produced less effective results when biological responses in the reference organisms were compared with the polluted ones. The assessment of the two conditions was most valuable when they referred to the 25-75% range of values comprised within the seasonal medians, recorded respectively in control and polluted sites. Impaired from steady states were most effectively distinguished when the control values were medians from two reference locations. Lately, the overall results indicate that both biomarkers are more suitably deployed through the translocation approach, revealing it to be more sensitive than traditional biomonitoring, at least in the sense that it may overcome problems related to the adaptation of native organisms to sub lethal chronic pollution levels. PMID:16083961

  8. Impulse fur Bibliotheken (Impulses for Libraries). Publications of Essen University Library 19.

    ERIC Educational Resources Information Center

    Helal, Ahmed H., Ed.

    This collection of 12 papers commemorates the retirement of Bernhard Adams. Adams had a 30-year career at the Bochum University Library (Germany) and advocated innovation and automation in libraries. The papers are: (1) "Gemeinsame Wegstrecken: Bernhard Adams zur Ehre" ("Common Milestones: In Honor of Bernhard Adams") (Harro Heim); (2) "Die…

  9. 76 FR 49674 - Changes in Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-11

    ... Hartford, 550 Main Courant. Street, 2nd Floor, Room 200, Hartford, CT 06103. Illinois: Adams City of Quincy..., Mayor, City of The Quincy Herald- Quincy, City Hall, 730 Whig. Maine Street, Quincy, IL 62301. Adams..., 2011; Mclaughlin, Chairman, 05-0757P). The Quincy Herald- Adams County Board, Whig. Adams...

  10. Central role of the exchange factor GEF-H1 in TNF-α–induced sequential activation of Rac, ADAM17/TACE, and RhoA in tubular epithelial cells

    PubMed Central

    Waheed, Faiza; Dan, Qinghong; Amoozadeh, Yasaman; Zhang, Yuqian; Tanimura, Susumu; Speight, Pam; Kapus, András; Szászi, Katalin

    2013-01-01

    Transactivation of the epidermal growth factor receptor (EGFR) by tumor necrosis factor-α (TNF-α) is a key step in mediating RhoA activation and cytoskeleton and junction remodeling in the tubular epithelium. In this study we explore the mechanisms underlying TNF-α–induced EGFR activation. We show that TNF-α stimulates the TNF-α convertase enzyme (TACE/a disintegrin and metalloproteinase-17), leading to activation of the EGFR/ERK pathway. TACE activation requires the mitogen-activated protein kinase p38, which is activated through the small GTPase Rac. TNF-α stimulates both Rac and RhoA through the guanine nucleotide exchange factor (GEF)-H1 but by different mechanisms. EGFR- and ERK-dependent phosphorylation at the T678 site of GEF-H1 is a prerequisite for RhoA activation only, whereas both Rac and RhoA activation require GEF-H1 phosphorylation on S885. Of interest, GEF-H1-mediated Rac activation is upstream from the TACE/EGFR/ERK pathway and regulates T678 phosphorylation. We also show that TNF-α enhances epithelial wound healing through TACE, ERK, and GEF-H1. Taken together, our findings can explain the mechanisms leading to hierarchical activation of Rac and RhoA by TNF-α through a single GEF. This mechanism could coordinate GEF functions and fine-tune Rac and RhoA activation in epithelial cells, thereby promoting complex functions such as sheet migration. PMID:23389627

  11. Influences of Three Presidents of the United States on Multicultural Education: A Series of Research Studies in Educational Policy--Third Installment: Examining Presidents John Quincy Adams, Theodore Roosevelt, and Harry S. Truman

    ERIC Educational Resources Information Center

    Baptiste, H. Prentice; Michal, Emil J., Jr.

    2004-01-01

    The recognition, development and implementation of multicultural education in America is a relatively new and emerging idea. Prior to the middle of the previous century, the concept of addressing and providing a meaningful educational experience for all students, including students of color, was non-existent. In recent years, through the work of…

  12. 2-(1-Adamant­yl)-1-{4-[(2-chloro-9-isopropyl-9H-purin-6-yl)amino­meth­yl]phen­yl}ethanone

    PubMed Central

    Rouchal, Michal; Nečas, Marek; de Carvalho, Fabiana Pires; Vícha, Robert

    2009-01-01

    The structure of the title compound, C27H32ClN5O, consists of two crystallographically independent conformers differing slightly in all geometric parameters. Both contain nearly planar purine and benzene ring systems [maximum deviations of 0.046 (3) and 0.005 (2) Å, respectively], the dihedral angles between them being 76.44 (6) and 82.39 (6)°, and an adamantane cage consisting of three fused cyclo­hexane rings in almost ideal chair conformations, with C—C—C angles in the range 108.7 (2)–110.6 (2)°. The carbonyl plane and the benzene ring are almost coplanar [dihedral angles of 6.43 (9) and 0.64 (8)° in the two conformers]. The crystal structure is stabilized by inter­molecular N—H⋯N inter­actions that link adjacent mol­ecules into dimers and by some non-bonding contacts of the C—H⋯Cl type. PMID:21581908

  13. (1-Adamant­yl){4-[(2-chloro-9-isopropyl-9H-purin-6-yl)aminometh­yl]phen­yl}methanone trichloro­methane solvate

    PubMed Central

    Rouchal, Michal; Nečas, Marek; Vícha, Robert

    2009-01-01

    In the title compound, C26H30ClN5O·CHCl3, the purine mol­ecule consists of essentially planar benzene and purine ring systems [maximum deviation 0.010 (4) Å for both ring systems] forming a dihedral angle of 85.52 (9)°. Inter­molecular N—H⋯N hydrogen bonds link adjacent mol­ecules into centrosymmetric dimers. The structure also contains inter­molecular C—H⋯O and C—H⋯N inter­actions. The benzene rings form offset face-to-face π–π stacking inter­actions with an inter­planar distance of 3.541 (4) Å and a centroid-to-centroid distance of 4.022 (4) Å. PMID:21583132

  14. Adam's Rage: Children of the Pinelands Speak: The Michael L. Printz Award Winning Novels: Authentic Current Literature as a Catalyst for Increased Student Growth, Motivation and Healing

    ERIC Educational Resources Information Center

    Cecchini, Stephanie Anne

    2012-01-01

    Young adults deserve our best as parents, educators and community members. The Michael L. Printz award winning books, instituted by the Young Adult Library Association, form a recent grouping of current literature. Novels worthy of the Printz Award explore physical, emotional, and social themes important in the lives of young adults. This library…

  15. Response to comments by Adam Smiarowski and Shane Mulè on: Christensen, N., and Lawrie, K., 2012. Resolution analyses for selecting an appropriate airborne electromagnetic (AEM) system, Exploration Geophysics, 43, 213-227

    NASA Astrophysics Data System (ADS)

    Christensen, Niels B.; Lawrie, Ken

    2015-06-01

    We analyse and compare the resolution improvement that can be obtained from including x-component data in the inversion of AEM data from the SkyTEM and TEMPEST systems. Except for the resistivity of the bottom layer, the SkyTEM system, even without including x-component data, has the better resolution of the parameters of the analysed models.

  16. 78 FR 64498 - Formations of, Acquisitions by, and Mergers of Bank Holding Companies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-29

    ...) 1 Memorial Drive, Kansas City, Missouri 64198-0001: 1. Adams Dairy Bancshares, Inc., Blue Springs, Missouri; to become a bank holding company by acquiring 100 percent of the voting shares of Adams...

  17. 75 FR 26294 - Notice of Availability of the Models for Plant-Specific Adoption of Technical Specifications Task...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-11

    ... (74 FR 58065-58067), is available electronically under ADAMS Accession Number ML100780154. Federal... . From this page, the public can gain entry into ADAMS, which provides text and image files of...

  18. Allergies, asthma, and dust

    MedlinePlus

    ... animal dander. Change furnace filters frequently. Use high efficiency particulate air (HEPA) filters. When cleaning: Wipe away ... about A.D.A.M.'s editorial policy , editorial process and privacy policy . A.D.A.M. is ...

  19. Thyroid Disease

    MedlinePlus

    ... base of your neck, just below your Adam's apple. This gland makes thyroid hormone that travels in ... base of your neck, just below your Adam's apple. This gland makes thyroid hormone that travels in ...

  20. Renal venogram

    MedlinePlus

    ... Grainger RC, Allison D, Adam, Dixon AK, eds. Diagnostic Radiology: A Textbook of Medical Imaging . 5th ed. New ... Grainger RC, Allison D, Adam, Dixon AK, eds. Diagnostic Radiology: A Textbook of Medical Imaging . 5th ed. New ...

  1. Aicardi syndrome

    MedlinePlus

    ... the infant is having spasms or a seizure. Images Corpus callosum of the brain References Glasmacher MA, ... A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

  2. Marguerite Arnet Residence, interior walls and front door, and door ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Marguerite Arnet Residence, interior walls and front door, and door leading to next room - Adam & Bessie Arnet Homestead, Marguerite Arnet Residence, 560 feet northeast of Adam & Bessie Arnet Residence, Model, Las Animas County, CO

  3. Marguerite Arnet Residence, exterior roof structure detail, looking northwest. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Marguerite Arnet Residence, exterior roof structure detail, looking northwest. - Adam & Bessie Arnet Homestead, Marguerite Arnet Residence, 560 feet northeast of Adam & Bessie Arnet Residence, Model, Las Animas County, CO

  4. Kidney removal - slideshow

    MedlinePlus

    ... Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M. Health Solutions, Ebix, Inc. ... Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. ...

  5. Hydrocele repair - slideshow

    MedlinePlus

    ... Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M. Health Solutions, Ebix, Inc. ... Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. ...

  6. NASA Now: The Sun: The Impact of Solar Activity on Earth

    NASA Video Gallery

    Meet Mitzi Adams, an astrophysicist studying the sun. Adams has been working as a solar scientist at NASA's Marshall Space Flight Center in Huntsville, Ala., since 1988. She analyzes data in an att...

  7. Broken or knocked out tooth

    MedlinePlus

    ... bones, stale bread, tough bagels and unpopped popcorn kernels. Always wear a seatbelt. Alternative Names Teeth - broken; ... A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM Health ...

  8. Presbyopia

    MedlinePlus

    ... or reading glasses, but it can affect depth perception. Sometimes, monovision can be produced through laser vision ... about A.D.A.M.'s editorial policy , editorial process and privacy policy . A.D.A.M. is ...

  9. Sirius B and the gravitational redshift - an historical review

    NASA Astrophysics Data System (ADS)

    Hetherington, N. S.

    1980-09-01

    Greenstein's rejection (1971) of Adam's claim (1925) that Sirius B has a gravitational shift of 19 km per second is critically examined. It is argued that Greenstein's attempt to ascribe Adams' result to contamination by metallic lines is unconvincing.

  10. Tonsil and adenoid removal - discharge

    MedlinePlus

    ... potatoes, and cream of wheat Applesauce Low-fat ice cream, yogurt, sherbet, and popsicles Smoothies Scrambled eggs Cool ... A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

  11. The First and Fifth Boylston Professors: A View of Two Worlds.

    ERIC Educational Resources Information Center

    Ried, Paul E.

    1988-01-01

    Maintains that John Quincy Adams'"Lectures on Rhetoric and Oratory" and Adams Sherman Hill's "Principles of Rhetoric" reveal significant differences in what their authors perceive to be the most salient environmental conditions facing their students. (JK)

  12. 78 FR 19540 - Memorandum of Understanding Between the U.S. Nuclear Regulatory Commission and the Bureau of Land...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-01

    ... at the NRC are available electronically at the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/adams.html . From this page, the public can gain entry into ADAMS, which provides text...

  13. 76 FR 42074 - Consideration of Rulemaking To Address Prompt Remediation of Residual Radioactivity During...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-18

    .... Background The NRC recently published the Decommissioning Planning Rule (DPR) (76 FR 33512; June 17, 2011....gov/reading-rm/adams.html . From this page, the public can gain entry into ADAMS, which provides...

  14. Endocarditis

    MedlinePlus

    ... 2015:chap 64. Fowler VG Jr, Scheld WM, Bayer AS. Endocarditis and Intravascular Infections. In: Mandell GL, ... about A.D.A.M.'s editorial policy , editorial process and privacy policy . A.D.A.M. is ...

  15. Steep Decline in Unintended Pregnancies in U.S., Study Finds

    MedlinePlus

    ... American society, said Dr. Adam Jacobs, director of family planning for Mount Sinai Hospital in New York City. " ... New York City; Adam Jacobs, M.D., director, family planning, Mount Sinai Hospital, New York City; March 3, ...

  16. 78 FR 72122 - Draft Emergency Preparedness Frequently Asked Questions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-02

    ... Commission (NRC) is making available for comment Emergency Preparedness Frequently Asked Question (EPFAQ) No... Library at http://www.nrc.gov/reading-rm/adams.html . To begin the search, select ``ADAMS Public...

  17. Acromegaly

    MedlinePlus

    ... in childhood) Images Endocrine glands References Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an Endocrine ... 2016, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

  18. ISS Update: Keeping Track of Station Inventory – 03.14.13

    NASA Video Gallery

    Public Affairs Officer Dan Huot interviews Rob Adams, Inventory and Stowage Officer, inside the Mission Control Center. Adams and his team keep track of the gear aboard the International Space Stat...

  19. Cancer treatment -- early menopause

    MedlinePlus

    ... against gravity. Some ideas include walking, yoga, hiking, dancing, lifting weights, gardening, and tennis. DO NOT smoke. ... A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

  20. 76 FR 9614 - Notice of Availability of the Proposed Models for Plant-Specific Adoption of Technical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-18

    ..., published in the Federal Register on March 23, 2006 (71 FR 14726-14745, ADAMS Accession Number ML060760206..., 2005 (70 FR 74037), is available electronically under ADAMS Accession Number ML102700373. Federal... provides text and image files of NRC's public documents. If you do not have access to the ADAMS, or...