2018-03-22
At Space Launch Complex 3 at Vandenberg Air Force Base in California, the gantry is rolled back on the United Launch Alliance (ULA) Atlas V to a Centaur upper stage aft stub adapter (ASA) and interstage adapter (ISA) for NASA's Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, or InSight, spacecraft to land on Mars. The next step will be arrival of InSight encapsulated in its payload faring for mating atop the rocket. InSight is the first mission to explore the Red Planet's deep interior. InSight is scheduled for liftoff May 5, 2018. InSight will be the first mission to look deep beneath the Martian surface. It will study the planet's interior by measuring its heat output and listen for marsquakes. InSight will use the seismic waves generated by marsquakes to develop a map of the planet’s deep interior. The resulting insight into Mars’ formation will provide a better understanding of how other rocky planets, including Earth, were created. NASA’s Jet Propulsion Laboratory in Pasadena, California, manages the InSight mission for the agency’s Science Mission Directorate. InSight is part of NASA's Discovery Program, managed by its Marshall Space Flight Center in Huntsville, Alabama. The spacecraft, including cruise stage and lander, was built and tested by Lockheed Martin Space in Denver. Several European partners, including France's space agency, the Centre National d'Étude Spatiales, and the German Aerospace Center, are supporting the mission. United Launch Alliance of Centennial, Colorado, is providing the Atlas V launch service. NASA’s Launch Services Program, based at its Kennedy Space Center in Florida, is responsible for launch management.
Insight, symptoms and executive functions in schizophrenia.
Simon, Andor E; Berger, Gregor E; Giacomini, Véronique; Ferrero, François; Mohr, Sylvia
2006-09-01
We investigated the relationship of insight with executive functions and symptoms in a group of stabilised inpatients with schizophrenia. Executive functions using an extensive battery constituted of several tests as well as psychopathology were assessed in 38 inpatients with a DSM-IV diagnosis of schizophrenia. Insight was assessed with the Scale to assess Unawareness of Mental Disorder (SUMD). A principal component analysis of the insight dimensions revealed a three-factor model which accounted for 98% of the variance. Of particular interest is the finding that a composite factor that accounted for 74% of the variance covered insight dimensions that represent a higher degree of insight (awareness of mental disorder, its social consequences, and attribution of symptoms). Only an association between letter fluency and this composite factor was found, which was weakly mediated by depressive symptoms. A stepwise multiple regression analysis revealed a relationship between antipsychotic dose and awareness of medication effect. No association of illness duration and insight was found. The findings of partial association between dimensions of insight and measures of executive function supports the growing evidence that insight is a multidimensional phenomenon. Accordingly, they emphasise that in the framework of therapeutic interventions, enhancement of higher levels of insight needs to take into account that patients suffering from schizophrenia have differential impairment in insight dimensions.
Rothmaler, Katrin; Nigbur, Roland; Ivanova, Galina
2017-01-27
Insight refers to a situation in which a problem solver immediately changes his understanding of a problem situation. This representational change can either be triggered by external stimuli, like a hint or the solution itself, or by internal solution attempts. In the present paper, the differences and similarities between these two phenomena, namely "extrinsic" and "intrinsic" insight, are examined. To this end, electroencephalogram (EEG) is recorded while subjects either recognize or generate solutions to German verbal compound remote associate problems (CRA). Based on previous studies, we compare the alpha power prior to insightful solution recognition with the alpha power prior to insightful solution generation. Results show that intrinsic insights are preceded by an increase in alpha power at right parietal electrodes, while extrinsic insights are preceded by a respective decrease. These results can be interpreted in two ways. In consistency with other studies, the increase in alpha power before intrinsic insights can be interpreted as an increased internal focus of attention. Accordingly, the decrease in alpha power before extrinsic insights may be associated with a more externally oriented focus of attention. Alternatively, the increase in alpha power prior to intrinsic insights can be interpreted as an active inhibition of solution-related information, while the alpha power decrease prior to extrinsic insights may reflect its activation. Regardless of the interpretation, the results provide strong evidence that extrinsic and intrinsic insight differ on the behavioral as well as the neurophysiological level. Copyright © 2016 Elsevier Ltd. All rights reserved.
Gaziel, M; Hasson-Ohayon, I; Morag-Yaffe, M; Schapir, L; Zalsman, G; Shoval, G
2015-02-01
The purpose of the current study was to assess the associations of illness perception-related variables with satisfaction with life (SwL) among adolescents with mental disorders. Insight into mental disorder (SAI-E), Internalized stigma of mental illness (ISMI) and Multidimensional Students' Life Satisfaction Scale (MSLSS) were administrated to 30 adolescent patients. Adapted version for parents of the SAI-E was also administrated to 37 of their parents. Significant positive correlations were found between insight into the illness, self-stigma and parental insight. Insight and self-stigma were significantly negatively related to the total score of SwL and few of its dimensions while parental insight was significantly associated only with the SwL dimensions of school and self. Regression models revealed main negative effects of insight and self-stigma on SwL and no interaction effect. The possible independent contribution of insight and self-stigma to SwL should be addressed in interventions designed for family and adolescents coping with mental illness. Special attention should be given to the possible negative implications that insight possesses. In lack of support of the moderation role of self-stigma, reported in studies among adults with mental illness, future studies should trace other variables in order to further understand the insight paradox among adolescents. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Controlled release of drugs in electrosprayed nanoparticles for bone tissue engineering.
Jayaraman, Praveena; Gandhimathi, Chinnasamy; Venugopal, Jayarama Reddy; Becker, David Laurence; Ramakrishna, Seeram; Srinivasan, Dinesh Kumar
2015-11-01
Generating porous topographic substrates, by mimicking the native extracellular matrix (ECM) to promote the regeneration of damaged bone tissues, is a challenging process. Generally, scaffolds developed for bone tissue regeneration support bone cell growth and induce bone-forming cells by natural proteins and growth factors. Limitations are often associated with these approaches such as improper scaffold stability, and insufficient cell adhesion, proliferation, differentiation, and mineralization with less growth factor expression. Therefore, the use of engineered nanoparticles has been rapidly increasing in bone tissue engineering (BTE) applications. The electrospray technique is advantageous over other conventional methods as it generates nanomaterials of particle sizes in the micro/nanoscale range. The size and charge of the particles are controlled by regulating the polymer solution flow rate and electric voltage. The unique properties of nanoparticles such as large surface area-to-volume ratio, small size, and higher reactivity make them promising candidates in the field of biomedical engineering. These nanomaterials are extensively used as therapeutic agents and for drug delivery, mimicking ECM, and restoring and improving the functions of damaged organs. The controlled and sustained release of encapsulated drugs, proteins, vaccines, growth factors, cells, and nucleotides from nanoparticles has been well developed in nanomedicine. This review provides an insight into the preparation of nanoparticles by electrospraying technique and illustrates the use of nanoparticles in drug delivery for promoting bone tissue regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.
Differential ammonia metabolism in Aedes aegypti fat body and midgut tissues
Scaraffia, Patricia Y.; Zhang, Quigfen; Thorson, Kelsey; Wysocki, Vicki H.; Miesfeld, Roger L.
2010-01-01
In order to understand at the tissue level how Aedes aegypti copes with toxic ammonia concentrations that result from the rapid metabolism of blood meal proteins, we investigated the incorporation of 15N from 15NH4Cl into amino acids using an in vitro tissue culture system. Fat body or midgut tissues from female mosquitoes were incubated in an Aedes saline solution supplemented with glucose and 15NH4Cl for 10–40 minutes. The media was then mixed with deuterium-labeled amino acids, dried and derivatized. The 15N-labeled and unlabeled amino acids in each sample were quantified by mass spectrometry techniques. The results demonstrate that both tissues efficiently incorporate ammonia into amino acids, however, the specific metabolic pathways are distinct. In the fat body, the 15N from 15NH4Cl is first incorporated into the amide side chain of Gln and then into the amino group of Gln, Glu, Ala and Pro. This process mainly occurs via the glutamine synthetase (GS) and glutamate synthase (GltS) pathway. In contrast, 15N in midgut is first incorporated into the amino group of Glu and Ala, and then into the amide side chain of Gln. Interestingly, our data show that the GS/GltS pathway is not functional in the midgut. Instead, midgut cells detoxify ammonia by glutamate dehydrogenase, alanine aminotransferase and GS. These data provide new insights into ammonia metabolism in A. aegypti mosquitoes. PMID:20206632
InSight MARCO Installation Cubesats
2018-03-17
At Vandenberg Air Force Base in California, twin communications-relay CubeSats, called Mars Cube One (MarCO) are installed on an Atlas V rocket. MarCO constitutes a technology demonstration being built by NASA's Jet Propulsion Laboratory, Pasadena in California. They will launch in on the same United Launch Alliance Atlas V rocket as NASA's Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, or InSight, spacecraft to land on Mars. CubeSats are a class of spacecraft based on a standardized small size and modular use of off-the-shelf technologies. Many have been made by university students, and dozens have been launched into Earth orbit using extra payload mass available on launches of larger spacecraft. InSight is the first mission to explore the Red Planet's deep interior. InSight is scheduled for liftoff May 5, 2018. InSight will be the first mission to look deep beneath the Martian surface. It will study the planet's interior by measuring its heat output and listen for marsquakes. InSight will use the seismic waves generated by marsquakes to develop a map of the planet’s deep interior. The resulting insight into Mars’ formation will provide a better understanding of how other rocky planets, including Earth, were created. NASA’s Jet Propulsion Laboratory in Pasadena, California, manages the InSight mission for the agency’s Science Mission Directorate. InSight is part of NASA's Discovery Program, managed by its Marshall Space Flight Center in Huntsville, Alabama. The spacecraft, including cruise stage and lander, was built and tested by Lockheed Martin Space in Denver. Several European partners, including France's space agency, the Centre National d'Étude Spatiales, and the German Aerospace Center, are supporting the mission. United Launch Alliance of Centennial, Colorado, is providing the Atlas V launch service. NASA’s Launch Services Program, based at its Kennedy Space Center in Florida, is responsible for launch management.
Gaylo, Alison; Schrock, Dillon C.; Fernandes, Ninoshka R. J.; Fowell, Deborah J.
2016-01-01
Effector T cells exit the inflamed vasculature into an environment shaped by tissue-specific structural configurations and inflammation-imposed extrinsic modifications. Once within interstitial spaces of non-lymphoid tissues, T cells migrate in an apparent random, non-directional, fashion. Efficient T cell scanning of the tissue environment is essential for successful location of infected target cells or encounter with antigen-presenting cells that activate the T cell’s antimicrobial effector functions. The mechanisms of interstitial T cell motility and the environmental cues that may promote or hinder efficient tissue scanning are poorly understood. The extracellular matrix (ECM) appears to play an important scaffolding role in guidance of T cell migration and likely provides a platform for the display of chemotactic factors that may help to direct the positioning of T cells. Here, we discuss how intravital imaging has provided insight into the motility patterns and cellular machinery that facilitates T cell interstitial migration and the critical environmental factors that may optimize the efficiency of effector T cell scanning of the inflamed tissue. Specifically, we highlight the local micro-positioning cues T cells encounter as they migrate within inflamed tissues, from surrounding ECM and signaling molecules, as well as a requirement for appropriate long-range macro-positioning within distinct tissue compartments or at discrete foci of infection or tissue damage. The central nervous system (CNS) responds to injury and infection by extensively remodeling the ECM and with the de novo generation of a fibroblastic reticular network that likely influences T cell motility. We examine how inflammation-induced changes to the CNS landscape may regulate T cell tissue exploration and modulate function. PMID:27790220
Gaylo, Alison; Schrock, Dillon C; Fernandes, Ninoshka R J; Fowell, Deborah J
2016-01-01
Effector T cells exit the inflamed vasculature into an environment shaped by tissue-specific structural configurations and inflammation-imposed extrinsic modifications. Once within interstitial spaces of non-lymphoid tissues, T cells migrate in an apparent random, non-directional, fashion. Efficient T cell scanning of the tissue environment is essential for successful location of infected target cells or encounter with antigen-presenting cells that activate the T cell's antimicrobial effector functions. The mechanisms of interstitial T cell motility and the environmental cues that may promote or hinder efficient tissue scanning are poorly understood. The extracellular matrix (ECM) appears to play an important scaffolding role in guidance of T cell migration and likely provides a platform for the display of chemotactic factors that may help to direct the positioning of T cells. Here, we discuss how intravital imaging has provided insight into the motility patterns and cellular machinery that facilitates T cell interstitial migration and the critical environmental factors that may optimize the efficiency of effector T cell scanning of the inflamed tissue. Specifically, we highlight the local micro-positioning cues T cells encounter as they migrate within inflamed tissues, from surrounding ECM and signaling molecules, as well as a requirement for appropriate long-range macro-positioning within distinct tissue compartments or at discrete foci of infection or tissue damage. The central nervous system (CNS) responds to injury and infection by extensively remodeling the ECM and with the de novo generation of a fibroblastic reticular network that likely influences T cell motility. We examine how inflammation-induced changes to the CNS landscape may regulate T cell tissue exploration and modulate function.
Tissue engineering of reproductive tissues and organs.
Atala, Anthony
2012-07-01
Regenerative medicine and tissue engineering technology may soon offer new hope for patients with serious injuries and end-stage reproductive organ failure. Scientists are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured reproductive tissues. In addition, the stem cell field is advancing, and new discoveries in this field will lead to new therapeutic strategies. For example, newly discovered types of stem cells have been retrieved from uterine tissues such as amniotic fluid and placental stem cells. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous adult cells have already entered the clinic. This article discusses these tissue engineering strategies for various organs in the male and female reproductive tract. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Eaten alive: novel insights into autophagy from multicellular model systems.
Zhang, Hong; Baehrecke, Eric H
2015-07-01
Autophagy delivers cytoplasmic material to lysosomes for degradation. First identified in yeast, the core genes that control this process are conserved in higher organisms. Studies of mammalian cell cultures have expanded our understanding of the core autophagy pathway, but cannot reveal the unique animal-specific mechanisms for the regulation and function of autophagy. Multicellular organisms have different types of cells that possess distinct composition, morphology, and organization of intracellular organelles. In addition, the autophagic machinery integrates signals from other cells and environmental conditions to maintain cell, tissue and organism homeostasis. Here, we highlight how studies of autophagy in flies and worms have identified novel core autophagy genes and mechanisms, and provided insight into the context-specific regulation and function of autophagy. Copyright © 2015 Elsevier Ltd. All rights reserved.
The pillars of land plants: new insights into stem development.
Serrano-Mislata, Antonio; Sablowski, Robert
2018-05-12
In spite of its central importance in evolution, plant architecture and crop improvement, stem development remains poorly understood relative to other plant organs. Here, we summarise current knowledge of stem ontogenesis and its regulation, including insights from new image analysis and biophysical approaches. The stem initiates in the rib zone (RZ) of the shoot apical meristem, under transcriptional control by DELLA and BLH proteins. Links have emerged between these regulators and cell proliferation, patterning and oriented growth in the RZ. During subsequent internode elongation, cell wall properties and mechanics have been analysed in detail, revealing pectin modification as a prominent control point. Recent work has also highlighted signalling to coordinate growth of stem tissues with different mechanical properties. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
2018-05-04
At Vandenberg Air Force Base in California, the gantry rolls back at Space Launch Complex 3 in preparation for the liftoff of NASA's Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, or InSight, Mars lander. The United Launch Alliance Atlas V rocket now is poised to boost the spacecraft with liftoff scheduled for 4:05 a.m. PDT (7:05 a.m. EDT). InSight will be the first mission to look deep beneath the Martian surface. It will study the planet's interior by measuring its heat output and listen for marsquakes. InSight will use the seismic waves generated by marsquakes to develop a map of the planet’s deep interior. The resulting insight into Mars’ formation will provide a better understanding of how other rocky planets, including Earth, were created.
Understanding Insight in the Context of Q
ERIC Educational Resources Information Center
Coghlan, David
2012-01-01
In Revans' learning formula, L = P + Q, Q represents "questioning insight", by which Revans means that insight comes out of the process of questioning programmed knowledge (P) in the light of experience. We typically focus on the content of an insight rather than on the act of insight. Drawing primarily on the work of Bernard Lonergan this paper…
Structural insights into humanization of anti-tissue factor antibody 10H10.
Teplyakov, Alexey; Obmolova, Galina; Malia, Thomas J; Raghunathan, Gopalan; Martinez, Christian; Fransson, Johan; Edwards, Wilson; Connor, Judith; Husovsky, Matthew; Beck, Heena; Chi, Ellen; Fenton, Sandra; Zhou, Hong; Almagro, Juan Carlos; Gilliland, Gary L
Murine antibody 10H10 raised against human tissue factor is unique in that it blocks the signaling pathway, and thus inhibits angiogenesis and tumor growth without interfering with coagulation. As a potential therapeutic, the antibody was humanized in a two-step procedure. Antigen-binding loops were grafted onto selected human frameworks and the resulting chimeric antibody was subjected to affinity maturation by using phage display libraries. The results of humanization were analyzed from the structural perspective through comparison of the structure of a humanized variant with the parental mouse antibody. This analysis revealed several hot spots in the framework region that appear to affect antigen binding, and therefore should be considered in human germline selection. In addition, some positions in the Vernier zone, e.g., residue 71 in the heavy chain, that are traditionally thought to be crucial appear to tolerate amino acid substitutions without any effect on binding. Several humanized variants were produced using both short and long forms of complementarity-determining region (CDR) H2 following the difference in the Kabat and Martin definitions. Comparison of such pairs indicated consistently higher thermostability of the variants with short CDR H2. Analysis of the binding data in relation to the structures singled out the ImMunoGeneTics information system® germline IGHV1-2*01 as dubious owing to two potentially destabilizing mutations as compared to the other alleles of the same germline and to other human germlines.
Insight in schizophrenia: from conceptualization to neuroscience.
Ouzir, Mounir; Azorin, Jean Michel; Adida, Marc; Boussaoud, Driss; Battas, Omar
2012-04-01
Lack of insight into illness is a prevalent and distinguishing feature of schizophrenia, which has a complex history and has been given a variety of definitions. Currently, insight is measured and treated as a multidimensional phenomenon, because it is believed to result from psychological, neuropsychological and organic factors. Thus, schizophrenia patients may display dramatic disorders including demoralization, depression and a higher risk of suicide, all of which are directly or indirectly related to a lack of insight into their illness, and make the treatment difficult. To improve the treatment of people with schizophrenia, it is thus crucial to advance research on insight into their illness. Insight is studied in a variety of ways. Studies may focus on the relationship between insight and psychopathology, may view behavioral outcomes or look discretely at the cognitive dysfunction versus anatomy level of insight. All have merit but they are dispersed across a wide body of literature and rarely are the findings integrated and synthesized in a meaningful way. The aim of this study was to synthesize findings across the large body of literature dealing with insight, to highlight its multidimensional nature, measurement, neuropsychology and social impact in schizophrenia. The extensive literature on the cognitive consequences of lack of insight and the contribution of neuroimaging techniques to elucidating neurological etiology of insight deficits, is also reviewed. © 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.
2018-05-04
American professional basketball player Chris Bosh poses for a photograph in front of the United Launch Alliance (ULA) Atlas-V rocket with NASA's InSight spacecraft onboard, Friday, May 4, 2018, at Vandenberg Air Force Base in California. Bosh joined other social media guests on a behind the scenes tour ahead of the planned launch. InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, is a Mars lander designed to study the "inner space" of Mars: its crust, mantle, and core. Photo Credit: (NASA/Bill Ingalls)
Prelude to corneal tissue engineering – Gaining control of collagen organization
Ruberti, Jeffrey W.; Zieske, James D.
2012-01-01
By most standard engineering practice principles, it is premature to credibly discuss the “engineering” of a human cornea. A professional design engineer would assert that we still do not know what a cornea is (and correctly so), therefore we cannot possibly build one. The proof resides in the fact that there are no clinically viable corneas based on classical tissue engineering methods available. This is possibly because tissue engineering in the classical sense (seeding a degradable scaffolding with a population synthetically active cells) does not produce conditions which support the generation of organized tissue. Alternative approaches to the problem are in their infancy and include the methods which attempt to recapitulate development or to produce corneal stromal analogs de novo which require minimal remodeling. Nonetheless, tissue engineering efforts, which have been focused on producing the fundamental functional component of a cornea (organized alternating arrays of collagen or “lamellae”) may have already provided valuable new insights and tools relevant to development, growth, remodeling and pathologies associated with connective tissue in general. This is because engineers ask a fundamentally different question (How can that be done?) than do biological scientists (How is that done?). The difference in inquiry has prompted us to closely examine (and to mimic) development as well as investigate collagen physicochemical behavior so that we may exert control over organization both in cell-culture (in vitro) and on the benchtop (de novo). Our initial results indicate that reproducing corneal stroma-like local and long-range organization of collagen may be simpler than we anticipated while controlling spacing and fibril morphology remains difficult, but perhaps not impossible in the (reasonably) near term. PMID:18775789
Nanomechanical signatures of oral submucous fibrosis in sub-epithelial connective tissue.
Anura, Anji; Das, Debanjan; Pal, Mousumi; Paul, Ranjan Rashmi; Das, Soumen; Chatterjee, Jyotirmoy
2017-01-01
Oral sub-mucous fibrosis (OSF), a potentially malignant disorder, exhibits extensive remodeling of extra-cellular matrix in the form of sub-epithelial fibrosis which is a possible sequel of assaults from different oral habit related irritants. It has been assumed that micro/nanobio-mechanical imbalance experienced in the oral mucosa due to fibrosis may be deterministic for malignant potential (7-13%) of this pathosis. Present study explores changes in mechanobiological attributes of sub-epithelial connective tissue of OSF and the normal counterpart. The atomic force microscopy was employed to investigate tissue topography at micro/nano levels. It documented the presence of closely packed parallel arrangement of dense collagen fibers with wide variation in bandwidth and loss of D-space in OSF as compared to normal. The AFM based indentation revealed that sub-epithelium of OSF tissue has lost its flexibility with increased Young's modulus, stiffness, adhesiveness and reduced deformation of the juxta-epithealial connective tissue towards the deeper layer. These significant variations in nano-mechanical properties of the connective tissue indicated plausible impacts on patho-physiological microenvironment. Excessive deposition of collagen I and diminished expression of collagen III, fibronectin along with presence of α-SMA positive myofibroblast in OSF depicted its pathological basis and indicated the influence of altered ECM on this pathosis. The mechanobiological changes in OSF were corroborative with change in collagen composition recorded through immunohistochemistry and RT-PCR. The revelation of comparative nanomechanical profiles of normal oral mucosa and OSF in the backdrop of their structural and cardinal molecular attributes thus became pivotal for developing holistic pathobiological insight about possible connects for malignant transformation of this pre-cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.
Biological Insights From 108 Schizophrenia-Associated Genetic Loci
Ripke, Stephan; Neale, Benjamin M; Corvin, Aiden; Walters, James TR; Farh, Kai-How; Holmans, Peter A; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A; Huang, Hailiang; Pers, Tune H; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A; Begemann, Martin; Belliveau, Richard A; Bene, Judit; Bergen, Sarah E; Bevilacqua, Elizabeth; Bigdeli, Tim B; Black, Donald W; Bruggeman, Richard; Buccola, Nancy G; Buckner, Randy L; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M; Carr, Vaughan J; Carrera, Noa; Catts, Stanley V; Chambert, Kimberley D; Chan, Raymond CK; Chan, Ronald YL; Chen, Eric YH; Cheng, Wei; Cheung, Eric FC; Chong, Siow Ann; Cloninger, C Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J; Curtis, David; Davidson, Michael; Davis, Kenneth L; Degenhardt, Franziska; Del Favero, Jurgen; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H; Farrell, Martilias S; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B; Friedl, Marion; Friedman, Joseph I; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Giegling, Ina; Giusti-Rodríguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M; Henskens, Frans A; Herms, Stefan; Hirschhorn, Joel N; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V; Hougaard, David M; Ikeda, Masashi; Joa, Inge; Julià, Antonio; Kahn, René S; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C; Kennedy, James L; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kähler, Anna K; Laurent, Claudine; Lee, Jimmy; Lee, S Hong; Legge, Sophie E; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M; Lubinski, Jan; Lönnqvist, Jouko; Macek, Milan; Magnusson, Patrik KE; Maher, Brion S; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W; McDonald, Colm; McIntosh, Andrew M; Meier, Sandra; Meijer, Carin J; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I; Metspalu, Andres; Michie, Patricia T; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W; Mors, Ole; Murphy, Kieran C; Murray, Robin M; Myin-Germeys, Inez; Müller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A; Nestadt, Gerald; Nicodemus, Kristin K; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O’Callaghan, Eadbhard; O’Dushlaine, Colm; O’Neill, F Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; Van Os, Jim; Pantelis, Christos; Papadimitriou, George N; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O; Pietiläinen, Olli; Pimm, Jonathan; Pocklington, Andrew J; Powell, John; Price, Alkes; Pulver, Ann E; Purcell, Shaun M; Quested, Digby; Rasmussen, Henrik B; Reichenberg, Abraham; Reimers, Mark A; Richards, Alexander L; Roffman, Joshua L; Roussos, Panos; Ruderfer, Douglas M; Salomaa, Veikko; Sanders, Alan R; Schall, Ulrich; Schubert, Christian R; Schulze, Thomas G; Schwab, Sibylle G; Scolnick, Edward M; Scott, Rodney J; Seidman, Larry J; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M; Sim, Kang; Slominsky, Petr; Smoller, Jordan W; So, Hon-Cheong; Spencer, Chris C A; Stahl, Eli A; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E; Strengman, Eric; Strohmaier, Jana; Stroup, T Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M; Szatkiewicz, Jin P; Söderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tosato, Sarah; Veijola, Juha; Waddington, John; Walsh, Dermot; Wang, Dai; Wang, Qiang; Webb, Bradley T; Weiser, Mark; Wildenauer, Dieter B; Williams, Nigel M; Williams, Stephanie; Witt, Stephanie H; Wolen, Aaron R; Wong, Emily HM; Wormley, Brandon K; Xi, Hualin Simon; Zai, Clement C; Zheng, Xuebin; Zimprich, Fritz; Wray, Naomi R; Stefansson, Kari; Visscher, Peter M; Adolfsson, Rolf; Andreassen, Ole A; Blackwood, Douglas HR; Bramon, Elvira; Buxbaum, Joseph D; Børglum, Anders D; Cichon, Sven; Darvasi, Ariel; Domenici, Enrico; Ehrenreich, Hannelore; Esko, Tõnu; Gejman, Pablo V; Gill, Michael; Gurling, Hugh; Hultman, Christina M; Iwata, Nakao; Jablensky, Assen V; Jönsson, Erik G; Kendler, Kenneth S; Kirov, George; Knight, Jo; Lencz, Todd; Levinson, Douglas F; Li, Qingqin S; Liu, Jianjun; Malhotra, Anil K; McCarroll, Steven A; McQuillin, Andrew; Moran, Jennifer L; Mortensen, Preben B; Mowry, Bryan J; Nöthen, Markus M; Ophoff, Roel A; Owen, Michael J; Palotie, Aarno; Pato, Carlos N; Petryshen, Tracey L; Posthuma, Danielle; Rietschel, Marcella; Riley, Brien P; Rujescu, Dan; Sham, Pak C; Sklar, Pamela; St Clair, David; Weinberger, Daniel R; Wendland, Jens R; Werge, Thomas; Daly, Mark J; Sullivan, Patrick F; O’Donovan, Michael C
2014-01-01
Summary Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here, we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain providing biological plausibility for the findings. Many findings have the potential to provide entirely novel insights into aetiology, but associations at DRD2 and multiple genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that play important roles in immunity, providing support for the hypothesized link between the immune system and schizophrenia. PMID:25056061
