PICK1 Loss of Function Occludes Homeostatic Synaptic Scaling

Homeostatic synaptic scaling calibrates neuronal excitability by adjusting synaptic strengths during prolonged changes in synaptic activity. The molecular mechanisms that regulate the trafficking of AMPA receptors (AMPARs) during synaptic scaling are largely unknown. Here, we show that chronic activity blockade reduces PICK1 protein level on a time scale that coincides with the accumulation of surface AMPARs. PICK1 loss of function alters the subunit composition and the abundance of GluA2-containing AMPARs. Due to aberrant trafficking of these receptors, the increase in synaptic strength in response to synaptic inactivity is occluded in neurons generated from PICK1 knock-out mouse. In agreement with electrophysiological recordings, no defect of AMPAR trafficking is observed in PICK1 knock-out neurons in response to elevated neuronal activity. Overall, our data reveal an important role of PICK1 in inactivity-induced synaptic scaling by regulating the subunit composition, abundance, and trafficking of GluA2-containing AMPARs

PICK1 Regulates Incorporation of Calcium-Permeable AMPA Receptors during Cortical Synaptic Strengthening

While AMPA-type glutamate receptors (AMPARs) found at principal neuron excitatory synapses typically contain the GluR2 subunit, several forms of behavioral experience have been linked to the de novo synaptic insertion of calcium-permeable (CP) AMPARs, defined by their lack of GluR2. In particular, whisker experience drives synaptic potentiation as well as the incorporation of CP-AMPARs in the neocortex. Previous studies implicate PICK1 (protein interacting with C kinase-1) in activity-dependent internalization of GluR2, suggesting one potential mechanism leading to the subsequent accumulation of synaptic CP-AMPARs and increased synaptic strength. Here we test this hypothesis by using a whisker stimulation paradigm in PICK1 knock-out mice. We demonstrate that PICK1 facilitates the surface expression of CP-AMPARs and is indispensable for their experience-dependent synaptic insertion. However, the failure to incorporate CP-AMPARs in PICK1 knock-outs does not preclude sensory-induced enhancement of synaptic currents. Our results indicate that synaptic strengthening in the early postnatal cortex does not require PICK1 or the addition of GluR2-lacking AMPARs. Instead, PICK1 permits changes in AMPAR subunit composition to occur in conjunction with synaptic potentiation. Copyrigh

The Influence of Iron Concentration on the Mechanical Properties of A356 Al Alloy for Car Rims Application

A356.0 aluminum-silicon alloy is a base material for car rims application. Car rims are critical components for a vehicle as they carry the load of the passengers, goods, and the weight of the vehicle itself, therefore they should be sufficiently strong to withstand the vertical load, fatigue load, impact load, the side load and the braking force. Car rims are made by gravity die casting process. During the casting process, the inclusion of iron-content parts entering the molten Al can take place which leads to higher iron (Fe) concentration. High Fe con concentration lowers the toughness and the ductility of car rims. This study investigates the maximum value of Fe concentration that can be tolerated for acceptable mechanical properties of Al-Si alloy A356.0 for car rims application. The Fe concentration studied was 0.12 %wt, 0.16 %wt, and 0.20 %wt. Evaluation was performed on tensile and impact properties of the specimens. The test results show that increased Fe concentration decreases elongation, yield strength and ultimate tensile strength (UTS). Furthermore, there is a quite large decrease in UTS (by 34 MPa) when Fe concentration increases only by 0.06 %wt. Impact strength decreases significantly from 15.47 to 2.91J/cm2 as Fe concentration content increases from 0.12 %wt. to 0.16 %wt. The porosity present in the casting is predicted to contribute to the ductility decrease. In addition, the decreasing value of UTS is predicted due to grain growth and dendrites formation. It is recommended that the maximum allowable Fe concentration for car rims application is 0.12 %wt

Strategy to Improve Recycling Yield of Aluminium Cans

Millions of canned drinks are consumed everyday globally and their wastes create an enviromental issue. Fortunately, the cans are made from aluminium (Al) so that it can be recycled. There are two main keypoints existing during the recycling process of Al cans, i.e. the aluminium loss or low Al-yield and low recycling yield. This work outlines the strategies to improve the recycling perfomance for Al beverage cans, i.e. by adding drossing flux, applying improved melting strategy, and cans decoating prior to melting. Drossing flux was added to assist the detachment of Al from the slag. Another improved melting strategy was worked out by decreasing exposure time cans to the furnace atmosphere during melting. All those above strategies result in an increase of recycle yield in a range of 4 % to 5 %

L'Ottocento editoriale e le sue radici. Alcune riflessioni su fabbrica, illustrazione, smercio dei libri

Il saggio, pubblicato anche come separatum, è la prefazione di LORETTA DE FRANCESCHI, Pubblicare, divulgare, leggere nell'Ottocento italiano, Manziana, Vecchiarelli, 2013 (collezione di sei saggi, l'ultimo dei quali inedito). Si sottolineano cinque punti: 1) Rapporti fra editoria e preparazione politica del Risorgimento. 2) Editoria di libri e periodici e formazione di un pensiero e di una formazione culturale unitaria. 3) Rapporti fra editori, tipografi e librai e le istituzioni dello Stato nascente. 4) Evoluzione delle morfologie tipografiche. 5) Biblioteche pubbliche e pubblica lettura nei loro rapporti con scuola e università. Si svolge un'ampia riflessione sullo sviluppo dei rapporti fra lettura individuale e libertà personale a partire dalla traduzione della Bibbia di Lutero; con speciale attenzione al ruolo riservato a libro e lettura nell'opera di John Foxe, Book of Martyrs, pubblicata in quattro successive edizioni riccamente illustrate. Il saggio è completato da 29 immagini. Si tratta di 4 edizioni di Machiavelli: Principe (Milano, 1817); Istorie (1796, Filadelfia); edizione pirata di Opere complete, Napoli, 1877 (es. Terni, bct), Der Fürstenspiegel, Der Antimachiavell, Jena 1912 (es. Weimar, Herzogin Anna-Amalia Bibliothek; Berlin, StaBi). Frontespizî di: Roscoes's Italian Novelists, London, Prewett, 1825, nell'es. dell'Harvard College Library. Tesoro dei novellieri italiani, Parigi, Baudry, 1847 (es. Madrid, Universidad Complutense). L'antologia dei prosatori italiani scelta da Panizzie stampata da John Taylor, London, 1828 (Cambridge, University Libr.). Verso del frontespizio di La Fontaine, Fables choisies, Paris, De l'Imprimerie d'Aug. Delalain, 1816 (es. Paris, Bibliothèque de France). Molte tavole dalle varie edizioni del Book of Martyrs, 1563, p. 1571 | 1570, p. 2104 | 1576, p. 1807 | 1583, p. 1911 (Courtesy: TAMO).Illustrazioni di J. E. Millais sa A. Trollope, Orley Farm, London, Chapman & Hall, 1862 (es. Oxford, Bodleian Library). Infine, sono riprodotti alcuni dipinti: P. A. Besnard, Matinée d'été, 1886 (Musée des Beaux-Arts, Reims). Winslow Homer, The New Novel, 1877 (Museum of Fine Arts, Springfield, Massachusetts). E. von Grützner, Lesender Prämonstratensermönch in der Klosterbibliothek, 1925 ca. Edward Hopper (1882-1967), Hotel by a Railroad, 1952 (Hirshhorn Museum and Sculpture Garden, Smithsonian Institution, Washington, DC).The paper, printed also as a an offprint, was originally issued as a Preface to LORETTA DE FRANCESCHI, Pubblicare, divulgare, leggere nell'Ottocento italiano, Manziana, Vecchiarelli, 2013, a collection of six essays, the last one unpublished. The paper underlines five topics: 1) The relations with the politic history of the Italian Risorgimento. 2) The role of books and periodical publishing in the building of national thinking and enculturation. 3) The relations between the rising of the Italian State and publishers, typographers, booksellers. 4) Morphemic features of the printing process during its history. 5) Public libraries and public reading, in their relations both with primary, undergraduate and uppergraduate instruction on the other side. A long review is made about the relations between reading and personal freedom, since Luther's translation of the Bible; special attention is devoted to the place of reading (with evidence about women's reading) in John Foxe's Book of Martyrs, published by John Day in four widely illustrated editions. A gallery of 29 images is appended to the paper, referring to: 4 editions of Machiavelli: Principe (Milano, 1817), Istorie (1796, Filadelfia). Pirate edition of Opere complete, Napoli, 1877 (es. Terni, bct), Der Fürstenspiegel, Der Antimachiavell, Jena 1912 (es. Weimar, Herzogin Anna-Amalia Bibliothek; Berlin, StaBi). Titlepages of: Roscoes's Italian Novelists, London, Prewett, 1825, in the copy belonging to the Harvard College Library. Tesoro dei novellieri italiani, Parigi, Baudry, 1847 (es. Madrid, Universidad Complutense). Panizzi's choice of Italian prose-writers, printed by John Taylor, London, 1828 (Cambridge, University Libr.). Verso of the titlepage of La Fontaine, Fables choisies, Paris, De l'Imprimerie d'Aug. Delalain, 1816 (es. Paris, Bibliothèque de France). Many tables from J. Foxe, Book of Martyrs, ed. 1563, p. 1571 | ed. 1570, p. 2104 | ed. 1576, p. 1807 | ed. 1583, p. 1911 (Courtesy: TAMO). A. Trollope, Orley Farm, London, Chapman & Hall, 1862, ill. by J. E. Millais (es. Oxford, Bodleian Library). Moreover, about the following paintings: P. A. Besnard, Matinée d'été, 1886 (Musée des Beaux-Arts, Reims). Winslow Homer, The New Novel, 1877 (Museum of Fine Arts, Springfield, Massachusetts). E. von Grützner, Lesender Prämonstratensermönch in der Klosterbibliothek, 1925 ca. Edward Hopper (1882-1967), Hotel by a Railroad, 1952 (Hirshhorn Museum and Sculpture Garden, Smithsonian Institution, Washington, DC

The m6A-epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity

Research over the past decade has provided strong support for the importance of various epigenetic mechanisms, including DNA and histone modifications in regulating activity-dependent gene expression in the mammalian central nervous system. More recently, the emerging field of epitranscriptomics revealed an equally important role of post-transcriptional RNA modifications in shaping the transcriptomic landscape of the brain. This review will focus on the methylation of the adenosine base at the N6 position, termed N methyladenosine (m6A), which is the most abundant internal modification that decorates eukaryotic messenger RNAs. Given its prevalence and dynamic regulation in the adult brain, the m6A-epitranscriptome provides an additional layer of regulation on RNA that can be controlled in a context- and stimulus-dependent manner. Conceptually, m6A serves as a molecular switch that regulates various aspects of RNA function, including splicing, stability, localization or translational control. The versatility of m6A function is typically determined through interaction or disengagement with specific classes of m6A-interacting proteins. Here we review recent advances in the field and provide insights into the roles of m6A in regulating brain function, from development to synaptic plasticity, learning and memory. We also discuss how aberrant m6A signaling may contribute to neurodevelopmental and neuropsychiatric disorders. This article is protected by copyright. All rights reserved

Amyloid-β-induced dysregulation of AMPA receptor trafficking

Evidence from neuropathological, genetic, animal model, and biochemical studies has indicated that the accumulation of amyloid-beta (Aβ) is associated with, and probably induces, profound neuronal changes in brain regions critical for memory and cognition in the development of Alzheimer's disease (AD). There is considerable evidence that synapses are particularly vulnerable to AD, establishing synaptic dysfunction as one of the earliest events in pathogenesis, prior to neuronal loss. It is clear that excessive Aβ levels can disrupt excitatory synaptic transmission and plasticity, mainly due to dysregulation of the AMPA and NMDA glutamate receptors in the brain. Importantly, AMPA receptors are the principal glutamate receptors that mediate fast excitatory neurotransmission. This is essential for synaptic plasticity, a cellular correlate of learning and memory, which are the cognitive functions that are most disrupted in AD. Here we review recent advances in the field and provide insights into the molecular mechanisms that underlie Aβ-induced dysfunction of AMPA receptor trafficking. This review focuses primarily on NMDA receptor- and metabotropic glutamate receptor-mediated signaling. In particular, we highlight several mechanisms that underlie synaptic long-term depression as common signaling pathways that are hijacked by the neurotoxic effects of Aβ

Strategy to Improve Recycling Yield of Aluminium Cans

Millions of canned drinks are consumed everyday globally and their wastes create an enviromental issue. Fortunately, the cans are made from aluminium (Al) so that it can be recycled. There are two main keypoints existing during the recycling process of Al cans, i.e. the aluminium loss or low Al-yield and low recycling yield. This work outlines the strategies to improve the recycling perfomance for Al beverage cans, i.e. by adding drossing flux, applying improved melting strategy, and cans decoating prior to melting. Drossing flux was added to assist the detachment of Al from the slag. Another improved melting strategy was worked out by decreasing exposure time cans to the furnace atmosphere during melting. All those above strategies result in an increase of recycle yield in a range of 4 % to 5 %