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3. Transgenic songbirds offer an opportunity to develop a genetic model for vocal learning

Author

Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Lois, Carlos, Scott, Benjamin Barnett, Agate, R. J., Nottebohm, F., Haripal, B., Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Lois, Carlos, Scott, Benjamin Barnett, Agate, R. J., Nottebohm, F., and Haripal, B.

Abstract

Zebra finches are widely used for studying the basic biology of vocal learning. The inability to introduce genetic modifications in these animals has substantially limited studies on the molecular biology of this behavior, however. We used an HIV-based lentivirus to produce germline transgenic zebra finches. The lentivirus encoded the GFP regulated by the human ubiquitin-C promoter [Lois C, Hong EJ, Pease S, Brown EJ, Baltimore D (2002) Science 295:868–872], which is active in a wide variety of cells. The virus was injected into the very early embryo (blastodisc stage) to target the primordial germline cells that later give rise to sperm and eggs. A total of 265 fertile eggs were injected with virus, and 35 hatched (13%); 23 of these potential founders (F0) were bred, and three (13%) produced germline transgenic hatchlings that expressed the GFP protein (F1). Two of these three founders (F0) have produced transgenic young at a rate of 12% and the third at a rate of 6%. Furthermore, two of the F1 generation transgenics have since reproduced, one having five offspring (all GFP positive) and the other four offsping (one GFP positive)., McKnight Endowment Fund for Neuroscience (McKnight Technological Innovations in Neuroscience Awards), Whitehall Foundation, Rockefeller University

Published
2010

4. Safe and effective navigation of autonomous robots in hazardous environments.

Author

Seward, D.W., Agate, R., Pace, C., Seward, D.W., Agate, R., and Pace, C.

Abstract

The development of autonomous mobile machines to perform useful tasks in real work environments is currently being impeded by concerns over effectiveness, commercial viability and, above all, safety. This paper introduces a case study of a robotic excavator to explore a series of issues around system development, navigation in unstructured environments, autonomous decision making and changing the behaviour of autonomous machines to suit the prevailing demands of users. The adoption of the Real-Time Control Systems (RCS) architecture (Albus, 1991) is proposed as a universal framework for the development of intelligent systems. In addition it is explained how the use of Partially Observable Markov Decision Processes (POMDP) (Kaelbling et al., 1998) can form the basis of decision making in the face of uncertainty and how the technique can be effectively incorporated into the RCS architecture. Particular emphasis is placed on ensuring that the resulting behaviour is both task effective and adequately safe, and it is recognised that these two objectives may be in opposition and that the desired relative balance between them may change. The concept of an autonomous system having “values” is introduced through the use of utility theory. Limited simulation results of experiments are reported which demonstrate that these techniques can create intelligent systems capable of modifying their behaviour to exhibit either ‘safety conscious’ or ‘task achieving’ personalities.

Published
2007

8. Human ESC-Derived Chimeric Mouse Models of Huntington's Disease Reveal Cell-Intrinsic Defects in Glial Progenitor Cell Differentiation.

Author

Osipovitch M, Asenjo Martinez A, Mariani JN, Cornwell A, Dhaliwal S, Zou L, Chandler-Militello D, Wang S, Li X, Benraiss SJ, Agate R, Lampp A, Benraiss A, Windrem MS, and Goldman SA

Subjects
Animals, Astrocytes metabolism, Astrocytes pathology, Cell Differentiation, Chimera, Demyelinating Diseases genetics, Demyelinating Diseases metabolism, Homeobox Protein Nkx-2.2, Homeodomain Proteins, Human Embryonic Stem Cells metabolism, Humans, Huntington Disease genetics, Huntington Disease metabolism, Mice, Mutation, Neurogenesis, Neuroglia metabolism, Nuclear Proteins, Stem Cells metabolism, Transcription Factors, Demyelinating Diseases pathology, Disease Models, Animal, Human Embryonic Stem Cells pathology, Huntingtin Protein genetics, Huntington Disease pathology, Neuroglia pathology, Stem Cells pathology
Abstract

Huntington's disease (HD) is characterized by hypomyelination and neuronal loss. To assess the basis for myelin loss in HD, we generated bipotential glial progenitor cells (GPCs) from human embryonic stem cells (hESCs) derived from mutant Huntingtin (mHTT) embryos or normal controls and performed RNA sequencing (RNA-seq) to assess mHTT-dependent changes in gene expression. In human GPCs (hGPCs) derived from 3 mHTT hESC lines, transcription factors associated with glial differentiation and myelin synthesis were sharply downregulated relative to normal hESC GPCs; NKX2.2, OLIG2, SOX10, MYRF, and their downstream targets were all suppressed. Accordingly, when mHTT hGPCs were transplanted into hypomyelinated shiverer mice, the resultant glial chimeras were hypomyelinated; this defect could be rescued by forced expression of SOX10 and MYRF by mHTT hGPCs. The mHTT hGPCs also manifested impaired astrocytic differentiation and developed abnormal fiber architecture. White matter involution in HD is thus a product of the cell-autonomous, mHTT-dependent suppression of glial differentiation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2019
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9. Children must be protected from the tobacco industry's marketing tactics.

Author

Hopkinson N, Wallis C, Higgins B, Gaduzo S, Sherrington R, Keilty S, Stern M, Britton J, Bush A, Moxham J, Sylvester K, Griffiths V, Sutherland T, Crossingham I, Raju R, Spencer C, Safavi S, Deegan P, Seymour J, Hickman K, Hughes J, Wieboldt J, Shaheen F, Peedell C, Mackenzie N, Nicholl D, Jolley C, Crooks G, Crooks G, Dow C, Deveson P, Bintcliffe O, Gray B, Kumar S, Haney S, Docherty M, Thomas A, Chua F, Dwarakanath A, Summers G, Prowse K, Lytton S, Ong YE, Graves J, Banerjee T, English P, Leonard A, Brunet M, Chaudhry N, Ketchell RI, Cummings N, Lebus J, Sharp C, Meadows C, Harle A, Stewart T, Parry D, Templeton-Wright S, Moore-Gillon J, Stratford- Martin J, Saini S, Matusiewicz S, Merritt S, Dowson L, Satkunam K, Hodgson L, Suh ES, Durrington H, Browne E, Walters N, Steier J, Barry S, Griffiths M, Hart N, Nikolic M, Berry M, Thomas A, Miller J, McNicholl D, Marsden P, Warwick G, Barr L, Adeboyeku D, Mohd Noh MS, Griffiths P, Davies L, Quint J, Lyall R, Shribman J, Collins A, Goldman J, Bloch S, Gill A, Man W, Christopher A, Yasso R, Rajhan A, Shrikrishna D, Moore C, Absalom G, Booton R, Fowler RW, Mackinlay C, Sapey E, Lock S, Walker P, Jha A, Satia I, Bradley B, Mustfa N, Haqqee R, Thomas M, Patel A, Redington A, Pillai A, Keaney N, Fowler S, Lowe L, Brennan A, Morrison D, Murray C, Hankinson J, Dutta P, Maddocks M, Pengo M, Curtis K, Rafferty G, Hutchinson J, Whitfield R, Turner S, Breen R, Naveed SU, Goode C, Esterbrook G, Ahmed L, Walker W, Ford D, Connett G, Davidson P, Elston W, Stanton A, Morgan D, Myerson J, Maxwell D, Harrris A, Parmar S, Houghton C, Winter R, Puthucheary Z, Thomson F, Sturney S, Harvey J, Haslam PL, Patel I, Jennings D, Range S, Mallia-Milanes B, Collett A, Tate P, Russell R, Feary J, O'Driscoll R, Eaden J, Round J, Sharkey E, Montgomery M, Vaughan S, Scheele K, Lithgow A, Partridge S, Chavasse R, Restrick L, Agrawal S, Abdallah S, Lacy-Colson A, Adams N, Mitchell S, Haja Mydin H, Ward A, Denniston S, Steel M, Ghosh D, Connellan S, Rigge L, Williams R, Grove A, Anwar S, Dobson L, Hosker H, Stableforth D, Greening N, Howell T, Casswell G, Davies S, Tunnicliffe G, Mitchelmore P, Phitidis E, Robinson L, Prowse K, Bafadhel M, Robinson G, Boland A, Lipman M, Bourke S, Kaul S, Cowie C, Forrest I, Starren E, Burke H, Furness J, Bhowmik A, Everett C, Seaton D, Holmes S, Doe S, Parker S, Graham A, Paterson I, Maqsood U, Ohri C, Iles P, Kemp S, Iftikhar A, Carlin C, Fletcher T, Emerson P, Beasley V, Ramsay M, Buttery R, Mungall S, Crooks S, Ridyard J, Ross D, Guadagno A, Holden E, Coutts I, Cullen K, O'Connor S, Barker J, Sloper K, Watson J, Smith P, Anderson P, Brown L, Nyman C, Milburn H, Clive A, Serlin M, Bolton C, Fuld J, Powell H, Dayer M, Woolhouse I, Georgiadi A, Leonard H, Dodd J, Campbell I, Ruiz G, Zurek A, Paton JY, Malin A, Wood F, Hynes G, Connell D, Spencer D, Brown S, Smith D, Cooper D, O'Kane C, Hicks A, Creagh-Brown B, Lordan J, Nickol A, Primhak R, Fleming L, Powrie D, Brown J, Zoumot Z, Elkin S, Szram J, Scaffardi A, Marshall R, Macdonald I, Lightbody D, Farmer R, Wheatley I, Radnan P, Lane I, Booth A, Tilbrook S, Capstick T, Hewitt L, McHugh M, Nelson C, Wilson P, Padmanaban V, White J, Davison J, O'Callaghan U, Hodson M, Edwards J, Campbell C, Ward S, Wooler E, Ringrose E, Bridges D, Matthew Hodson, John Edwards, Colin Campbell, Simon Ward, Edwina Wooler, Elizabeth Ringrose, Diana Bridges, Rosalind Backham, Kim Randall, Tracey Mathieson, Long A, Parkes M, Clarke S, Allen B, Connelly C, Forster G, Hoadley J, Martin K, Barnham K, Khan K, Munday M, Edwards C, O'Hara D, Turner S, Pieri-Davies S, Ford K, Daniels T, Wright J, Towns R, Fern K, Butcher J, Burgin K, Winter B, Freeman D, Olive S, Gray L, Pye K, Roots D, Cox N, Davies CA, Wicker J, Hilton K, Lloyd J, MacBean V, Wood M, Kowal J, Downs J, Ryan H, Guyatt F, Nicoll D, Lyons E, Narasimhan D, Rodman A, Walmsley S, Newey A, Buxton M, Dewar M, Cooper A, Reilly J, Lloyd J, Macmillan AB, Roots D, Olley A, Voase N, Martin S, McCarvill I, Christensen A, Agate R, Heslop K, Timlett A, Hailes K, Davey C, Pawulska B, Lane A, Ioakim S, Hough A, Treharne J, Jones H, Winter-Burke A, Miller L, Connolly B, Bingham L, Fraser U, Bott J, Johnston C, Graham A, Curry D, Sumner H, Costello CA, Bartoszewicz C, Badman R, Williamson K, Taylor A, Purcell H, Barnett E, Molloy A, Crawfurd L, Collins N, Monaghan V, Mir M, Lord V, Stocks J, Edwards A, Greenhalgh T, Lenney W, McKee M, McAuley D, Majeed A, Cookson J, Baker E, Janes S, Wedzicha W, Lomas Dean D, Harrison B, Davison T, Calverley P, Wilson R, Stockley R, Ayres J, Gibson J, Simpson J, Burge S, Warner J, Lenney W, Thomson N, Davies P, Woodcock A, Woodhead M, Spiro S, Ormerod L, Bothamley G, Partridge M, Shields M, Montgomery H, Simonds A, Barnes P, Durham S, Malone S, Arabnia G, Olivier S, Gardiner K, and Edwards S

Subjects
Adolescent, Child, Humans, Marketing standards, Product Packaging standards, Tobacco Industry standards, United Kingdom, Marketing legislation & jurisprudence, Product Packaging legislation & jurisprudence, Tobacco Industry legislation & jurisprudence, Tobacco Products
Published
2013
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10. A cDNA microarray from the telencephalon of juvenile male and female zebra finches.

Author

Wade J, Peabody C, Coussens P, Tempelman RJ, Clayton DF, Liu L, Arnold AP, and Agate R

Subjects
Animals, Female, Gene Library, Male, Songbirds, Vocalization, Animal physiology, Gene Expression physiology, Oligonucleotide Array Sequence Analysis methods, Sex Characteristics, Telencephalon metabolism
Abstract

Studies over roughly the last decade have emphasized the importance of gene expression in the development of structure and function of the songbird forebrain. However, few tools have been available to efficiently identify the critical factors. To that end, we have produced a normalized cDNA library from juvenile zebra finch telencephalon, and have spotted inserts from 2400 randomly selected cDNA clones on microarrays (1664 unique sequences). We have also added several previously cloned cDNAs of interest, including three representing genes encoded on sex chromosomes. Hybridizations comparing Cy3- and Cy5-labeled cDNA from the telencephalon of day 25 male and female zebra finches confirmed sexually dimorphic expression of the Z- and W-linked genes, demonstrating the utility of these microarrays for detecting differential expression and providing information about the relative expression of these genes in the brains of juveniles of this age.

Published
2004
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