scholarly journals 1048. Long-Term Regulated Gene Expression in Non-Human Primates Using a Single Non-Recombinogenic AAV Vector

2004 ◽  
Vol 9 ◽  
pp. S402 ◽  
Keyword(s):  
Gene Expression ◽  
Aav Vector ◽  
Regulated Gene Expression

Stage 1 Registered Report Manuscript - Transcriptional Correlates of Savings Memory: Is Forgetting Due to Decay or Retrieval Failure?

2020 ◽  
Author(s):  
Robert Calin-Jageman ◽  
Irina Calin-Jageman ◽  
Tania Rosiles ◽  
Melissa Nguyen ◽  
Annette Garcia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Memory Trace ◽  
Aplysia Californica ◽  
Retrieval Failure ◽  
Initial Learning ◽  
Rigorous Test ◽  
Regulated Gene Expression ◽  
Stage 1 ◽  
Weak Similarity

[[This is a Stage 1 Registered Report manuscript. The project was submitted for review to eNeuro. Upon revision and acceptance, this version of the manuscript was pre-registered on the OSF (9/11/2019, https://osf.io/fqh8j) (but due to an oversight not posted as a preprint until July 2020). A Stage 2 manuscript is now posted as a pre-print (https://psyarxiv.com/h59jv) and is under review at eNeuro. A link to the final Stage 2 manuscript will be added when available.]]There is fundamental debate about the nature of forgetting: some have argued that it represents the decay of the memory trace, others that the memory trace persists but becomes inaccessible due to retrieval failure. These different accounts of forgetting make different predictions about savings memory, the rapid re-learning of seemingly forgotten information. If forgetting is due to decay then savings requires re-encoding and should thus involve the same mechanisms as initial learning. If forgetting is due to retrieval-failure then savings should be mechanistically distinct from encoding. In this registered report we conducted a pre-registered and rigorous test between these accounts of forgetting. Specifically, we used microarray to characterize the transcriptional correlates of a new memory (1 day from training), a forgotten memory (8 days from training), and a savings memory (8 days from training but with a reminder on day 7 to evoke a long-term savings memory) for sensitization in Aplysia californica (n = 8 samples/group). We find that the transcriptional correlates of savings are [highly similar / somewhat similar / unique] relative to new (1-day-old) memories. Specifically, savings memory and a new memory share [X] of [Y] regulated transcripts, show [strong / moderate / weak] similarity in sets of regulated transcripts, and show [r] correlation in regulated gene expression, which is [substantially / somewhat / not at all] stronger than at forgetting. Overall, our results suggest that forgetting represents [decay / retrieval-failure / mixed mechanisms].

Homogeneity and long-term stability of tetracycline-regulated gene expression with low basal activity by using the rtTA2S-M2 transactivator and insulator-flanked reporter vectors

Gene ◽  
2004 ◽  
Vol 327 (1) ◽  
pp. 61-73 ◽  
Author(s):  
Zhican Qu ◽  
Jaideep V Thottassery ◽  
Sabrina Van Ginkel ◽  
Marina Manuvakhova ◽  
Louise Westbrook ◽  
...  
Keyword(s):  
Gene Expression ◽  
Term Stability ◽  
Long Term Stability ◽  
Basal Activity ◽  
Regulated Gene Expression

scholarly journals Control and Augmentation of Long-Term Plasmid Transgene ExpressionIn Vivoin Murine Muscle Tissue andEx Vivoin Patient Mesenchymal Tissue

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
David Morrissey ◽  
Jan P. van Pijkeren ◽  
Simon Rajendran ◽  
Sara A. Collins ◽  
Garrett Casey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgene Expression ◽  
Ex Vivo ◽  
Inducible Promoter ◽  
Luciferase Expression ◽  
Mesenchymal Tissue ◽  
Adenoviral Delivery ◽  
Regulated Gene Expression

Purpose. In vivogene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expressionin vivoin mice andex vivoin human tissues.Methods.Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadricepsin vivowas examined. Temporal control was assessed using a doxycycline-inducible system. Anex vivomodel was developed and optimised using murine tissue, and applied inex vivohuman tissue.Results. In vivoplasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detectedex vivoin human muscle and tendon.Conclusions.Plasmid constructs resulted in long-termin vivogene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in humanex vivomesenchymal tissue was demonstrated for the first time.

scholarly journals Novel Transcriptional Regulatory Signals in the Adeno-Associated Virus Terminal Repeat A/D Junction Element

2000 ◽  
Vol 74 (18) ◽  
pp. 8732-8739 ◽  
Author(s):  
Rebecca P. Haberman ◽  
Thomas J. McCown ◽  
Richard Jude Samulski
Keyword(s):  
Gene Expression ◽  
Fluorescent Protein ◽  
Terminal Repeat ◽  
Cmv Promoter ◽  
Adeno Associated Virus ◽  
Regulated Expression ◽  
Regulated Gene Expression

ABSTRACT Adeno-associated virus (AAV) type 2 vectors transfer stable, long-term gene expression to diverse cell types in vivo. Many gene therapy applications require the control of long-term transgene expression, and AAV vectors, similar to other gene transfer systems, are being evaluated for delivery of regulated gene expression cassettes. Previously, we (R. P. Haberman, T. J. McCown, and R. J. Samulski, Gene Ther. 5:1604–1611, 1998) demonstrated the use of the tetracycline-responsive system for long-term regulated expression in rat brains. In that study, we also observed residual expression in the “off” state both in vitro and in vivo, suggesting that the human cytomegalovirus (CMV) major immediate-early minimal promoter or other cis-acting elements (AAV terminal repeats [TR]) were contributing to this activity. In the present study, we identify that the AAV TR, minus the tetracycline-responsive minimal CMV promoter, will initiate mRNA expression from vector templates. Using deletion analysis and specific PCR-derived TR reporter gene templates, we mapped this activity to a 37-nucleotide stretch in theA/D elements of the TR. Although the mRNA derived from the TR is generated from a non-TATA box element, the use of mutant templates failed to identify function of canonical initiator sequences as previously described. Finally, we demonstrated the presence of green fluorescent protein expression both in vitro and in vivo in brain by using recombinant virus carrying only the TR element. Since the AAV terminal repeat is a necessary component of all recombinant AAV vectors, this TR transcriptional activity may interfere with all regulated expression cassettes and may be a problem in the development of novel TR split gene vectors currently being considered for genes too large to be packaged.

Long-term, noninvasive imaging of regulated gene expression in living mice

genesis ◽  
2001 ◽  
Vol 29 (3) ◽  
pp. 116-122 ◽  
Author(s):  
Mazahir T. Hasan ◽  
Kai Schönig ◽  
Stefan Berger ◽  
Walter Graewe ◽  
Hermann Bujard
Keyword(s):  
Gene Expression ◽  
Noninvasive Imaging ◽  
Regulated Gene Expression

Nutrient-regulated gene expression in eukaryotes

2006 ◽  
Vol 73 ◽  
pp. 85-96 ◽  
Author(s):  
Richard J. Reece ◽  
Laila Beynon ◽  
Stacey Holden ◽  
Amanda D. Hughes ◽  
Karine Rébora ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Control ◽  
Direct Interaction ◽  
Signalling Pathways ◽  
A Cell ◽  
One Step ◽  
Higher Eukaryotes ◽  
Regulated Gene Expression

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.

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