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- LeVaillant, C. J., et al.
(författare)
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Significant changes in endogenous retinal gene expression assessed 1 year after a single intraocular injection of AAV-CNTF or AAV-BDNF
- 2016
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Ingår i: Molecular Therapy - Methods and Clinical Development. - : Elsevier BV. - 2329-0501. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Use of viral vectors to deliver therapeutic genes to the central nervous system holds promise for the treatment of neurodegenerative diseases and neurotrauma. Adeno-associated viral (AAV) vectors encoding brain-derived neurotrophic factor (BDNF) or ciliary derived neurotrophic factor (CNTF) promote the viability and regeneration of injured adult rat retinal ganglion cells. However, these growth-inducing transgenes are driven by a constitutively active promoter, thus we examined whether long-term AAV-mediated secretion of BDNF or CNTF affected endogenous retinal gene expression. One year after the intravitreal injection of AAV-green fluorescent protein (GFP), bi-cistronic AAV-BDNF-GFP or AAV-CNTF-GFP, mRNA was extracted and analyzed using custom 96 well polymerase chain reaction arrays. Of 93 test genes, 56% showed significantly altered expression in AAV-BDNF-GFP and/or AAV-CNTF-GFP retinas compared with AAV-GFP controls. Of these genes, 73% showed differential expression in AAV-BDNF versus AAV-CNTF injected eyes. To focus on retinal ganglion cell changes, quantitative polymerase chain reaction was undertaken on mRNA (16 genes) obtained from fixed retinal sections in which the ganglion cell layer was enriched. The sign and extent of fold changes in ganglion cell layer gene expression differed markedly from whole retinal samples. Sustained and global alteration in endogenous mRNA expression after gene therapy should be factored into any interpretation of experimental/clinical outcomes, particularly when introducing factors into the central nervous system that require secretion to evoke functionality. © 2016 Official journal of the American Society of Gene & Cell Therapy
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| 3. |
- Nemchin, A. A., et al.
(författare)
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U-Pb isotope systematics and impact ages recorded by a chemically diverse population of glasses from an Apollo 14 lunar soil
- 2022
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier. - 0016-7037 .- 1872-9533. ; 321, s. 206-243
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Tidskriftsartikel (refereegranskat)abstract
- Glass beads formed by ejection of impact-melted lunar rocks and soils are an important component of lunar soils. These glasses range from 100s of microns to up to a few cm in diameter and contain variable, but usually relatively low (several hundred ppb to a few ppm), quantities of U. Because Pb is a volatile element, it tends to be lost from the melts, so individual impact glasses can be dated by the U-Th-Pb isotopic systems. The presence of two additional Pb components in lunar glasses, likely linked to addition of lunar Pb to the beads during their residence on the lunar surface and from terrestrial laboratory contamination, require corrections to the data before accurate formation ages of the glasses can be determined. Here we report a U-Th-Pb isotopic and geochemical study of impact glasses from the Apollo 14 soil 14163, which documents multiple impacts into chemically diverse targets that can be linked to the main groups of rocks found on the Moon, i.e., mare basalts, highlands plagioclase-rich rocks, and KREEP (from high contents of K, REE and P) enriched rocks. The impact ages show a bimodal distribution with peaks at ~3500-3700 Ma and < 1000 Ma, similar to that obtained previously by Ar-40-Ar-39 dating of other suites of lunar regolith glasses. Our data suggest two predominant age peaks at ~100 Ma and ~500 Ma, with other statistically definable clusters of ages also possible. As Pb is relatively resistant to subsolidus diffusive loss in these glasses, the age clusters probably represent primary formation ages during impact events, although processes such as preferential preservation of young glasses and impact conditions necessary for production of regolith glasses need further quantification. (C) 2021 The Authors. Published by Elsevier Ltd.
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