Regulated ATF5 loss-of-function in adult mice blocks formation and causes regression/eradication of gliomas

Glioblastomas are among the most incurable cancers. Our past findings indicated that glioblastoma cells, but not neurons or glia, require the transcription factor ATF5 (activating transcription factor 5) for survival. However, it was unknown whether interference with ATF5 function can prevent or promote regression/eradication of malignant gliomas in vivo. To address this issue, we created a mouse model by crossing a human glial fibrillary acidic protein (GFAP) promoter-tetracycline transactivator mouse line with tetracycline operon-dominant negative-ATF5 (d/n-ATF5) mice to establish bi-transgenic mice. In this model, d/n-ATF5 expression is controlled by doxycycline and the promoter for GFAP, a marker for stem/progenitor cells as well as gliomas. Endogenous gliomas were produced with high efficiency by retroviral delivery of platelet-derived growth factor (PDGF)-B and p53-short hairpin RNA (shRNA) in adult bi-transgenic mice in which expression of d/n-ATF5 was spatially and temporally regulated. Induction of d/n-ATF5 before delivery of PDGF-B/p53-shRNA virus greatly reduced the proportion of mice that formed tumors. Moreover, d/n-ATF5 induction after tumor formation led to regression/eradication of detectable gliomas without evident damage to normal brain cells in all 24 mice assessed

Coastal barrier stratigraphy for Holocene high-resolution sea-level reconstruction

The uncertainties surrounding present and future sea-level rise have revived the debate around sea-level changes through the deglaciation and mid- to late Holocene, from which arises a need for high-quality reconstructions of regional sea level. Here, we explore the stratigraphy of a sandy barrier to identify the best sea-level indicators and provide a new sea-level reconstruction for the central Portuguese coast over the past 6.5 ka. The selected indicators represent morphological features extracted from coastal barrier stratigraphy, beach berm and dune-beach contact. These features were mapped from high-resolution ground penetrating radar images of the subsurface and transformed into sea-level indicators through comparison with modern analogs and a chronology based on optically stimulated luminescence ages. Our reconstructions document a continuous but slow sea-level rise after 6.5 ka with an accumulated change in elevation of about 2 m. In the context of SW Europe, our results show good agreement with previous studies, including the Tagus isostatic model, with minor discrepancies that demand further improvement of regional models. This work reinforces the potential of barrier indicators to accurately reconstruct high-resolution mid- to late Holocene sea-level changes through simple approaches

The Lower Ordovician Tøyen Shale succession in the Fågelsång-3 drill core, Scania, Sweden

The Ordovician Tøyen Shale Formation of the recently retrieved Fågelsång-3 drill core provides some important information on the graptolite biostratigraphy of the unit and its completeness in the region. The drill core reached downwards into the Kiaerograptus supremus Biozone of late Tremadocian age. Above a major fault zone, faunas with a number of specimens referred to Pseudophyllograptus densus are indicative of a late Dapingian age. Rare specimens of Azygograptus sp. also help constrain the age. The presence of Arienigraptus zhejiangensis indicates that the base of the Darriwilian Komstad Limestone Formation is of Levisograptus austrodentatus Biozone age. Specimens of Tetragraptus cor and Levisograptus sinicus in a shale bed within the lower part of the Komstad Limestone Formation can be referred to the upper subzone of the L. austrodentatus Biozone, the Levisograptus sinicus Subzone. This fauna represents the youngest graptolite fauna beneath the massive Komstad Limestone Formation. The Tøyen Shale Formation can be shown to be highly incomplete in Scania, possibly due to post-depositional tectonic deformation and faulting