MicroRNA Controlled Adenovirus Mediates Anti-Cancer Efficacy without Affecting Endogenous MicroRNA Activity

MicroRNAs are small non-coding RNA molecules that regulate mRNA translation and stability by binding to complementary sequences usually within the 3′ un-translated region (UTR). We have previously shown that the hepatic toxicity caused by wild-type Adenovirus 5 (Ad5WT) in mice can be prevented by incorporating 4 binding sites for the liver-specific microRNA, mir122, into the 3′ UTR of E1A mRNA. This virus, termed Ad5mir122, is a promising virotherapy candidate and causes no obvious liver pathology. Herein we show that Ad5mir122 maintains wild-type lytic activity in cancer cells not expressing mir122 and assess any effects of possible mir122 depletion in host cells. Repeat administration of 2×1010 viral particles of Admir122 to HepG2 tumour bearing mice showed significant anti-cancer efficacy. RT-QPCR showed that E1A mRNA was down-regulated 29-fold in liver when compared to Ad5WT. Western blot for E1A confirmed that all protein variants were knocked down. RT-QPCR for mature mir122 in infected livers showed that quantity of mir122 remained unaffected. Genome wide mRNA microarray profiling of infected livers showed that although the transcript level of >3900 different mRNAs changed more than 2-fold following Ad5WT infection, less than 600 were changed by Ad5mir122. These were then filtered to select mRNAs that were only altered by Ad5mir122 and the remaining 21 mRNAs were compared to predicted mir122 targets. No mir122 target mRNAs were affected by Ad5 mir122. These results demonstrate that the exploitation of microRNA regulation to control virus replication does not necessarily affect the level of the microRNA or the endogenous mRNA targets

First Precambrian palaeomagnetic data from the Mawson Craton (East Antarctica) and tectonic implications

A pilot palaeomagnetic study was conducted on the recently dated with in situ SHRIMP U-Pb method at 1134 ± 9 Ma (U-Pb, zircon and baddeleyite) Bunger Hills dykes of the Mawson Craton (East Antarctica). Of the six dykes sampled, three revealed meaningful results providing the first well-dated Mesoproterozoic palaeopole at 40.5°S, 150.1°E (A95 = 20°) for the Mawson Craton. Discordance between this new pole and two roughly coeval poles from Dronning Maud Land and Coats Land (East Antarctica) demonstrates that these two terranes were not rigidly connected to the Mawson Craton ca. 1134 Ma. Comparison between the new pole and that of the broadly coeval Lakeview dolerite from the North Australian Craton supports the putative ~40° late Neoproterozoic relative rotation between the North Australian Craton and the combined South and West Australian cratons. A mean ca. 1134 Ma pole for the Proto-Australia Craton is calculated by combining our new pole and that of the Lakeview dolerite after restoring the 40° intracontinental rotation. A comparison of this mean pole with the roughly coeval Abitibi dykes pole from Laurentia confirms that the SWEAT reconstruction of Australia and Laurentia was not viable for ca. 1134 Ma

Earth: Atmospheric Evolution of a Habitable Planet

Our present-day atmosphere is often used as an analog for potentially habitable exoplanets, but Earth's atmosphere has changed dramatically throughout its 4.5 billion year history. For example, molecular oxygen is abundant in the atmosphere today but was absent on the early Earth. Meanwhile, the physical and chemical evolution of Earth's atmosphere has also resulted in major swings in surface temperature, at times resulting in extreme glaciation or warm greenhouse climates. Despite this dynamic and occasionally dramatic history, the Earth has been persistently habitable--and, in fact, inhabited--for roughly 4 billion years. Understanding Earth's momentous changes and its enduring habitability is essential as a guide to the diversity of habitable planetary environments that may exist beyond our solar system and for ultimately recognizing spectroscopic fingerprints of life elsewhere in the Universe. Here, we review long-term trends in the composition of Earth's atmosphere as it relates to both planetary habitability and inhabitation. We focus on gases that may serve as habitability markers (CO2, N2) or biosignatures (CH4, O2), especially as related to the redox evolution of the atmosphere and the coupled evolution of Earth's climate system. We emphasize that in the search for Earth-like planets we must be mindful that the example provided by the modern atmosphere merely represents a single snapshot of Earth's long-term evolution. In exploring the many former states of our own planet, we emphasize Earth's atmospheric evolution during the Archean, Proterozoic, and Phanerozoic eons, but we conclude with a brief discussion of potential atmospheric trajectories into the distant future, many millions to billions of years from now. All of these 'Alternative Earth' scenarios provide insight to the potential diversity of Earth-like, habitable, and inhabited worlds.Comment: 34 pages, 4 figures, 4 tables. Review chapter to appear in Handbook of Exoplanet

New paleomagnetic data from Late Neoproterozoic sedimentary successions in Southern Urals, Russia: implications for the Late Neoproterozoic paleogeography of the Iapetan realm

We present the results of paleomagnetic study of Ediacaran sedimentary successions from the Southern Urals. The analysis of the sedimentary rocks of the Krivaya Luka, Kurgashlya and Bakeevo Formations reveal stable mid-temperature and high-temperature remanence components.Mid-temperature components were acquired during Devonian (Bakeevo Formation) and Late Carboniferous–Early Permian remagnetization events. The high-temperature components in Kurgashlya and Bakeevo Formations are interpreted to be primar , because they are supported by a positive conglomerate test (Bakeevo Formation) and magnetostratigraphic pattern (Kurgashlya Formation). Thehigh-temperature component in the Krivaya Luka Formation is interpreted to be a Late Ediacaran overprint. Our new paleomagnetic poles together with some previously published Ediacaran poles from Baltica and Laurentia are used herein to produce a series of paleogeographic reconstructions of the opening of the Iapetus Ocean