1,389 research outputs found

    New tricks for p53 regulation - restraint by protein coding RNAs

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    P53 is most well-known for its tumor suppressive function in differentiated cells. Its activities in embryonic stem cells (ESCs) are, however, less well understood. For many years it was thought that p53 is not active at all in ESCs and unable to elicit a DNA damage response in this cell type. In the last few years, it emerged that p53 may have some functions in ESCs. Nevertheless, it remained a mystery how its activity is controlled in ESCs. A recent report demonstrates that p53 activity is regulated by a novel RNA-containing negative feedback loop that promotes apoptosis specifically in ESCs. This study not only demonstrates unequivocally that p53 is active in ESCs, it further illustrates a novel mechanism of gene regulation-by protein coding RNAs. © 2015 Blattner

    The Jury: Trial and Error in the American Courtroom

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    A Review of The Jury: Trial and Error in the American Courtroom by Stephen J. Adle

    Regulation of the DNA Damage Response to DSBs by Post-Translational Modifications

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    Damage to the genetic material can affect cellular function in many ways. Therefore, maintenance of the genetic integrity is of primary importance for all cells. Upon DNA damage, cells respond immediately with proliferation arrest and repair of the lesion or apoptosis. All these consequences require recognition of the lesion and transduction of the information to effector systems. The accomplishment of DNA repair, but also of cell cycle arrest and apoptosis furthermore requires protein-protein interactions and the formation of larger protein complexes. More recent research shows that the formation of many of these aggregates depends on post-translational modifications. In this article, we have summarized the different cellular events in response to a DNA double strand break, the most severe lesion of the DNA

    Antimony doping of Si layers grown by solid-phase epitaxy

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    We report here that layers of Si formed by solid-phase epitaxial growth (SPEG) can be doped intentionally. The sample consists initially of an upper layer of amorphous Si (~1 µm thick), a very thin intermediate layer of Sb (nominally 5 Å), and a thin lower layer of Pd (~500 Å), all electron-gun deposited on top of a single-crystal substrate (1–10 Ω cm, p type, orientation). After a heating cycle which induces epitaxial growth, electrically active Sb atoms are incorporated into the SPEG layer, as shown by the following facts: (a) the SPEG layer forms a p-n junction against the p-type substrate, (b) the Hall effect indicates strong n-type conduction of the layer, and (c) Auger electron spectra reveal the presence of Sb in the layer

    Using non-speech sounds to provide navigation cues

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    This article describes 3 experiments that investigate the possibiity of using structured nonspeech audio messages called earcons to provide navigational cues in a menu hierarchy. A hierarchy of 27 nodes and 4 levels was created with an earcon for each node. Rules were defined for the creation of hierarchical earcons at each node. Participants had to identify their location in the hierarchy by listening to an earcon. Results of the first experiment showed that participants could identify their location with 81.5% accuracy, indicating that earcons were a powerful method of communicating hierarchy information. One proposed use for such navigation cues is in telephone-based interfaces (TBIs) where navigation is a problem. The first experiment did not address the particular problems of earcons in TBIs such as “does the lower quality of sound over the telephone lower recall rates,” “can users remember earcons over a period of time.” and “what effect does training type have on recall?” An experiment was conducted and results showed that sound quality did lower the recall of earcons. However; redesign of the earcons overcame this problem with 73% recalled correctly. Participants could still recall earcons at this level after a week had passed. Training type also affected recall. With personal training participants recalled 73% of the earcons, but with purely textual training results were significantly lower. These results show that earcons can provide good navigation cues for TBIs. The final experiment used compound, rather than hierarchical earcons to represent the hierarchy from the first experiment. Results showed that with sounds constructed in this way participants could recall 97% of the earcons. These experiments have developed our general understanding of earcons. A hierarchy three times larger than any previously created was tested, and this was also the first test of the recall of earcons over time

    Recommendation model based on opinion diffusion

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    Information overload in the modern society calls for highly efficient recommendation algorithms. In this letter we present a novel diffusion based recommendation model, with users' ratings built into a transition matrix. To speed up computation we introduce a Green function method. The numerical tests on a benchmark database show that our prediction is superior to the standard recommendation methods.Comment: 5 pages, 2 figure

    Drug discovery in the p53 pathway

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    Oligocene niche shift, Miocene diversification – cold tolerance and accelerated speciation rates in the St. John’s Worts (Hypericum, Hypericaceae)

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    Background: Our aim is to understand the evolution of species-rich plant groups that shifted from tropical into cold/temperate biomes. It is well known that climate affects evolutionary processes, such as how fast species diversify, species range shifts, and species distributions. Many plant lineages may have gone extinct in the Northern Hemisphere due to Late Eocene climate cooling, while some tropical lineages may have adapted to temperate conditions and radiated; the hyper-diverse and geographically widespread genus Hypericum is one of these. Results: To investigate the effect of macroecological niche shifts on evolutionary success we combine historical biogeography with analyses of diversification dynamics and climatic niche shifts in a phylogenetic framework. Hypericum evolved cold tolerance c. 30 million years ago, and successfully colonized all ice-free continents, where today ~500 species exist. The other members of Hypericaceae stayed in their tropical habitats and evolved into ~120 species. We identified a 15–20 million year lag between the initial change in temperature preference in Hypericum and subsequent diversification rate shifts in the Miocene. Conclusions: Contrary to the dramatic niche shift early in the evolution of Hypericum most extant species occur in temperate climates including high elevations in the tropics. These cold/temperate niches are a distinctive characteristic of Hypericum. We conclude that the initial release from an evolutionary constraint (from tropical to temperate climates) is an important novelty in Hypericum. However, the initial shift in the adaptive landscape into colder climates appears to be a precondition, and may not be directly related to increased diversification rates. Instead, subsequent events of mountain formation and further climate cooling may better explain distribution patterns and species-richness in Hypericum. These findings exemplify important macroevolutionary patterns of plant diversification during large-scale global climate change
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