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Adenovirus E1A Activation Domain Regulates H3 Acetylation Affecting Varied Steps in Transcription at Different Viral Promoters.
How histone acetylation promotes transcription is not clearly understood. Here, we confirm an interaction between p300 and the adenovirus 2 large E1A activation domain (AD) and map the interacting regions in E1A by observing colocalization at an integrated lacO array of fusions of LacI-mCherry to E1A fragments with YFP-p300. Viruses with mutations in E1A subdomains were constructed and analyzed for kinetics of early viral RNA expression and association of acetylated H3K9, K18, K27, TBP, and RNA polymerase II (Pol II) across the viral genome. The results indicate that this E1A interaction with p300 is required for H3K18 and H3K27 acetylation at the E2early, E3, and E4 promoters and is required for TBP and Pol II association with the E2early promoter. In contrast, H3K18/27 acetylation was not required for TBP and Pol II association with the E3 and E4 promoters but was required for E4 transcription at a step subsequent to Pol II preinitiation complex assembly.IMPORTANCE Despite a wealth of data associating promoter and enhancer region histone N-terminal tail lysine acetylation with transcriptional activity, there are relatively few examples of studies that establish causation between these histone posttranslational modifications and transcription. While hypoacetylation of histone H3 lysines 18 and 27 is associated with repression, the step(s) in the overall process of transcription that is blocked at a hypoacetylated promoter is not clearly established in most instances. Studies presented here confirm that the adenovirus 2 large E1A protein activation domain interacts with p300, as reported previously (P. Pelka, J. N. G. Ablack, J. Torchia, A. S. Turnell, R. J. A. Grand, J. S. Mymryk, Nucleic Acids Res 37:1095-1106, 2009, https://doi.org/10.1093/nar/gkn1057), and that the resulting acetylation of H3K18/27 affects varied steps in transcription at different viral promoters
Photometric analysis of a space shuttle water venting
Presented here is a preliminary interpretation of a recent experiment conducted on Space Shuttle Discovery (Mission STS 29) in which a stream of liquid supply water was vented into space at twilight. The data consist of video images of the sunlight-scattering water/ice particle cloud that formed, taken by visible light-sensitive intensified cameras both onboard the spacecraft and at the AMOS ground station near the trajectory's nadir. This experiment was undertaken to study the phenomenology of water columns injected into the low-Earth orbital environment, and to provide information about the lifetime of ice particles that may recontact Space Shuttle orbits later. The findings about the composition of the cloud have relevance to ionospheric plasma depletion experiments and to the dynamics of the interaction of orbiting spacecraft with the environment
Investigating owner use of dietary supplements in dogs with idiopathic epilepsy
Epilepsy is the most common chronic neurological disorder in dogs. Some diets have been shown to have a positive impact upon the seizure activity in dogs with idiopathic epilepsy (IE), while other diets and dietary supplements (DS), although marketed as providing health benefits, lack conclusive scientific evidence on their actual beneficial effects.
A web-based owner questionnaire was designed to assess how and why owners of dogs with IE use different dietary regimes and DS. The study cohort, with 297 valid responses, consisted mainly of pure-breed (82.5%) male neutered (52.9%) dogs. Over two-thirds of owners (67.7%) changed their dog's diet after their dog received a diagnosis of IE. Nearly half of the owners (45.8%) reported giving DS, the most common being coconut oil or derived medium-chain triglyceride oil (71.3%). Some owner justifications of DS use included improvement of seizure frequency (88.2%), seizure severity (61.8%) and protection from potential drug side effects (62.5%).
Many owners give DS to their dog with IE. The pharmacokinetic properties of anti-epileptic drugs, such as efficacy, absorption and clearance can be influenced by other medications, diets and possibly by DS. We propose that use of DS should be considered and monitored by veterinary surgeons in epilepsy management
Stage managing bipolar disorder.
OBJECTIVES: Clinical staging is widespread in medicine - it informs prognosis, clinical course, and treatment, and assists individualized care. Staging places an individual on a probabilistic continuum of increasing potential disease severity, ranging from clinically at-risk or latency stage through first threshold episode of illness or recurrence, and, finally, to late or end-stage disease. The aim of the present paper was to examine and update the evidence regarding staging in bipolar disorder, and how this might inform targeted and individualized intervention approaches.
METHODS: We provide a narrative review of the relevant information.
RESULTS: In bipolar disorder, the validity of staging is informed by a range of findings that accompany illness progression, including neuroimaging data suggesting incremental volume loss, cognitive changes, and a declining likelihood of response to pharmacological and psychosocial treatments. Staging informs the adoption of a number of approaches, including the active promotion of both indicated prevention for at-risk individuals and early intervention strategies for newly diagnosed individuals, and the tailored implementation of treatments according to the stage of illness.
CONCLUSIONS: The nature of bipolar disorder implies the presence of an active process of neuroprogression that is considered to be at least partly mediated by inflammation, oxidative stress, apoptosis, and changes in neurogenesis. It further supports the concept of neuroprotection, in that a diversity of agents have putative effects against these molecular targets. Clinically, staging suggests that the at-risk state or first episode is a period that requires particularly active and broad-based treatment, consistent with the hope that the temporal trajectory of the illness can be altered. Prompt treatment may be potentially neuroprotective and attenuate the neurostructural and neurocognitive changes that emerge with chronicity. Staging highlights the need for interventions at a service delivery level and implementing treatments at the earliest stage of illness possible
Deriving Telescope Mueller Matrices Using Daytime Sky Polarization Observations
Telescopes often modify the input polarization of a source so that the
measured circular or linear output state of the optical signal can be
signficantly different from the input. This mixing, or polarization
"cross-talk", is defined by the optical system Mueller matrix. We describe here
an efficient method for recovering the input polarization state of the light
and the full 4 x 4 Mueller matrix of the telescope with an accuracy of a few
percent without external masks or telescope hardware modification. Observations
of the bright, highly polarized daytime sky using the Haleakala 3.7m AEOS
telescope and a coude spectropolarimeter demonstrate the technique.Comment: Accepted for publication in PAS
Characteristic QSO Accretion Disk Temperatures from Spectroscopic Continuum Variability
Using Sloan Digital Sky Survey (SDSS) quasar spectra taken at multiple
epochs, we find that the composite flux density differences in the rest frame
wavelength range 1300-6000 AA can be fit by a standard thermal accretion disk
model where the accretion rate has changed from one epoch to the next (without
considering additional continuum emission components). The fit to the composite
residual has two free parameters: a normalizing constant and the average
characteristic temperature . In turn the characteristic temperature
is dependent on the ratio of the mass accretion rate to the square of the black
hole mass. We therefore conclude that most of the UV/optical variability may be
due to processes involving the disk, and thus that a significant fraction of
the UV/optical spectrum may come directly from the disk.Comment: 31 pages, 8 figure
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