Commandeering of the cellular HuR protein by alphaviruses affects the regulation of host post-transcriptional gene expression

2013 Spring.Includes bibliographical references.It was previously shown that cellular HuR protein binds to a U-rich region in the 3'UTR of Sindbis virus RNA resulting in stabilization of viral transcripts and increased replication efficiency. While the presence of this U-rich region is generally conserved among alphaviruses, a subset lacks a typical U-rich region. The 3'UTR of two alphaviruses - Ross River virus and Chikungunya virus - that do not contain a typical U-rich region were tested for HuR interactions by Electrophoretic Mobility Shift Assay. HuR protein bound these 3'UTRs with nanomolar affinities, similar to what was observed for the U-rich region of Sindbis virus. These observations demonstrate that the critical role for HuR-mediated viral RNA stabilization is likely a conserved property of most, if not all, members of the virus family. By analyzing deletion derivatives, we mapped the novel HuR binding sites in these two viruses to specific regions in their 3'UTR. Next, we uncovered four novel aspects of virus-host interaction and pathogenesis related to the high affinity interaction between the 3'UTR of alphaviruses and the cellular HuR protein. First, HuR protein, which is usually localized predominantly to the nucleus, dramatically accumulates in the cytoplasm during Sindbis virus (SinV) infection. Studies involving the transfection of constructs that express viral 3'UTR RNA fragments indicated that the mechanism of induction of HuR accumulation to the cytoplasm in infected cells is due to the viral RNA acting as a sponge for the protein. Second, HuR interaction with numerous cellular mRNAs was found to be drastically decreased during a SinV infection and was associated with dramatic destabilization of the cellular transcripts as determined by mRNA half-life analysis. Third, we found that the reduced amounts of free HuR during a SinV infection results in the increased targeting of mRNAs by miRNAs. Together, these data indicate that in the process of commandeering the cellular HuR protein for its own use, alphaviruses are also effectively destabilizing numerous cellular mRNAs. Interestingly, many of the cellular mRNAs affected by alphaviruses play key roles in inflammation, innate immune responses and other fundamental cellular processes. Finally, we observed a novel effect of SinV infection on alternative polyadenylation of cellular transcripts. This is likely a direct result of sequestration of the HuR protein in the cytoplasm by the virus, preventing the protein from influencing nuclear polyadenylation site choice. Intriguingly, SinV infection influences the poly(A) site choice of the HuR pre-mRNA, favoring a more translatable isoform to promote the overexpression of this viral host factor. Therefore, the alphaviral-induced alterations in cellular mRNA stability and polyadenylation identified in this thesis may play a very important but underappreciated role in pathogenesis

Astronaut Rescue Air Pack (ARAP) and Emergency Egress Air Pack (EEAP)

Two designs for a lightweight, low profile, mobile rescue apparatus providing a 15-minute air supply and self-contained two-way communications assembly are described. Units are designed for astronaut use in hazardous environments

Evaluating air traffic flow management in a collaborative decision-making environment

The collaborative decision-making (CDM) framework introduced into ground delay programs in the late 1990s is an integral component of FAA's traffic flow management (TFM) procedures. CDM allows FAA to act as a mediator when managing TFM programs, transferring as much decision making as possible to the individual airlines. Although this approach has been highly successful in practice, it creates a new question for the research community: How should proposed enhancements to TFM be evaluated in a CDM environment? A sequential evaluation procedure, developed in this paper, addresses this question. The procedure includes airline disruption responses and a quasi-compression operation, attempting to mimic the three-stage CDM process. To model airline disruption responses, an integer optimization model was developed to balance operational and passenger considerations in determining which flights to cancel, swap, or delay. The value of this procedure is demonstrated by analyzing an optimization-based TFM approach in the CDM environment

Total ionizing dose characterization of a commercially fabricated asynchronous FFT for space applications

Journal ArticleThe total ionizing dose characterization of the radiation-hardened implementation of a novel architecture for high-performance, energy efficiency FFT engines is presented. Simulations and test chip measurement results indicate that a radiation-tolerant 1024-point FFT based on this architecture will achieve an efficiency of 120 nJ/Unit-Transform and 2 ms throughput. The proof-of-concept chip shows a total ionizing dose hardness of 1 Mrad (SiO2)

Paper Session III-A - On-Orbit Characterization of Electric Propulsion in Leo Satellites

Because of the current high cost for space experiments on large and small space qualified platforms, alternate methods of space characterization must be explored. Utilizing commercial or military satellites as testbeds for subsystems is a potential platform for small devices. Electric propulsion is a viable and upcoming subsystem that is of high interest to planetary mission engineers as well as commercial satellite developers. The cost of space demonstration, and the risk associated with nonspace tested components, is a major driver in the reluctant admittance into the satellite and space experiment world for electric propulsion. It is proposed that by incorporating small lightweight electric propulsion devices onto small satellites as external or bolt-on experiments, an increase in the number of flight opportunities can occur. Specific problems that will be addressed are spacecraft body interaction, contamination effects, thermal interface problems, power conditioning control electronics, and propulsion feed system interfaces

A Historical and Contextual Review of the Adverse Psychological Effects of the Trauma of Colonialization on Alaska Native Peoples

Through a historical review, the authors sought to provide an analysis of the adverse psychological effects of the traumatization of colonialization in Alaska Native Peoples. In the context of oppression, the authors discuss the potentially harmful implications of approaching psychology from a framework development largely out of Western philosophical thought and the medical model. In an attempt to be more culturally sensitive to the unique history and needs of Alaska Natives, the contextual FHORT model is proposed as a more appropriate conceptual framework to start from. Details of the various facets of colonialization and their associations and suspected contributions to disparities in both health and mental health factors in Alaska Natives are discussed. This is followed by a dialogue of contemporary problems Indigenous People face and how psychology can play a supportive role in the healing process. Currently, much of the research on Alaska Natives is limited to more largescale population-based studies incorporating American Indians and Alaska Natives as one larger demographic; however, significant regional differences exist. Although this previous research is valuable, and some aspects may be transferable to the Alaska Native population, more specific research, as it applies to the provision of behavioral health services to Alaska Natives is necessary

Blinded by magic: eye-movements reveal the misdirection of attention

Recent studies (e.g., Kuhn & Tatler, 2005) have suggested that magic tricks can provide a powerful and compelling domain for the study of attention and perception. In particular, many stage illusions involve attentional misdirection, guiding the observer’s gaze to a salient object or event, while another critical action, such as sleight of hand, is taking place. Even if the critical action takes place in full view, people typically fail to see it due to inattentional blindness. In an eye-tracking experiment, participants watched videos of a new magic trick, wherein a coin placed beneath a napkin disappears, reappearing under a different napkin. Appropriately deployed attention would allow participants to detect the secret event that underlies the illusion (a moving coin), as it happens in full view and is visible for approximately 550 ms. Nevertheless, we observed high rates of inattentional blindness. Unlike prior research, eye-movements during the critical event showed different patterns for participants, depending upon whether they saw the moving coin. The results also showed that when participants watched several practice videos without any moving coin, they became far more likely to detect the coin in the critical trial. Taken together, the findings are consistent with perceptual load theory (Lavie & Tsal, 1994)

Feasibility study of the solar scientific instruments for Spacelab/Orbiter

The feasibility and economics of mounting and operating a set of solar scientific instruments in the backup Skylab Apollo Telescope Mount (ATM) hardware was evaluated. The instruments used as the study test payload and integrated into the ATM were: the Solar EUV Telescope/Spectrometer; the Solar Active Region Observing Telescope; and the Lyman Alpha White Light Coronagraph. The backup ATM hardware consists of a central cruciform structure, called the "SPAR', a "Sun End Canister' and a "Multiple Docking Adapter End Canister'. Basically, the ATM hardware and software provides a structural interface for the instruments; a closely controlled thermal environment; and a very accurate attitude and pointing control capability. The hardware is an identical set to the hardware that flow on Skylab

Effects of Hypoxia on Egg Capsule Conductance in Ambystoma (Class Amphibia, Order Caudata)

Aquatic amphibian eggs frequently encounter hypoxic conditions that have the potential to limit oxygen uptake and thereby slow embryonic development and hatching. Oxygen limitation might be avoided if egg capsule surface area and oxygen conductance increased in response to hypoxia. We investigated this possibility in two salamander species, Ambystoma annulatum and Ambystoma talpoideum. The effective surface area of egg capsules increased in response to hypoxia, which increased the conductance for oxygen and enhanced oxygen transport. The ability of amphibian eggs to adjust their conductance in response to oxygen availability may increase survival in hypoxic environments

Differential Double Excitation Cross Sections in Proton-Helium Collisions Studied by Energy-Loss Spectroscopy

We have measured ion energy-loss spectra for 150 keV proton-helium collisions as a function of the projectile scattering angle. From the data we obtained double excitation cross sections differential in the proton scattering angle as well as the ratios of both double excitation and single ionization to single excitation. In these ratios pronounced peak structures are observed at about 0.7 mrad. Two alternative interpretations of these peak structures are offered: They may be due to binary collisions between the projectile and the target electrons, or they could be a manifestation of an interference between different transition amplitudes leading to the same final state of the collision