Interactions between Upf1 and the Decapping Factors Edc3 and Pat1 in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, mRNA transcripts with premature termination codons are targeted for deadenylation independent decapping and 5′ to 3′ decay in a quality control pathway termed nonsense-mediated decay (NMD). Critical factors in NMD include Upf1, Upf2, and Upf3, as well as the decapping enzyme, Dcp2/Dcp1. Loss of Upf2 or Upf3 leads to the accumulation of not only Upf1 and Dcp2 in P-bodies, but also of the decapping-activators Pat1, Dhh1, and Lsm1. An interaction between Upf1 and Dcp2 has been identified, which might recruit Dcp2 to the NMD decapping complex. To determine the nature and significance of the Dcp2-Upf1 interaction, we utilized the yeast two-hybrid assay to assess Upf1 interactions with various mRNA decapping factors. We find that although Dcp2 can interact with Upf1, this interaction is indirect and is largely dependent on the Edc3 protein, which interacts with the N-terminal domain of Upf1 at an overlapping, but not identical, site as Upf2. We also found that Pat1 has an independent two-hybrid interaction with the N-terminus of Upf1. Assessment of both reporter and endogenous NMD transcripts suggest that the decapping stimulators, including Edc3 and Pat1, as well as Edc1 and Edc2, are not essential for NMD under normal conditions. This work defines a larger decapping complex involved in NMD, but indicates that components of that complex are not required for general NMD and might either regulate a subset of NMD transcripts or be essential for proper NMD under different environmental conditions

Holocene Glaciation of the Arrigetch Peaks, Brooks Range, Alaska

Eleven cirque glaciers and associated deposits within the granitic Arrigetch Peaks of the west-central Brooks Range face north, minimizing insolation. Shading by surrounding mountainous terrain decreases insolation on these landforms even more significantly, favoring the formation of glacier-cored moraines. Comparison of glacier photographs taken in 1911, 1962, and 1979 reveals a record of decelerating recession. Geomorphic and lichenometric mapping suggests at least three to possibly eight phases of Holocene glacial expansion. These date between ~5000 and 300 yr B.P., based on the application of a central Brooks Range Rhizocarpon geographicum growth curve

Evaluation of an online toolkit for carers of people with life-limiting illness at the end-of-life: health professionals’ perspectives

Carers of people with a life-limiting illness report unmet information, practical, and emotional support needs, and are often unaware of services available to help improve preparedness, wellbeing, and reduce strain. CarerHelp is the first e-health toolkit that focuses on the information and support needs of carers of people with a life-limiting illness at the end-of-life, using a pathway approach. This study investigated the usefulness of CarerHelp, from the perspective of health professionals who care for these people. Through a 10-min online survey, health professionals provided feedback about their user experience and perceived usefulness of the website. Their expert opinion was sought to ascertain whether CarerHelp could increase carers’ preparedness and confidence to support the person for whom they are caring and thereby improve carers’ own psychological wellbeing. Health professionals also evaluated whether CarerHelp adequately raised awareness of support services available. CarerHelp was perceived as a useful resource for increasing preparedness for the caring role, including physical tasks and emotional support. Health professionals reported that CarerHelp would increase carers’ knowledge of services, confidence to care and ability for self-care. Health professionals endorsed CarerHelp as a useful information source, guide for support, and would promote CarerHelp to clients and their families

Wetting and energetics in nanoparticle etching of graphene

Molten metallic nanoparticles have recently been used to construct graphene nanostructures with crystallographic edges. The mechanism by which this happens, however, remains unclear. Here, we present a simple model that explains how a droplet can etch graphene. Two factors possibly contribute to this process: a difference between the equilibrium wettability of graphene and the substrate that supports it, or the large surface energy associated with the graphene edge. We calculate the etching velocities due to either of these factors and make testable predictions for evaluating the significance of each in graphene etching. This model is general and can be applied to other materials systems as well. As an example, we show how our model can be used to extend a current theory of droplet motion on binary semiconductor surfaces

Double-diffusive magnetic buoyancy instability in a quasi-two-dimensional Cartesian geometry

Magnetic buoyancy, believed to occur in the solar tachocline, is both an important part of large-scale solar dynamo models and the picture of how sunspots are formed. Given that in the tachocline region the ratio of magnetic diffusivity to thermal diffusivity is small it is important, for both the dynamo and sunspot formation pictures, to understand magnetic buoyancy in this regime. Furthermore, the tachocline is a region of strong shear and such investigations must involve structures that become buoyant in the double-diffusive regime which are generated entirely from a shear flow. In a previous study, we have illustrated that shear-generated doublediffusive magnetic buoyancy instability is possible in the tachocline. However, this study was severely limited due to the computational requirements of running three-dimensional magnetohydrodynamic simulations over diffusive time-scales. A more comprehensive investigation is required to fully understand the double-diffusive magnetic buoyancy instability and its dependency on a number of key parameters; such an investigation requires the consideration of a reduced model. Here we consider a quasi-two-dimensional model where all gradients in the x direction are set to zero. We show how the instability is sensitive to changes in the thermal diffusivity and also show how different initial configurations of the forced shear flow affect the behaviour of the instability. Finally, we conclude that if the tachocline is thinner than currently stated then the double-diffusive magnetic buoyancy instability can more easily occur

Variable Acceleration Force Calibration System (VACS)

Conventionally, force balances have been calibrated manually, using a complex system of free hanging precision weights, bell cranks, and/or other mechanical components. Conventional methods may provide sufficient accuracy in some instances, but are often quite complex and labor-intensive, requiring three to four man-weeks to complete each full calibration. To ensure accuracy, gravity-based loading is typically utilized. However, this often causes difficulty when applying loads in three simultaneous, orthogonal axes. A complex system of levers, cranks, and cables must be used, introducing increased sources of systematic error, and significantly increasing the time and labor intensity required to complete the calibration. One aspect of the VACS is a method wherein the mass utilized for calibration is held constant, and the acceleration is changed to thereby generate relatively large forces with relatively small test masses. Multiple forces can be applied to a force balance without changing the test mass, and dynamic forces can be applied by rotation or oscillating acceleration. If rotational motion is utilized, a mass is rigidly attached to a force balance, and the mass is exposed to a rotational field. A large force can be applied by utilizing a large rotational velocity. A centrifuge or rotating table can be used to create the rotational field, and fixtures can be utilized to position the force balance. The acceleration may also be linear. For example, a table that moves linearly and accelerates in a sinusoidal manner may also be utilized. The test mass does not have to move in a path that is parallel to the ground, and no re-leveling is therefore required. Balance deflection corrections may be applied passively by monitoring the orientation of the force balance with a three-axis accelerometer package. Deflections are measured during each test run, and adjustments with respect to the true applied load can be made during the post-processing stage. This paper will present the development and testing of the VASC concept

Method of Calibrating a Force Balance

A calibration system and method utilizes acceleration of a mass to generate a force on the mass. An expected value of the force is calculated based on the magnitude and acceleration of the mass. A fixture is utilized to mount the mass to a force balance, and the force balance is calibrated to provide a reading consistent with the expected force determined for a given acceleration. The acceleration can be varied to provide different expected forces, and the force balance can be calibrated for different applied forces. The acceleration may result from linear acceleration of the mass or rotational movement of the mass

Once Daily Therapy With Isosorbide-5-Mononitrate Causes Endothelial Dysfunction in Humans Evidence of a Free-Radical–Mediated Mechanism

ObjectivesThe aim of the study was to determine if isosorbide-5-mononitrate (IS-5-MN) 120 mg, taken once daily for 7 days, is associated with evidence of endothelial dysfunction and whether this effect is determined by increased free radical production.BackgroundTolerance to nitroglycerin is associated with increased free radical production and abnormal endothelial function. To date, no data is available concerning the effect of IS-5-MN, administered in clinically employed dosages, on endothelial function in humans.MethodsA total of 19 healthy volunteers were randomized in a double-blind fashion to therapy with IS-5-MN (120 mg once daily) or placebo. After 7 days of treatment, forearm blood flow responses to acetylcholine (Ach; 7.5, 15, and 30 μg/min) and N-monomethyl-L-arginine (L-NMMA; 1, 2, and 4 μmol/min) were measured. In a separate study, after 7 days of therapy with IS-5-MN 120 mg once daily, the responses to Ach were assessed during intra-arterial coinfusion of vitamin C (24 mg/min) or saline.ResultsAs compared with placebo, IS-5-MN caused significant blunting of the responses to both Ach (peak responses: placebo 127 ± 31%; IS-5-MN 52 ± 24%) and L-NMMA (peak responses: placebo 41 ± 5%; IS-5-MN 22 ± 8%). Vitamin C completely restored the forearm blood flow responses to Ach (peak responses: vitamin C 180 ± 33%; saline 107 ± 17%).ConclusionsWe document for the first time that IS-5-MN impairs endothelial function in humans in vivo. Suggesting a role of oxygen free radicals, nitrate-induced abnormalities in endothelium-dependent vasomotor responses were reversed by the antioxidant vitamin C