Heterologous prion-forming proteins interact to cross-seed aggregation in Saccharomyces cerevisiae

AbstractThe early stages of protein misfolding remain incompletely understood, as most mammalian proteinopathies are only detected after irreversible protein aggregates have formed. Cross-seeding, where one aggregated protein templates the misfolding of a heterologous protein, is one mechanism proposed to stimulate protein aggregation and facilitate disease pathogenesis. Here, we demonstrate the existence of cross-seeding as a crucial step in the formation of the yeast prion [PSI+], formed by the translation termination factor Sup35. We provide evidence for the genetic and physical interaction of the prion protein Rnq1 with Sup35 as a predominant mechanism leading to self-propagating Sup35 aggregation. We identify interacting sites within Rnq1 and Sup35 and determine the effects of breaking and restoring a crucial interaction. Altogether, our results demonstrate that single-residue disruption can drastically reduce the effects of cross-seeding, a finding that has important implications for human protein misfolding disorders.</jats:p

High temperature measurement of water vapor absorption

An investigation was undertaken to measure the absorption coefficient, at a wavelength of 10.6 microns, for mixtures of water vapor and a diluent gas at high temperature and pressure. The experimental concept was to create the desired conditions of temperature and pressure in a laser absorption wave, similar to that which would be created in a laser propulsion system. A simplified numerical model was developed to predict the characteristics of the absorption wave and to estimate the laser intensity threshold for initiation. A non-intrusive method for temperature measurement utilizing optical laser-beam deflection (OLD) and optical spark breakdown produced by an excimer laser, was thoroughly investigated and found suitable for the non-equilibrium conditions expected in the wave. Experiments were performed to verify the temperature measurement technique, to screen possible materials for surface initiation of the laser absorption wave and to attempt to initiate an absorption wave using the 1.5 kW carbon dioxide laser. The OLD technique was proven for air and for argon, but spark breakdown could not be produced in helium. It was not possible to initiate a laser absorption wave in mixtures of water and helium or water and argon using the 1.5 kW laser, a result which was consistent with the model prediction

Strategies for using remotely sensed data in hydrologic models

Present and planned remote sensing capabilities were evaluated. The usefulness of six remote sensing capabilities (soil moisture, land cover, impervious area, areal extent of snow cover, areal extent of frozen ground, and water equivalent of the snow cover) with seven hydrologic models (API, CREAMS, NWSRFS, STORM, STANFORD, SSARR, and NWSRFS Snowmelt) were reviewed. The results indicate remote sensing information has only limited value for use with the hydrologic models in their present form. With minor modifications to the models the usefulness would be enhanced. Specific recommendations are made for incorporating snow covered area measurements in the NWSRFS Snowmelt model. Recommendations are also made for incorporating soil moisture measurements in NWSRFS. Suggestions are made for incorporating snow covered area, soil moisture, and others in STORM and SSARR. General characteristics of a hydrologic model needed to make maximum use of remotely sensed data are discussed. Suggested goals for improvements in remote sensing for use in models are also established

Combining remotely sensed and other measurements for hydrologic areal averages

A method is described for combining measurements of hydrologic variables of various sampling geometries and measurement accuracies to produce an estimated mean areal value over a watershed and a measure of the accuracy of the mean areal value. The method provides a means to integrate measurements from conventional hydrological networks and remote sensing. The resulting areal averages can be used to enhance a wide variety of hydrological applications including basin modeling. The correlation area method assigns weights to each available measurement (point, line, or areal) based on the area of the basin most accurately represented by the measurement. The statistical characteristics of the accuracy of the various measurement technologies and of the random fields of the hydrologic variables used in the study (water equivalent of the snow cover and soil moisture) required to implement the method are discussed

Prion-associated toxicity is rescued by elimination of cotranslational chaperones

The nascent polypeptide-associated complex (NAC) is a highly conserved but poorly characterized triad of proteins that bind near the ribosome exit tunnel. The NAC is the first cotranslational factor to bind to polypeptides and assist with their proper folding. Surprisingly, we found that deletion of NAC subunits in Saccharomyces cerevisiae rescues toxicity associated with the strong [PSI+] prion. This counterintuitive finding can be explained by changes in chaperone balance and distribution whereby the folding of the prion protein is improved and the prion is rendered nontoxic. In particular, the ribosome-associated Hsp70 Ssb is redistributed away from Sup35 prion aggregates to the nascent chains, leading to an array of aggregation phenotypes that can mimic both overexpression and deletion of Ssb. This toxicity rescue demonstrates that chaperone modification can block key steps of the prion life cycle and has exciting implications for potential treatment of many human protein conformational disorders

Trajectories of university adjustment in the United Kingdom: Emotion management and emotional self-efficacy protect against initial poor adjustment

Little is known about individual differences in the pattern of university adjustment. This study explored longitudinal associations between emotional self-efficacy, emotion management, university adjustment, and academic achievement in a sample of first year undergraduates in the United Kingdom (N=331). Students completed measures of adjustment to university at three points during their first year at university. Latent Growth Mixture Modeling identified four trajectories of adjustment: (1) low, stable adjustment, (2) medium, stable adjustment, (3) high, stable adjustment, and (4) low, increasing adjustment. Membership of the low, stable adjustment group was predicted by low emotional self-efficacy and low emotion management scores, measured at entry into university. This group also had increased odds of poor academic achievement, even when grade at entry to university was controlled. Students who increased in adjustment had high levels of emotion management and emotional self-efficacy, which helped adaptation. These findings have implications for intervention

Multiple-point statistical simulation for hydrogeological models: 3D training image development and conditioning strategies

Most studies about the application of geostatistical simulations based on multiple-point statistics (MPS) to hydrogeological modelling focus on relatively fine-scale models and concentrate on the estimation of facies-level, structural uncertainty. Much less attention is paid to the use of input data and optimal construction of training images. For instance, even though the training image should capture a set of spatial geological characteristics to guide the simulations, the majority of the research still relies on 2D or quasi-3D training images. In the present study, we demonstrate a novel strategy for 3D MPS modelling characterized by: (i) realistic 3D training images, and (ii) an effective workflow for incorporating a diverse group of geological and geophysical data sets. The study covers an area of 2810 km2 in the southern part of Denmark. MPS simulations are performed on a subset of the geological succession (the lower to middle Miocene sediments) which is characterized by relatively uniform structures and dominated by sand and clay. The simulated domain is large and each of the geostatistical realizations contains approximately 45 million voxels with size 100 m × 100 m × 5 m. Data used for the modelling include water well logs, high-resolution seismic data, and a previously published 3D geological model. We apply a series of different strategies for the simulations based on data quality, and develop a novel method to effectively create observed sand/clay spatial trends. The training image is constructed as a small 3D voxel model covering an area of 90 km2. We use an iterative training image development strategy and find that even slight modifications in the training image create significant changes in simulations. Thus, the study underlines that it is important to consider both the geological environment, and the type and quality of input information in order to achieve optimal results from MPS modelling. In this study we present a possible workflow to build the training image and effectively handle different types of input information to perform large-scale geostatistical modellin

Resonant electron transmission through a finite quantum spin chain

Electron transport in a finite one dimensional quantum spin chain (with ferromagnetic exchange) is studied within an $s-d$ exchange Hamiltonian. Spin transfer coefficients strongly depend on the sign of the $s-d$ exchange constant. For a ferromagnetic coupling, they exhibit a novel resonant pattern, reflecting the salient features of the combined electron-spin system. Spin-flip processes are inelastic and feasible at finite voltage or at finite temperature.Comment: 4 pages including 4 .eps figure

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Helping education undergraduates to use appropriate criteria for evaluating accounts of motivation

The aim of the study was to compare students in a control group with those in a treatment group with respect to evaluative comments on psychological accounts of motivation. The treatment group systematically scrutinized the nature and interpretation of evidence that supported different accounts, and the assumptions, logic, coherence and clarity of accounts. Content analysis of 74 scripts (using three categories) showed that the control group students made more assertions than either evidential or evaluative points, whereas the treatment group used evaluative statements as often as they used assertion. The findings provide support for privileging activities that develop understanding of how knowledge might be contested, and suggest a need for further research on pedagogies to serve this end. The idea is considered that such understanding has a pivotal role in the development of critical thinking