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

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

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

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

Multi-Scale Geomorphic Assessment Approach for Streams in the Southern Illinois Region: Case Study, Big Creek Watershed, Pulaski and Union Counties, Illinois

Human alteration of stream channels and land use initiates responses in a fluvial system that can increase flooding, erosion, and sedimentation, which, in turn, impact aquatic habitat, property, and water quality. Geomorphic assessment approaches have been developed to evaluate channel response to disturbances for various regions of the United States and there is concern regarding the appropriateness of applying them in regions for which they were not developed, particularly Illinois. Channel responses to disturbances tend to be more subtle in Illinois as compared to the dramatic responses in the mountainous northwest, arid southwest, and coastal plains. Also, channel disturbance issues are complex and dynamic, consequently the evaluation of these issues requires extensive training and formal research experience. Due to pressure by policy makers and resource managers for rapid assessments and natural channel designs for stream restorations, some assessment approaches have been developed and applied by non-geomorphologists and extended beyond credible use. Lack of standardization between approaches has proven difficult to compare disturbance response mechanisms within and between physiographic regions, as well as establishing long-term research of these mechanisms. A standardized, systematic geomorphic assessment approach for evaluating past conditions, extant character, and potential future adjustments of stream channels in Illinois was developed and evaluated. The methodology draws from components of approaches developed in the United States. The approach was applied to the Big Creek watershed in the Cache River Basin in the southern region of Illinois – a fluvial system that has been severely impacted both directly and indirectly by human activities. The geomorphic assessment approach has three levels of investigation that incorporates temporal- and spatial-scale analysis, standardizes the systematic collection of data, compares and contrasts multiple lines of evidence to characterize the watershed and channels, and utilizes three approaches to evaluate prevailing channel process response mechanisms to infer potential future channel adjustments. Several components overcame inconsistent datasets found in Big Creek and integrated multi-scale information to infer future several channel adjustment processes. The results for the case study watershed, Big Creek, revealed that the complex geology and multiple human disturbances has produced four separate channel responses that will require separate, but integrated, attention of the watershed and channel reaches.Ope

Benchmark Sediment Monitoring Program for Illinois Streams: Analysis of 36 Years of Sediment Data (WY 1981-2016)

publishedpeer reviewedOpe

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

Best Practice Update: Incorporating Psychogastroenterology Into Management of Digestive Disorders

Chronic digestive diseases, including irritable bowel syndrome, gastroesophageal reflux disease, and inflammatory bowel diseases, cannot be disentangled from their psychological context—the substantial burden of these diseases is co-determined by symptom and disease severity and the ability of patients to cope with their symptoms without significant interruption to daily life. The growing field of psychogastroenterology focuses on the application of scientifically based psychological principles and techniques to the alleviation of digestive symptoms. In this Clinical Practice Update, we describe the structure and efficacy of 2 major classes of psychotherapy—cognitive behavior therapy and gut-directed hypnotherapy. We focus on the impact of these brain–gut psychotherapies on gastrointestinal symptoms, as well as their ability to facilitate improved coping, resilience, and self-regulation. The importance of the gastroenterologist in the promotion of integrated psychological care cannot be overstated, and recommendations are provided on how to address psychological issues and make an effective referral for brain–gut psychotherapy in routine practice