Prion protein repeat expansion results in increased aggregation and reveals phenotypic variability

Mammalian prion diseases are fatal neurodegenerative disorders dependent on the prion protein PrP. Expansion of the oligopeptide repeats (ORE) found in PrP is associated with inherited prion diseases. Patients with ORE frequently harbor PrP aggregates, but other factors may contribute to pathology, as they often present with unexplained phenotypic variability. We created chimeric yeast-mammalian prion proteins to examine the influence of the PrP ORE on prion properties in yeast. Remarkably, all chimeric proteins maintained prion characteristics. The largest repeat expansion chimera displayed a higher propensity to maintain a self-propagating aggregated state. Strikingly, the repeat expansion conferred increased conformational flexibility, as observed by enhanced phenotypic variation. Furthermore, the repeat expansion chimera displayed an increased rate of prion conversion, but only in the presence of another aggregate, the [RNQ(+)] prion. We suggest that the PrP ORE increases the conformational flexibility of the prion protein, thereby enhancing the formation of multiple distinct aggregate structures and allowing more frequent prion conversion. Both of these characteristics may contribute to the phenotypic variability associated with PrP repeat expansion diseases

Are rivers just bigstreams? Using a pulse method to measure nitrogen demand in a large river

Given recent focus on large rivers as conduits for excess nutrients to coastal zones, their role in processing and retaining nutrients has been overlooked and understudied. Empirical measurements of nutrient uptake in large rivers are lacking, despite a substantial body of knowledge on nutrient transport and removal in smaller streams. Researchers interested in nutrient transport by rivers (discharge \u3e10000 L/s) are left to extrapolate riverine nutrient demand using a modeling framework or a mass balance approach. To begin to fill this knowledge gap, we present data using a pulse method to measure inorganic nitrogen. (N) transport and removal in the Upper Snake River, Wyoming, USA (seventh order, discharge 12000 L/s). We found that the Upper Snake had surprisingly high biotic demand relative to smaller streams in the same river network for both ammonium (NH4+) and nitrate (NO3-). Placed in the context of a meta-analysis of previously published nutrient uptake studies, these data suggest that large rivers may have similar biotic demand for N as smaller tributaries. We also found that demand for different forms of inorganic N (NH4+ vs. NO3-) scaled differently with stream size. Data from rivers like the Upper Snake and larger are essential for effective water quality management at the scale of river networks. Empirical measurements of solute dynamics in large rivers are needed to understand the role of whole river networks (as opposed to stream reaches) in patterns of nutrient export at regional and continental scales

A Framework for Quality K-12 Engineering Education: Research and Development

Recent U.S. national documents have laid the foundation for highlighting the connection between science, technology, engineering and mathematics at the K-12 level. However, there is not a clear definition or a well-established tradition of what constitutes a quality engineering education at the K-12 level. The purpose of the current work has been the development of a framework for describing what constitutes a quality K-12 engineering education. The framework presented in this paper is the result of a research project focused on understanding and identifying the ways in which teachers and schools implement engineering and engineering design in their classrooms. The development of the key indicators that are included in the framework were determined based on an extensive review of the literature, established criteria for undergraduate and professional organizations, document content analysis of state academic content standards in science, mathematics, and technology, and in consultation with experts in the fields of engineering and engineering education. The framework is designed to be used as a tool for evaluating the degree to which academic standards, curricula, and teaching practices address the important components of a quality K-12 engineering education. Additionally, this framework can be used to inform the development and structure of future K-12 engineering and STEM education standards and initiatives

Changing Seasonal Rainfall Distribution With Climate Directs Contrasting Impacts at Evapotranspiration and Water Yield in the Western Mediterranean Region

Over the past century, climate change has been reflected in altered precipitation regimes worldwide. Because evapotranspiration is sensitive to both water availability and atmospheric demand for water vapor, it is essential to assess the likely consequences of future changes of these climate variables to evapotranspiration and, thus, runoff. We propose a simplified approach for annual evapotranspiration predictions, based on seasonal evapotranspiration estimates, accounting for the strong seasonality of meteorological conditions typical of Mediterranean climate, still holding the steady state assumption of basin water balance at mean annual scale. Sardinian runoff decreased over the 1975-2010 period by more than 40% compared to the preceding 1922-1974 period. Most of annual runoff in Sardinian basins is produced by winter precipitation, a wet season with relatively high evaporation rates. We derived linear seasonal evapotranspiration responses to seasonal precipitation, and, in turn, a relationship between the parameters of the linear functions and the seasonal vapor pressure deficit (D), accounting for residuals with basin properties. We then used these relationships to predict evapotranspiration and runoff using future Intergovernmental Panel on Climate Change climate scenarios, considering changing precipitation and D seasonality. We show that evapotranspiration is insensitive to D scenario changes. Although both evapotranspiration and runoff are sensitive to precipitation seasonality, future changes in runoff are related only to changes of winter precipitation, while evapotranspiration changes are related to those of spring and summer precipitation. Future scenario predicting further runoff decline is particularly alarming for the Sardinian water resources system, requiring new strategies and designs in water resources planning and management.Peer reviewe

Multiple tracers demonstrate distinct sources of dissolved organic matter to lakes of the Mackenzie Delta, western Canadian Arctic

Author Posting. © American Society of Limnology and Oceanography, 2011. This article is posted here by permission of American Society of Limnology and Oceanography for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography 56 (2011): 1297-1309, doi:10.4319/lo.2011.56.4.1297.Lakes of the Mackenzie Delta occur across a gradient that contains three clear end members: those that remain connected to river-water channels throughout the summer; those that receive only brief inputs of river water during an annual spring flood but contain dense macrophyte stands; and those that experience significant permafrost thaw along their margins. We measured dissolved organic carbon (DOC) concentration, dissolved organic matter (DOM) absorption and fluorescence, and stable isotopes of DOM, DOM precursor materials, and bacteria to elucidate the importance of river water, macrophytes, and thermokarst as DOM sources to Mackenzie Delta lakes. Despite standing stocks of macrophyte C that are sevenfold to 12-fold greater than those of total DOC, stable isotopes indicated that autochthonous sources contributed less than 15% to overall DOM in macrophyte-rich lakes. Instead, fluorescence and absorption indicated that the moderate summertime increase in DOC concentration in macrophyte-rich lakes was the result of infrequent flushing, while bacterial δ13C indicated rapid bacterial removal of autochthonous DOC from the water column. In thermokarst lakes, summertime increases in DOC concentration were substantial, and stable isotopes indicated that much of this increase came from C released as a result of thermokarst-related processes. Our results indicate that these distinct sources of DOM to neighboring arctic Delta lakes may drive between-lake differences in C cycling and energy flow. Rapidly assimilated macrophyte DOM should be an important contributor to microbial food webs in our study lakes. In contrast, the accumulation of thermokarst-origin DOM allows for a significant role in physico-chemistry but indicates a lesser contribution of this DOM to higher trophic levels.This study was supported by a Discovery Grant and Northern Research Supplement from the Natural Sciences and Engineering Research Council of Canada (NSERC) to L.F.W.L.; funds from the Science Horizons Youth Internship Program, Northern Scientific Training Program, and NSERC Northern Research Internship. Personal financial support to S.E.T. was provided by a Simon Fraser University CD Nelson Memorial Graduate Scholarship, an NSERC Canada Graduate Scholarship-Doctoral, and a Garfield Weston Award for Northern Research

Metabolism, Gas Exchange, and Carbon Spiraling in Rivers

Ecosystem metabolism, that is, gross primary productivity (GPP) and ecosystem respiration (ER), controls organic carbon (OC) cycling in stream and river networks and is expected to vary predictably with network position. However, estimates of metabolism in small streams outnumber those from rivers such that there are limited empirical data comparing metabolism across a range of stream and river sizes. We measured metabolism in 14 rivers (discharge range 14–84 m3 s−1) in the Western and Midwestern United States (US). We estimated GPP, ER, and gas exchange rates using a Lagrangian, 2-station oxygen model solved in a Bayesian framework. GPP ranged from 0.6–22 g O2 m−2 d−1 and ER tracked GPP, suggesting that autotrophic production supports much of riverine ER in summer. Net ecosystem production, the balance between GPP and ER was 0 or greater in 4 rivers showing autotrophy on that day. River velocity and slope predicted gas exchange estimates from these 14 rivers in agreement with empirical models. Carbon turnover lengths (that is, the distance traveled before OC is mineralized to CO2) ranged from 38 to 1190 km, with the longest turnover lengths in high-sediment, arid-land rivers. We also compared estimated turnover lengths with the relative length of the river segment between major tributaries or lakes; the mean ratio of carbon turnover length to river length was 1.6, demonstrating that rivers can mineralize much of the OC load along their length at baseflow. Carbon mineralization velocities ranged from 0.05 to 0.81 m d−1, and were not different than measurements from small streams. Given high GPP relative to ER, combined with generally short OC spiraling lengths, rivers can be highly reactive with regard to OC cycling. © 2015, Springer Science+Business Media New York

Real-Time Magnetic Resonance Imaging to Study Orthostatic Intolerance Mechanisms in Human Beings: Proof of Concept

Background:Discerning the mechanisms driving orthostatic symptoms in human beings remains challenging. Therefore, we developed a novel approach combining cardiac and cerebral real‐time magnetic resonance imaging, beat‐to‐beat physiological monitoring, and orthostatic stress testing through lower‐body negative pressure (LBNP). We conducted a proof‐of‐concept study in a patient with severe orthostatic hypotension.Methods and Results:We included a 46‐year‐old man with pure autonomic failure. Without and during −30 mmHg LBNP, we obtained 3T real‐time magnetic resonance imaging of the cardiac short axis and quantitative flow measurements in the pulmonary trunk and middle cerebral artery. Blood pressure was 118/74 mmHg during supine rest and 58/35 mmHg with LBNP. With LBNP, left ventricular stroke volume decreased by 44.6%, absolute middle cerebral artery flow by 37.6%, and pulmonary trunk flow by 40%.Conclusions:Combination of real‐time magnetic resonance imaging, LBNP, and continuous blood pressure monitoring provides a promising new approach to study orthostatic intolerance mechanisms in human beings

An operative approach to address severe genu valgum deformity in the Ellis-van Creveld syndrome

BACKGROUND: The genu valgum deformity seen in the Ellis-van Creveld syndrome is one of the most severe angular deformities seen in any orthopaedic condition. It is likely a combination of a primary genetic-based dysplasia of the lateral portion of the tibial plateau combined with severe soft-tissue contractures that tether the tibia into valgus deformations. Progressive weight-bearing induces changes, accumulating with growth, acting on the initially distorted and valgus-angulated proximal tibia, worsening the deformity with skeletal maturation. The purpose of this study is to present a relatively large case series of a very rare condition that describes a surgical technique to correct the severe valgus deformity in the Ellis-van Creveld syndrome by combining extensive soft-tissue release with bony realignment. METHODS: 1. Complete proximal to distal surgical decompression of the peroneal nerve. 2. Radical release and mobilization of the severe quadriceps contracture and iliotibial band contracture. 3. Distal lateral hamstring lengthening/tenotomy and lateral collateral ligament release. 4. Proximal and distal realignment of the subluxed/dislocated patella, medial and lateral retinacular release, vastus medialis advancement, patellar chondroplasty, medial patellofemoral ligament plication, and distal patellar realignment by Roux-Goldthwait technique or patellar tendon transfer with tibial tubercle relocation. 5. Proximal tibial varus osteotomy with partial fibulectomy and anterior compartment release. 6. Occasionally, distal femoral osteotomy. RESULTS: In all cases, the combination of radical soft-tissue release, patellar realignment and bony osteotomy resulted in 10° or less of genu valgum at the time of surgical correction. Complications of surgery included three patients (five limbs) with knee stiffness that was successfully manipulated, one peroneal nerve palsy, one wound slough and hematoma requiring a skin graft, and one pseudoarthrosis requiring removal of hardware and repeat fixation. At last follow-up, radiographic correction of no more than 20° of genu valgum was maintained in all but four patients (four limbs). Two patients (three limbs) had or currently require revision surgery due to recurrence of the deformity. CONCLUSION: The operative approach presented in this study has resulted in correction of the severe genu valgum deformity in Ellis-van Creveld syndrome to 10° or less of genu valgum at the time of surgery. Although not an outcomes study, a correction of no more than 20° genu valgum has been maintained in many of the cases included in the study. Further clinical follow-up is still warranted. LEVEL OF EVIDENCE: IV