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

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

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

Autonomous detection and anticipation of jam fronts from messages propagated by inter-vehicle communication

In this paper, a minimalist, completely distributed freeway traffic information system is introduced. It involves an autonomous, vehicle-based jam front detection, the information transmission via inter-vehicle communication, and the forecast of the spatial position of jam fronts by reconstructing the spatiotemporal traffic situation based on the transmitted information. The whole system is simulated with an integrated traffic simulator, that is based on a realistic microscopic traffic model for longitudinal movements and lane changes. The function of its communication module has been explicitly validated by comparing the simulation results with analytical calculations. By means of simulations, we show that the algorithms for a congestion-front recognition, message transmission, and processing predict reliably the existence and position of jam fronts for vehicle equipment rates as low as 3%. A reliable mode of operation already for small market penetrations is crucial for the successful introduction of inter-vehicle communication. The short-term prediction of jam fronts is not only useful for the driver, but is essential for enhancing road safety and road capacity by intelligent adaptive cruise control systems.Comment: Published in the Proceedings of the Annual Meeting of the Transportation Research Board 200

Particulate organic carbon and nitrogen export from major Arctic rivers

Author Posting. © American Geophysical Union, 2016. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 30 (2016): 629–643, doi:10.1002/2015GB005351.Northern rivers connect a land area of approximately 20.5 million km2 to the Arctic Ocean and surrounding seas. These rivers account for ~10% of global river discharge and transport massive quantities of dissolved and particulate materials that reflect watershed sources and impact biogeochemical cycling in the ocean. In this paper, multiyear data sets from a coordinated sampling program are used to characterize particulate organic carbon (POC) and particulate nitrogen (PN) export from the six largest rivers within the pan-Arctic watershed (Yenisey, Lena, Ob', Mackenzie, Yukon, Kolyma). Together, these rivers export an average of 3055 × 109 g of POC and 368 × 109 g of PN each year. Scaled up to the pan-Arctic watershed as a whole, fluvial export estimates increase to 5767 × 109 g and 695 × 109 g of POC and PN per year, respectively. POC export is substantially lower than dissolved organic carbon export by these rivers, whereas PN export is roughly equal to dissolved nitrogen export. Seasonal patterns in concentrations and source/composition indicators (C:N, δ13C, Δ14C, δ15N) are broadly similar among rivers, but distinct regional differences are also evident. For example, average radiocarbon ages of POC range from ~2000 (Ob') to ~5500 (Mackenzie) years before present. Rapid changes within the Arctic system as a consequence of global warming make it challenging to establish a contemporary baseline of fluvial export, but the results presented in this paper capture variability and quantify average conditions for nearly a decade at the beginning of the 21st century.National Science Foundation Grant Numbers: 0229302, 0732985; U.S. Geological Survey; Department of Indian and Northern Affairs2016-11-1

Summer CO2 evasion from streams and rivers in the Kolyma River basin, north-east Siberia

Inland water systems are generally supersaturated in carbon dioxide (CO2) and are increasingly recognized as playing an important role in the global carbon cycle. The Arctic may be particularly important in this respect, given the abundance of inland waters and carbon contained in Arctic soils; however, a lack of trace gas measurements from small streams in the Arctic currently limits this understanding.We investigated the spatial variability of CO2 evasion during the summer low-flow period from streams and rivers in the northern portion of the Kolyma River basin in north-eastern Siberia. To this end, partial pressure of carbon dioxide (pCO2) and gas exchange velocities (k) were measured at a diverse set of streams and rivers to calculate CO2 evasion fluxes. We combined these CO2 evasion estimates with satellite remote sensing and geographic information system techniques to calculate total areal CO2 emissions. Our results show that small streams are substantial sources of atmospheric CO2 owing to high pCO2 and k, despite being a small portion of total inland water surface area. In contrast, large rivers were generally near equilibrium with atmospheric CO2. Extrapolating our findings across the Panteleikha-Ambolikha sub-watersheds demonstrated that small streams play a major role in CO2 evasion, accounting for 86% of the total summer CO2 emissions from inland waters within these two sub-watersheds. Further expansion of these regional CO2 emission estimates across time and space will be critical to accurately quantify and understand the role of Arctic streams and rivers in the global carbon budget

Reassessing changes in diurnal temperature range: Intercomparison and evaluation of existing global data set estimates

Changes in diurnal temperature range (DTR) over global land areas are compared from a broad range of independent data sets. All data sets agree that global-mean DTR has decreased significantly since 1950, with most of that decrease occurring over 1960–1980. The since-1979 trends are not significant, with inter-data set disagreement even over the sign of global changes. Inter-data set spread becomes greater regionally and in particular at the grid box level. Despite this, there is general agreement that DTR decreased in North America, Europe, and Australia since 1951, with this decrease being partially reversed over Australia and Europe since the early 1980s. There is substantive disagreement between data sets prior to the middle of the twentieth century, particularly over Europe, which precludes making any meaningful conclusions about DTR changes prior to 1950, either globally or regionally. Several variants that undertake a broad range of approaches to postprocessing steps of gridding and interpolation were analyzed for two of the data sets. These choices have a substantial influence in data sparse regions or periods. The potential of further insights is therefore inextricably linked with the efficacy of data rescue and digitization for maximum and minimum temperature series prior to 1950 everywhere and in data sparse regions throughout the period of record. Over North America, station selection and homogeneity assessment is the primary determinant. Over Europe, where the basic station data are similar, the postprocessing choices are dominant. We assess that globally averaged DTR has decreased since the middle twentieth century but that this decrease has not been linear

Effects of Temperature–Climate Patterns on the Production of Some Competitive Species on Grounds of Modelling

Climate change has serious effects on the setting up and the operation of natural ecosystems. Small increase in temperature could cause rise in the amount of some species or potential disappearance of others. During our researches, the dispersion of the species and biomass production of a theoretical ecosystem were examined on the effect of the temperature–climate change. The answers of the ecosystems which are given to the climate change could be described by means of global climate modelling and dynamic vegetation models. The examination of the operation of the ecosystems is only possible in huge centres on supercomputers because of the number and the complexity of the calculation. The number of the calculation could be decreased to the level of a PC by considering the temperature and the reproduction during modelling a theoretical ecosystem, and several important theoretical questions could be answered