The Analysis of Exosomal Tau Release and its Regulation

The secretion of Tau protein from cells combined with its trans-cellular uptake has been hypothesised as a central component in the progression of Tauopathic neurodegenerative diseases. Exosomes, small (30 – 140 nm) vesicles released from cells, may represent a privileged route for secretion and transmission of neurodegenerative proteins. We hypothesised that 1) Tau protein may be released from cells in exosomes 2) that this process may be regulated by the interaction of Tau with the chaperone network and SUMOylation of Tau and 3) exosomes may transmit Tau to naïve cells. We established and characterised the exosomal release of Tau from SH-SY5Y cells; all isoforms of Tau studied, including endogenous SH-SY5Y Tau, were detected in exosomal fractions. Exosomal 2N4R-Tau was C-terminally truncated and intra-luminal. We investigated the role of Tau-Hsc70 interaction in its exosomal release and identified the co-chaperone DNAjC5 as a key mediator in this process. SUMOylation of Tau protein was also identified as a key process regulating its exosomal release. We furthermore gathered evidence connecting Tau protein dysfunction (P301L-Tau; oligomerisation) and exosomal release, implicating exosomal Tau release as a potentially disease relevant process. In order to model the transmission of Tau between cells, we studied the uptake of a) Tau recovered from cells and b) Tau secreted from cells. However, naïve SH-SY5Y cells were able to internalise extracellular Tau only to a low extent. When co-cultured, Tau protein transferred efficiently between cells. This process was potentiated by lysosomal compromise and dependent upon cell density. Finally, we determined that exosomes isolated from SH-SY5Y cells with ectopic expression of P301L-Tau were selectively toxic to primary mouse cortical neurons. Overall the work presented here confirms the exosomal release of Tau protein and links this process to pathological Tau. Our work identifies key cellular mechanisms governing the exosomal release of Tau that may serve as points of departure for future studies investigating the release and transmission of Tau, and the role of exosomes therein

Effect of Local Materials on the Silver Sorption and Strength of Ceramic Water Filters

In this paper, we present a systematic evaluation of the effects of local clays and the manufacturing process on the performance of ceramic water filters (CWFs) impregnated with silver compounds, which are used for point-of-use water treatment in developing countries. Mineral composition, silver sorption/desorption, and strength are the important characteristics that influence effectiveness and durability of CWFs during transport and use. Laboratory tests were conducted on ceramic samples obtained from five CWF factories around the world to determine their mineral composition, silver sorption/desorption, and flexural strength. The results of this study showed that clays that contain traces of crystalline albite or crystalline pyroxene have better sorption of silver species than those that do not. The results showed that the Freundlich model provided the best fit for both ionic silver and silver nanoparticles for all of the ceramic materials that were tested. Thus, this model can be used to optimize the manufacturing process and the application of silver. Silver nanoparticles were desorbed more slowly than ionic silver, so they last longer in the ceramic material. Water that contains a high concentration of divalent ions is not recommended for preparing solutions of silver nanoparticles due to aggregation of the particles, which limits their sorption by the ceramic materials. In this study, the mineralogy of the source materials was found to have the most significant influence on the strength of ceramic filters

A serine sensor for multicellularity in a bacterium

We report the discovery of a simple environmental sensing mechanism for biofilm formation in the bacterium Bacillus subtilis that operates without the involvement of a dedicated RNA or protein. Certain serine codons, the four TCN codons, in the gene for the biofilm repressor SinR caused a lowering of SinR levels under biofilm-inducing conditions. Synonymous substitutions of these TCN codons with AGC or AGT impaired biofilm formation and gene expression. Conversely, switching AGC or AGT to TCN codons upregulated biofilm formation. Genome-wide ribosome profiling showed that ribosome density was higher at UCN codons than at AGC or AGU during biofilm formation. Serine starvation recapitulated the effect of biofilm-inducing conditions on ribosome occupancy and SinR production. As serine is one of the first amino acids to be exhausted at the end of exponential phase growth, reduced translation speed at serine codons may be exploited by other microbes in adapting to stationary phase. DOI: http://dx.doi.org/10.7554/eLife.01501.00

Next-Generation Technology and Electoral Democracy: Understanding the Changing Environment

Democracies around the world are facing growing threats to their electoral systems in the digital age. Foreign interference in the form of dis- and misinformation has already influenced the results of democratic elections and altered the course of history. This special report, the result of a research project conducted in partnership with the Konrad-Adenauer-Stiftung (KAS) Canada, examines these cyberthreats from a Canadian and German perspective. Both Canada and Germany share common goals centred around protecting human rights, democracy and the rule of law, and international peace and security. Using case studies from experts in fields such as computer science, law and public policy, the special report offers recommendations to guide policy makers and stakeholders on how to protect elections from next-generation technologies and the threats they pose to democracy

Wetland Management Strategies that Maximize Marsh Bird Use in the Midwest: Annual Performance Report Period: 1 July 2016 – 30 June 2017

We determined marsh bird use across a wide range of wetland types (e.g., emergent, non-vegetated, riparian), hydrologic regimes (e.g., temporary, seasonal, semi-permanent), management practices (e.g., active, passive, unmanaged), and past disturbance regimes (e.g., natural and restored, impounded and unimpounded) in Illinois during late spring and early summer in 2015–2017. Our objectives were to 1) compare marsh bird use of restored and natural wetlands, 2) determine characteristics of wetlands and the surrounding landscape that influence marsh bird use of restored and natural wetlands, 3) compare marsh bird use of wetland impoundments managed for waterfowl across a continuum of management intensities and strategies to predict how these actions can increase use by both waterfowl and marsh birds. Additionally, we surveyed marsh birds using the standard protocols on wetlands concurrently surveyed within the Illinois Critical Trends Assessment Program (CTAP) for comparison of methodologies. We will provide marsh bird and other wetland-associated bird data to the Midwest Avian Data Center and the Avian Knowledge Network (AKN) and other conservation partners.Our data will be used as a basis for establishment of multi-group management strategies for marsh birds in the Midwest. These data will be especially useful as the Illinois Department of Natural Resources (IDNR) finalizes their Wetlands Campaign and Conservation Strategy as part of the Illinois Comprehensive Wildlife Conservation Plan and Strategy (i.e., wildlife action plan; ICWCPS). Moreover, our research addresses several priorities outlined in the Midwest bird monitoring framework outlined by Koch et al. (2010), including furthering understanding of the ecology and conservation priorities for migrating birds, evaluating effectiveness of conservation actions such as wetland restoration, and increasing access to bird data relative to landscape characteristics for use in conservation planning.Unites States Fish and Wildlife Service Contract Number: F14AP00485unpublishednot peer reviewedOpe

Monopiles subjected to uni- and multi-lateral cyclic loading

Offshore wind turbines are subjected to significant environmental loads from a combination of current, wind and wave action. Under such conditions, the directions of these environmental loads vary over the service life of the structure and therefore the cyclic lateral loading on the foundation also changes direction. The work reported in this paper examines the effects of multi-directional loading on the performance of offshore wind turbine monopile foundations. Tests were carried out in a model sand bed and a mobile loading platform was manufactured to apply loading on the pile in various directions. Tests were also carried out where the cyclic loading was applied under both one-way and two-way loading. The observations indicate significant differences in the stiffness of monopiles between uni-directional and multi-directional lateral cyclic loading. Multi-directional lateral cyclic loading generally results in higher displacements and lower stiffness compared to uni-directional loading, most likely due to shear deformation of a larger volume of soil mass adjacent to the pile

Genome-wide screen for genes involved in eDNA release during biofilm formation by

Staphylococcus aureus is a leading cause of both nosocomial and community-acquired infection. Biofilm formation at the site of infection reduces antimicrobial susceptibility and can lead to chronic infection. During biofilm formation, a subset of cells liberate cytoplasmic proteins and DNA, which are repurposed to form the extracellular matrix that binds the remaining cells together in large clusters. Using a strain that forms robust biofilms in vitro during growth under glucose supplementation, we carried out a genome-wide screen for genes involved in the release of extracellular DNA (eDNA). A high-density transposon insertion library was grown under biofilm-inducing conditions, and the relative frequency of insertions was compared between genomic DNA (gDNA) collected from cells in the biofilm and eDNA from the matrix. Transposon insertions into genes encoding functions necessary for eDNA release were identified by reduced representation in the eDNA. On direct testing, mutants of some of these genes exhibited markedly reduced levels of eDNA and a concomitant reduction in cell clustering. Among the genes with robust mutant phenotypes were gdpP, which encodes a phosphodiesterase that degrades the second messenger cyclic-di-AMP, and xdrA, the gene for a transcription factor that, as revealed by RNA-sequencing analysis, influences the expression of multiple genes, including many involved in cell wall homeostasis. Finally, we report that growth in biofilm-inducing medium lowers cyclic-di-AMP levels and does so in a manner that depends on the gdpP phosphodiesterase gene. Keywords: Staphylococcus aureus; biofilm; eDNA; cyclic-di-AMPNational Institutes of Health (U.S.) (Grant P01-AI083214

Acoustic emission as an aid to understanding raceway damage in rolling element bearings [Abstract]

Acoustic Emission (AE) sensors were used to detect signals arising from a cylindrical roller bearing with artificial defects seeded onto the outer raceway. High frequency analysis indicated the condition of the bearings through the determination of an increase in the structural resonances of the system as the size of an artificial defect was increased. As higher loads were applied, frequencies around 100kHz were excited, indicating the release of AE possibly attributed to friction and the plastic deformation as peaks, induced through engraving of the raceway, were over-rolled and worn down. Sensitivity of AE to this level in bearings indicates that detection of subsurface cracking may be possible in future work, providing early indication of incipient failure