An Investigation of Acid Rock Drainage in Glacial Streams Through Multivariate Exploratory Analysis and the Biotic Ligand Model in the Cordillera Blanca, Peru.

Water chemistry in the Cordillera Blanca, Peru, where glaciers provide crucial freshwater to the arid Andes Mountains, was characterized during the dry season (June-August), 2014. Metal concentrations, anion concentrations, and physical and chemical parameters were assessed at 94 sample sites in seven river valleys. Nonparametric multivariate exploratory statistics were used to compare sample sites. Compared to other river valleys, high metal concentrations were evident in the Quilcayhuanca valley. Water chemistry and visual signs indicated that acid rock drainage (ARD) is occurring in the Cordillera Blanca, likely due to glacial recession. Hierarchical clustering analysis was performed on the results of a principal components analysis on the chemical data. The results of these two analyses showed cobalt, manganese, and nickel were the top metals that distinguished the different clusters. In addition to the exploratory analysis, the Biotic Ligand Model (BLM) was used to predict toxicity to aquatic life based on the chemical measurements at the sampling sites. Approximately 20% of the sites had predicted toxic responses to metals and another 20% of the sites were outside of the pH tolerance range of individual species. These sites outside of the pH ranges were assumed to cause toxicity to the aquatic organisms due to hydrogen ions rather than metals. From this, the altered water quality in headwater streams in the Cordillera Blanca is predicted to be detrimental to aquatic life. The reduction in water quality makes the understanding of these headwater streams critical in efforts to mitigate the loss of crucial water resources

Comprehensive Analysis of Escape-Cone Losses from Luminescent Waveguides

Luminescent waveguides (LWs) occur in a wide range of applications, from solar concentrators to doped fiber amplifiers. Here we report a comprehensive analysis of escape-cone losses in LWs, which are losses associated with internal rays making an angle less than the critical angle with a waveguide surface. For applications such as luminescent solar concentrators, escape-cone losses often dominate all others. A statistical treatment of escape-cone losses is given accounting for photoselection, photon polarization, and the Fresnel relations, and the model is used to analyze light absorption and propagation in waveguides with isotropic and orientationally aligned luminophores. The results are then compared to experimental measurements performed on a fluorescent dye-doped poly(methyl methacrylate) waveguide

Bringing bioinformatics to schools with the 4273pi project

The work was supported by the Science and Technology Facilities Council (STFC) under Grants STFC ST/R000328/1 (including salary to S.A.B., D.B., H.P., T.R.M. and non-salary costs) and STFC ST/T000872/1 (including salary to S.A.B., D.B., K.C., T.R.M. and non-salary costs), the Darwin Trust of Edinburgh (https://darwintrust.bio.ed.ac.uk; including salary to S.A.B. and H.P. and non-salary costs), the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund under Wellcome Trust Grant number 204804/Z/16/Z (salary to H.P.), a Public Engagement with Genetics Tier 2 Grant from the Genetics Society (https://genetics.org.uk; non-salary costs), the Natural Environment Research Council (NERC) under Grant NE/P000592/1 (including salary to N.C. and M.G.R. and non-salary costs), the Biotechnology and Biological Sciences Research Council (BBSRC) under Grant BB/S018506/1 (including salary to F.A. and non-salary costs), the School of Biological Sciences at the University of Edinburgh (https://www.ed.ac.uk/biology; including salary to S.A.B. and H.P. and non-salary costs) and its Institute of Evolutionary Biology (https://www.ed.ac.uk/biology/evolutionary-biology; non-salary costs), the Access for Rural Communities project (ARC) at University of St Andrews (https://www.st-andrews.ac.uk/study/access/projects/arc; non-salary costs) and the Engineering and Physical Sciences Research Council (EPSRC) under Grant EP/V52038X/1 (including salary to S.A.B. and non-salary costs). E.W.J.W. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society [208779/Z/17/Z] (including salary to E.W.J.W.).Over the last few decades, the nature of life sciences research has changed enormously, generating a need for a workforce with a variety of computational skills such as those required to store, manage, and analyse the large biological datasets produced by next-generation sequencing. Those with such expertise are increasingly in demand for employment in both research and industry. Despite this, bioinformatics education has failed to keep pace with advances in research. At secondary school level, computing is often taught in isolation from other sciences, and its importance in biological research is not fully realised, leaving pupils unprepared for the computational component of Higher Education and, subsequently, research in the life sciences. The 4273pi Bioinformatics at School project (https://4273pi.org) aims to address this issue by designing and delivering curriculum-linked, hands-on bioinformatics workshops for secondary school biology pupils, with an emphasis on equitable access. So far, we have reached over 180 schools across Scotland through visits or teacher events, and our open education resources are used internationally. Here, we describe our project, our aims and motivations, and the practical lessons we have learned from implementing a successful bioinformatics education project over the last 5 years.Publisher PDFPeer reviewe

Microscale modelling of the deformation of a martensitic steel using the Voronoi Tessellation method

peer-reviewedThe deformation of a martensitic steel (P91) at the microscale is investigated using the finite element method. The approach takes into account the hierarchical grain-packet-block microstructure of the steel as determined experimentally by electron backscatter diffraction (EBSD). The orientation relationship for P91 between the prior austenite grain (PAG) and the martensitic packet/block is determined and found to be consistent with the Kurdjumow-Sachs (K-S) relationship. This relationship is incorporated within a finite-element model to represent the material microstructure, using a representative volume element (RVE) generated by a modified centroidal Voronoi tesselation (VT) approach. A non-linear, rate dependent, finite strain crystal plasticity model is used to simulate the mechanical response of the material at the micro- and macro-level and the sensitivity of the results to the model assumptions is investigated. It is found that the global (macro) mechanical response predicted by the RVE generated using the modified VT model is in good agreement with that predicted by an RVE taken directly from the measured EBSD microstructure. The influence of block/packet/grain boundaries on the local (micro) deformation is examined and it is found that the microscale prediction obtained using the RVE based on the modified VT microstructure, with an appropriate choice of microstructural parameters, is consistent with that obtained using the measured EBSD map

Regulation of PURA gene transcription by three promoters generating distinctly spliced 5-prime leaders: a novel means of fine control over tissue specificity and viral signals

<p>Abstract</p> <p>Background</p> <p>Purα is an evolutionarily conserved cellular protein participating in processes of DNA replication, transcription, and RNA transport; all involving binding to nucleic acids and altering conformation and physical positioning. The distinct but related roles of Purα suggest a need for expression regulated differently depending on intracellular and external signals.</p> <p>Results</p> <p>Here we report that human <it>PURA </it>(<it>hPURA</it>) transcription is regulated from three distinct and widely-separated transcription start sites (TSS). Each of these TSS is strongly homologous to a similar site in mouse chromosomal DNA. Transcripts from TSS I and II are characterized by the presence of large and overlapping 5'-UTR introns terminated at the same splice receptor site. Transfection of lung carcinoma cells with wild-type or mutated <it>hPURA </it>5' upstream sequences identifies different regulatory elements. TSS III, located within 80 bp of the translational start codon, is upregulated by E2F1, CAAT and NF-Y binding elements. Transcription at TSS II is downregulated through the presence of adjacent consensus binding elements for interferon regulatory factors (IRFs). Chromatin immunoprecipitation reveals that IRF-3 protein binds <it>hPURA </it>promoter sequences at TSS II in vivo. By co-transfecting <it>hPURA </it>reporter plasmids with expression plasmids for IRF proteins we demonstrate that several IRFs, including IRF-3, down-regulate <it>PURA </it>transcription. Infection of NIH 3T3 cells with mouse cytomegalovirus results in a rapid decrease in levels of <it>mPURA </it>mRNA and Purα protein. The viral infection alters the degree of splicing of the 5'-UTR introns of TSS II transcripts.</p> <p>Conclusions</p> <p>Results provide evidence for a novel mechanism of transcriptional control by multiple promoters used differently in various tissues and cells. Viral infection alters not only the use of <it>PURA </it>promoters but also the generation of different non-coding RNAs from 5'-UTRs of the resulting transcripts.</p

Green Tea Polyphenols Rescue of Brain Defects Induced by Overexpression of DYRK1A

Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They present also learning impairments modeling those encountered in Down syndrome. Previous MRI and histological analyses of a transgenic mice generated using a human YAC construct that contains five genes including DYRK1A reveal that DYRK1A is involved, during development, in the control of brain volume and cell density of specific brain regions. Gene dosage correction induces a rescue of the brain volume alterations. DYRK1A is also involved in the control of synaptic plasticity and memory consolidation. Increased gene dosage results in brain morphogenesis defects, low BDNF levels and mnemonic deficits in these mice. Epigallocatechin gallate (EGCG) — a member of a natural polyphenols family, found in great amount in green tea leaves — is a specific and safe DYRK1A inhibitor. We maintained control and transgenic mice overexpressing DYRK1A on two different polyphenol-based diets, from gestation to adulthood. The major features of the transgenic phenotype were rescued in these mice

Macrophage origin limits functional plasticity in helminth-bacterial co-infection

Rapid reprogramming of the macrophage activation phenotype is considered important in the defense against consecutive infection with diverse infectious agents. However, in the setting of persistent, chronic infection the functional importance of macrophage-intrinsic adaptation to changing environments vs. recruitment of new macrophages remains unclear. Here we show that resident peritoneal macrophages expanded by infection with the nematode Heligmosomoides polygyrus bakeri altered their activation phenotype in response to infection with Salmonella enterica ser. Typhimurium in vitro and in vivo. The nematode-expanded resident F4/80high macrophages efficiently upregulated bacterial induced effector molecules (e.g. MHC-II, NOS2) similarly to newly recruited monocyte-derived macrophages. Nonetheless, recruitment of blood monocyte-derived macrophages to Salmonella infection occurred with equal magnitude in co-infected animals and caused displacement of the nematode-expanded, tissue resident-derived macrophages from the peritoneal cavity. Global gene expression analysis revealed that although nematode-expanded resident F4/80high macrophages made an anti-bacterial response, this was muted as compared to newly recruited F4/80low macrophages. However, the F4/80high macrophages adopted unique functional characteristics that included enhanced neutrophil-stimulating chemokine production. Thus, our data provide important evidence that plastic adaptation of MΦ activation does occur in vivo, but that cellular plasticity is outweighed by functional capabilities specific to the tissue origin of the cell

World-Wide FINGERS Network: A global approach to risk reduction and prevention of dementia

© 2020 The Authors. Alzheimer\u27s & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer\u27s Association Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer\u27s disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline—from at-risk asymptomatic states to early symptomatic stages—in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies

A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

A Tale of Four “Carp”: Invasion Potential and Ecological Niche Modeling

. We assessed the geographic potential of four Eurasian cyprinid fishes (common carp, tench, grass carp, black carp) as invaders in North America via ecological niche modeling (ENM). These “carp” represent four stages of invasion of the continent (a long-established invader with a wide distribution, a long-established invader with a limited distribution, a spreading invader whose distribution is expanding, and a newly introduced potential invader that is not yet established), and as such illustrate the progressive reduction of distributional disequilibrium over the history of species' invasions.We used ENM to estimate the potential distributional area for each species in North America using models based on native range distribution data. Environmental data layers for native and introduced ranges were imported from state, national, and international climate and environmental databases. Models were evaluated using independent validation data on native and invaded areas. We calculated omission error for the independent validation data for each species: all native range tests were highly successful (all omission values <7%); invaded-range predictions were predictive for common and grass carp (omission values 8.8 and 19.8%, respectively). Model omission was high for introduced tench populations (54.7%), but the model correctly identified some areas where the species has been successful; distributional predictions for black carp show that large portions of eastern North America are at risk.ENMs predicted potential ranges of carp species accurately even in regions where the species have not been present until recently. ENM can forecast species' potential geographic ranges with reasonable precision and within the short screening time required by proposed U.S. invasive species legislation