Antithrombin-III Mitigates Thrombin-Mediated Endothelial Cell Contraction and Sickle Red Blood Cell Adhesion in Microscale Flow

Individuals with sickle cell disease (SCD) have persistently elevated thrombin generation that results in a state of systemic hypercoagulability. Antithrombin-III (ATIII), an endogenous serine protease inhibitor, inhibits several enzymes in the coagulation cascade, including thrombin. Here, we utilize a biomimetic microfluidic device to model the morphology and adhesive properties of endothelial cells (ECs) activated by thrombin and examine the efficacy of ATIII in mitigating the adhesion of SCD patient-derived red blood cells (RBCs) and EC retraction. Microfluidic devices were fabricated, seeded with ECs, and incubated under physiological shear stress. Cells were then activated with thrombin with or without an ATIII pretreatment. Blood samples from subjects with normal haemoglobin (HbAA) and subjects with homozygous SCD (HbSS) were used to examine RBC adhesion to ECs. Endothelial cell surface adhesion molecule expression and confluency in response to thrombin and ATIII treatments were also evaluated. We found that ATIII pretreatment of ECs reduced HbSS RBC adhesion to thrombin-activated endothelium. Furthermore, ATIII mitigated cellular contraction and reduced surface expression of von Willebrand factor and vascular cell adhesion molecule-1 (VCAM-1) mediated by thrombin. Our findings suggest that, by attenuating thrombin-mediated EC damage and RBC adhesion to endothelium, ATIII may alleviate the thromboinflammatory manifestations of SCD

Strengthening global-change science by integrating aeDNA with paleoecoinformatics

Ancient environmental DNA (aeDNA) data are close to enabling insights into past global-scale biodiversity dynamics at unprecedented taxonomic extent and resolution. However, achieving this potential requires solutions that bridge bioinformatics and paleoecoinformatics. Essential needs include support for dynamic taxonomic inferences, dynamic age inferences, and precise stratigraphic depth. Moreover, aeDNA data are complex and heterogeneous, generated by dispersed researcher networks, with methods advancing rapidly. Hence, expert community governance and curation are essential to building high-value data resources. Immediate recommendations include uploading metabarcoding-based taxonomic inventories into paleoecoinformatic resources, building linkages among open bioinformatic and paleoecoinformatic data resources, harmonizing aeDNA processing workflows, and expanding community data governance. These advances will enable transformative insights into global-scale biodiversity dynamics during large environmental and anthropogenic changes

Prioritizing taxa for genetic reference database development to advance inland water conservation

Biodiversity loss has accelerated over the past century and freshwater species overall are among those experiencing greatest declines. Genetic resources have the potential to help evaluate the full magnitude of this loss and represent a key tool to effectively allocate conservation resources and monitor the success of restoration efforts. The full power of genetic resources will be realized when the daunting task of referencing all DNA sequences of freshwater organisms is complete. Here, we quantified the availability and distribution of barcode and genome data for freshwater macroscopic organisms in Canada, a country rich in inland water resources and thus particularly vulnerable to aquatic species losses. Impressively, most inland water species (86 %) were represented by barcodes recorded in the BOLD Systems database, while very few had full genomes available (<4 %) in the NCBI database. We identified barcode data deficiencies in northern regions and for taxa assessed as most at risk or without sufficient information for conservation status classification. As expected, the speciose insect group had a lower-than-average number of records per species and a high proportion of data deficient species without adequate barcode coverage. This study highlights where future sequencing resources should be prioritized within initiatives such as the Canada BioGenome Project and BIOSCAN Canada and provides a workflow that could be applied internationally to inform conservation management plans and to mitigate biodiversity loss

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Lake sedimentary dna research on past terrestrial and aquatic biodiversity: Overview and recommendations

The use of lake sedimentary DNA to track the long-term changes in both terrestrial and aquatic biota is a rapidly advancing field in paleoecological research. Although largely applied nowadays, knowledge gaps remain in this field and there is therefore still research to be conducted to ensure the reliability of the sedimentary DNA signal. Building on the most recent literature and seven original case studies, we synthesize the state-of-the-art analytical procedures for effective sampling, extraction, amplification, quantification and/or generation of DNA inventories from sedimentary ancient DNA (sedaDNA) via high-throughput sequencing technologies. We provide recommendations based on current knowledge and best practises.</jats:p

On the nature of striae in strontium barium niobate

Strontium barium niobate crystals were grown by the Czochralski technique. These crystals were 15--20 mm in diameter and 25 to 75 mm long. Two types stride, designated as coarse and fine, were characterized. The coarse stride are optically dense and are spaced by 100 to 500 {mu}m apart; the fine striae are optically less dense and spaced 5--50 {mu}m apart. The origins of the stride are attributed to thermal fluctuations in the melt related to the control system and to rotation of the growing crystal in non-isothermal radial gradients. Analysis of the crystals would indicated that the coarse striae may contain increased concentrations of sodium

Nitrogen Forms Influence Microcystin Concentration and Composition via Changes in Cyanobacterial Community Structure

The eutrophication of freshwaters is a global health concern as lakes with excess nutrients are often subject to toxic cyanobacterial blooms. Although phosphorus is considered the main element regulating cyanobacterial biomass, nitrogen (N) concentration and more specifically the availability of different N forms may influence the overall toxicity of blooms. In this study of three eutrophic lakes prone to cyanobacterial blooms, we examined the effects of nitrogen species and concentrations and other environmental factors in influencing cyanobacterial community structure, microcystin (MC) concentrations and MC congener composition. The identification of specific MC congeners was of particular interest as they vary widely in toxicity. Different nitrogen forms appeared to influence cyanobacterial community structure leading to corresponding effects on MC concentrations and composition. Total MC concentrations across the lakes were largely explained by a combination of abiotic factors: dissolved organic nitrogen, water temperature and ammonium, but Microcystis spp. biomass was overall the best predictor of MC concentrations. Environmental factors did not appear to affect MC congener composition directly but there were significant associations between specific MC congeners and particular species. Based on redundancy analyses (RDA), the relative biomass of Microcystis aeruginosa was associated with MC-RR, M. wesenbergii with MC-LA and Aphanizomenon flos-aquae with MC-YR. The latter two species are not generally considered capable of MC production. Total nitrogen, water temperature, ammonium and dissolved organic nitrogen influenced the cyanobacterial community structure, which in turn resulted in differences in the dominant MC congener and the overall toxicity.ISSN:1932-620

Concentration of nutrients (<i>μ</i>M) from April to October in the three study lakes.

<p>A) TP, B) SRP, C) TN, D) DON, E) NH₄⁺, and F) NO₃⁻+NO₂⁻. BRO INT, integrated samples from the epilimnion of lake Bromont; BRO META, samples from the metalimnion of lake Bromont; PSF, Petit Lac St. François; WAT, Lake Waterloo.</p