54 research outputs found

    Effect of estrogen on manganese-induced toxicity on embryonic astrocytes

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    Manganese (Mn) is a natural trace metal that is essential for many physiological functions in the human body. Astrocytes in the central nervous system are susceptible reservoirs for Mn accumulation. Estrogen, a steroidal hormone, has been shown to mitigate Mn-induced toxicity in cultures of postnatal astrocytes. However, differences in expression/inducibility of glutamate transporters and glutamine synthetase, transmitters, and the natural gonadal steroids and their receptors are known to occur in astrocyte cultures derived from various stages of fetal and postnatal development. Cultures of embryonic (E18) hippocampal astrocytes were examined in this study for the ability of 17 β-estradiol (E2) to protect them from Mn toxicity by up regulating gene expression of a glutamate transporter. Primary rat hippocampal astrocytes were pretreated with β-Estradiol (E2) in vitro and subsequently, Mn sulfate (MnSO4). The amount of toxic damage to the astrocytes was measured by quantifying glial fibrillary acidic protein (GFAP) with a sandwiched Enzyme-Linked Immunosorbent Assay (ELISA). ELISA analysis indicated Mn exposure at 100 μM, 300 μM, or 600 μM significantly increased GFAP levels. However, E2 concentrations at 10 nM or 30 nM significantly reduced Mn-induced GFAP concentrations at 100 μM. Cells pretreated with 10 nM or 30 nM of E2 significantly lowered GFAP levels. The Water-Soluble Tetrazolium-8 (WST-8) method was utilized to determine cell viability. The WST-8 assay showed that Mn concentrations of 100 μM, 300 μM, or 600 μM significantly reduced the dehydrogenase activity, thereby decreasing the number of viable astrocytes. Enzyme activity with 600 μM of Mn was significantly decreased when compared with 100 μM of Mn, revealing a dose-dependent effect. However, the dehydrogenase activity in cells treated with 600 μM Mn was significantly increased when pretreated with 10 nM of E2. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) was used to measure changes in glutamate transporter-1 gene expression in astrocytes after pretreatment of E2 and subsequently, Mn. PCR analysis showed that when cells were exposed to 300 μM Mn, the GLT-1 gene expression was reduced compared to the control. Data also showed that the GLT-1 mRNA was upregulated in cells pretreated with 10 nM E2. When the cells were pretreated with 10 nM E2 and subsequently, 300 μM Mn, there was an increase in the GLT-1 gene expression. The experimental results indicate that E2 can attenuate some Mn-induced toxicity in E18 astrocytes

    Catalyzing collaborations: Prescribed interactions at conferences determine team formation

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    Collaboration plays a key role in knowledge production. Here, we show that patterns of interaction during conferences can be used to predict who will subsequently form a new collaboration, even when interaction is prescribed rather than freely chosen. We introduce a novel longitudinal dataset tracking patterns of interaction among hundreds of scientists during multi-day conferences encompassing different scientific fields over the span of 5 years. We find that participants who formed new collaborations interacted 63% more on average than those who chose not to form new teams, and that those assigned to a higher interaction scenario had more than an eightfold increase in their odds of collaborating. We propose a simple mathematical framework for the process of team formation that incorporates this observation as well as the effect of memory beyond interaction time. The model accurately reproduces the collaborations formed across all conferences and outperforms seven other candidate models. This work not only suggests that encounters between individuals at conferences play an important role in shaping the future of science, but that these encounters can be designed to better catalyze collaborations.Comment: 8 pages and 4 figures, main text; 8 pages and 3 figures supplementary informatio

    Model binding experiments with cucurbit[7]uril and p-sulfonatocalix[4]arene support use of explicit solvation term in governing equation for binding equilibria

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    The thermodynamics of model host–guest-binding reactions is examined in depth using isothermal titration calorimetry. In conflict with classical thermodynamics, the results indicate that the equilibrium-binding quotient, K, is not a constant for all pairings. This outcome is predicted by an equation for binding equilibria that includes an explicit term for the change in solvation free energy that accompanies the formation of a binary complex. Application of this framework to the experimentally observed concentration dependence of K allows one to obtain the energetic contribution of the solvent, a linked equilibrium denoted here as ΔGH2O. The estimated values of ΔGH2O are large and unfavourable for the binding of selected guest molecules to two hosts, cucurbit[7]uril and p-sulfonatocalix[4]arene. Intriguingly, the estimated values of ΔGH2O are near zero for the binding of two hydrophobic guest molecules to β-cyclodextrin, leading to a thought-provoking discussion on the driving force behind the hydrophobic effect

    Estimated discharge of microplastics via urban stormwater during individual rain events

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    Urban stormwater runoff is an important pathway for the introduction of microplastics and other anthropogenic pollutants into aquatic environments. Highly variable concentrations of microplastics have been reported globally in runoff, but knowledge of key factors within urban environments contributing to this variability remains limited. Furthermore, few studies to date have quantitatively assessed the release of microplastics to receiving waters via runoff. The objectives of this study were to assess the influence of different catchment characteristics on the type and amount of microplastics in runoff and to provide an estimate of the quantity of microplastics discharged during rain events. Stormwater samples were collected during both dry periods (baseflow) and rain events from 15 locations throughout the city of Calgary, Canada’s fourth largest city. These catchments ranged in size and contained different types of predominant land use. Microplastics were found in all samples, with total concentrations ranging from 0.7 to 200.4 pcs/L (mean = 31.9 pcs/L). Fibers were the most prevalent morphology identified (47.7 ± 33.0%), and the greatest percentage of microplastics were found in the 125–250 µm size range (26.6 ± 22.9%) followed by the 37–125 µm size range (24.0 ± 22.3%). Particles were predominantly black (33.5 ± 33.8%), transparent (22.6 ± 31.3%), or blue (16.0 ± 21.6%). Total concentrations, dominant morphologies, and size distributions of microplastics differed between rain events and baseflow, with smaller particles and higher concentrations being found during rain events. Concentrations did not differ significantly amongst catchments with different land use types, but concentrations were positively correlated with maximum runoff flow rate, catchment size, and the percentage of impervious surface area within a catchment. Combining microplastic concentrations with hydrograph data collected during rain events, we estimated that individual outfalls discharged between 1.9 million to 9.6 billion microplastics to receiving waters per rain event. These results provide further evidence that urban stormwater runoff is a significant pathway for the introduction of microplastics into aquatic environments and suggests that mitigation strategies for microplastic pollution should focus on larger urbanized catchments

    An AzTEC 1.1 mm survey of the GOODS-N field – II. Multiwavelength identifications and redshift distribution

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    We present results from a multiwavelength study of 29 sources (false detection probabilities <5 per cent) from a survey of the Great Observatories Origins Deep Survey-North (GOODS-N) field at 1.1 mm using the Astronomical Thermal Emission Camera (AzTEC). Comparing with existing 850 μm Submillimetre Common-User Bolometer Array (SCUBA) studies in the field, we examine differences in the source populations selected at the two wavelengths. The AzTEC observations uniformly cover the entire survey field to a 1σ depth of ~1 mJy. Searching deep 1.4 GHz Very Large Array (VLA) and Spitzer 3–24 μm catalogues, we identify robust counterparts for 21 1.1 mm sources, and tentative associations for the remaining objects. The redshift distribution of AzTEC sources is inferred from available spectroscopic and photometric redshifts. We find a median redshift of z= 2.7 , somewhat higher than z= 2.0 for 850 μm selected sources in the same field, and our lowest redshift identification lies at a spectroscopic redshift z= 1.1460 . We measure the 850 μm to 1.1 mm colour of our sources and do not find evidence for '850 μm dropouts', which can be explained by the low signal-to-noise ratio of the observations. We also combine these observed colours with spectroscopic redshifts to derive the range of dust temperatures T, and dust emissivity indices β for the sample, concluding that existing estimates T ~ 30 K and β ~ 1.75 are consistent with these new data

    Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

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    OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

    Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

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    The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
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