ResearchPad - sulfates https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Simultaneous administration of imipenem/cilastatin/relebactam with selected intravenous antimicrobials, a stewardship approach]]> https://www.researchpad.co/article/elastic_article_15724 Imipenem/cilastatin/relebactam is a β-lactam/β-lactamase inhibitor that has been recently FDA approved for complicated intra-abdominal and urinary tract infections under the brand name Recarbrio®. It has activity against imipenem non-susceptible Pseudomonas species as well as KPC-producing Enterobacteriaceae. Optimization of PK/PD of antimicrobials particularly in critically-ill patients is essential, but unfortunately, is hindered by separate administration that requires significant resources. The objective of the study is to investigate the compatibility of Y-site administration of imipenem/cilastatin/relebactam with a wide range of antimicrobials. After admixture, physical characteristics, pH changes and turbidity were measured for each 2-drug combination at a time. With the exception of amphotericin B deoxycholate, and posaconazole, imipenem/cilastatin/relebactam was compatible with a variety of antimicrobial agents. The compatibility profile described, will facilitate incorporation into hospital protocols, contribute to therapy optimization and guide clinicians to avoid successive administration, consequently resulting in reduction of total infusion time, optimization of PK/PD, economizing nursing time and cost containment.

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<![CDATA[SULF1 suppresses Wnt3A-driven growth of bone metastatic prostate cancer in perlecan-modified 3D cancer-stroma-macrophage triculture models]]> https://www.researchpad.co/article/elastic_article_14741 Bone marrow stroma influences metastatic prostate cancer (PCa) progression, latency, and recurrence. At sites of PCa bone metastasis, cancer-associated fibroblasts and tumor-associated macrophages interact to establish a perlecan-rich desmoplastic stroma. As a heparan sulfate proteoglycan, perlecan (HSPG2) stores and stabilizes growth factors, including heparin-binding Wnt3A, a positive regulator of PCa cell growth. Because PCa cells alone do not induce CAF production of perlecan in the desmoplastic stroma, we sought to discover the sources of perlecan and its growth factor-releasing modifiers SULF1, SULF2, and heparanase in PCa cells and xenografts, bone marrow fibroblasts, and macrophages. SULF1, produced primarily by bone marrow fibroblasts, was the main glycosaminoglycanase present, a finding validated with primary tissue specimens of PCa metastases with desmoplastic bone stroma. Expression of both HSPG2 and SULF1 was concentrated in αSMA-rich stroma near PCa tumor nests, where infiltrating pro-tumor TAMs also were present. To decipher SULF1’s role in the reactive bone stroma, we created a bone marrow biomimetic hydrogel incorporating perlecan, PCa cells, macrophages, and fibroblastic bone marrow stromal cells. Finding that M2-like macrophages increased levels of SULF1 and HSPG2 produced by fibroblasts, we examined SULF1 function in Wnt3A-mediated PCa tumoroid growth in tricultures. Comparing control or SULF1 knockout fibroblastic cells, we showed that SULF1 reduces Wnt3A-driven growth, cellularity, and cluster number of PCa cells in our 3D model. We conclude that SULF1 can suppress Wnt3A-driven growth signals in the desmoplastic stroma of PCa bone metastases, and SULF1 loss favors PCa progression, even in the presence of pro-tumorigenic TAMs.

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<![CDATA[Probabilistic analysis of a concrete column in an aggressive soil environment]]> https://www.researchpad.co/article/5c8acce9d5eed0c4849902cb

Sulphate attack is one of the most important factors that limit the lifetime of pure concrete constructions. Harsh environmental conditions have a large impact on the operational costs of concrete columns or piles dipped into soil. The results are non-deterministic; therefore, reliability analysis is often used. The strength characteristics of the substrate around the construction were modelled as one-dimensional prismatic beams related with random p-y curves. Sulphate deterioration is defined as a set of random variables jointed with two dimensional mechanical systems at acceptable levels. Fick’s second law describes the penetration of sulphate ingress into pure concrete with explicit numerical solutions for boundary conditions and an increase in the transition factor under the progress of sulphate ingress. This process was partially solved via analytical methods for sulphate ion transport and numerically for a random field. This solves the mechanical task and determines the system reliability. A numerical example is provided to illustrate the proposed method to prevent unexpected structural failures during column service life. The proposed methodology can assist designers and can help to make decisions on existing foundations to ensure the safety of geotechnical construction.

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<![CDATA[The availability, prices and affordability of essential medicines in Malawi: A cross-sectional study]]> https://www.researchpad.co/article/5c6c75d2d5eed0c4843d025a

Introduction

The Malawian government recently introduced cost-covering consultation fees for self-referral patients in tertiary public hospitals. Previously, patients received medicines free of charge in government-owned health facilities, but must pay elsewhere. Before the government implements a payment policy in other areas of health care, it is important to investigate the prices, affordability and availability of essential medicines in Malawi.

Methods

Data on availability and prices of 50 essential medicines were collected in 44 health facilities in two major cities and two districts. These included 12 public facilities, 11 facilities of the Christian Health Association of Malawi (CHAM), nine retail pharmacies, eight wholesalers and four private clinics/hospitals. Price, availability and affordability were assessed based on the methodology developed by the World Health Organization and Health Action International, which compares local prices to international reference prices.

Results and discussion

The overall availability of medicines was 48.5% in public facilities, 71.1% in retail pharmacies, 62.9% in CHAM facilities and 57.5% in private clinics. The availability of essential medicines varied from 0% for ethosuximide to 100% for amoxicillin and cotrimoxazole tablets. Antibiotic formulations for adults were widely available, in contrast to the low availability of pediatric formulations. Several medicines for non-communicable diseases like sodium valproate, phenytoin, paraldehyde, captopril and simvastatin showed poor availability and affordability. The overall median price ratio compared to the international reference price was 1.11 for wholesalers, 2.54 in CHAM facilities, 2.70 in retail pharmacies, and 4.01 in private clinics, which is low compared to other countries. But nevertheless, for 18 out of 32 medicines assessed, the cost of one course exceeded the statutory minimum daily wage, making them unaffordable to a majority of the population. Therefore, continued provision of free public health care is still of critical importance for the foreseeable future until other financing mechanisms have been explored.

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<![CDATA[TAMMiCol: Tool for analysis of the morphology of microbial colonies]]> https://www.researchpad.co/article/5c0ed741d5eed0c484f13db7

Many microbes are studied by examining colony morphology via two-dimensional top-down images. The quantification of such images typically requires each pixel to be labelled as belonging to either the colony or background, producing a binary image. While this may be achieved manually for a single colony, this process is infeasible for large datasets containing thousands of images. The software Tool for Analysis of the Morphology of Microbial Colonies (TAMMiCol) has been developed to efficiently and automatically convert colony images to binary. TAMMiCol exploits the structure of the images to choose a thresholding tolerance and produce a binary image of the colony. The images produced are shown to compare favourably with images processed manually, while TAMMiCol is shown to outperform standard segmentation methods. Multiple images may be imported together for batch processing, while the binary data may be exported as a CSV or MATLAB MAT file for quantification, or analysed using statistics built into the software. Using the in-built statistics, it is found that images produced by TAMMiCol yield values close to those computed from binary images processed manually. Analysis of a new large dataset using TAMMiCol shows that colonies of Saccharomyces cerevisiae reach a maximum level of filamentous growth once the concentration of ammonium sulfate is reduced to 200 μM. TAMMiCol is accessed through a graphical user interface, making it easy to use for those without specialist knowledge of image processing, statistical methods or coding.

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<![CDATA[Effects of medical ozone upon healthy equine joints: Clinical and laboratorial aspects]]> https://www.researchpad.co/article/5b28b146463d7e116be9c9ab

Objective

The aim of this study was to verify whether transient inflammatory reactions induced by intra-articular medicinal ozone administration affect joint components, by in vivo evaluation of inflammatory (prostaglandin E2, Substance P, Interleukin-6, Interleukine-1, Tumor Necrosis Factor), anti-inflammatory (Interleukin-10) and oxidative (superoxide dismutase activity and oxidative burst) biomarkers and extracellular matrix degradation products (chondroitin sulphate and hyaluronic acid) in synovial fluid.

Methods

The effects of medicinal ozone were analyzed at two ozone concentrations (groups A and B, 20 and 40 μg/ml, respectively), using oxygen-injected joints as controls (group C); each group received ten treatments (15 ml gas per treatment). Physical evaluation, evaluation of lameness, ultrasonography, and synovial fluid analysis were performed.

Results

All joints presented mild and transient effusion throughout the study. Group B exhibited the highest lameness score on day 14 (P<0.05), detected by the lameness measurement system, probably because of the higher ozone concentration. All groups exhibited increased ultrasonography scores on day 14 (P < 0.05). Groups A and B exhibited increased proteins concentrations on day 21 (P<0.05). There was no change in hyaluronic acid concentration or the percentage of high-molecular weight hyaluronic acid throughout the experiment. Chondroitin sulfate concentrations decreased in group B, and did not change in group A and C, indicating that neither treatment provoked extracellular matrix catabolism. Cytokine and eicosanoid concentrations were not significantly changed.

Conclusions

The ozonetherapy did not cause significant inflammation process or cartilage degradation, therefore, ozonetherapy is safe at both evaluated doses.

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<![CDATA[Downscaling Global Emissions and Its Implications Derived from Climate Model Experiments]]> https://www.researchpad.co/article/5989dacfab0ee8fa60bb5bca

In climate change research, future scenarios of greenhouse gas and air pollutant emissions generated by integrated assessment models (IAMs) are used in climate models (CMs) and earth system models to analyze future interactions and feedback between human activities and climate. However, the spatial resolutions of IAMs and CMs differ. IAMs usually disaggregate the world into 10–30 aggregated regions, whereas CMs require a grid-based spatial resolution. Therefore, downscaling emissions data from IAMs into a finer scale is necessary to input the emissions into CMs. In this study, we examined whether differences in downscaling methods significantly affect climate variables such as temperature and precipitation. We tested two downscaling methods using the same regionally aggregated sulfur emissions scenario obtained from the Asian-Pacific Integrated Model/Computable General Equilibrium (AIM/CGE) model. The downscaled emissions were fed into the Model for Interdisciplinary Research on Climate (MIROC). One of the methods assumed a strong convergence of national emissions intensity (e.g., emissions per gross domestic product), while the other was based on inertia (i.e., the base-year remained unchanged). The emissions intensities in the downscaled spatial emissions generated from the two methods markedly differed, whereas the emissions densities (emissions per area) were similar. We investigated whether the climate change projections of temperature and precipitation would significantly differ between the two methods by applying a field significance test, and found little evidence of a significant difference between the two methods. Moreover, there was no clear evidence of a difference between the climate simulations based on these two downscaling methods.

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<![CDATA[Zinc Modulates Endotoxin-Induced Human Macrophage Inflammation through ZIP8 Induction and C/EBPβ Inhibition]]> https://www.researchpad.co/article/5989dafdab0ee8fa60bc5313

Two vital functions of the innate immune system are to initiate inflammation and redistribute micronutrients in favor of the host. Zinc is an essential micronutrient used in host defense. The zinc importer ZIP8 is uniquely induced through stimulation of the NF-κB pathway by LPS in monocytes and functions to regulate inflammation in a zinc-dependent manner. Herein we determined the impact of zinc metabolism following LPS-induced inflammation in human macrophages. We observed that ZIP8 is constitutively expressed in resting macrophages and strikingly elevated following LPS exposure, a response that is unique compared to the 13 other known zinc import proteins. During LPS exposure, extracellular zinc concentrations within the physiological range markedly reduced IL-10 mRNA expression and protein release but increased mRNA expression of TNFα, IL-8, and IL-6. ZIP8 knockdown inhibited LPS-driven cellular accumulation of zinc and prevented zinc-dependent reduction of IL-10 release. Further, zinc supplementation reduced nuclear localization and activity of C/EBPβ, a transcription factor known to drive IL-10 expression. These studies demonstrate for the first time that zinc regulates LPS-mediated immune activation of human macrophages in a ZIP8-dependent manner, reducing IL-10. Based on these findings we predict that macrophage zinc metabolism is important in host defense against pathogens.

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<![CDATA[An African grassland responds similarly to long-term fertilization to the Park Grass experiment]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf714

We compared the results of a long-term (65 years) experiment in a South African grassland with the world’s longest-running ecological experiment, the Park Grass study at Rothamsted, U.K. The climate is warm and humid in South Africa and cool and temperate in England. The African grassland has been fertilized with two forms of nitrogen applied at four levels, phosphorus and lime in a crossed design in 96 plots. In 1951, about 84% of plant cover consisted of Themeda triandra, Tristachya leucothrix and Setaria nigrirostris. Currently, the dominant species are Panicum maximum, Setaria sphacelata and Eragrostis curvula, making up 71% of total biomass. As in the Park Grass experiment, we found a significant (additive) interaction effect on ANPP of nitrogen and phosphorus, and a (marginally significant) negative correlation between ANPP and species richness. Unlike the Park Grass experiment, there was no correlation between ANPP and species richness when pH was included as a covariate. There was also a significant negative effect of nitrogen amount and nitrogen form and a positive effect of lime on species richness and species diversity. Soil pH had an important effect on species richness. Liming was insufficient to balance the negative effects on species richness of nitrogen fertilization. There was a significant effect of pH on biomass of three abundant species. There were also significant effects of light on the biomass of four species, with only Panicum maximum having a negative response to light. In all of the abundant species, adding total species richness and ANPP to the model increased the amount of variance explained. The biomass of Eragrostis curvula and P. maximum were negatively correlated with species richness while three other abundant species increased with species richness, suggesting that competition and facilitation were active. Consistent with the results from the Park Grass and other long-term fertilization experiments of grasslands, we found a positive effect of soil pH and a negative effect of nitrogen amount on species richness, a more acutely negative effect on species richness of acidic ammonium sulphate fertilizer than limestone ammonium nitrate, a negative relationship between species richness and biomass, and a positive effect on species richness of lime interacting with nitrogen.

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<![CDATA[The Heparan Sulfate Proteoglycan Glypican-6 Is Upregulated in the Failing Heart, and Regulates Cardiomyocyte Growth through ERK1/2 Signaling]]> https://www.researchpad.co/article/5989db0aab0ee8fa60bc9b20

Pressure overload is a frequent cause of heart failure. Heart failure affects millions of patients worldwide and is a major cause of morbidity and mortality. Cell surface proteoglycans are emerging as molecular players in cardiac remodeling, and increased knowledge about their regulation and function is needed for improved understanding of cardiac pathogenesis. Here we investigated glypicans (GPC1-6), a family of evolutionary conserved heparan sulfate proteoglycans anchored to the extracellular leaflet of the cell membrane, in experimental and clinical heart failure, and explored the function of glypican-6 in cardiac cells in vitro. In mice subjected to pressure overload by aortic banding (AB), we observed elevated glypican-6 levels during hypertrophic remodeling and dilated, end-stage heart failure. Consistently, glypican-6 mRNA was elevated in left ventricular myocardium from explanted hearts of patients with end-stage, dilated heart failure with reduced ejection fraction. Glypican-6 levels correlated negatively with left ventricular ejection fraction in patients, and positively with lung weight after AB in mice. Glypican-6 mRNA was expressed in both cardiac fibroblasts and cardiomyocytes, and the corresponding protein displayed different sizes in the two cell types due to tissue-specific glycanation. Importantly, adenoviral overexpression of glypican-6 in cultured cardiomyocytes increased protein synthesis and induced mRNA levels of the pro-hypertrophic signature gene ACTA1 and the hypertrophy and heart failure signature genes encoding natriuretic peptides, NPPA and NPPB. Overexpression of GPC6 induced ERK1/2 phosphorylation, and co-treatment with the ERK inhibitor U0126 attenuated the GPC6-induced increase in NPPA, NPPB and protein synthesis. In conclusion, our data suggests that glypican-6 plays a role in clinical and experimental heart failure progression by regulating cardiomyocyte growth through ERK signaling.

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<![CDATA[Cottonseed Oil in Diets for Broilers in the Pre-Starter and Starter Phases]]> https://www.researchpad.co/article/5989db1fab0ee8fa60bcef62

The objective of this study was to evaluate the effect of different levels of crude cottonseed oil in isoenergetic diets, with or without supplementation of ferrous sulfate, on performance variables, relative weight of organs, and blood parameters of broilers, and on the economic viability of diets in the periods from 1 to 7 and 1 to 21 days of age. A total of 600 male birds of the Ross line were distributed in a completely randomized design in a (4×2) factorial arrangement with eight treatments (0, 2, 4, and 6% cottonseed oil with and without ferrous sulfate), and five replicates. The following variables were studied: feed intake, weight gain, feed conversion, weight of organs, blood parameters, and yield of carcass and cuts at 21 days. No effects of the levels of cottonseed oil were found on the performance of animals aged 1 to 7 days, or on the relative weights of the organs. In this same period, the weight gain, and the relative weights of heart, liver, and intestine of the animals that received ferrous sulfate were decreased, and feed conversion was worsened. In the period from 1 to 21 days, weight gain increased linearly with the increase in the levels of cottonseed oil. Blood parameters were not influenced by the diets. Crude cottonseed oil can be utilized in diets for broilers in the periods from 1 to 7 and 1 to 21 days of age at up to 6% of inclusion, and supplementation with ferrous sulfate is unnecessary if the differences in metabolization of the cottonseed oil are considered, with and without, it during the diet formulation process.

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<![CDATA[Neisserial Heparin Binding Antigen (NHBA) Contributes to the Adhesion of Neisseria meningitidis to Human Epithelial Cells]]> https://www.researchpad.co/article/5989daf8ab0ee8fa60bc3be2

Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein ubiquitously expressed by Neisseria meningitidis strains and an antigen of the Bexsero® vaccine. NHBA binds heparin through a conserved Arg-rich region that is the target of two proteases, the meningococcal NalP and human lactoferrin (hLf). In this work, in vitro studies showed that recombinant NHBA protein was able to bind epithelial cells and mutations of the Arg-rich tract abrogated this binding. All N-terminal and C-terminal fragments generated by NalP or hLf cleavage, regardless of the presence or absence of the Arg-rich region, did not bind to cells, indicating that a correct positioning of the Arg-rich region within the full length protein is crucial. Moreover, binding was abolished when cells were treated with heparinase III, suggesting that this interaction is mediated by heparan sulfate proteoglycans (HSPGs). N. meningitidis nhba knockout strains showed a significant reduction in adhesion to epithelial cells with respect to isogenic wild-type strains and adhesion of the wild-type strain was inhibited by anti-NHBA antibodies in a dose-dependent manner. Overall, the results demonstrate that NHBA contributes to meningococcal adhesion to epithelial cells through binding to HSPGs and suggest a possible role of anti-Bexsero® antibodies in the prevention of colonization.

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<![CDATA[Electrode Mass Balancing as an Inexpensive and Simple Method to Increase the Capacitance of Electric Double-Layer Capacitors]]> https://www.researchpad.co/article/5989da87ab0ee8fa60b9c71e

Symmetric electric double-layer capacitors (EDLCs) have equal masses of the same active material in both electrodes. However, having equal electrode masses may prevent the EDLC to have the largest possible specific capacitance if the sizes of the hydrated anions and cations in the electrolyte differ because the electrodes and the electrolyte may not be completely utilized. Here we demonstrate how this issue can be resolved by mass balancing. If the electrode masses are adjusted according to the size of the ions, one can easily increase an EDLC’s specific capacitance. To that end, we performed galvanostatic cycling to measure the capacitances of symmetric EDLCs with different electrode mass ratios using four aqueous electrolytes— Na2SO4, H2SO4, NaOH, and KOH (all with a concentration of 1 M)—and compared these to the theoretical optimal electrode mass ratio that we calculated using the sizes of the hydrated ions. Both the theoretical and experimental values revealed lower-than-1 optimal electrode ratios for all electrolytes except KOH. The largest increase in capacitance was obtained for EDLCs with NaOH as electrolyte. Specifically, we demonstrate an increase of the specific capacitance by 8.6% by adjusting the electrode mass ratio from 1 to 0.86. Our findings demonstrate that electrode mass balancing is a simple and inexpensive method to increase the capacitance of EDLCs. Furthermore, our results imply that one can reduce the amount of unused material in EDLCs and thus decrease their weight, volume and cost.

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<![CDATA[Calcified coccoid from Cambrian Miaolingian: Revealing the potential cellular structure of Epiphyton]]> https://www.researchpad.co/article/5c940571d5eed0c484538979

Epiphyton, Renalcis, and Girvanella are ubiquitous genera of calcified cyanobacteria/algae from Early Paleozoic shallow-marine limestones. One genus, Epiphyton, is characterized by a particular dendritic outline, and extensive research has revealed the morphology of calcified remains although little information on cellular structure is known. The mass occurrence of calcified Epiphyton in microbialites from Cambrian Miaolingian, the Mianchi area of North China is preserved as black clots within thrombolites and have dendritic and spherical outlines when viewed with a petrographic microscope. These remains, visible under scanning electron microscope (SEM), also comprise spherical or rectangle capsules. These capsules are made up from external envelopes and internal calcite with numerous pits, which closely resemble modern benthic coccoid cyanobacteria. These pits are between 2 μm and 4 μm in diameter and are interpreted here to represent the remnants of degraded coccoid cells, while the calcite that surrounds these pits is interpreted as calcified thin extracellular polymeric substances (EPS). In contrast, associated capsular envelopes represent thick EPS mineralized by calcium carbonate with an admixture of Al-Mg-Fe silicates. Dendritic ‘thalli’ are typically stacked apically because of the repeated growth and calcification of these capsules. Carbon and oxygen isotope results are interpreted to indicate that both photosynthesis and heterotrophic bacterial metabolism (especially sulfate reducing bacteria) contributed to carbonate precipitation by elevated alkalinity. Epiphyton are therefore here interpreted as colonies of calcified coccoid cyanobacteria, and the carbonate-oversaturated seawater during the Cambrian was conducive to their mineralization.

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<![CDATA[Nestedness in Arbuscular Mycorrhizal Fungal Communities along Soil pH Gradients in Early Primary Succession: Acid-Tolerant Fungi Are pH Generalists]]> https://www.researchpad.co/article/5989db3dab0ee8fa60bd5647

Soil acidity is a major constraint on plant productivity. Arbuscular mycorrhizal (AM) fungi support plant colonization in acidic soil, but soil acidity also constrains fungal growth and diversity. Fungi in extreme environments generally evolve towards specialists, suggesting that AM fungi in acidic soil are acidic-soil specialists. In our previous surveys, however, some AM fungi detected in strongly acidic soils could also be detected in a soil with moderate pH, which raised a hypothesis that the fungi in acidic soils are pH generalists. To test the hypothesis, we conducted a pH-manipulation experiment and also analyzed AM fungal distribution along a pH gradient in the field using a synthesized dataset of the previous and recent surveys. Rhizosphere soils of the generalist plant Miscanthus sinensis were collected both from a neutral soil and an acidic soil, and M. sinensis seedlings were grown at three different pH. For the analysis of field communities, rhizosphere soils of M. sinensis were collected from six field sites across Japan, which covered a soil pH range of 3.0–7.4, and subjected to soil trap culture. AM fungal community compositions were determined based on LSU rDNA sequences. In the pH-manipulation experiment the acidification of medium had a significant impact on the compositions of the community from the neutral soil, but the neutralization of the medium had no effect on those of the community from the acidic soil. Furthermore, the communities in lower -pH soils were subsets of (nested in) those in higher-pH soils. In the field communities a significant nestedness pattern was observed along the pH gradient. These observations suggest that the fungi in strongly acidic soils are pH generalists that occur not only in acidic soil but also in wide ranges of soil pH. Nestedness in AM fungal community along pH gradients may have important implications for plant community resilience and early primary succession after disturbance in acidic soils.

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<![CDATA[Cysteine Metabolism and Oxidative Processes in the Rat Liver and Kidney after Acute and Repeated Cocaine Treatment]]> https://www.researchpad.co/article/5989daaeab0ee8fa60baa6c5

The role of cocaine in modulating the metabolism of sulfur-containing compounds in the peripheral tissues is poorly understood. In the present study we addressed the question about the effects of acute and repeated (5 days) cocaine (10 mg/kg i.p.) administration on the total cysteine (Cys) metabolism and on the oxidative processes in the rat liver and kidney. The whole pool of sulfane sulfur, its bound fraction and hydrogen sulfide (H2S) were considered as markers of anaerobic Cys metabolism while the sulfate as a measure of its aerobic metabolism. The total-, non-protein- and protein- SH group levels were assayed as indicators of the redox status of thiols. Additionally, the activities of enzymes involved in H2S formation (cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3-MST) and GSH metabolism (γ-glutamyl transpeptidase, γ-GT; glutathione S-transferase, GST) were determined. Finally, we assayed the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) as markers of oxidative stress and lipid peroxidation, respectively. In the liver, acute cocaine treatment, did not change concentrations of the whole pool of sulfane sulfur, its bound fraction, H2S or sulfate but markedly decreased levels of non-protein SH groups (NPSH), ROS and GST activity while γ-GT was unaffected. In the kidney, acute cocaine significantly increased concentration of the whole pool of sulfane sulfur, reduced the content of its bound fraction but H2S, sulfate and NPSH levels were unchanged while ROS and activities of GST and γ-GT were reduced. Acute cocaine enhanced activity of the CSE and 3-MST in the liver and kidney, respectively. Repeatedly administered cocaine enhanced the whole pool of sulfane sulfur and reduced H2S level simultaneously increasing sulfate content both in the liver and kidney. After repeated cocaine, a significant decrease in ROS was still observed in the liver while in the kidney, despite unchanged ROS content, a marked increase in MDA level was visible. The repeated cocaine decreased 3-MST and increased γ-GT activities in both organs but reduced GST in the kidney. Our results show that cocaine administered at a relatively low dose shifts Cys metabolism towards the formation of sulfane sulfur compounds which possess antioxidant and redox regulatory properties and are a source of H2S which can support mitochondrial bioenergetics.

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<![CDATA[Enhancement of Microbial Biodesulfurization via Genetic Engineering and Adaptive Evolution]]> https://www.researchpad.co/article/5989dac1ab0ee8fa60bb0d6b

In previous work from our laboratories a synthetic gene encoding a peptide (“Sulpeptide 1” or “S1”) with a high proportion of methionine and cysteine residues had been designed to act as a sulfur sink and was inserted into the dsz (desulfurization) operon of Rhodococcus erythropolis IGTS8. In the work described here this construct (dszAS1BC) and the intact dsz operon (dszABC) cloned into vector pRESX under control of the (Rhodococcus) kstD promoter were transformed into the desulfurization-negative strain CW25 of Rhodococcus qingshengii. The resulting strains (CW25[pRESX-dszABC] and CW25[pRESX-dszAS1BC]) were subjected to adaptive selection by repeated passages at log phase (up to 100 times) in minimal medium with dibenzothiophene (DBT) as sole sulfur source. For both strains DBT metabolism peaked early in the selection process and then decreased, eventually averaging four times that of the initial transformed cells; the maximum specific activity achieved by CW25[pRESX-dszAS1BC] exceeded that of CW25[pRESX-dszABC]. Growth rates increased by 7-fold (CW25[pRESX-dszABC]) and 13-fold (CW25[pRESX-dszAS1BC]) and these increases were stable. The adaptations of CW25[pRESX-dszAS1BC] were correlated with a 3-5X increase in plasmid copy numbers from those of the initial transformed cells; whole genome sequencing indicated that during its selection processes no mutations occurred to any of the dsz, S1, or other genes and promoters involved in sulfur metabolism, stress response, or DNA methylation, and that the effect of the sulfur sink produced by S1 is likely very small compared to the cells’ overall cysteine and methionine requirements. Nevertheless, a combination of genetic engineering using sulfur sinks and increasing Dsz capability with adaptive selection may be a viable strategy to increase biodesulfurization ability.

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<![CDATA[The dynamics of nitrogen derived from a chemical nitrogen fertilizer with treated swine slurry in paddy soil-plant systems]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdcdae

A well-managed chemical nitrogen (N) fertilization practice combined with treated swine slurry (TSS) is necessary to improve sustainability and N use efficiency in rice farming. However, little is known about the fate of N derived from chemical N fertilizer with and without TSS in paddy soil-plant systems. The objectives of this study were (1) to estimate the contribution of applied N fertilizer to N turnover in rice paddy soil with different N fertilization practices that were manipulated by the quantity of treated swine slurry and chemical N fertilizer (i.e., HTSS+LAS, a high amount of TSS with a low amount of ammonium sulfate; LTSS+HAS, a low amount of TSS with a high amount of ammonium sulfate; AS, ammonium sulfate with phosphorus and potassium; C, the control) and (2) to compare the rice response to applied N derived from each N fertilization practice. Rice biomass yield, 15N recovery in both rice grain and stems, soil total N (TN), soil inorganic N, and soil 15N recovery were analyzed. Similar amounts of 15N uptake by rice in the TSS+AS plots were obtained, indicating that the effects of the different quantities of TSS on chemical fertilizer N recovery in rice during the experimental period were not significant. The soil 15N recoveries of HTSS+LAS, LTSS+HAS, and AS in each soil layer were not significantly different. For the HTSS+LAS, LTSS+HAS and AS applications, total 15N recoveries were 42%, 43% and 54%, respectively. Because the effects of reducing the use of chemical N fertilizer were attributed to enhancing soil quality and cost-effectiveness, HTSS+LAS could be an appropriate N fertilization practice for improving the long-term sustainability of paddy soil-plant systems. However, N losses, especially through the coupled nitrification-denitrification process, can diminish the benefits that HTSS+LAS offers.

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<![CDATA[Examination of Duct Physiology in the Human Mammary Gland]]> https://www.researchpad.co/article/5989da94ab0ee8fa60ba1231

Background

The human breast comprise several ductal systems, or lobes, which contain a small amount of fluid containing cells, hormones, proteins and metabolites. The complex physiology of these ducts is likely a contributing factor to the development of breast cancer, especially given that the vast majority of breast cancers begin in a single lobular unit.

Methods

We examined the levels of total protein, progesterone, estradiol, estrone sulfate, dehydroepiandrosterone sulfate, and macrophages in ductal fluid samples obtained from 3 ducts each in 78 women, sampled twice over a 6 month period. Samples were processed for both cytological and molecular analysis. Intraclass correlation coefficients and mixed models were utilized to identify significant data.

Results

We found that the levels of these ductal fluid components were generally uncorrelated among ducts within a single breast and over time, suggesting that each lobe within the breast has a distinct physiology. However, we also found that estradiol was more correlated in women who were nulliparous or produced nipple aspirate fluid.

Conclusions

Our results provide evidence that the microenvironment of any given lobular unit is unique to that individual unit, findings that may provide clues about the initiation and development of ductal carcinomas.

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<![CDATA[Factors Affecting Elevated Arsenic and Methyl Mercury Concentrations in Small Shield Lakes Surrounding Gold Mines near the Yellowknife, NT, (Canada) Region]]> https://www.researchpad.co/article/5989da8cab0ee8fa60b9e3e7

Gold mines in the Yellowknife, NT, region—in particular, the Giant Mine—operated from 1949–99, releasing 237,000 tonnes of waste arsenic trioxide (As2O3) dust, among other compounds, from gold ore extraction and roasting processes. For the first time, we show the geospatial distribution of roaster-derived emissions of several chemical species beyond the mine property on otherwise undisturbed taiga shield lakes within a 25 km radius of the mine, 11 years after its closing. Additionally, we demonstrate that underlying bedrock is not a significant source for the elevated concentrations in overlying surface waters. Aquatic arsenic (As) concentrations are well above guidelines for drinking water (10 μg/L) and protection for aquatic life (5 μg/L), ranging up to 136 μg/L in lakes within 4 km from the mine, to 2.0 μg/L in lakes 24 km away. High conversion ratios of methyl mercury were shown in lakes near the roaster stack as well, with MeHg concentrations reaching 44% of total mercury. The risk of elevated exposures by these metals is significant, as many lakes used for recreation and fishing near the City of Yellowknife are within this radius of elevated As and methyl Hg concentrations.

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