Gene knockout of glutathione reductase results in increased sensitivity to heavy metals in Acidithiobacillus caldus

Acidithiobacillus caldus plays an important role in bioleaching of low-grade metal ore. It can promote the release of heavy metals in mining-associated habitats and survive in high concentrations of heavy metals. Functions of glutathione reductase (GR) in cell defense against reactive oxygen species caused by heavy metals have been elucidated in some eukaryotic cells and bacteria; however, no information is available in A. caldus. In this research, the methods of bioinformatics, gene expression, GR activity assays were used to detect and characterize the glutathione reductase gene from the A. caldus MTH-04 strain. Then, A. caldus gr knockout mutant and gr overexpression strain were constructed, and the heavy metal tolerant properties and transcriptional levels of ROS related genes of them were compared to study the function of GR. The results showed that, a putative gr gene F0726_RS04210 was detected in the genome of A. caldus MTH-04. The purified recombinant protein of F0726_RS04210 showed remarkable GR activity at optimal pH 7.0 and 30°C using in vitro assay. The evolutionary relationship of GR from A. caldus MTH-04 was close to that from Escherichia coli K12. Gene knockout or overexpression of gr in A. caldus did not affect the growth rate on S0 medium, suggesting that GR did not play a key role in the activation of sulfur. Deletion of gr resulted in increased sensitivity to heavy metals (Cu2+ and Zn2+) in A. caldus, and the gr overexpression strain showed enhanced tolerance to heavy metals. Furthermore, transcription analysis also revealed strong correlations between GR and the antioxidant pathway. The above results suggest that GR can play an important role in heavy metal tolerance in A. caldus

Differential Responses of MET Activations to MET kinase Inhibitor and Neutralizing Antibody

Background: Aberrant MET tyrosine kinase signaling is known to cause cancer initiation and progression. While MET inhibitors are in clinical trials against several cancer types, the clinical efficacies are controversial and the molecular mechanisms toward sensitivity remain elusive. Methods: With the goal to investigate the molecular basis of MET amplification (MET amp ) and hepatocyte growth factor (HGF) autocrine-driven tumors in response to MET tyrosine kinase inhibitors (TKI) and neutralizing antibodies, we compared cancer cells harboring MET amp (MKN45 and MHCCH97H) or HGF-autocrine (JHH5 and U87) for their sensitivity and downstream biological responses to a MET-TKI (INC280) and an anti-MET monoclonal antibody (MetMab) in vitro, and for tumor inhibition in vivo. Results: We find that cancer cells driven by MET amp are more sensitive to INC280 than are those driven by HGF-autocrine activation. In MET amp cells, INC280 induced a DNA damage response with activation of repair through the p53BP1/ATM signaling pathway. Although MetMab failed to inhibit MET amp cell proliferation and tumor growth, both INC280 and MetMab reduced HGF-autocrine tumor growth. In addition, we also show that HGF stimulation promoted human HUVEC cell tube formation via the Src pathway, which was inhibited by either INC280 or MetMab. These observations suggest that in HGF-autocrine tumors, the endothelial cells are the secondary targets MET inhibitors. Conclusions: Our results demonstrate that MET amp and HGF-autocrine activation favor different molecular mechanisms. While combining MET TKIs and ATM inhibitors may enhance the efficacy for treating tumors harboring MET amp , a combined inhibition of MET and angiogenesis pathways may improve the therapeutic efficacy against HGF-autocrine tumors

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Response of Mechanical Properties of Polyvinyl Chloride Geomembrane to Ambient Temperature in Axial Tension

Aiming at the mechanical response of geomembrane (GEM) in membrane-faced rockfill dam (MFRD) to different ambient temperatures, the mechanical properties in axial tension of polyvinyl chloride (PVC) GEM were studied by experiment and theoretical analysis. First, fifteen groups of axial tensile tests for longitudinal/transverse specimens were conducted at different temperatures in the temperature environment laboratory, the stress–strain curve and Young’s modulus were obtained, and the variation of Young’s modulus with temperature was analyzed by Boltzmann function fitting. Second, the glass transition temperature of PVC GEM was obtained by differential scanning calorimetry (DSC), and the difference in mechanical properties between longitudinal and transverse specimens of PVC GEM was analyzed by thermomechanical analyzer (TMA) thermodynamic test. The results showed that the lower the temperature, the greater the Young’s modulus, and the smaller the linear interval of stress and strain, while the higher the temperature, the result is opposite. The difference in mechanical properties between the two directions is related to the ambient temperature. The orientation of polymer structure accounts for the difference in mechanical properties by theoretical analysis. The fitting results of Boltzmann function have a certain reference value for numerical simulation. In design of the membrane impervious structure in MFRD, the ambient temperature should be considered fully, and the longitudinal/transverse welding splicing should be avoided as far as possible. The current test specification should test the mechanical performance of GEM at normal operating temperature of reservoir instead of the test and quality evaluation at a single temperature. The temperature should be considered comprehensively in construction to avoid damaging the performance of impervious structure and ensure the service life

Emission Behaviors of Inorganic Ultrafine Particles during Zhundong Coal Oxy-Fuel Combustion with Characterized Oxygen Input Fractions Comparable to Air Combustion

Zhundong low-rank coal is very likely to be utilized extensively in oxy-fired boilers in the near future. Its PM10 (particulate matter with an aerodynamic diameter of &le;10 &mu;m) emission behaviors during oxy-fuel combustion need to be carefully studied before its large-scale use. The present study examines the emission behaviors of inorganic ultrafine particles (PM0.5, with an aerodynamic diameter of &le;0.5 &mu;m), as well as PM10 during the combustion of Zhundong coal in air and oxy-fuel conditions (O2/CO2) at three characterized O2 input fractions, i.e., 21, 27 and 32 vol.%. The combustion experiments were carried out in a high-temperature drop-tube furnace (HDTF) at a combustion temperature of 1500 &deg;C. The results show that PM0.5 is composed of Na, S, Mg and Ca, with total fractions of ~90%, while PM0.5&ndash;10 (with an aerodynamic diameter between 0.5 and 10 &mu;m) predominantly contains Ca (~50&ndash;65%). At three characterized oxygen fractions during oxy-fuel combustion (OXY21, 27 and 32), the promoted O2 fraction was found to increase the yields of both PM0.5 and PM0.5&ndash;10. A higher particle-burning temperature and a lower CO2 fraction promote the reactions of both organically bound elements and inorganic minerals, increasing the partitioning of Mg and Ca and causing an increased yield of PM0.5. The yield of PM0.5 from air is high and similar to that from OXY32 while the yield of PM0.5&ndash;10 from air is similar to that from OXY27. The high yield of PM0.5 from air is mainly generated by the highest yields of Ca in four conditions

Research on the RRB+ Tree for Resource Reservation

Part 2: Session 2: Cloud Resource ManagementInternational audienceThe performance of the data structure has a significant impact on the overall performance of the advance resource reservation in the distributed computing. Because the query and update operations of the B+ tree are of high efficiency, so this paper proposes a B+ tree structure suitable for resource reservation the RRB+ tree. Also, we design and implement the corresponding algorithms of query, insertion and deletion. Different with the B+ tree that insert and delete one key word at a time, the RRB+ tree insert one reservation request and delete one tree node every time. The RRB+ tree is of a higher precision of expression. With the fixed reservation admission control algorithm and the same rate of acceptance, the experimental results show that the RRB+ tree is easier to operate for the complex and changing network environment, and have a higher utilization of storage space

Lead adsorption on loess under high ammonium environment

Lead (Pb) is one of the most toxic, hazardous pollutants available in landfill leachate. Loess-amended soil buffers are found suitable and effective in attenuating migration of Pb and the other trace metals. High concentration of ammonium (NH4+ > 1000 mg/l) is also reported in landfill leachate, and therefore, it is essential to investigate the transport of lead under such condition. In this study, the mechanisms and the capacity of loess to adsorb Pb under high NH4+ concentration were investigated. Adsorption isotherm test data were obtained for 25 °C, 35 °C and 45 °C. The maximum adsorption capacity is estimated to be 2101.97 mg/g at 25 °C and 4292.8 mg/g at 45 °C under 1000 mg/l NH4+. The binding sites of Pb on loess are positively related to each other at low temperatures (25–35 °C). The thermodynamic analysis indicates that adsorption process is endothermic and non-spontaneous and the system randomness increases with reaction time. The kinetic test data, fitted with a pseudo-second-order kinetic model and an intraparticle diffusion model, suggests that removal of Pb is driven by both membrane and intraparticle diffusions. The SEM, XRD and FTIR analyses indicate flocculation, precipitations as well as some ion exchange processes, which perhaps combinedly increases adsorption of both NH4+ and Pb in loess. The two kinds of precipitations are involved for the removal of Pb. The precipitations of PbCO3, Pb(OH)2 and PbCO3·2H2O are formed by the reactions between calcite and lead. The other precipitation of white basic salt (Pb2O(NO3)2) is formed by the reactions among Pb2+, NO3− and aqueous ammonia under alkaline environment of loess slurry