Comparison of Zaire and Bundibugyo ebolavirus polymerase complexes and susceptibility to antivirals through a newly developed Bundibugyo minigenome system

2021 ◽  
Author(s):  
Corri B. Levine ◽  
Chad E. Mire ◽  
Thomas W. Geisbert
Keyword(s):  
Untranslated Region ◽  
Inhibitory Effect ◽  
Limited Information ◽  
Replication System ◽  
Polymerase Complex ◽  
Infection Treatment ◽  
Republic Of The Congo ◽  
Genome Transcription ◽  
Zaire Ebolavirus ◽  
The Impact

Members of the genus Ebolavirus cause lethal disease in humans with Zaire ebolavirus (EBOV) being the most pathogenic (up to 90% morality) and Bundibugyo ebolavirus (BDBV) the least pathogenic (∼37% mortality). Historically, there has been a lack of research on BDBV and there is no means to study BDBV outside of a high-containment laboratory. Here, we describe a minigenome replication system to study BDBV transcription and compare the efficacy of small molecule inhibtors between EBOV and BDBV. Using this system, we examined the ability of the polymerase complex proteins from EBOV and BDBV to interact and form a functional unit as well as the impact of the genomic untranslated ends, known to contain important signals for transcription (3’-untranslated region) and replication (5’-untranslated region). Varying levels of compatibility were observed between proteins of the polymerase complex from each ebolavirus resulting in differences in genome transcription efficiency. Most pronounced was the effect of the nucleoprotein and the 3’-untranslated region. These data suggest that there are intrinsic specificities in the polymerase complex and untranslated signaling regions that could offer insight regarding observed pathogenic differences. Further adding to the differences in the polymerase complexes, post-transfection/infection treatment with the compound remdesivir (GS-5734) showed a greater inhibitory effect against BDBV compared to EBOV. The delayed growth kinetics of BDBV and the greater susceptibility to polymerase inhibitors indicate that disruption of the polymerase complex may be a viable target for therapeutics. Importance Ebolavirus disease is a viral infection and is fatal in 25-90% of cases, depending on the viral species and the amount of supportive care available. Two species have caused outbreaks in the Democratic Republic of the Congo, Zaire ebolavirus (EBOV) and Bundibugyo ebolavirus (BDBV). Pathogenesis and clinical outcome differ between these two species but there is still limited information regarding the viral mechanism for these differences. Previous studies suggest that BDBV replicates slower than EBOV but it is unknown if this is due to differences in the polymerase complex and its role in transcription and replication. This study details the construction of a minigenome replication system which can be used in a biosafety level (BSL) 2 laboartory. This system will be important for studying the polymerase complex of BDBV and comparing it with other filoviruses and can be used as a tool for screening inhibitors of viral growth.

Conflicts in Biafra, Katanga and Cabinda as a result of the geopolitical legacy of colonialism

2020 ◽  
Vol 2020 (10-3) ◽  
pp. 238-246
Author(s):  
Olga Dzhenchakova
Keyword(s):  
Democratic Republic ◽  
Economic Factor ◽  
Colonial Period ◽  
Sub Saharan Africa ◽  
Negative Consequences ◽  
Post Colonial ◽  
Republic Of The Congo ◽  
Sub Saharan ◽  
The Republic ◽  
The Impact

The article considers the impact of the colonial past of some countries in sub-Saharan Africa and its effect on their development during the post-colonial period. The negative consequences of the geopolitical legacy of colonialism are shown on the example of three countries: Nigeria, the Democratic Republic of the Congo and the Republic of Angola, expressed in the emergence of conflicts in these countries based on ethno-cultural, religious and socio-economic contradictions. At the same time, the focus is made on the economic factor and the consequences of the consumer policy of the former metropolises pursuing their mercantile interests were mixed.

Simulation of the Impact of Higher Ammonia Recycle Loads Caused by Upgrading Anaerobic Sludge Digesters

2005 ◽  
Vol 40 (4) ◽  
pp. 491-499 ◽  
Author(s):  
Jeremy T. Kraemer ◽  
David M. Bagley
Keyword(s):  
Anaerobic Digestion ◽  
Biogas Production ◽  
Treatment Plant ◽  
Anaerobic Sludge ◽  
Content Increase ◽  
Limited Information ◽  
Dynamic Simulations ◽  
Treatment Train ◽  
Temperature Liquid ◽  
The Impact

Abstract Upgrading conventional single-stage mesophilic anaerobic digestion to an advanced digestion technology can increase sludge stability, reduce pathogen content, increase biogas production, and also increase ammonia concentrations recycled back to the liquid treatment train. Limited information is available to assess whether the higher ammonia recycle loads from an anaerobic sludge digestion upgrade would lead to higher discharge effluent ammonia concentrations. Biowin, a commercially available wastewater treatment plant simulation package, was used to predict the effects of anaerobic digestion upgrades on the liquid train performance, especially effluent ammonia concentrations. A factorial analysis indicated that the influent total Kjeldahl nitrogen (TKN) and influent alkalinity each had a 50-fold larger influence on the effluent NH3 concentration than either the ambient temperature, liquid train SRT or anaerobic digestion efficiency. Dynamic simulations indicated that the diurnal variation in effluent NH3 concentration was 9 times higher than the increase due to higher digester VSR. Higher recycle NH3 loads caused by upgrades to advanced digestion techniques can likely be adequately managed by scheduling dewatering to coincide with periods of low influent TKN load and ensuring sufficient alkalinity for nitrification.

Impact of Nanotechnology Patents on Green Development of China's Building Industry

2020 ◽  
Vol 14 (2) ◽  
pp. 141-152
Author(s):  
Xialing Sun ◽  
Rui Zhang ◽  
Xue Chen ◽  
Pengpeng Li ◽  
Jin Guo
Keyword(s):  
Total Factor Productivity ◽  
Inhibitory Effect ◽  
Building Industry ◽  
Factor Productivity ◽  
The Sustainable Development ◽  
Technological Support ◽  
Green Development ◽  
Panel Data Regression ◽  
The Impact ◽  
Building Engineering

Background: The sustainable development of the building industry has drawn increasing attention around the world. Nanomaterials and nanotechnology play an important role in the processes of energy saving and reducing consumption in the building industry. Nanotechnology patents provide key technological support for the green development of the building industry. Based on patent data in China, this paper quantitatively analyzed the application of nanotechnology patents in the building industry and the time trend, regional differences, and evolution of China's nano-patent applications in the building field. Methods: In this study, the environmental total factor productivity of the building industry considering carbon constraints was determined and then used as the dependent variable to measure the green development of the building industry. On this basis, a panel data regression model was constructed to determine the impact of nano-patents on the green development of the building industry. Results: Nanotechnology patents in the building industry can significantly improve total factor productivity. From the perspective of patent composition, technology-based patents that focus on substantial innovation can significantly promote the green development of the building industry, whereas strategic patents show a significant inhibitory effect. Regionally, the western region of China has the advantage of being less developed and thus more efficient than the central and eastern regions in the application of new nano-products. Finally, the research also showed a significant lag in the application of China's nanotechnology patents and low implementation efficiency. Conclusion: Nano patents can promote green development in the building industry, but there is room for improvement in the speed with which laboratory inventions are transformed into building engineering applications.

Psychological Impacts of COVID-19 During the First Nationwide Lockdown in Vietnam: Web-Based, Cross-Sectional Survey Study (Preprint)

2020 ◽  
Author(s):  
Khanh Ngoc Cong Duong ◽  
Tien Nguyen Le Bao ◽  
Phuong Thi Lan Nguyen ◽  
Thanh Vo Van ◽  
Toi Phung Lam ◽  
...  
Keyword(s):  
Psychological Distress ◽  
General Population ◽  
Psychological Health ◽  
Online Survey ◽  
Survey Study ◽  
Limited Information ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Event Scale ◽  
The Impact

BACKGROUND The first nationwide lockdown due to the COVID-19 pandemic was implemented in Vietnam from April 1 to 15, 2020. Nevertheless, there has been limited information on the impact of COVID-19 on the psychological health of the public. OBJECTIVE This study aimed to estimate the prevalence of psychological issues and identify the factors associated with the psychological impact of COVID-19 during the first nationwide lockdown among the general population in Vietnam. METHODS We employed a cross-sectional study design with convenience sampling. A self-administered, online survey was used to collect data and assess psychological distress, depression, anxiety, and stress of participants from April 10 to 15, 2020. The Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety, and Stress Scale-21 (DASS-21) were utilized to assess psychological distress, depression, anxiety, and stress of participants during social distancing due to COVID-19. Associations across factors were explored using regression analysis. RESULTS A total of 1385 respondents completed the survey. Of this, 35.9% (n=497) experienced psychological distress, as well as depression (n=325, 23.5%), anxiety (n=195, 14.1%), and stress (n=309, 22.3%). Respondents who evaluated their physical health as average had a higher IES-R score (beta coefficient [B]=9.16, 95% CI 6.43 to 11.89), as well as higher depression (B=5.85, 95% CI 4.49 to 7.21), anxiety (B=3.64, 95% CI 2.64 to 4.63), and stress (B=5.19, 95% CI 3.83 to 6.56) scores for DASS-21 than those who rated their health as good or very good. Those who self-reported their health as bad or very bad experienced more severe depression (B=9.57, 95% CI 4.54 to 14.59), anxiety (B=7.24, 95% CI 3.55 to 10.9), and stress (B=10.60, 95% CI 5.56 to 15.65). Unemployment was more likely to be associated with depression (B=3.34, 95% CI 1.68 to 5.01) and stress (B=2.34, 95% CI 0.84 to 3.85). Regarding worries about COVID-19, more than half (n=755, 54.5%) expressed concern for their children aged <18 years, which increased their IES-R score (B=7.81, 95% CI 4.98 to 10.64) and DASS-21 stress score (B=1.75, 95% CI 0.27 to 3.24). The majority of respondents (n=1335, 96.4%) were confident about their doctor’s expertise in terms of COVID-19 diagnosis and treatment, which was positively associated with less distress caused by the outbreak (B=–7.84, 95% CI –14.58 to –1.11). CONCLUSIONS The findings highlight the effect of COVID-19 on mental health during the nationwide lockdown among the general population in Vietnam. The study provides useful evidence for policy decision makers to develop and implement interventions to mitigate these impacts. CLINICALTRIAL

scholarly journals Aquatic Toxicity of Photocatalyst Nanoparticles to Green Microalgae Chlorella vulgaris

Water ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 77
Author(s):  
Cristina Adochite ◽  
Luminita Andronic
Keyword(s):  
Chlorella Vulgaris ◽  
Advanced Oxidation Process ◽  
Growth Parameters ◽  
Aquatic Toxicity ◽  
Basal Medium ◽  
Inhibitory Effect ◽  
Synthesis Methods ◽  
Potent Inhibitory Effect ◽  
Density Surface ◽  
The Impact

In the last years, nanoparticles such as TiO2, ZnO, NiO, CuO and Fe2O3 were mainly used in wastewater applications. In addition to the positive aspects concerning using nanoparticles in the advanced oxidation process of wastewater containing pollutants, the impact of these nanoparticles on the environment must also be investigated. The toxicity of nanoparticles is generally investigated by the nanomaterials’ effect on green algae, especially on Chlorella vulgaris. In this review, several aspects are reviewed: the Chlorella vulgaris culture monitoring and growth parameters, the effect of different nanoparticles on Chlorella vulgaris, the toxicity of photocatalyst nanoparticles, and the mechanism of photocatalyst during oxidative stress on the photosynthetic mechanism of Chlorella vulgaris. The Bold basal medium (BBM) is generally recognized as an excellent standard cultivation medium for Chlorella vulgaris in the known environmental conditions such as temperature in the range 20–30 °C and light intensity of around 150 μE·m2·s−1 under a 16/8 h light/dark cycle. The nanoparticles synthesis methods influence the particle size, morphology, density, surface area to generate growth inhibition and further algal deaths at the nanoparticle-dependent concentration. Moreover, the results revealed that nanoparticles caused a more potent inhibitory effect on microalgal growth and severely disrupted algal cells’ membranes.

scholarly journals miR-208b Reduces the Expression of Kcnj5 in a Cardiomyocyte Cell Line

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 719
Author(s):  
Julia Hupfeld ◽  
Maximilian Ernst ◽  
Maria Knyrim ◽  
Stephanie Binas ◽  
Udo Kloeckner ◽  
...  
Keyword(s):  
Untranslated Region ◽  
Electrical Remodeling ◽  
Sequencing Data ◽  
Western Blots ◽  
Cardiovascular Pathology ◽  
Hypertrophic Response ◽  
Channel Dependent ◽  
Cardiac Excitation ◽  
The Impact ◽  
Generation Sequencing

MicroRNAs (miRs) contribute to different aspects of cardiovascular pathology, among them cardiac hypertrophy and atrial fibrillation. Cardiac miR expression was analyzed in a mouse model with structural and electrical remodeling. Next-generation sequencing revealed that miR-208b-3p was ~25-fold upregulated. Therefore, the aim of our study was to evaluate the impact of miR-208b on cardiac protein expression. First, an undirected approach comparing whole RNA sequencing data to miR-walk 2.0 miR-208b 3′-UTR targets revealed 58 potential targets of miR-208b being regulated. We were able to show that miR-208b mimics bind to the 3′ untranslated region (UTR) of voltage-gated calcium channel subunit alpha1 C and Kcnj5, two predicted targets of miR-208b. Additionally, we demonstrated that miR-208b mimics reduce GIRK1/4 channel-dependent thallium ion flux in HL-1 cells. In a second undirected approach we performed mass spectrometry to identify the potential targets of miR-208b. We identified 40 potential targets by comparison to miR-walk 2.0 3′-UTR, 5′-UTR and CDS targets. Among those targets, Rock2 and Ran were upregulated in Western blots of HL-1 cells by miR-208b mimics. In summary, miR-208b targets the mRNAs of proteins involved in the generation of cardiac excitation and propagation, as well as of proteins involved in RNA translocation (Ran) and cardiac hypertrophic response (Rock2).

scholarly journals Petasin and isopetasin reduce CGRP release from trigeminal afferents indicating an inhibitory effect on TRPA1 and TRPV1 receptor channels

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Johanna Kleeberg-Hartmann ◽  
Birgit Vogler ◽  
Karl Messlinger
Keyword(s):  
Inhibitory Effect ◽  
Transient Receptor Potential Channels ◽  
Mustard Oil ◽  
Root Extract ◽  
Dependent Manner ◽  
Trpv1 Receptor ◽  
Cgrp Release ◽  
Ganglion Neurons ◽  
Sites Of Action ◽  
The Impact

Abstract Background Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1. Methods We used well-established in vitro preparations, the hemisected rodent skull and dissected trigeminal ganglia, to examine the CGRP release from rat and mouse cranial dura mater and trigeminal ganglion neurons, respectively, after pre-incubation with petasin and isopetasin. Mustard oil and capsaicin were used to stimulate TRPA1 and TRPV1 receptor channels. CGRP concentrations were measured with a CGRP enzyme immunoassay. Results Pre-incubation with either petasin or isopetasin reduced mustard oil- and capsaicin-evoked CGRP release compared to vehicle in an approximately dose-dependent manner. These results were validated by additional experiments with mice expressing functionally deleted TRPA1 or TRPV1 receptor channels. Conclusions Earlier findings of TRPA1 receptor channels being involved in the site of action of petasin and isopetasin are confirmed. Furthermore, we suggest an important inhibitory effect on TRPV1 receptor channels and assume a cooperative action between the two TRP receptors. These mechanisms may contribute to the migraine prophylactic effect of petasins.

scholarly journals The Impact of Climate Change on the Resistance of Rice Near-Isogenic Lines with Resistance Genes Against Brown Planthopper

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yun-Hung Kuang ◽  
Yu-Fu Fang ◽  
Shau-Ching Lin ◽  
Shin-Fu Tsai ◽  
Zhi-Wei Yang ◽  
...  
Keyword(s):  
Climate Change ◽  
Resistance Genes ◽  
Environmental Changes ◽  
Gene Pyramiding ◽  
Brown Planthopper ◽  
Inhibitory Effect ◽  
Near Isogenic Lines ◽  
Impact Of Climate Change ◽  
Isogenic Lines ◽  
The Impact

Abstract Background The impact of climate change on insect resistance genes is elusive. Hence, we investigated the responses of rice near-isogenic lines (NILs) that carry resistance genes against brown planthopper (BPH) under different environmental conditions. Results We tested these NILs under three environmental settings (the atmospheric temperature with corresponding carbon dioxide at the ambient, year 2050 and year 2100) based on the Intergovernmental Panel on Climate Change prediction. Comparing between different environments, two of nine NILs that carried a single BPH-resistant gene maintained their resistance under the environmental changes, whereas two of three NILs showed gene pyramiding with two maintained BPH resistance genes despite the environmental changes. In addition, two NILs (NIL-BPH17 and NIL-BPH20) were examined in their antibiosis and antixenosis effects under these environmental changes. BPH showed different responses to these two NILs, where the inhibitory effect of NIL-BPH17 on the BPH growth and development was unaffected, while NIL-BPH20 may have lost its resistance during the environmental changes. Conclusion Our results indicate that BPH resistance genes could be affected by climate change. NIL-BPH17 has a strong inhibitory effect on BPH feeding on phloem and would be unaffected by environmental changes, while NIL-BPH20 would lose its ability during the environmental changes.

scholarly journals The RNA Architecture of the SARS-CoV-2 3′-Untranslated Region

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1473
Author(s):  
Junxing Zhao ◽  
Jianming Qiu ◽  
Sadikshya Aryal ◽  
Jennifer L. Hackett ◽  
Jingxin Wang
Keyword(s):  
Untranslated Region ◽  
Dimethyl Sulfate ◽  
Nonstructural Proteins ◽  
Stem Loop ◽  
Cis Acting ◽  
Chemical Probing ◽  
Mutational Profiling ◽  
Genome Transcription ◽  
Polymerase Binding ◽  
Transcription And Replication

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. The 3′ untranslated region (UTR) of this β-CoV contains essential cis-acting RNA elements for the viral genome transcription and replication. These elements include an equilibrium between an extended bulged stem-loop (BSL) and a pseudoknot. The existence of such an equilibrium is supported by reverse genetic studies and phylogenetic covariation analysis and is further proposed as a molecular switch essential for the control of the viral RNA polymerase binding. Here, we report the SARS-CoV-2 3′ UTR structures in cells that transcribe the viral UTRs harbored in a minigene plasmid and isolated infectious virions using a chemical probing technique, namely dimethyl sulfate (DMS)-mutational profiling with sequencing (MaPseq). Interestingly, the putative pseudoknotted conformation was not observed, indicating that its abundance in our systems is low in the absence of the viral nonstructural proteins (nsps). Similarly, our results also suggest that another functional cis-acting element, the three-helix junction, cannot stably form. The overall architectures of the viral 3′ UTRs in the infectious virions and the minigene-transfected cells are almost identical.

scholarly journals Effects of Technological Progress from Different Sources on Haze Pollution in China

2021 ◽  
Vol 13 (5) ◽  
pp. 2730
Author(s):  
Yuan Zhao ◽  
Tian Zhang ◽  
Ting Wu ◽  
Shujing Xu ◽  
Shuwang Yang
Keyword(s):  
Technological Progress ◽  
Generalized Method Of Moments ◽  
National Level ◽  
Inhibitory Effect ◽  
Dynamic Panel Model ◽  
Independent Innovation ◽  
Haze Pollution ◽  
Technology Introduction ◽  
The Impact ◽  
Different Sources

Technological progress has always been regarded as an important factor affecting haze pollution. A large number of academic studies have focused on the effect of technological progress on haze pollution, but there are few discussions on the effects of technological progress from different sources. In view of this, a dynamic panel model is constructed, and a systematic generalized method of moments (GMM) method is applied to empirically test the overall impact of technological progress from different sources on haze pollution and the regional heterogeneity of the impact. The results show that the overall and regional impact of technological progress from different sources on haze pollution is entirely different. Among them, for the whole country, independent innovation has a significant inhibitory effect on haze pollution, and technology introduction has aggravated haze pollution to a certain extent. At the regional level, all types of technological progress in the east can effectively reduce haze, the central region having haze reduction results consistent with the overall national level, and in the west, independent innovation and direct introduction can effectively reduce haze, while reverse technology spillover is ineffective. Therefore, policy recommendations such as improving the ability of independent innovation, improving the quality of technology introduction, and coordinating regional technology against haze are put forward.

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