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1

Larkin, Andrew, Howard Waitzkin, Ella Fassler, and Kesavan Rajasekharan Nayar. "How missing evidence-based medicine indicators can inform COVID-19 vaccine distribution policies: a scoping review and calculation of indicators from data in randomised controlled trials." BMJ Open 12, no. 12 (December 2022): e063525. http://dx.doi.org/10.1136/bmjopen-2022-063525.

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ObjectiveReports of efficacy, effectiveness and harms of COVID-19 vaccines have not used key indicators from evidence-based medicine (EBM) that can inform policies about vaccine distribution. This study aims to clarify EBM indicators that consider baseline risks when assessing vaccines’ benefits versus harms: absolute risk reduction (ARR) and number needed to be vaccinated (NNV), versus absolute risk of the intervention (ARI) and number needed to harm (NNH).MethodsWe used a multimethod approach, including a scoping review of the literature; calculation of risk reductions and harms from data concerning five major vaccines; analysis of risk reductions in population subgroups with varying baseline risks; and comparisons with prior vaccines.FindingsThe scoping review showed few reports regarding ARR, NNV, ARI and NNH; comparisons of benefits versus harms using these EBM methods; or analyses of varying baseline risks. Calculated ARRs for symptomatic infection and hospitalisation were approximately 1% and 0.1%, respectively, as compared with relative risk reduction of 50%–95% and 58%–100%. NNV to prevent one symptomatic infection and one hospitalisation was in the range of 80–500 and 500–4000. Based on available data, ARI and NNH as measures of harm were difficult to calculate, and the balance between benefits and harms using EBM measures remained uncertain. The effectiveness of COVID-19 vaccines as measured by ARR and NNV was substantially higher in population subgroups with high versus low baseline risks.ConclusionsPriorities for vaccine distribution should target subpopulations with higher baseline risks. Similar analyses using ARR/NNV and ARI/NNH would strengthen evaluations of vaccines’ benefits versus harms. An EBM perspective on vaccine distribution that emphasises baseline risks becomes especially important as the world’s population continues to face major barriers to vaccine access—sometimes termed ‘vaccine apartheid’.
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2

Chang, Jui-Shin, and Shau-Chi Chi. "GHSC70 Is Involved in the Cellular Entry of Nervous Necrosis Virus." Journal of Virology 89, no. 1 (October 15, 2014): 61–70. http://dx.doi.org/10.1128/jvi.02523-14.

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ABSTRACTNervous necrosis virus (NNV) is a devastating pathogen of cultured marine fish and has affected more than 40 fish species. NNV belongs to the betanodaviruses ofNodaviridaeand is a nonenveloped icosahedral particle with 2 single-stranded positive-sense RNAs. To date, knowledge regarding NNV entry into the host cell remains limited, and no NNV-specific receptor protein has been published. Using grouper fin cell line GF-1 and purified NNV capsid protein in a virus overlay protein binding assay (VOPBA), grouper heat shock cognate protein 70 (GHSC70) and grouper voltage-dependent anion selective channel protein 2 (GVDAC2) were investigated as NNV receptor protein candidates. We cloned and sequenced the genes for GHSC70 and GVDAC2 and expressed them inEscherichia colifor antiserum preparation. Knockdown of the expression of GHSC70 and GVDAC2 genes with specific short interfering RNAs (siRNAs) significantly downregulated viral RNA expression in NNV-infected GF-1 cells. By performing an immunoprecipitation assay, we confirmed that GHSC70 interacted with NNV capsid protein, while VDAC2 did not. Immunofluorescence staining and flow cytometry analysis revealed the presence of the GHSC70 protein on the cell surface. After a blocking assay, we detected the NNV RNA2 levels after 1 h of adsorption to GF-1 cells; the level was significantly lower in the cells pretreated with the GHSC70 antiserum than in nontreated cells. Therefore, we suggest that GHSC70 participates in the NNV entry of GF-1 cells, likely functioning as an NNV receptor or coreceptor protein.IMPORTANCEFish nodavirus has caused mass mortality of more than 40 fish species worldwide and resulted in huge economic losses in the past 20 years. Among the four genotypes of fish nodaviruses, the red-spotted grouper nervous necrosis virus (RGNNV) genotype exhibits the widest host range. In our previous study, we developed monoclonal antibodies with high neutralizing efficiency against grouper NNV in GF-1 cells, indicating that NNV-specific receptor(s) may exist on the GF-1 cell membrane. However, no NNV receptor protein has been published. In this study, we found GHSC70 to be an NNV receptor (or coreceptor) candidate through VOBPA and provided several lines of evidence demonstrating that GHSC70 protein has a role in the NNV entry step of GF-1 cells. To the best of our knowledge, this is the first report identifying grouper HSC70 and its role in NNV entry into GF-1 cells.
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3

Lee, Hyunkyoung, Seong Kyeong Bae, Munki Kim, Min Jung Pyo, Minkyung Kim, Sujeoung Yang, Chung-kil Won, et al. "Anticancer Effect of Nemopilema nomurai Jellyfish Venom on HepG2 Cells and a Tumor Xenograft Animal Model." Evidence-Based Complementary and Alternative Medicine 2017 (2017): 1–12. http://dx.doi.org/10.1155/2017/2752716.

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Various kinds of animal venoms and their components have been widely studied for potential therapeutic applications. This study evaluated whether Nemopilema nomurai jellyfish venom (NnV) has anticancer activity. NnV strongly induced cytotoxicity of HepG2 cells through apoptotic cell death, as demonstrated by alterations of chromatic morphology, activation of procaspase-3, and an increase in the Bax/Bcl-2 ratio. Furthermore, NnV inhibited the phosphorylation of PI3K, PDK1, Akt, mTOR, p70S6K, and 4EBP1, whereas it enhanced the expression of p-PTEN. Interestingly, NnV also inactivated the negative feedback loops associated with Akt activation, as demonstrated by downregulation of Akt at Ser473 and mTOR at Ser2481. The anticancer effect of NnV was significant in a HepG2 xenograft mouse model, with no obvious toxicity. HepG2 cell death by NnV was inhibited by tetracycline, metalloprotease inhibitor, suggesting that metalloprotease component in NnV is closely related to the anticancer effects. This study demonstrates, for the first time, that NnV exerts highly selective cytotoxicity in HepG2 cells via dual inhibition of the Akt and mTOR signaling pathways, but not in normal cells.
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Morick, Danny, Or Faigenbaum, Margarita Smirnov, Yakov Fellig, Adi Inbal, and Moshe Kotler. "Mortality Caused by Bath Exposure of Zebrafish (Danio rerio) Larvae to Nervous Necrosis Virus Is Limited to the Fourth Day Postfertilization." Applied and Environmental Microbiology 81, no. 10 (March 6, 2015): 3280–87. http://dx.doi.org/10.1128/aem.04175-14.

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ABSTRACTNervous necrosis virus (NNV) is a member of theBetanodavirusgenus that causes fatal diseases in over 40 species of fish worldwide. Mortality among NNV-infected fish larvae is almost 100%. In order to elucidate the mechanisms responsible for the susceptibility of fish larvae to NNV, we exposed zebrafish larvae to NNV by bath immersion at 2, 4, 6, and 8 days postfertilization (dpf). Here, we demonstrate that developing zebrafish embryos are resistant to NNV at 2 dpf due to the protection afforded by the egg chorion and, to a lesser extent, by the perivitelline fluid. The zebrafish larvae succumbed to NNV infection during a narrow time window around the 4th dpf, while 6- and 8-day-old larvae were much less sensitive, with mortalities of 24% and 28%, respectively.
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5

Huang, Po-Yu, Han-Chia Hsiao, Szu-Wen Wang, Shao-Fu Lo, Ming-Wei Lu, and Li-Li Chen. "Screening for the Proteins That Can Interact with Grouper Nervous Necrosis Virus Capsid Protein." Viruses 12, no. 9 (September 4, 2020): 985. http://dx.doi.org/10.3390/v12090985.

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Nervous necrosis virus (NNV) can infect many species of fish and has an 80–100% mortality rate. NNV capsid protein (NNVCP) is the only structural protein of NNV, but there are few studies on the protein–protein interaction between NNVCP and the host cell. To investigate NNV morphogenesis, native NNV capsid protein (NNVCP) was used to screen for protein–protein interactions in this study. The results identified that 49 grouper optic nerve proteins can interact with NNVCP and may function as putative receptor or co-receptor, cytoskeleton, glucose metabolism and ATP generation, immunity, mitochondrial ion regulation, and ribosomal proteins. Creatine kinase B-type (CKB) is one of those 49 optic nerve proteins. CKB, a kind of enzyme of ATP generation, was confirmed to interact with NNVCP by far-Western blot and showed to colocalize with NNVCP in GF-1 cells. Compared to the control, the expression of CKB was significantly induced in the brain and eyes infected with NNV. Moreover, the amount of replication of NNV is relatively high in cells expressing CKB. In addition to providing the database of proteins that can interact with NNVCP for subsequent analysis, the results of this research also verified that CKB plays an important role in the morphogenesis of NNV.
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6

Xiao Joe, Joan Tang, Henry Tan Shi Sung, Jen-Leih Wu, Yu-Shen Lai, and Ming-Wei Lu. "Dietary Administration of Novel Multistrain Probiotics from Healthy Grouper Intestines Promotes the Intestinal Immune Response against NNV Infection." Life 11, no. 10 (October 7, 2021): 1053. http://dx.doi.org/10.3390/life11101053.

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Epinephelus lanceolatus (giant grouper) is a high-value cultured species in the Asia-Pacific region. However, nervous necrosis virus (NNV) is an infectious viral disease that affects over 120 species of marine cultured species and causes high mortality, ranging from 90–100% in the grouper industry. Probiotics isolated from the intestines of healthy individuals have provided insight into novel approaches involved in the defense against viral pathogens. In this study, we isolated three strains of bacteria as candidate probiotics from healthy grouper intestines and a 28-day feeding trial was performed. At day 21, the nervous necrosis virus (NNV) challenge test was conducted for 7 days to evaluate the antiviral effect of candidate probiotics. The results showed that candidate probiotics could improve growth conditions, such as weight gain (WG) and specific growth rate (SGR), and increase the utilization of feed. Furthermore, the candidate probiotic mixture had the ability to protect against NNV, which could decrease the mortality rate by 100% in giant grouper after NNV challenge. Subsequently, we analyzed the mechanism of the candidate probiotic mixture’s defense against NNV. A volcano plot revealed 203 (control vs. NNV), 126 (NNV vs. probiotics − NNV), and 5 (control vs. probiotics − NNV) differentially expressed transcripts in intestinal tissue. Moreover, principal components analysis (PCA) and cluster analysis heatmap showed large differences among the three groups. Functional pathway analysis showed that the candidate probiotic mixture could induce the innate and adaptive immunity of the host to defend against virus pathogens. Therefore, we hope that potential candidate probiotics could be successfully applied to the industry to achieve sustainable aquaculture.
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7

Yang, Shieh Yueh, Jen Leih Wu, Chun Hsi Tso, Fang Huar Ngou, Hsin Yiu Chou, Fan Hua Nan, Herng Er Horng, and Ming Wei Lu. "A novel quantitative immunomagnetic reduction assay for Nervous necrosis virus." Journal of Veterinary Diagnostic Investigation 24, no. 5 (August 1, 2012): 911–17. http://dx.doi.org/10.1177/1040638712455796.

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Rapid, sensitive, and automatic detection platforms are among the major approaches of controlling viral diseases in aquaculture. An efficient detection platform permits the monitoring of pathogen spread and helps to enhance the economic benefits of commercial aquaculture. Nervous necrosis virus (NNV), the cause of viral encephalopathy and retinopathy, is among the most devastating aquaculture viruses that infect marine fish species worldwide. In the present study, a highly sensitive magnetoreduction assay was developed for detecting target biomolecules with a primary focus on NNV antigens. A standard curve of the different NNV concentrations that were isolated from infected Malabar grouper ( Epinephelus malabaricus) was established before experiments were conducted. The test solution was prepared by homogeneous dispersion of magnetic nanoparticles coated with rabbit anti-NNV antibody. The magnetic nanoparticles in the solution were oscillated by magnetic interaction with multiple externally applied, alternating current magnetic fields. The assay’s limit of detection was approximately 2 × 101 TCID50/ml for NNV. Moreover, the immunomagnetic reduction readings for other aquatic viruses (i.e., 1 × 107 TCID50/ml for Infectious pancreatic necrosis virus and 1 × 106.5 TCID50/ml for grouper iridovirus) were below the background noise in the NNV solution, demonstrating the specificity of the new detection platform.
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8

Valero, Yulema, José G. Olveira, Carmen López-Vázquez, Carlos P. Dopazo, and Isabel Bandín. "BEI Inactivated Vaccine Induces Innate and Adaptive Responses and Elicits Partial Protection upon Reassortant Betanodavirus Infection in Senegalese Sole." Vaccines 9, no. 5 (May 4, 2021): 458. http://dx.doi.org/10.3390/vaccines9050458.

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Nervous necrosis virus (NNV), the causative agent of viral encephalopathy and retinopathy (VER), is one of the most threatening viruses affecting marine and freshwater fish species worldwide. Senegalese sole is a promising fish species in Mediterranean aquaculture but also highly susceptible to NNV and VER outbreaks, that puts its farming at risk. The development of vaccines for aquaculture is one of best tools to prevent viral spread and sudden outbreaks, and virus inactivation is the simplest and most cost-effective method available. In this work, we have designed two inactivated vaccines based on the use of formalin or binary ethylenimine (BEI) to inactivate a reassortant NNV strain. After vaccination, the BEI-inactivated vaccine triggered the production of specific IgM-NNV antibodies and stimulated innate and adaptive immune responses at transcriptional level (rtp3, mx, mhcii and tcrb coding genes). Moreover, it partially improved survival after an NNV in vivo challenge, reducing the mid-term viral load and avoiding the down-regulation of immune response post-challenge. On the other hand, the formalin-inactivated vaccine improved the survival of fish upon infection without inducing the production of IgM-NNV antibodies and only stimulating the expression of herc4 and mhcii genes (in head-kidney and brain, respectively) during the vaccination period; this suggests that other immune-related pathways may be involved in the partial protection provoked. Although these vaccines against NNV showed encouraging results, further studies are needed to improve sole protection and to fully understand the underlying immune mechanism.
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9

Santos, Isabel A., Cristina Martins, and Isabel Pereira. "NOMINAL GENDER AND NUMBER IN THE DEVELOPMENT OF THE TIMORESE VARIETY OF PORTUGUESE." Diacrítica 32, no. 2 (July 2, 2019): 33. http://dx.doi.org/10.21814/diacritica.439.

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This study contributes to the description of East-Timorese Portuguese (ETP), focusing on the variable patterns of nominal agreement in number and gender operating in this variety. The relevance of the research hinges on the fact that ETP is an understudied non-native variety (NNV) of Portuguese. Given its emergent state, the study of this particular variety can furthermore shed light on the historical process that led to the formation of other NNV. NNV are a product of the non-native acquisition of a language that, in a given territory, takes on official status, this is to say, is a second language (SL). Comparing production data by NNV speakers and by foreign language (FL) learners can elucidate both common and specific patterns of behavior. In this study, texts written by ETP speakers and by PFL learners were compared. Results revealed similar trends in both samples, but also a greater preference of ETP speakers for not complying to full nominal agreement. In general, data suggest that variable patterns of nominal agreement are likely to emerge as a defining property of ETP, as is currently the case in other NNV of Portuguese, thus diverging from European Portuguese (EP).
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10

Barki, Hadjer, Latifa Khaouane, and Salah Hanini. "Modelling of Adsorption of Methane, Nitrogen, Carbon Dioxide, Their Binary Mixtures, and Their Ternary Mixture on Activated Carbons Using Artificial Neural Network." Kemija u industriji 68, no. 7-8 (2019): 289–302. http://dx.doi.org/10.15255/kui.2019.002.

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This work examines the use of neural networks in modelling the adsorption process of gas mixtures (CO<sub>2</sub>, CH<sub>4</sub>, and N<sub>2</sub>) on different activated carbons. Seven feed-forward neural network models, characterized by different structures, were constructed with the aim of predicting the adsorption of gas mixtures. A set of 417, 625, 143, 87, 64, 64, and 40 data points for NN1 to NN7, respectively, were used to test the neural networks. Of the total data, 60 %, 20 %, and 20 % were used, respectively, for training, validation, and testing of the seven models. Results show a good fit between the predicted and experimental values for each model; good correlations were found (<i>R</i> = 0.99656 for NN1, <i>R</i> = 0.99284 for NN2, <i>R</i> = 0.99388 for NN3, <i>R</i> = 0.99639 for <i>Q</i><sub>1</sub> for NN4, <i>R</i> = 0.99472 for <i>Q</i><sub>2</sub> for NN4, R = 0.99716 for <i>Q</i><sub>1</sub> for NN5, <i>R</i> = 0.99752 for <i>Q</i><sub>3</sub> for NN5, <i>R</i> = 0.99746 for <i>Q</i><sub>2</sub> for NN6, <i>R</i> = 0.99783 for <i>Q</i><sub>3</sub> for NN6, <i>R</i> = 0.9946 for <i>Q</i><sub>1</sub> for NN7, <i>R</i> = 0.99089 for <i>Q</i><sub>2</sub> for NN7, and <i>R</i> = 0.9947 for <i>Q</i><sub>3</sub> for NN7). Moreover, the comparison between the predicted results and the classical models (Gibbs model, Generalized dual-site Langmuir model, and Ideal Adsorption Solution Theory) shows that the neural network models gave far better results.
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Yanuhar, Uun, and Nico Rahman Caesar. "The Involvement of Pigment-Protein Fraction from Microalga Nannochloropsis oculata in Expression of Heat Shock Protein 70 with Nervous Necrosis Viral Infection on Grouper." Indonesian Journal of Natural Pigments 1, no. 1 (February 14, 2019): 1. http://dx.doi.org/10.33479/ijnp.2019.01.1.1.

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The aim of this study is to investigate the expression of heat shock protein 70 (HSP70) on grouper infected by Nervous Necrosis Viral (NNV) with involvement of pigment-protein fraction (PPF) from Nannocloropsis oculata (N.oculata). Fish treatments were divided into three group, which are control, fish with PPF from N.oculata, and fish with PPF and NNV. After treatment for 23 d, fish were sacrificed, and their brain was harvested for protein analysis using SDS-Page. Fish blood was collected to examine the expression of HSP70 by hemagglutination and western blot analysis. The results showed that the expression of HSP70 was observed after treatment with PPF in NNV infected brain tissue and blood cell proved by SDS-Page and Western blot analysis. Thus, PPF is responsible for the expression of HSP70 in infected tissues, indicating that PPF appears to have a function as an inhibitor of proliferation of NNV.
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Leela Sudarsanan Amulya and Perumal Subramanian. "Influence of Indian snake (Naja naja) venom on cognition and biochemical functions in N- Nitrosodiethylamine treated Drosophila melanogaster." International Journal of Research in Pharmaceutical Sciences 13, no. 1 (March 25, 2022): 126–36. http://dx.doi.org/10.26452/ijrps.v13i1.33.

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The flies (Drosophila melanogaster) were segregated into four groups. 1st Group is normal-control, 2nd group is wild type flies administered with 0.01% NDEA, 3rd group is wild type flies administered with 0.01% NDEA + 0.01% Naja naja snake venom (NNV) and 4th group is flies administered with 0.01% NNV alone were administered via food medium for 21 days. After the experimental period, the behavioural changes were analyzed. The behavioural assays include negative geotaxis, phototaxis, smell chemotaxis, taste chemotaxis, thermotaxis, and hygrotaxis were carried out in all groups of flies. The behavioural changes were found to be deteriorated in NDEA administered flies when related to the control but the behaviour is likely to regularise in NDEA+NNV administered flies. The protein carbonyl levels and levels of thiobarbuturic acid reactive substance (TBARS), protein thiol and lipid peroxides were noticeably elevated in NDEA administered flies as matched to control flies and similarly be likely to regularize in the NDEA+NNV group. Likewise, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and reduced glutathione (GSH) were diminished in the group of NDEA administered and were noticeably more in the group of NDEA+NNV administered group. NNV has been stated to possess pharmacologically active components such as disintegrins, cobratoxin, hannalgesin, cytotoxin II, etc. which could possess antioxidant, antibacterial, hypotensive, cancer suppressive, anticoagulant, and analgesic activities. Our present study provides evidences that these components could normalize cognitive behaviour and attenuate oxidative stress in a genetically important model organism D. melanogaster.
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13

Falco, Alberto, Melissa Bello-Perez, Rocío Díaz-Puertas, Matthew Mold, and Mikolaj Adamek. "Update on the Inactivation Procedures for the Vaccine Development Prospects of a New Highly Virulent RGNNV Isolate." Vaccines 9, no. 12 (December 7, 2021): 1441. http://dx.doi.org/10.3390/vaccines9121441.

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Viral nervous necrosis (VNN) caused by the nervous necrosis virus (NNV) affects a broad range of primarily marine fish species, with mass mortality rates often seen among larvae and juveniles. Its genetic diversification may hinder the effective implementation of preventive measures such as vaccines. The present study describes different inactivation procedures for developing an inactivated vaccine against a new NNV isolate confirmed to possess deadly effects upon the European seabass (Dicentrarchus labrax), an important Mediterranean farmed fish species that is highly susceptible to this disease. First, an NNV isolate from seabass adults diagnosed with VNN was rescued and the sequences of its two genome segments (RNA1 and RNA2) were classified into the red-spotted grouper NNV (RGNNV) genotype, closely clustering to the highly pathogenic 283.2009 isolate. The testing of different inactivation procedures revealed that the virus particles of this isolate showed a marked resistance to heat (for at least 60 °C for 120 min with and without 1% BSA) but that they were fully inactivated by 3 mJ/cm2 UV-C irradiation and 24 h 0.2% formalin treatment, which stood out as promising NNV-inactivation procedures for potential vaccine candidates. Therefore, these procedures are feasible, effective, and rapid response strategies for VNN control in aquaculture.
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Johnstone, Carolina, Montse Pérez, Marta Arizcun, Cristina García-Ruiz, and Elena Chaves-Pozo. "Reservoirs of Red-Spotted Grouper Nervous Necrosis Virus (RGNNV) in Squid and Shrimp Species of Northern Alboran Sea." Viruses 14, no. 2 (February 6, 2022): 328. http://dx.doi.org/10.3390/v14020328.

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The production of the aquaculture industry has increased to be equal to that of the world fisheries in recent years. However, aquaculture production faces threats such as infectious diseases. Betanodaviruses induce a neurological disease that affects fish species worldwide and is caused by nervous necrosis virus (NNV). NNV has a nude capsid protecting a bipartite RNA genome that consists of molecules RNA1 and RNA2. Four NNV strains distributed worldwide are discriminated according to sequence homology of the capsid protein encoded by RNA2. Since its first description over 30 years ago, the virus has expanded and reassortant strains have appeared. Preventive treatments prioritize the RGNNV (red-spotted grouper nervous necrosis virus) strain that has the highest optimum temperature for replication and the broadest range of susceptible species. There is strong concern about the spreading of NNV in the mariculture industry through contaminated diet. To surveil natural reservoirs of NNV in the western Mediterranean Sea, we collected invertebrate species in 2015 in the Alboran Sea. We report the detection of the RGNNV strain in two species of cephalopod mollusks (Alloteuthis media and Abralia veranyi), and in one decapod crustacean (Plesionika heterocarpus). According to RNA2 sequences obtained from invertebrate species and reported to date in the Mediterranean Sea, the strain RGNNV is predominant in this semienclosed sea. Neither an ecosystem- nor host-driven distribution of RGNNV were observed in the Mediterranean basin.
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Khotimah, Fitriyah Husnul, Alimuddin Alimuddin, Dinar Tri Soelistyowati, Sri Nuryati, Ketut Sugama, Ahmad Muzaki, Indah Mastuti, et al. "EVALUATION OF RESISTANCE AND GENE EXPRESSION OF BARRAMUNDI, Lates calcarifer POST-INFECTION OF NERVOUS NECROSIS VIRUS." Indonesian Aquaculture Journal 17, no. 2 (December 30, 2022): 97. http://dx.doi.org/10.15578/iaj.17.2.2022.97-106.

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The most common problem in barramundi Lates calcarifer seedling production is the high mortality (> 90%) caused by nervous necrosis virus (NNV) infection. This research aims to evaluate the resistance and gene expression of barramundi challenged by NNV. Two populations were used in this study, i.e., Australian, and Situbondo-originated barramundi populations. The immune-related gene expression levels in the liver, head of kidney, and spleen were observed at 48 and 96 hours after post-infection (hpi). Barramundi’s survival and blood parameters were evaluated post-NNV infection. The results showed that the highest survival was revealed in Situbondo’s barramundi (42.0±4.47%) compared to Australian barramundi (20.0±7.07%) and no mortality was observed in the control without NNV infection. The higher survival rate in barramundi from Situbondo was in line with the blood profile. The number of red blood cell from Situbondo barramundi post-NNV infection (ST) at 96 hpi was higher (P<0.05) than Australian barramundi post-NNV infection (AT). The number of white blood cell of ST at 48 hpi was higher (P<0.05) than AT, but started to decrease at 96 hpi in ST barramundi. The total white blood cell in AT barramundi increased from 48 to 192 hpi. TNFα and IL1-β gene expression levels were significantly higher in the liver, head kidney, and spleen of Situbondo compared to Australian barramundi at 48 hpi, while MHCIIα gene expression in Situbondo’s was significantly higher compared to Australian barramundi at 96 hpi. These results indicate the important roles of all the genes in the barramundi’s immune responses against viral infection. Based on the results of the research, Situbondo’s barramundi has the potential to be used as a candidate for generating broodstock of disease-resistant strain.
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González-Fernández, Carmen, and Alberto Cuesta. "Nanoplastics Increase Fish Susceptibility to Nodavirus Infection and Reduce Antiviral Immune Responses." International Journal of Molecular Sciences 23, no. 3 (January 27, 2022): 1483. http://dx.doi.org/10.3390/ijms23031483.

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Nanoplastics (NPs) might cause different negative effects on aquatic organisms at different biological levels, ranging from single cells to whole organisms, including cytotoxicity, reproduction, behavior or oxidative stress. However, the impact of NPs on disease resistance is almost unknown. The objective of this study was to assess whether exposure to 50 nm functionalized polystyrene NPs impacts fish susceptibility to viral diseases both in vitro and in vivo. In particular, we focused on the nervous necrosis virus (NNV), which affects many fish species, producing viral encephalopathy and retinopathy (VER), and causes great economic losses in marine aquaculture. In vitro and in vivo approaches were used. A brain cell line (SaB-1) was exposed to 1 μg mL−1 of functionalized polystyrene NPs (PS-NH2, PS-COOH) and then infected with NNV. Viral titers were increased in NP-exposed cells whilst the transcription of inflammatory and antiviral markers was lowered when compared to those cells only infected with NNV. In addition, European sea bass (Dicentrarchus labrax) juveniles were intraperitoneally injected with the same NPs and then challenged with NNV. Our results indicated that NPs increased the viral replication and clinical signs under which the fish died although the cumulate mortality was unaltered. Again, exposure to NPs produced a lowered inflammatory and antiviral response. Our results highlight that the presence of NPs might impact the infection process of NNV and fish resistance to the disease, posing an additional risk to marine organisms.
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Toubanaki, Dimitra K., Antonia Efstathiou, and Evdokia Karagouni. "Transcriptomic Analysis of Fish Hosts Responses to Nervous Necrosis Virus." Pathogens 11, no. 2 (February 3, 2022): 201. http://dx.doi.org/10.3390/pathogens11020201.

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Nervous necrosis virus (NNV) has been responsible for mass mortalities in the aquaculture industry worldwide, with great economic and environmental impact. The present review aims to summarize the current knowledge of gene expression responses to nervous necrosis virus infection in different fish species based on transcriptomic analysis data. Four electronic databases, including PubMed, Web of Science, and SCOPUS were searched, and more than 500 publications on the subject were identified. Following the application of the appropriate testing, a total of 24 articles proved eligible for this review. NNV infection of different host species, in different developmental stages and tissues, presented in the eligible publications, are described in detail, revealing and highlighting genes and pathways that are most affected by the viral infection. Those transcriptome studies of NNV infected fish are oriented in elucidating the roles of genes/biomarkers for functions of special interest, depending on each study’s specific emphasis. This review presents a first attempt to provide an overview of universal host reaction mechanisms to viral infections, which will provide us with new perspectives to overcome NNV infection to build healthier and sustainable aquaculture systems.
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Sah Putra, Bakhtiar, Paul M. Hick, Evelyn Hall, Richard J. Whittington, Razi Khairul, Evarianti, Nurbariah, and Joy A. Becker. "Prevalence of Infectious Spleen and Kidney Necrosis Virus (ISKNV), Nervous Necrosis Virus (NNV) and Ectoparasites in Juvenile Epinephelus spp. Farmed in Aceh, Indonesia." Pathogens 9, no. 7 (July 16, 2020): 578. http://dx.doi.org/10.3390/pathogens9070578.

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A cross-sectional survey was used to estimate the prevalence of infections with the Infectious spleen and kidney necrosis virus (ISKNV, Megalocytivirus), nervous necrosis virus (NNV, Betanodavirus), and infestations with ectoparasites during the rainy season in juvenile grouper (Epinephelus spp.) farmed in Aceh, Indonesia. The survey was intended to detect aquatic pathogens present at 10% prevalence with 95% confidence, assuming 100% sensitivity and specificity using a sample size of 30 for each diagnostic test. Eight populations of grouper from seven farms were sampled. Additional targeted sampling was conducted for populations experiencing high mortality. Infection with NNV was detected at all farms with seven of the eight populations being positive. The apparent prevalence for NNV ranged from 0% (95% CI: 0–12) to 73% (95% CI: 54–88). All of the fish tested from the targeted samples (Populations 9 and 10) were positive for NNV and all had vacuolation of the brain and retina consistent with viral nervous necrosis (VNN). Coinfections with ISKNV were detected in five populations, with the highest apparent prevalence being 13% (95% CI: 4–31%). Trichodina sp., Cryptocaryon irritans and Gyrodactylus sp. were detected at three farms, with 66% to 100% of fish being infested. Hybrid grouper sourced from a hatchery were 5.4 and 24.9 times more likely to have a NNV infection and a higher parasite load compared to orange-spotted grouper collected from the wild (p < 0.001). This study found that VNN remains a high-impact disease in grouper nurseries in Aceh, Indonesia.
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Du, Hehe, Zhenjie Cao, Zhiru Liu, Guotao Wang, Ying Wu, Xiangyu Du, Caoying Wei, Yun Sun, and Yongcan Zhou. "Cromileptes altivelis microRNA Transcriptome Analysis upon Nervous Necrosis Virus (NNV) Infection and the Effect of cal-miR-155 on Cells Apoptosis and Virus Replication." Viruses 14, no. 10 (October 3, 2022): 2184. http://dx.doi.org/10.3390/v14102184.

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MicroRNAs (miRNAs) could regulate various biological processes. Nervous necrosis virus (NNV) is one of the primary germs of the Humpback grouper (Cromileptes altivelis), a commercial fish of great importance for Asian aquaculture. However, there is limited available information on the host-virus interactions of C. altivelis. miRNAs have been shown to play key roles in the host response to infection by a variety of pathogens. To better understand the regulatory mechanism of miRNAs, we constructed miRNA transcriptomes and identified immune-related miRNAs of C. altivelis spleen in response to NNV infection. Reads from the three libraries were mapped onto the Danio rerio reference genome. As a result, a total of 942 mature miRNAs were determined, with 266 known miRNAs and 676 novel miRNAs. Among them, thirty-two differentially expressed miRNAs (DEmiRs) were identified compared to the PBS control. These DEmiRs were targeted on 895 genes, respectively, by using miRanda v3.3a. Then, 14 DEmiRs were validated by qRT-PCR and showed consistency with those obtained from high-throughput sequencing. In order to study the relationship between viral infection and host miRNA, a cell line from C. altivelis brain (CAB) was used to examine the expressions of five known DEmiRs (miR-132-3p, miR-194a, miR-155, miR-203b-5p, and miR-146) during NNV infection. The results showed that one miRNA, cal-miRNA-155, displayed significantly increased expression in response to the virus infection. Subsequently, it was proved that overexpression of cal-miR-155 enhanced cell apoptosis with or without NNV infection and inhibited virus replication in CAB cells. Oppositely, the cal-miRNA-155 inhibitor markedly suppressed apoptosis in CAB cells. The results of the apoptosis-related genes mRNA expression also showed the regulation of cal-miR-155 on the apoptosis process in CAB cells. These findings verify that miR-155 might exert a function as a pro-apoptotic factor in reply to NNV stimulation in CAB cells and help us further study the molecular mechanisms of the pathogenesis of NNV in C. altivelis.
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Choudhary, Indu, Du Hwang, Hyunkyoung Lee, Won Yoon, Jinho Chae, Chang Han, Seungshic Yum, Changkeun Kang, and Euikyung Kim. "Proteomic Analysis of Novel Components of Nemopilema nomurai Jellyfish Venom: Deciphering the Mode of Action." Toxins 11, no. 3 (March 8, 2019): 153. http://dx.doi.org/10.3390/toxins11030153.

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Nowadays, proliferation of jellyfish has become a severe matter in many coastal areas around the world. Jellyfish Nemopilema nomurai is one of the most perilous organisms and leads to significant deleterious outcomes such as harm to the fishery, damage the coastal equipment, and moreover, its envenomation can be hazardous to the victims. Till now, the components of Nemopilema nomurai venom (NnV) are unknown owing to scant transcriptomics and genomic data. In the current research, we have explored a proteomic approach to identify NnV components and their interrelation with pathological effects caused by the jellyfish sting. Altogether, 150 proteins were identified, comprising toxins and other distinct proteins that are substantial in nematocyst genesis and nematocyte growth by employing two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI/TOF/MS). The identified toxins are phospholipase A2, phospholipase D Li Sic Tox beta IDI, a serine protease, putative Kunitz-type serine protease inhibitor, disintegrin and metalloproteinase, hemolysin, leukotoxin, three finger toxin MALT0044C, allergens, venom prothrombin activator trocarin D, tripeptide Gsp 9.1, and along with other toxin proteins. These toxins are relatively well characterized in the venoms of other poisonous species to induce pathogenesis, hemolysis, inflammation, proteolysis, blood coagulation, cytolysis, hemorrhagic activity, and type 1 hypersensitivity, suggesting that these toxins in NnV can also cause similar deleterious consequences. Our proteomic works indicate that NnV protein profile represents valuable source which leads to better understanding the clinical features of the jellyfish stings. As one of the largest jellyfish in the world, Nemopilema nomurai sting is considered to be harmful to humans due to its potent toxicity. The identification and functional characterization of its venom components have been poorly described and are beyond our knowledge. Here is the first report demonstrating the methodical overview of NnV proteomics research, providing significant information to understand the mechanism of NnV envenomation. Our proteomics findings can provide a platform for novel protein discovery and development of practical ways to deal with jellyfish stings on human beings.
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García-Álvarez, Miguel Ángel, Marta Arizcun, Elena Chaves-Pozo, and Alberto Cuesta. "Profile of Innate Immunity in Gilthead Seabream Larvae Reflects Mortality upon Betanodavirus Reassortant Infection and Replication." International Journal of Molecular Sciences 23, no. 9 (May 3, 2022): 5092. http://dx.doi.org/10.3390/ijms23095092.

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Historically, gilthead seabream (Sparus aurata) has been considered a fish species resistant to nervous necrosis virus (NNV) disease. Nevertheless, mortality in seabream hatcheries, associated with typical clinical signs of the viral encephalopathy and retinopathy (VER) disease has been confirmed to be caused by RGNNV/SJNNV reassortants. Because of this, seabream larvae at 37 and 86 days post-hatching (dph) were infected by immersion with RGNNV/SJNNV and SJNNV/RGNNV reassortants under laboratory conditions, and mortality, viral replication and immunity were evaluated. Our results show that gilthead seabream larvae, mainly those at 37 dph, are susceptible to infection with both NNV reassortant genotypes, with the highest impact from the RGNNV/SJNNV reassortant. In addition, viral replication occurs at both ages (37 and 86 dph) but the recovery of infective particles was only confirmed in 37 dph larvae,; this value was also highest with the RGNNV/SJNNV reassortant. Larvae immunity, including the expression of antiviral, inflammatory and cell-mediated cytotoxicity genes, was affected by NNV infection. Levels of the natural killer lysin (Nkl) peptide were increased in SJNNV/RGNNV-infected larvae of 37 dph, though hepcidin was not. Our results demonstrate that the seabream larvae are susceptible to both NNV reassortants, though mainly to RGNNV/SJNNV, in an age-dependent manner.
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Chen, Yuan-Yu, Chih-Lu Wu, Chia-Wei Hsu, Chih-Hui Wang, Chung-Rui Su, Chun-Jen Huang, Hau-Ren Chen, Lai-Kwan Chau, and Shau-Chun Wang. "Trace Determination of Grouper Nervous Necrosis Virus in Contaminated Larvae and Pond Water Samples Using Label-Free Fiber Optic Nanoplasmonic Biosensor." Biosensors 12, no. 10 (October 21, 2022): 907. http://dx.doi.org/10.3390/bios12100907.

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We developed a fast (<20 min), label-free fiber optic particle plasmon resonance (FOPPR) immunosensing method to detect nervous necrosis virus (NNV), which often infects high-value economic aquatic species, such as grouper. Using spiked NNV particles in a phosphate buffer as samples, the standard calibration curve obtained was linear (R2 = 0.99) and the limit of detection (LOD) achieved was 2.75 × 104 TCID50/mL, which is superior to that obtained using enzyme-linked immunosorbent assay (ELISA). By using an enhancement method called fiber optic nanogold-linked immunosorbent assay (FONLISA), the LOD can be further improved to <1 TCID50/mL, which is comparable to that found by the conventional qPCR method. Employing the larvae homogenate samples of NNV-infected grouper, the results obtained by the FOPPR biosensor agree with those obtained by the quantitative polymerase chain reaction (qPCR) method. We also examined pond water samples from an infected container in an indoor aquaculture facility. The lowest detectable level of NNV coat protein was found to be 0.17 μg/mL, which is one order lower than the LOD reported by ELISA. Therefore, we demonstrated the potential of the FOPPR biosensor as an outbreak surveillance tool, which is able to give warning indication even when the trend of larvae death toll increment is still not clear.
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Bandín, Isabel, and Sandra Souto. "Betanodavirus and VER Disease: A 30-year Research Review." Pathogens 9, no. 2 (February 9, 2020): 106. http://dx.doi.org/10.3390/pathogens9020106.

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The outbreaks of viral encephalopathy and retinopathy (VER), caused by nervous necrosis virus (NNV), represent one of the main infectious threats for marine aquaculture worldwide. Since the first description of the disease at the end of the 1980s, a considerable amount of research has gone into understanding the mechanisms involved in fish infection, developing reliable diagnostic methods, and control measures, and several comprehensive reviews have been published to date. This review focuses on host–virus interaction and epidemiological aspects, comprising viral distribution and transmission as well as the continuously increasing host range (177 susceptible marine species and epizootic outbreaks reported in 62 of them), with special emphasis on genotypes and the effect of global warming on NNV infection, but also including the latest findings in the NNV life cycle and virulence as well as diagnostic methods and VER disease control.
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Okapuu, Julie M., Estelle Chétrit, Brigitte Lefebvre, and Caroline Quach. "How Many Individuals with Asthma Need to Be Vaccinated to Prevent One Case of Invasive Pneumococcal Disease?" Canadian Journal of Infectious Diseases and Medical Microbiology 25, no. 3 (2014): 147–50. http://dx.doi.org/10.1155/2014/510373.

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BACKGROUND: The American Advisory Committee on Immunization Practices recommended the inclusion of adults with asthma in the high-risk category for pneumococcal vaccination based on a twofold increase in risk of invasive pneumococcal disease (IPD).OBJECTIVE: To determine whether, among individuals with asthma, the number needed to vaccinate (NNV) using pneumococcal conjugate vaccine (PCV)-13 or 23-valent pneumococcal polysaccharide vaccine (PPV-23) warrants its addition to the high-risk category for pneumococcal vaccination in Canada.METHODS: Using IPD incidence (per 10,000 individuals) figures from published articles (4.2 in high-risk asthmatics, 2.3 in low-risk asthmatics and 1.2 in healthy individuals), the NNV to prevent one case of IPD in asthmatics five to 17 years of age and 18 to 50 years of age was calculated, factoring in the proportion of pneumococcal serotypes included in vaccines (based on data from Quebec) and accounting for the possibility of waning vaccine efficacy (VE) using four scenarios.RESULTS: Assuming a VE of 65% for PCV-13 in asthmatics, the NNV would be 704 to 820 in low-risk and 386 to 449 in high-risk children; and 355 to 1532 in low-risk and 195 to 839 in high-risk adults (range depends on waning scenario). Assuming a VE of 65% for PPV-23 in asthmatics, the NNV would be 581 to 677 in low-risk and 318 to 371 in high-risk children; and 246 to 1059 in low-risk and 135 to 580 in high-risk adults.CONCLUSION: The NNV with both PCV-13 and PPV-23 in asthmatic children and adults is comparable with that of other high-risk conditions such as age ≥65 years. Therefore, the addition of asthma to the list of high-risk conditions for pneumococcal vaccination is warranted.
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Kolakofsky, Daniel, Laurent Roux, Dominique Garcin, and Rob W. H. Ruigrok. "Paramyxovirus mRNA editing, the ‘rule of six’ and error catastrophe: a hypothesis." Journal of General Virology 86, no. 7 (July 1, 2005): 1869–77. http://dx.doi.org/10.1099/vir.0.80986-0.

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The order Mononegavirales includes three virus families that replicate in the cytoplasm: the Paramyxoviridae, composed of two subfamilies, the Paramyxovirinae and Pneumovirinae, the Rhabdoviridae and the Filoviridae. These viruses, also called non-segmented negative-strand RNA viruses (NNV), contain five to ten tandemly linked genes, which are separated by conserved junctional sequences that act as mRNA start and poly(A)/stop sites. For the NNV, downstream mRNA synthesis depends on termination of the upstream mRNA, and all NNV RNA-dependent RNA polymerases reiteratively copy (‘stutter’ on) a short run of template uridylates during transcription to polyadenylate and terminate their mRNAs. The RNA-dependent RNA polymerase of a subset of the NNV, all members of the Paramyxovirinae, also stutter in a very controlled fashion to edit their phosphoprotein gene mRNA, and Ebola virus, a filovirus, carries out a related process on its glycoprotein mRNA. Remarkably, all viruses that edit their phosphoprotein mRNA are also governed by the ‘rule of six’, i.e. their genomes must be of polyhexameric length (6n+0) to replicate efficiently. Why these two seemingly unrelated processes are so tightly linked in the Paramyxovirinae has been an enigma. This paper will review what is presently known about these two processes that are unique to viruses of this subfamily, and will discuss whether this enigmatic linkage could be due to the phenomenon of RNA virus error catastrophe.
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Gye, Hyun Jung, Myung-Joo Oh, and Toyohiko Nishizawa. "Lack of nervous necrosis virus (NNV) neutralizing antibodies in convalescent sevenband grouper Hyporthodus septemfasciatus after NNV infection." Vaccine 36, no. 14 (March 2018): 1863–70. http://dx.doi.org/10.1016/j.vaccine.2018.02.063.

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Hynes, D., B. Edwards, D. Mann, S. Landry, S. Joosten, and G. Hamilton. "O008 The effect of flow limited breathing and endotypes on night to night variability of sleep apnoea severity." SLEEP Advances 3, Supplement_1 (October 1, 2022): A4. http://dx.doi.org/10.1093/sleepadvances/zpac029.007.

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Abstract Background Obstructive sleep apnoea (OSA) is a condition involving repetitive collapse of the upper airway during sleep. The diagnosis and characterisation of OSA is based primarily off the apnoea-hypopnoea index (AHI) in a single-night sleep study. Recent data have demonstrated night to night variability (NNV) in OSA severity. Knowledge of which patients have more variable OSA would improve long-term risk stratification and management. However, patient and polysomnographic characteristics associated with high NNV have not been completely explored. This study aims to determine whether the pattern of flow limited breathing (FLB) and underlying endotypes of patients with OSA are predictive of those with high NNV in OSA severity. Methods 71 patients with OSA were identified from the placebo arm of randomized controlled trials testing novel OSA interventions. Each patient had undergone two sleep studies. Patient characteristics, medical history and data from both sleep studies were accessed. Sleep data were processed using established algorithms to quantify the degree of FLB as well as OSA endotypes. Differences between each night were analysed for agreement, and for change in the severity of OSA. Progress to date Ethics approval has been obtained and data has been processed for statistical analysis. Intended outcome and impact It is expected that NNV will be high in those with mild to moderate OSA, and the pattern of FLB and endotypes across multiple nights will help predict those with more variable compared to stable disease.
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Hwang, Du Hyeon, Phil-Ok Koh, Ramachandran Loganathan Mohan Prakash, Jinho Chae, Changkeun Kang, and Euikyung Kim. "Comparative Study of Toxic Effects and Pathophysiology of Envenomations Induced by Carybdea brevipedalia (Cnidaria: Cubozoa) and Nemopilema nomurai (Cnidaria: Scyphozoa) Jellyfish Venoms." Toxins 14, no. 12 (November 28, 2022): 831. http://dx.doi.org/10.3390/toxins14120831.

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Jellyfish stings can result in local tissue damage and systemic pathophysiological sequelae. Despite constant occurrences of jellyfish stings in oceans throughout the world, the toxinological assessment of these jellyfish envenomations has not been adequately reported in quantitative as well as in qualitative measurements. Herein, we have examined and compared the in vivo toxic effects and pathophysiologic alterations using experimental animal models for two representative stinging jellyfish classes, i.e., Cubozoa and Scyphozoa. For this study, mice were administered with venom extracts of either Carybdea brevipedalia (Cnidaria: Cubozoa) or Nemopilema nomurai (Cnidaria: Scyphozoa). From the intraperitoneal (IP) administration study, the median lethal doses leading to the deaths of mice 24 h post-treatment after (LD50) for C. brevipedalia venom (CbV) and N. nomurai venom (NnV) were 0.905 and 4.4697 mg/kg, respectively. The acute toxicity (i.e., lethality) of CbV was much higher with a significantly accelerated time to death value compared with those of NnV. The edematogenic activity induced by CbV was considerably (83.57/25 = 3.343-fold) greater than NnV. For the evaluation of their dermal toxicities, the epidermis, dermis, subcutaneous tissues, and skeletal muscles were evaluated toxinologically/histopathologically following the intradermal administration of the venoms. The minimal hemorrhagic doses (MHD) of the venoms were found to be 55.6 and 83.4 μg/mouse for CbV and NnV, respectively. Furthermore, the CbV injection resulted in extensive alterations of mouse dermal tissues, including severe edema, and hemorrhagic/necrotic lesions, with the minimum necrotizing dose (MND) of 95.42 µg/kg body weight. The skin damaging effects of CbV appeared to be considerably greater, compared with those of NnV (MND = 177.99 µg/kg). The present results indicate that the toxicities and pathophysiologic effects of jellyfish venom extracts may vary from species to species. As predicted from the previous reports on these jellyfish envenomations, the crude venom extracts of C. brevipedalia exhibit much more potent toxicity than that of N. nomurai in the present study. These observations may contribute to our understanding of the toxicities of jellyfish venoms, as well as their mode of toxinological actions, which might be helpful for establishing the therapeutic strategies of jellyfish stings.
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Valero, Yulema, Carmen López-Vázquez, Sandra Souto, José G. Olveira, Alberto Cuesta, and Isabel Bandín. "Differential Nervous Necrosis Virus (NNV) Replication in Five Putative Susceptible Cell Lines." Pathogens 10, no. 12 (November 30, 2021): 1565. http://dx.doi.org/10.3390/pathogens10121565.

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Viral encephalopathy and retinopathy caused by nervous necrosis virus (NNV), is one of the most threatening viral diseases affecting marine fish worldwide. In vitro propagation of NNV strains is essential for the design of effective control measures. In the present study we analysed both the susceptibility and the permissiveness of five fish cell lines (E-11, GF-1, SAF-1, DLB-1, and SaB-1) to three NNV strains (one RGNNV, one SJNNV, and one reassortant RGNNV/SJNNV). E-11 and DLB-1 were demonstrated to be highly susceptible to NNV strains, with average adsorption efficiency (AE) values higher than 90%. SAF-1 also showed high susceptibility (AE 88%), whereas GF-1 can be regarded as moderately susceptible (AE around 50%). On the contrary, SaB-1 can be considered a poorly susceptible cell line (AE values below 20%). E-11 and GF-1 cell lines provided the highest production rates for RGNNV and RG/SJ (around 103) and both cell lines can be regarded as fully permissive for these viral types. However, the SJNNV production rate in GF-1 was only 17.8 and therefore this cell line should be considered semi-permissive for this genotype. In SAF-1 cells, moderate viral replication was recorded but differences in intracellular and extracellular production suggest that viral progeny was not efficiently released. In DLB-1 and SaB-1 the final viral titres obtained in E-11 were lower than those of the inoculum. However, RNA1 synthesis values seem to indicate that RGNNV replication in DLB-1 and SAF-1 could have been underestimated, probably due to a poor adaptation of the virus grown in these cell lines to E-11. Based on all these results, E-11 seems to be the most appropriate cell for in vitro culture of RGNNV, SJNNV, and reassortant strains.
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Zhang, Yuqi, Fujing Dong, Jing Xing, Xiaoqian Tang, Xiuzhen Sheng, Heng Chi, and Wenbin Zhan. "Characterization of Nervous Necrosis Virus (NNV) Nonstructural Protein B2 and Its Enhancement on Virus Proliferation." Viruses 14, no. 12 (December 17, 2022): 2818. http://dx.doi.org/10.3390/v14122818.

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The nerve necrosis virus (NNV), a pathogen of viral nervous necrosis disease in several important mariculture economic fish species, causes economic loss. Its nonstructural protein B2 encoded by the sub-genomic RNA3 affects the amplification of the virus. In this study, the B2 protein was recombinantly expressed, the polyclonal antibodies were produced and the dynamics of the B2 protein and genomes were measured in vivo and in vitro after NNV infection. Then, the effects of the overexpressed B2 protein on virus proliferation were investigated. The results showed that the polyclonal antibodies can recognize the B2 protein in both SSN-1 cells and the brain/eye of the grouper. The RNA3 expression significantly increased at 12 h and kept rising till the end of the experiment; it was 106.9 copies/μL at 120 h. The B2 protein could be first detected at 3 h post-infection, which was earlier than the capsid protein was first detected (12 h post-infection). The B2 protein can be detected in the brain, eye and heart on day 3 and the copy number of genomes reached a maximum at 6 d post-infection. There was a low expression of NNV genomes in the liver, spleen and kidney, and no virus was detected in the gill, stomach and intestine. In the meantime, the B2 protein was successfully expressed in GF-1 cells and significantly enhanced virus proliferation, which produced an earlier cytopathic effect and higher cell death rates after 3 d post-infection than the control. In conclusion, the B2 protein acts as an early expressed protein during virus replication and proliferation and is involved in the early infection of NNV. The results may provide insight into the early stage of virus infection and prevention of the disease.
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Lin, Tianwen, Jing Xing, Xiaoqian Tang, Xiuzhen Sheng, Heng Chi, and Wenbin Zhan. "Development and Evaluation of a Bicistronic DNA Vaccine against Nervous Necrosis Virus in Pearl Gentian Grouper (Epinephelus lanceolatus × Epinephelus fuscoguttatus)." Vaccines 10, no. 6 (June 14, 2022): 946. http://dx.doi.org/10.3390/vaccines10060946.

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Nervous necrosis virus (NNV) can cause enormous economic losses in mariculture. Vaccines are promising ways to control the disease. In this study: the interferon regulatory factor 3 (IRF3) gene of pearl gentian grouper was cloned and functionally analyzed; then a bicistronic DNA vaccine encoding both capsid protein (CP) and IRF3 was constructed; then the cellular, humoral, and local immune responses in the grouper after immunization were investigated; and then the protective effects after the NNV challenge were investigated. The results showed that the vaccine successfully expressed CP and IRF3. After immunization, the lymphocytes were recruited at the injection site in the muscles. The percentage of sIgM+ lymphocytes in the head, kidney, and spleen significantly increased and peaked at 28.8 ± 3.1% and 42.6 ± 4.2% at the 3rd to 4th weeks. Six immune-related genes were significantly up-regulated. In the meantime, the total antibodies, anti-NNV specific antibodies, and neutralizing antibody titers in serum increased. After the challenge with 105, 106 or 107 TCID50/fish, the relative percent survival rate was 81.25%, 73.91%, and 66.67%, respectively. In 106 TCID50/fish groups, the percentages of sIgM+ lymphocytes, antibodies, and the viral load were investigated. In conclusion, the bicistronic vaccine significantly induced humoral and cellular responses in pearl gentian grouper and provided effective protection against NVV infection.
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Islam, Sk Injamamul, Saloa Saloa, Sarower Mahfuj, Md Jakiul Islam, and Moslema Jahan Mou. "Computer-aided drug design of Azadirachta indica compounds against nervous necrosis virus by targeting grouper heat shock cognate protein 70 (GHSC70): quantum mechanics calculations and molecular dynamic simulation approaches." Genomics & Informatics 20, no. 3 (September 30, 2022): e33. http://dx.doi.org/10.5808/gi.21063.

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Nervous necrosis virus (NNV) is a deadly infectious disease that affects several fish species. It has been found that the NNV utilizes grouper heat shock cognate protein 70 (GHSC70) to enter the host cell. Thus, blocking the virus entry by targeting the responsible protein can protect the fishes from disease. The main objective of the study was to evaluate the inhibitory potentiality of 70 compounds of Azadirachta indica (Neem plant) which has been reported to show potential antiviral activity against various pathogens, but activity against the NNV has not yet been reported. The binding affinity of 70 compounds was calculated against the GHSC70 with the docking and molecular dynamics (MD) simulation approaches. Both the docking and MD methods predict 4 (PubChem CID: 14492795, 10134, 5280863, and 11119228) inhibitory compounds that bind strongly with the GHSC70 protein with a binding affinity of –9.7, –9.5, –9.1, and –9.0 kcal/mol, respectively. Also, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the compounds confirmed the drug-likeness properties. As a result of the investigation, it may be inferred that Neem plant compounds may act as significant inhibitors of viral entry into the host cell. More in-vitro testing is needed to establish their effectiveness.
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Gerlier, Laetitia, Judith Hackett, Richard Lawson, Sofia Dos Santos Mendes, and Martin Eichner. "Translation of the UK Pediatric Influenza Vaccination Programme in Primary Schools to 13 European Countries Using a Dynamic Transmission Model." Journal of Health Economics and Outcomes Research 5, no. 1 (August 18, 2017): 109–24. http://dx.doi.org/10.36469/9802.

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Objectives: To simulate the impact of a pediatric influenza vaccination programme using quadrivalent live attenuated influenza vaccine (QLAIV) in Europe by applying coverage rates achieved in the United Kingdom during the 2014–2015 season and to compare the model outcomes to the UK results. Methods: We used a deterministic, age-structured, dynamic transmission model adapted to the demography, contact patterns and influenza incidence of 13 European countries, with a 10-year horizon. The reference strategy was the unchanged country-specific coverage rate, using quadrivalent inactivated vaccine (assumed efficacy against infection from 45% in 1-year-old children to 60% in healthy adults). In the evaluated strategy, 56.8% of 5–10-year-old children were additionally vaccinated with QLAIV (assumed efficacy 80%), as was the case in 2014–2015 in the United Kingdom’s primary school pilot areas. Symptomatic influenza cases and associated medical resources (primary care consultations [PCC], hospitalization, intensive care unit [ICU] admissions) were calculated. The evaluated versus reference strategies were compared using odds ratios (ORs) for PCC in the target (aged 5–10-years) and non-target adult (aged &gt;17 years) populations as well as number needed to vaccinate (NNV) with QLAIV to avert one PCC, hospitalization or ICU admission. Model outcomes, averaged over 10 seasons, were compared with published real-life data from the United Kingdom for the 2014–2015 season. Results: Over 13 countries and 10 years, the evaluated strategy prevented 32.8 million of symptomatic influenza cases (172.3 vs 205.2 million). The resulting range of ORs for PCC was 0.18–0.48 among children aged 5–10-years, and the published OR in the United Kingdom was 0.06 (95% confidence interval [0.01; 0.62]). In adults, the range of ORs for PCC was 0.60–0.91 (UK OR=0.41 [0.19; 0.86]). NNV ranges were 6–19 per averted PCC (UK NNV=16), 530–1524 per averted hospitalization (UK NNV=317) and 5298–15 241 per averted ICU admission (UK NNV=2205). Conclusions: Across a range of European countries, our model shows the beneficial direct and indirect impact of a paediatric vaccination programme using QLAIV in primary school-aged children, consistent with what was observed during a single season in the United Kingdom. Recommendations for the implementation of pediatric vaccination programmes are, therefore, supported in Europe.
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Olveira, José G., Sandra Souto, Isabel Bandín, and Carlos P. Dopazo. "Development and Validation of a SYBR Green Real Time PCR Protocol for Detection and Quantification of Nervous Necrosis Virus (NNV) Using Different Standards." Animals 11, no. 4 (April 12, 2021): 1100. http://dx.doi.org/10.3390/ani11041100.

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The nervous necrosis virus (NNV) is a threat to fish aquaculture worldwide, especially in Mediterranean countries. Fast and accurate diagnosis is essential to control it, and viral quantification is required to predict the level of risk of new viral detections in field samples. For both, reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) is used by diagnostic laboratories. In the present study, we developed an RT-qPCR procedure for the diagnosis and simultaneous quantification of NNV isolates from any of the four genotypes. The method proved to be highly sensitive in terms of crude virus titer: 5.56–9.88 TCID50/mL (tissue culture infectious dose per mL), depending on the viral strain, and averaging 8.8 TCID50/mL or 0.08 TCID50/reaction. Other standards also yielded very low detection limits: 16.3 genome copies (cps) of purified virus per mL, 2.36 plasmid cps/mL, 7.86 in vitro synthetized RNA cps/mL, and 3.16 TCID50/mL of virus from infected tissues. The diagnostic parameters evaluated in fish samples were much higher in comparison to cell culture isolation and nested PCR. In addition, the high repeatability and reproducibility of the procedure, as well as the high coefficient of determination (R2) of all the calibration curves with any type of standard tested, ensure the high reliability of the quantification of NNV using this RT-qPCR procedure, regardless of the viral type detected and from the type of standard chosen.
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Lampert, Yael, Ran Berzak, Nadav Davidovich, Arik Diamant, Nir Stern, Aviad P. Scheinin, Dan Tchernov, and Danny Morick. "Indigenous versus Lessepsian Hosts: Nervous Necrosis Virus (NNV) in Eastern Mediterranean Sea Fish." Viruses 12, no. 4 (April 10, 2020): 430. http://dx.doi.org/10.3390/v12040430.

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Viruses are among the most abundant and diverse biological components in the marine environment. In finfish, viruses are key drivers of host diversity and population dynamics, and therefore, their effect on the marine environment is far-reaching. Viral encephalopathy and retinopathy (VER) is a disease caused by the marine nervous necrosis virus (NNV), which is recognized as one of the main infectious threats for marine aquaculture worldwide. For over 140 years, the Suez Canal has acted as a conduit for the invasion of Red Sea marine species into the Mediterranean Sea. In 2016–2017, we evaluated the prevalence of NNV in two indigenous Mediterranean species, the round sardinella (Sardinella aurita) and the white steenbras (Lithognathus mormyrus) versus two Lessepsian species, the Randall’s threadfin bream (Nemipterus randalli) and the Lessepsian lizardfish (Saurida lessepsianus). A molecular method was used to detect NNV in all four fish species tested. In N. randalli, a relatively newly established invasive species in the Mediterranean Sea, the prevalence was significantly higher than in both indigenous species. In S. lessepsianus, prevalence varied considerably between years. While the factors that influence the effective establishment of invasive species are poorly understood, we suggest that the susceptibility of a given invasive fish species to locally acquired viral pathogens such as NVV may be important, in terms of both its successful establishment in its newly adopted environment and its role as a reservoir ‘host’ in the new area.
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36

Lempert, Henrietta. "The effect of animacy on children's noun order in verb-final sequences." Journal of Child Language 15, no. 3 (October 1988): 551–66. http://dx.doi.org/10.1017/s0305000900012563.

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ABSTRACTThis study examined whether pragmatic ordering factors account for the apparent preference for ANIMATE-INANIMATE (AI) order in passive and active sentences. If so, learning noun order relations in NNV sequences with an INANIMATE PATIENT + ANIMATE AGENT (It's the drum the boy plays) should be more difficult than with an ANIMATE PATIENT + ANIMATE AGENT (It's the girl the boy chases). Seventy children aged 3;0 to 5;3 were trained with either AAV or IAV exemplars, and then tested for their noun order in NNV utterances when describing animate agent + animate patient and animate agent + inanimate patient pictures. As judged by post-training performance, AAV and AIV training had comparable effects at age three, but IAV resulted in better learning at ages four and five. It was argued that the latter benefited from the correlation between animacy and subject in English sentences.
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37

Sousa, Caio Victor, Austin Fernandez, Jungyun Hwang, and Amy Shirong Lu. "The Effect of Narrative on Physical Activity via Immersion During Active Video Game Play in Children: Mediation Analysis." Journal of Medical Internet Research 22, no. 3 (March 31, 2020): e17994. http://dx.doi.org/10.2196/17994.

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Background Active video games (AVGs) can increase physical activity (PA) and help produce higher physiological expenditure. Animated narrative videos (NVs) possess unique immersive and motivational properties. When added to AVGs, they have been found to increase moderate-to-vigorous physical activity (MVPA) as opposed to the original no video condition. However, there is no evidence of whether that was due to the NV or the addition of an animated video to an AVG. Objective This study aimed to investigate the differential effect of adding an NV versus a nonnarrative video (NNV) to an AVG on PA parameters and physiological responses and to explore the mediating role of immersion. Methods A total of 22 children aged 8 to 12 years were randomly assigned to the NV or NNV condition. They were instructed to play an AVG (on Xbox Kinect) for as long as they wanted. We used accelerometers to estimate the time spent (in minutes) in MVPA. Heart rate (HR) and rate of perceived exertion (RPE) were measured before, during, and after the AVG play session. The participants then reported their experience of narrative immersion via a questionnaire. Results The NV group had significantly higher narrative immersion (mean 3.50, SD 0.55 vs mean 2.91, SD 0.59; P=.03) and MVPA (mean 19.46, SD 13.31 vs mean 7.85, SD 5.83; P=.02) than the NNV group. Narrative immersion was positively correlated with MVPA (r=0.52; P=.01) and average HR during AVG (r=0.43; P=.05). Mediation analysis indicated that narrative immersion mediated the effect of NV (NV vs NNV) on MVPA (direct effect: beta=7.51; P=.01). The indirect effect was that NV was positively correlated with the mediator variable narrative immersion (beta=.59; P=.03), which was itself marginally associated with MVPA (beta=6.95; P=.09); when narrative immersion was included in the model, the regression coefficient was attenuated. Conclusions AVG with added narratives elicits more narrative immersion, resulting in more minutes in MVPA. Narrative immersion served as a mediator between NV and MVPA via its elicitation of an elevated HR without increasing RPE. The inclusion of immersive narratives in AVG could be helpful for inducing MVPA, to enhance AVG engagement without additional exertion.
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Wang, Qing, Cheng Peng, Min Yang, Fengqi Huang, Xuzhuo Duan, Shaowen Wang, Huitao Cheng, Huirong Yang, Huihong Zhao, and Qiwei Qin. "Single-cell RNA-seq landscape midbrain cell responses to red spotted grouper nervous necrosis virus infection." PLOS Pathogens 17, no. 6 (June 29, 2021): e1009665. http://dx.doi.org/10.1371/journal.ppat.1009665.

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Viral nervous necrosis (VNN) is an acute and serious fish disease caused by nervous necrosis virus (NNV) which has been reported massive mortality in more than fifty teleost species worldwide. VNN causes damage of necrosis and vacuolation to central nervous system (CNS) cells in fish. It is difficult to identify the specific type of cell targeted by NNV, and to decipher the host immune response because of the functional diversity and highly complex anatomical and cellular composition of the CNS. In this study, we found that the red spotted grouper NNV (RGNNV) mainly attacked the midbrain of orange-spotted grouper (Epinephelus coioides). We conducted single-cell RNA-seq analysis of the midbrain of healthy and RGNNV-infected fish and identified 35 transcriptionally distinct cell subtypes, including 28 neuronal and 7 non-neuronal cell types. An evaluation of the subpopulations of immune cells revealed that macrophages were enriched in RGNNV-infected fish, and the transcriptional profiles of macrophages indicated an acute cytokine and inflammatory response. Unsupervised pseudotime analysis of immune cells showed that microglia transformed into M1-type activated macrophages to produce cytokines to reduce the damage to nerve tissue caused by the virus. We also found that RGNNV targeted neuronal cell types was GLU1 and GLU3, and we found that the key genes and pathways by which causes cell cytoplasmic vacuoles and autophagy significant enrichment, this may be the major route viruses cause cell death. These data provided a comprehensive transcriptional perspective of the grouper midbrain and the basis for further research on how viruses infect the teleost CNS.
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Lei, Yingying, Yu Xiong, Dagang Tao, Tao Wang, Tianlun Chen, Xufei Du, Gang Cao, Jiagang Tu, and Jinxia Dai. "Construction of Attenuated Strains for Red-Spotted Grouper Nervous Necrosis Virus (RGNNV) via Reverse Genetic System." Viruses 14, no. 8 (August 6, 2022): 1737. http://dx.doi.org/10.3390/v14081737.

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The nervous necrosis virus (NNV) mainly attacks the central nervous system of fish to cause viral nervous necrosis, which is an acute and serious prevalent disease in fish. Among different genotypes of NNV, red-spotted grouper nervous necrosis virus (RGNNV) is the most widely reported, with the highest number of susceptible species. To better understand the pathogenicity of RGNNV, we first developed a reverse genetic system for recombinant RGNNV rescue using B7GG and striped snakehead (SSN-1) cells. Furthermore, we constructed attenuated RGNNV strains rRGNNV-B2-M1 and rRGNNV-B2-M2 with the loss of B2 protein expression, which grew slower and induced less Mx1 expression than that of wild-type RGNNV. Moreover, rRGNNV-B2-M1 and rRGNNV-B2-M2 were less virulent than the wild-type RGNNV. Our study provides a potential tool for further research on the viral protein function, virulence pathogenesis, and vaccine development of RGNNV, which is also a template for the rescue of other fish viruses.
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40

Sasaki, Yoshinori. "Material and presentation condition effects on sentence interpretation task performance: methodological examinations of the competition experiment." Second Language Research 13, no. 1 (January 1997): 66–91. http://dx.doi.org/10.1191/026765897666381479.

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Ten native English learners of Japanese, ten intermediate native English learners of Japanese and ten native Japanese speakers of English each were requested to report what they thought was the subject or actor of a series of English NVN word strings, in which case marking and lexical-semantics cues were systematically manipulated. These NVN strings were aurally presented first alone, and subsequently the same strings were presented for the second time together with noncanonical NNV and VNN strings. Similarly, their counterpart Japanese NNV strings were first presented alone, and secondly with noncanonical VNN and NVN strings. The results revealed that 1) a greater animacy effect (‘animacy noun as a subject’ bias) was detected when the sentence verb was see rather than eat(or each of their Japanese counterparts); 2) English accusative pronouns generally created greater case biases than nominative ones; and 3) native English speakers interpreting Japanese word strings responded differently under the two presentation conditions.
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López-Vázquez, Carmen, Sandra Souto, José G. Olveira, Ana Riaza, Óscar González, Cristina Brea, Alejandro M. Labella, Dolores Castro, and Isabel Bandín. "Nervous Necrosis Virus (NNV) Booster Vaccination Increases Senegalese Sole Survival and Enhances Immunoprotection." Animals 13, no. 1 (December 23, 2022): 51. http://dx.doi.org/10.3390/ani13010051.

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A re-immunization programme has been tested to improve the protective response elicited in sole by a previously developed BEI-inactivated betanodavirus vaccine. The vaccine was prepared using a reassortant RGNNV/SJNNV strain which is highly pathogenic for sole, and vaccination assays were performed by intraperitoneal injection. Experimental design included a prime- and a booster-vaccination group, which consisted of individuals that received a second vaccine injection at 30 days post vaccination), and their respective controls. A month after prime/booster vaccination, fish were challenged by intramuscular injection with the homologous NNV strain. Samples were collected at different times post vaccination and post challenge to assess the immune response and viral replication. Booster dose enhanced the protection against NNV infection because a significant increase in survival was recorded when compared with prime-vaccinated individuals (relative percent survival 77 vs. 55). In addition, a clear decrease in viral replication in the brain of challenged sole was observed. During the immune induction period, no differences in IgM production were observed between prime- and booster-vaccinated fish, and the expression of the antigen presenting cells (APC)-related molecule MHC class II antigen was the only differential stimulation recorded in the re-immunized individuals. However, a significant upregulation of mhcII and the lymphocytes T helper (Th) marker cd4 was observed after the challenge in the booster-vaccinated group, suggesting these cells play a role in the protection conferred by the booster injection. In addition, after viral infection, re-immunized fish showed specific and neutralizing antibody production and overexpression of other immune-related genes putatively involved in the control of NNV replication.
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Evain, Mikael, Philippe Schnürle, Angélique Leprêtre, Fanny Verrier, Louise Watremez, Joseph Offei Thompson, Philippe de Clarens, Daniel Aslanian, and Maryline Moulin. "Crustal structure of the East African Limpopo margin, a strike-slip rifted corridor along the continental Mozambique Coastal Plain and North Natal Valley." Solid Earth 12, no. 8 (August 20, 2021): 1865–97. http://dx.doi.org/10.5194/se-12-1865-2021.

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Abstract. Coincident wide-angle and multi-channel seismic data acquired within the scope of the PAMELA Moz3-5 project allow us to reconsider the formation mechanism of East African margins offshore of southern Mozambique. This study specifically focuses on the sedimentary and deep-crustal architecture of the Limpopo margin (LM) that fringes the eastern edge of the Mozambique’s Coastal Plain (MCP) and its offshore southern prolongation the North Natal Valley (NNV). It relies primarily on the MZ3 profile that runs obliquely from the northeastern NNV towards the Mozambique basin (MB) with additional inputs from a tectonostratigraphy analysis of industrial onshore–offshore seismic lines and nearby or crossing velocity models from companion studies. Over its entire N–S extension the LM appears segmented into (1) a western domain that shows the progressive eastward crustal thinning and termination of the MCP/NNV continental crust and its overlying pre-Neocomian volcano-sedimentary basement and (2) a central corridor of anomalous crust bounded to the east by the Mozambique fracture zone (MFZ) and the oceanic crust of the MB. A prominent basement high marks the boundary between these two domains. Its development was most probably controlled by a steep and deeply rooted fault, i.e., the Limpopo fault. We infer that strike-slip or slightly transtensional rifting occurred along the LM and was accommodated along this Limpopo fault. At depth we propose that ductile shearing was responsible for the thinning of the continental crust and an oceanward flow of lower crustal material. This process was accompanied by intense magmatism that extruded to form the volcanic basement and gave the corridor its peculiar structure and mixed nature. The whole region remained at a relative high level during the rifting period and a shallow marine environment dominated the pre-Neocomian period during the early phase of continent–ocean interaction. It is only some time after break-up in the MB and the initiation of the MFZ that decoupling occurred between the MCP/NNV and the corridor, allowing for the latter to subside and become covered by deep marine sediments. A scenario for the early evolution and formation of the LM is proposed taking into account both recent kinematic and geological constraints. It implies that no or little change in extensional direction occurred between the intra-continental rifting and subsequent phase of continent–ocean interaction.
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Choudhary, Indu, Duhyeon Hwang, Jinho Chae, Wonduk Yoon, Changkeun Kang, and Euikyung Kim. "Proteomic Changes during the Dermal Toxicity Induced by Nemopilema nomurai Jellyfish Venom in HaCaT Human Keratinocyte." Toxins 13, no. 5 (April 27, 2021): 311. http://dx.doi.org/10.3390/toxins13050311.

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Jellyfish venom is well known for its local skin toxicities and various lethal accidents. The main symptoms of local jellyfish envenomation include skin lesions, burning, prickling, stinging pain, red, brown, or purplish tracks on the skin, itching, and swelling, leading to dermonecrosis and scar formation. However, the molecular mechanism behind the action of jellyfish venom on human skin cells is rarely understood. In the present study, we have treated the human HaCaT keratinocyte with Nemopilema nomurai jellyfish venom (NnV) to study detailed mechanisms of actions behind the skin symptoms after jellyfish envenomation. Using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF/MS), cellular changes at proteome level were examined. The treatment of NnV resulted in the decrease of HaCaT cell viability in a concentration-dependent manner. Using NnV (at IC50), the proteome level alterations were determined at 12 h and 24 h after the venom treatment. Briefly, 70 protein spots with significant quantitative changes were picked from the gels for MALDI-TOF/MS. In total, 44 differentially abundant proteins were successfully identified, among which 19 proteins were increased, whereas 25 proteins were decreased in the abundance levels comparing with their respective control spots. DAPs involved in cell survival and development (e.g., Plasminogen, Vinculin, EMILIN-1, Basonuclin2, Focal adhesion kinase 1, FAM83B, Peroxisome proliferator-activated receptor-gamma co-activator 1-alpha) decreased their expression, whereas stress or immune response-related proteins (e.g., Toll-like receptor 4, Aminopeptidase N, MKL/Myocardin-like protein 1, hypoxia up-regulated protein 1, Heat shock protein 105 kDa, Ephrin type-A receptor 1, with some protease (or peptidase) enzymes) were up-regulated. In conclusion, the present findings may exhibit some possible key players during skin damage and suggest therapeutic strategies for preventing jellyfish envenomation.
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Gessner, Bradford D., Raul E. Isturiz, Vincenza Snow, and Luis Jodar. "2727. Numbers Needed to Vaccinate for Prevention of Adult Pneumonia with Pneumococcal Conjugate Vaccine: Which Values Should Determine Policy?" Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S960. http://dx.doi.org/10.1093/ofid/ofz360.2404.

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Abstract Background At the meeting of the Advisory Committee on Immunization Practices (ACIP) on February 28, 2019, the US Centers for Disease Control and Prevention (CDC) and the Pneumococcal Work Group (PWG) presented data to inform the public health question of whether the 13-valent pneumococcal conjugate vaccine (PCV13) should continue to be recommended for routine immunization of all adults age 65 years and older in the United States. Methods We reviewed all three available studies reporting adult PCV13 vaccine effectiveness against all-cause pneumonia, calculated numbers needed to vaccinate (NNV), and compared these results to NNV data presented to the ACIP based on etiologically and radiologically confirmed vaccine-type (VT) disease. Studies included a randomized controlled trial of inpatient pneumonia among Dutch persons age 65+ years, a US CDC-led observational study among the US Medicare population of inpatient pneumonia, and an observational study of inpatient and outpatient pneumonia in Germany. Results Based on a background incidence of etiologically and radiologically confirmed VT community-acquired pneumonia of 17–76 per 100,000 per year and PCV13 VE of 43%, the CDC presented to ACIP an annual NNV estimate for preventing one pneumonia case of 3,000 to 14,000. For the three studies we reviewed, VEs were 6% to 12% against all-cause pneumonia and background all-cause pneumonia incidences were 891 to 1776 per 100,000 per year. Assuming a 5-year PCV13 duration of protection, for these three studies NNVs to prevent a case of pneumonia were 95 to 277, or 11- to 147-fold lower than what was presented at ACIP. Conclusion To avoid inaccurate conclusions for potentially efficient interventions, calculations of NNVs, rate reductions, and economic benefits should include sensitive outcomes, such as all-cause pneumonia, in addition to more specific but lower sensitivity outcomes such as VT, radiologically confirmed pneumonia. Disclosures All authors: No reported disclosures.
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Yamada A., Graciela, Víctor Bazán R., and Nadia Fuentes N. "Parámetros productivos de cuyes G en la costa central del Perú." Revista de Investigaciones Veterinarias del Perú 29, no. 3 (September 6, 2018): 877. http://dx.doi.org/10.15381/rivep.v29i3.14748.

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El objetivo de la investigación fue determinar los parámetros productivos de cuyes G a nivel de la costa central del Perú. Se recolectó información de datos productivos de 180 partos de 39 cuyes G reproductoras con 452 crías destetadas a los 16.26 días en promedio entre abril de 2016 y mayo de 2017 en la estación experimental de Huaral del C.I. IVITA de la Universidad Nacional Mayor de San Marcos. Se evaluó el número de nacidos (NN), números de nacidos vivos (NNV), peso de las crías al nacimiento (PCrN), peso de la camada al nacimiento (PCN), número de destetados (ND), peso de las crías al destete (PcrD), peso de la camada al destete (PCD) y tasa de mortalidad (M). Los resultados fueron: NN de 2.82 ± 1.14 crías por parto (1-5 crías), NNV de 2.80 ± 1.13 crías, PCrN de 139.3 ± 30.9 g, PCN de 389.6 ± 121.3 g, ND de 2.58 ± 1.02 crías, PCrD de 248.0 ± 62.3 g, PCD de 640.6 ± 211.9 g y M de 8.89%. Solo se encontró diferencia significativa en PCrD por efecto del número de partos (p˂0.05).
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46

Qi, Chunxia, and Shunliang Huang. "Variable-Coefficient Exact Solutions for Nonlinear Differential Equations by a New Bernoulli Equation-Based Subequation Method." Mathematical Problems in Engineering 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/923408.

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A new Bernoulli equation-based subequation method is proposed to establish variable-coefficient exact solutions for nonlinear differential equations. For illustrating the validity of this method, we apply it to the asymmetric (2 + 1)-dimensional NNV system and the Kaup-Kupershmidt equation. As a result, some new exact solutions with variable functions coefficients for them are successfully obtained.
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47

Mahardika, K., I. Mastuti, D. Syahidah, S. Ismi, and Zafran. "Disease surveillance of cultured marine fish in the North of Bali, Indonesia." IOP Conference Series: Earth and Environmental Science 890, no. 1 (October 1, 2021): 012035. http://dx.doi.org/10.1088/1755-1315/890/1/012035.

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Abstract A regular surveillance of marine fish diseases was conducted from March to November 2019 in order to determine the occurrence time of the diseases within the mariculture centre of the North of Bali, Indonesia. The monthly surveillance was conducted by collecting 15 fish samples from each of the three hatcheries in Gerokgak and Penyabangan villages and of the two floating net cages in Pegametan Bay, Sumberkima village. Bacterial concentrations were grouped into 4 categories including low, moderate, high and very high. Surveillance data were analyzed using bivariate descriptive statistical methods. The results showed some important findings. First, the results of the study showed that NNV infection was found during the transitional seasons in March to June and September to November. Parasite infection were more frequent observed in fish with high and very high bacterial population. Second, high concentration of total bacteria in fish-feces occurred throughout the year. The prevalence of NNV infection and bacterial populations at the high to very high concentration were mostly occurred in the cultured fish in hatcheries at the size of 1-10 g, while in cultured fish at the net cages were mostly occurred at the size of > 50 g.
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48

González-Fernández, Carmen, Elena Chaves-Pozo, and Alberto Cuesta. "Identification and Regulation of Interleukin-17 (IL-17) Family Ligands in the Teleost Fish European Sea Bass." International Journal of Molecular Sciences 21, no. 7 (March 31, 2020): 2439. http://dx.doi.org/10.3390/ijms21072439.

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Interleukin-17 (IL-17) cytokine comprises a family of six ligands in mammals with proinflammatory functions, having an important role in autoimmune disorders and against bacterial, viral, and fungal pathogens. While IL-17A and IL-17F ligands are mainly produced by Th cells (Th17 cells), the rest of the ligands are expressed by other immune and non-immune cells and have different functions. The identification of IL-17 ligands in fish has revealed the presence of six members, counterparts to mammalian ones, and a teleost-specific form, the fish IL-17N. However, tissue distribution, the regulation of gene expression, and scarce bioactivity assays point to similar functions compared to mammalian ones, though this yet to be investigated and confirmed. Thus, we have identified seven IL-17 ligands in the teleost European sea bass (Dicentrarchus labrax), for the first time, corresponding to IL-17A/F1, IL-17A/F2, IL-17A/F3, IL-17C1, IL-17C2, IL-17D, and IL-17N, according to the predicted protein sequences and phylogenetic analysis. They are constitutively and widely transcribed in sea bass tissues, with some of them being mainly expressed in the thymus, brain or intestine. Upon in vitro stimulation of head-kidney leucocytes, the mRNA levels of all sea bass IL-17 ligands were up-regulated by phytohemagglutinin treatment, a well-known T cell mitogen, suggesting a major expression in T lymphocytes. By contrast, the infection of sea bass juveniles with nodavirus (NNV), a very pathogenic virus for this fish species, resulted in the up-regulation of the transcription of IL-17C1 in the head-kidney and of IL-17C1 and IL-17D in the brain, the target tissue for NNV replication. By contrast, NNV infection led to a down-regulated transcription of IL-17A/F1, IL-17A/F2, IL-17C1, IL-17C2, and IL-17D in the head-kidney and of IL-17A/F1 and IL-17A/F3 in the brain. The data are discussed accordingly with the IL-17 ligand expression and the immune response under the different situations tested.
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Gye, Hyun Jung, and Toyohiko Nishizawa. "Purification of nervous necrosis virus (NNV) particles by anion-exchange chromatography." Journal of Virological Methods 238 (December 2016): 21–28. http://dx.doi.org/10.1016/j.jviromet.2016.10.001.

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50

Gye, Hyun Jung, and Toyohiko Nishizawa. "Treatment with carbonate buffer decreases antigenicity of nervous necrosis virus (NNV)." Aquaculture 500 (February 2019): 192–95. http://dx.doi.org/10.1016/j.aquaculture.2018.10.010.

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