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1.
Chaos ; 30(4): 041102, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32357675

RESUMO

In this work, we analyze the growth of the cumulative number of confirmed infected cases by a novel coronavirus (COVID-19) until March 27, 2020, from countries of Asia, Europe, North America, and South America. Our results show that (i) power-law growth is observed in all countries; (ii) by using the distance correlation, the power-law curves between countries are statistically highly correlated, suggesting the universality of such curves around the world; and (iii) soft quarantine strategies are inefficient to flatten the growth curves. Furthermore, we present a model and strategies that allow the government to reach the flattening of the power-law curves. We found that besides the social distancing of individuals, of well known relevance, the strategy of identifying and isolating infected individuals in a large daily rate can help to flatten the power-laws. These are the essential strategies followed in the Republic of Korea. The high correlation between the power-law curves of different countries strongly indicates that the government containment measures can be applied with success around the whole world. These measures are scathing and to be applied as soon as possible.


Assuntos
Betacoronavirus , Infecções por Coronavirus/transmissão , Modelos Estatísticos , Pneumonia Viral/transmissão , Quarentena/métodos , Ásia/epidemiologia , Betacoronavirus/crescimento & desenvolvimento , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Europa (Continente)/epidemiologia , Geografia Médica , Atividades Humanas , Humanos , América do Norte/epidemiologia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Prevalência , América do Sul/epidemiologia
2.
Sci Rep ; 10(1): 7635, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376987

RESUMO

Proteolytic cleavage of influenza A virus (IAV) hemagglutinin by host proteases is crucial for virus infectivity and spread. The transmembrane serine protease TMPRSS2 was previously identified as the essential protease that can cleave hemagglutinin of many subtypes of influenza virus and spike protein of coronavirus. Herein, we found that a guanine rich tract, capable of forming intramolecular G-quadruplex in the presence of potassium ions, in the promoter region of human TMPRSS2 gene was quite important for gene transcriptional activity, hence affecting its function. Furthermore, 7 new synthesized benzoselenoxanthene analogues were found to enable stabilizing such G-quadruplex. More importantly, compounds can down-regulate TMPRSS2 gene expression, especially endogenous TMPRSS2 protein levels, and consequently suppress influenza A virus propagation in vitro. Our results provide a new strategy for anti-influenza A virus infection by small molecules targeting the TMPRSS2 gene G-quadruplex and thus inhibiting TMPRSS2 expression, which is valuable for developing small molecule drugs against influenza A virus and also may be a potential candidate as anti- SARS-CoV-2 (Severe Acute Respiratory Syndrome CoV 2) lead molecules.


Assuntos
Vírus da Influenza A/crescimento & desenvolvimento , Compostos Organosselênicos , Serina Endopeptidases/genética , Linhagem Celular , Pegada de DNA , Descoberta de Drogas , Quadruplex G , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Vírus da Influenza A/fisiologia , Compostos Organosselênicos/química , Compostos Organosselênicos/farmacologia , Regiões Promotoras Genéticas , Transcrição Genética
3.
Cell ; 181(4): 865-876.e12, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32353252

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has highlighted the need for antiviral approaches that can target emerging viruses with no effective vaccines or pharmaceuticals. Here, we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (prophylactic antiviral CRISPR in human cells), for viral inhibition that can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus (IAV) in human lung epithelial cells. We designed and screened CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs targeting SARS-CoV-2. This approach effectively reduced H1N1 IAV load in respiratory epithelial cells. Our bioinformatic analysis showed that a group of only six crRNAs can target more than 90% of all coronaviruses. With the development of a safe and effective system for respiratory tract delivery, PAC-MAN has the potential to become an important pan-coronavirus inhibition strategy.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Sistemas CRISPR-Cas , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , RNA Viral/antagonistas & inibidores , Células A549 , Antibioticoprofilaxia/métodos , Sequência de Bases , Betacoronavirus/genética , Betacoronavirus/crescimento & desenvolvimento , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Simulação por Computador , Sequência Conservada , Coronavirus/efeitos dos fármacos , Coronavirus/genética , Coronavirus/crescimento & desenvolvimento , Infecções por Coronavirus/tratamento farmacológico , Células Epiteliais/virologia , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Pulmão/patologia , Pulmão/virologia , Proteínas do Nucleocapsídeo/genética , Pandemias , Filogenia , Pneumonia Viral/tratamento farmacológico , RNA Replicase/genética , Proteínas não Estruturais Virais/genética
5.
Phys Rev Lett ; 124(17): 174501, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32412279

RESUMO

Very lean hydrogen flames were thought to quench in narrow confined geometries. We show for the first time how flames with very low fuel concentration undergo an unprecedented propagation in narrow gaps: H_{2}-air flames can survive very adverse conditions by breaking the reaction front into isolated flame cells that travel steadily in straight lines or split to perform a fractal-like propagation that resembles the pathway of starving fungi or bacteria. The combined effect of hydrogen mass diffusivity and intense heat losses act as the two main mechanisms that explain the experimental observations.


Assuntos
Hidrogênio/química , Modelos Teóricos , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Fogo , Fungos/crescimento & desenvolvimento , Fungos/metabolismo , Modelos Biológicos , Modelos Químicos
8.
Exp Parasitol ; 214: 107904, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32371061

RESUMO

Hydatidosis or cystic echinococcosis is a disease caused by the larval stage of Echinococcus granulosus sensu lato. Chemotherapy can be used alone or in combination with surgery or percutaneous treatment. Benzimidazoles are the only agents used and approved for treatment, but their efficacy is extremely variable. Therefore, it is necessary to find new drugs to improve the treatment of this disease. In the last decades, the biological properties of essential oils and their components began to be investigated as alternatives in the treatment of different ailments. The aim of the present work was to evaluate the in vitro efficacy of the essential oil of Cinnamomum zeylanicum (cinnamon) and cinnamaldehyde against protoscoleces and metacestodes of E. granulosus. The essential oil and cinnamaldehyde, its major component, showed a dose and time dependent effect against protoscoleces. However, cinnamaldehyde showed a greater protoscolicidal effect than the essential oil. The maximum protoscolicidal effect was found with 50 µg/mL of cinnamaldehyde. Viability decreased by 1.7 ± 0.8% after 4 days of incubation and reached 0% at 8 days. Interestingly, there were no significant differences between the activity of cinnamaldehyde at the concentrations of 25 and 10 µg/mL and the efficacy observed with the essential oil at 200 and 50 µg/mL, respectively. Cinnamaldehyde also had a strong in vitro effect against murine cysts, while only the higher concentration of the essential oil caused ultrastructural alterations. Working with components instead of with essential oils has some advantages, particularly in relation to the reproducibility of the formulations and their effectiveness. For this reason, the results obtained in this work are promising in the search for pharmaceutical alternatives for the treatment of cystic echinococcosis.


Assuntos
Acroleína/análogos & derivados , Anticestoides/farmacologia , Cinnamomum zeylanicum/química , Echinococcus granulosus/efeitos dos fármacos , Óleos Voláteis/farmacologia , Acroleína/farmacologia , Animais , Equinococose/tratamento farmacológico , Echinococcus granulosus/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento
9.
Sheng Wu Gong Cheng Xue Bao ; 36(4): 605-611, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32347055

RESUMO

Cyclophilin A (CypA) is a widely distributed and highly conserved protein in organisms. It has peptidyl-prolyl cis/trans isomerase activity and is a receptor for cyclosporin A (CsA). Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses. Seven types of coronaviruses are currently known to infect humans, among which SARS-CoV, MERS-CoV, and SARS-CoV-2 are fatal for humans. It is well established that CypA is essential for the replication of various coronaviruses such as SARS-CoV, CoV-229E, CoV-NL63, and FCoV. Additionally, CsA and its derivatives (ALV, NIM811, etc.) have obvious inhibitory effects on a variety of coronaviruses. These results suggest that CypA is a potential antiviral target and the existing drug CsA might be used as an anti-coronavirus drug. At the end of 2019, SARS-CoV-2 raged in China, which seriously theatern human health and causes huge economic lases. In view of this, we describe the effects of CypA on the replication of coronaviruses and the antiviral activities of its inhibitors, which will provide the scientific basis and ideas for the development of antiviral drugs for SARS-CoV-2.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus , Coronavirus/efeitos dos fármacos , Coronavirus/crescimento & desenvolvimento , Ciclofilina A/antagonistas & inibidores , Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Pandemias , Pneumonia Viral , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/crescimento & desenvolvimento , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Ciclosporina/química , Humanos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/crescimento & desenvolvimento , Replicação Viral/efeitos dos fármacos
10.
Ecotoxicology ; 29(4): 485-492, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32297060

RESUMO

Experiments examining mercury (Hg) toxicity in Daphnia are usually conducted in highly standardized conditions that prevent the formation of biofilm. Although such standardization has many advantages, extrapolation of results to natural conditions and inference of ecological effects is challenging. This is especially true since biofilms can accumulate metals/metalloids and play a key role in their transfer to higher trophic level organisms. In this study, we experimentally tested the effects of spontaneously appearing biofilm in Daphnia cultures on accumulation of Hg and its natural antagonist selenium (Se) in Daphnia magna. We added Hg (in the form of mercury (II) chloride) at two concentrations (0.2 µg/L and 2 µg/L) to experimental microcosms and measured the uptake of Hg and Se by D. magna in the presence and absence of biofilm. To test for consistent and replicable results, we ran two identical experimental sets one week apart. Biofilm presence significantly reduced the accumulation of Hg, while increasing the tissue Se content in D. magna, and these findings were reproducible across experimental sets. These findings indicate that highly standardized tests may not be adequate to predict the bioaccumulation and potential toxicity of metals/metalloids under natural conditions.


Assuntos
Biofilmes/efeitos dos fármacos , Daphnia/metabolismo , Mercúrio/metabolismo , Selênio/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Biofilmes/crescimento & desenvolvimento
11.
J Appl Oral Sci ; 28: e20190501, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32236356

RESUMO

INTRODUCTION: The acquired pellicle formation is the first step in dental biofilm formation. It distinguishes dental biofilms from other biofilm types. OBJECTIVE: To explore the influence of salivary pellicle formation before biofilm formation on enamel demineralization. METHODOLOGY: Saliva collection was approved by Indiana University IRB. Three donors provided wax-stimulated saliva as the microcosm bacterial inoculum source. Acquired pellicle was formed on bovine enamel samples. Two groups (0.5% and 1% sucrose-supplemented growth media) with three subgroups (surface conditioning using filtered/pasteurized saliva; filtered saliva; and deionized water (DIW)) were included (n=9/subgroup). Biofilm was then allowed to grow for 48 h using Brain Heart Infusion media supplemented with 5 g/l yeast extract, 1 mM CaCl2.2H2O, 5% vitamin K and hemin (v/v), and sucrose. Enamel samples were analyzed for Vickers surface microhardness change (VHNchange), and transverse microradiography measuring lesion depth (L) and mineral loss (∆Z). Data were analyzed using two-way ANOVA. RESULTS: The two-way interaction of sucrose concentration × surface conditioning was not significant for VHNchange (p=0.872), ∆Z (p=0.662) or L (p=0.436). Surface conditioning affected VHNchange (p=0.0079), while sucrose concentration impacted ∆Z (p<0.0001) and L (p<0.0001). Surface conditioning with filtered/pasteurized saliva resulted in the lowest VHNchange values for both sucrose concentrations. The differences between filtered/pasteurized subgroups and the two other surface conditionings were significant (filtered saliva p=0.006; DIW p=0.0075). Growing the biofilm in 1% sucrose resulted in lesions with higher ∆Z and L values when compared with 0.5% sucrose. The differences in ∆Z and L between sucrose concentration subgroups was significant, regardless of surface conditioning (both p<0.0001). CONCLUSION: Within the study limitations, surface conditioning using human saliva does not influence biofilm-mediated enamel caries lesion formation as measured by transverse microradiography, while differences were observed using surface microhardness, indicating a complex interaction between pellicle proteins and biofilm-mediated demineralization of the enamel surface.


Assuntos
Biofilmes/crescimento & desenvolvimento , Esmalte Dentário/microbiologia , Saliva/química , Sacarose/química , Desmineralização do Dente/microbiologia , Animais , Bovinos , Esmalte Dentário/química , Película Dentária/microbiologia , Dureza , Microrradiografia/métodos , Pasteurização , Valores de Referência , Saliva/microbiologia , Sacarose/análise , Propriedades de Superfície
12.
Nat Cell Biol ; 22(4): 372-379, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32231306

RESUMO

The availability of nucleotides has a direct impact on transcription. The inhibition of dihydroorotate dehydrogenase (DHODH) with leflunomide impacts nucleotide pools by reducing pyrimidine levels. Leflunomide abrogates the effective transcription elongation of genes required for neural crest development and melanoma growth in vivo1. To define the mechanism of action, we undertook an in vivo chemical suppressor screen for restoration of neural crest after leflunomide treatment. Surprisingly, we found that alterations in progesterone and progesterone receptor (Pgr) signalling strongly suppressed leflunomide-mediated neural crest effects in zebrafish. In addition, progesterone bypasses the transcriptional elongation block resulting from Paf complex deficiency, rescuing neural crest defects in ctr9 morphant and paf1(alnz24) mutant embryos. Using proteomics, we found that Pgr binds the RNA helicase protein Ddx21. ddx21-deficient zebrafish show resistance to leflunomide-induced stress. At a molecular level, nucleotide depletion reduced the chromatin occupancy of DDX21 in human A375 melanoma cells. Nucleotide supplementation reversed the gene expression signature and DDX21 occupancy changes prompted by leflunomide. Together, our results show that DDX21 acts as a sensor and mediator of transcription during nucleotide stress.


Assuntos
RNA Helicases DEAD-box/genética , Melanócitos/metabolismo , Crista Neural/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Receptores de Progesterona/genética , Proteínas de Peixe-Zebra/genética , Animais , Linhagem Celular Tumoral , RNA Helicases DEAD-box/metabolismo , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Leflunomida/farmacologia , Melanócitos/efeitos dos fármacos , Melanócitos/patologia , Crista Neural/efeitos dos fármacos , Crista Neural/crescimento & desenvolvimento , Nucleotídeos , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Progesterona/metabolismo , Ligação Proteica , Receptores de Progesterona/metabolismo , Transdução de Sinais , Estresse Fisiológico/genética , Elongação da Transcrição Genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
13.
An Acad Bras Cienc ; 92(1): e20180983, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321012

RESUMO

Currently, in Argentina 368 species of true ferns (i.e. Polypodiopsida class) are distributed throughout the country, however, only four of them have been mentioned until now as weeds and ruderal species. The goal of this work was to generate an update of weedy ferns from Argentina, including morphology, distribution, and type of weed according to their impact on natural habitats and/or human activities. All Argentinian fern species were analyzed based on references, herbarium specimens, and field trips. As a result of our study 25 species were recorded from Argentina and classified as segetal, ecological, or aquatic weeds, and ruderal and/or toxic species. Current taxonomic identity, diagnostic characters, origins, habitats, geographical distribution, common names, and impact and potential risks were indicated by species. In addition, we provide a dichotomous key to species, presence of these species in southern South American countries, as well as and photographs in natural habitat. This work represents the first review on native and exotic ferns from Argentina that cause an impact on human activities or disturbe native habitats. The results provide information for the development of weed management tools and priority areas to implement them.


Assuntos
Biodiversidade , Ecossistema , Gleiquênias/crescimento & desenvolvimento , Atividades Humanas , Plantas Daninhas/crescimento & desenvolvimento , Argentina , Gleiquênias/classificação , Humanos , Filogenia , Plantas Daninhas/classificação
14.
An Acad Bras Cienc ; 92 Suppl 1: e20180697, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348410

RESUMO

The objective of this study was to estimate variance components for performance and carcass traits in a paternal broiler line. The (co)variance components were estimated by the restricted maximum likelihood method applied to the animal model, including the fixed effect of group (sex and hatch) and additive genetic and residual as random effects. Estimated heritability for performance traits ranged from 0.09 to 0.42. The genetic correlations between traits ranged from -0.50 to 0.97. The heritability estimates of feed intake, weight gain, and feed conversion from 35 to 41 days of age were of low magnitude. The genetic correlations among them were favorable to genetic selection. These results suggest that moderate genetic gain can be obtained to the feed intake and weight gain when the selection criterion is the body weight and prime cuts traits. The feed conversion that had low heritability estimation and low genetic correlation with the body weight and prime cut traits needs to pay greater attention due to the economic importance in the high-meat production lineage breeding programs.


Assuntos
Galinhas/genética , Característica Quantitativa Herdável , Animais , Peso Corporal/genética , Galinhas/crescimento & desenvolvimento , Fenótipo , Ganho de Peso/genética
15.
An Acad Bras Cienc ; 92 Suppl 1: e20190053, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348413

RESUMO

The yellow clam Mesodesma mactroides (Reeve, 1854) is a sand mollusc with historical and socioeconomic importance in Brazil, Uruguay and Argentina. A guaranteed form to access a successful reestablishment of the species in their natural environment is directly linked to their reproduction biology. Then, our report introduces the embryonic and larval development of the yellow clam reared in laboratory for such purposes. M. mactroides broodstock were selected as specimens who possess a mean total shell length and weight of 66 ± 3.82 mm and 27.15 ± 4.07 g for an afterwards spawn induction through stripping technique. Regarding the embryonic development, newly fertilized oocytes exhibited a mean diameter of 51.20 ± 6.64 µm. The first polar corpuscle, trochophores and D-veliger appeared at 20 min, 18 and 24 h after fertilization, respectively. Umbonate and pediveliger larvae were noticed on the 8th and 25th day, respectively, with complete metamorphosis occurring only at the 27th day, when all larvae were retained in a 200 µm nylon mesh. Therefore, with that basic understanding of the embryonic and larval development of M. mactroides in the laboratory, forwards studies will focus in establish a technological package for this species.


Assuntos
Bivalves/embriologia , Bivalves/crescimento & desenvolvimento , Animais , Bivalves/classificação , Laboratórios , Larva/crescimento & desenvolvimento , Óvulo/crescimento & desenvolvimento
16.
Sheng Wu Gong Cheng Xue Bao ; 36(4): 700-706, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32347064

RESUMO

The responsibility of root is absorbing water and nutrients, it is an important plant tissue, but easily to be affected by biotic and abiotic stresses, affecting crop growth and yield. The design of a synthetic root-specific promoter provides candidate promoters for the functional analysis and efficient expression of stress-related genes in crop roots. In this study, a synthetic root-specific module (pro-SRS) was designed using tandem four-copies of root specific cis-acting elements (OSE1ROOTNODULE, OSE2ROOTNODULE, SP8BFIBSP8AIB, and ROOTMOTIFAPOX1), and fused with minimal promoter from the CaMV 35S promoter to synthesize an artificially synthetic SRSP promoter. The SRSP promoter was cloned in pCAMBIA2300.1 by replacing CaMV 35S promoter so as to drive GUS expression. The constructs with SRSP promoter were transformed in tobacco by Agrobacterium-mediated method. SRSP promoter conferred root-specific expression in transgenic tobacco plants through Real-time PCR (RT-PCR) analysis and GUS histochemical staining analysis. It is indicated that the repeated arrangement of cis-acting elements can realize the expected function of the promoter. This study laid a theoretical foundation for the rational design of tissue-specific promoters.


Assuntos
Regulação da Expressão Gênica de Plantas , Raízes de Plantas , Regiões Promotoras Genéticas , Tabaco , Agrobacterium/genética , Clonagem Molecular , Raízes de Plantas/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Estresse Fisiológico , Tabaco/genética , Tabaco/crescimento & desenvolvimento , Transformação Genética
17.
Sheng Wu Gong Cheng Xue Bao ; 36(4): 707-715, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32347065

RESUMO

OsRhoGDI2 was isolated as a putative partner of Rho protein family member OsRacD from rice panicles by yeast two-hybrid, but its function remains unknown. In order to identify the function of OsRhoGDI2, OsRhoGDI2 knockout mutants were created by CRISPR/Cas9 technology. The results showed that two different homozygous mutants were obtained in T0 generation, and eight kinds homozygous mutants were identified in T1 generation. Sequence analysis revealed that the base substitution or base deletion occurred near the editing targets of the gene in knockout rice, and it could be expected that the truncated OsRhoGDI2 proteins lacking the RhoGDI conserved domain would be generated. Phenotype analysis showed that the OsRhoGDI2 knockout rice plants were significantly lower than the control plants. Statistical analysis confirmed that the significant decrease of plant height was due to the shortening of the second and third internodes, suggesting that OsRhoGDI2 gene may be related with rice height control.


Assuntos
Genes de Plantas , Oryza , Sistemas CRISPR-Cas , Genes de Plantas/genética , Oryza/genética , Oryza/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Inibidor beta de Dissociação do Nucleotídeo Guanina rho/genética
18.
Emerg Microbes Infect ; 9(1): 837-842, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32301390

RESUMO

The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests the possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect these variants. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variants as an attenuated vaccine or laboratory tool should be evaluated.


Assuntos
Infecções por Coronavirus/patologia , Modelos Animais de Doenças , Mesocricetus , Pneumonia Viral/patologia , Vírus da SARS/genética , Vírus da SARS/patogenicidade , Deleção de Sequência , Glicoproteína da Espícula de Coronavírus/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Chlorocebus aethiops , Infecções por Coronavirus/virologia , Feminino , Especificidade de Hospedeiro , Humanos , Pulmão/patologia , Masculino , Pandemias , Pneumonia Viral/virologia , Vírus da SARS/crescimento & desenvolvimento , Vírus da SARS/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/química , Células Vero , Virulência
19.
Int J Food Microbiol ; 322: 108576, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32240921

RESUMO

Aflatoxin contamination in food and feed products has been brought into sharp focus over the last few decades in the world. However, there is no effective strategy for solving the problem thus far. Therefore, basic research on the aflatoxin-producer Aspergillus flavus is an urgent need. The vital role of mitogen-activated protein kinases (MAPKs) in signal transduction has been documented in various pathogenic fungi, but their functions in A. flavus have rarely been investigated. Herein, we characterized the detailed function of one of these MAPKs, AflSlt2. Targeted deletion of AflSlt2 gene indicates that this kinase is required for vegetative growth, conidia generation, and sclerotium formation. The analysis of AflSlt2 deletion mutant revealed hypersensitivity to cell wall-damaging chemicals and resistance against hydrogen peroxide. Interestingly, the ability of the ΔAflSlt2 mutant to generate aflatoxins in medium was significantly increased compared to wild type. However, a pathogenicity assay indicated that the ΔAflSlt2 mutant was deficient in peanut infection. Site-directed mutation study uncovered that the function of AflSlt2 was dependent on the phosphorylated residues (Thr-186 and Tyr-188) within the activation loop and the phosphotransfer residue (Lys-52) within the subdomain II. Interestingly, an autophosphorylation mutant of AflSlt2 (AflSlt2R66S) displayed wild type-like phenotypes. Bringing these observations together, we propose that Slt2-MAPK pathway is involved in development, stress response, aflatoxin biosynthesis, and pathogenicity in A. flavus. This study may be useful to unveil the regulation mechanism of aflatoxin biosynthesis and provide strategy to control A. flavus contamination.


Assuntos
Aflatoxinas/biossíntese , Arachis/microbiologia , Aspergillus flavus/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Aspergillus flavus/crescimento & desenvolvimento , Aspergillus flavus/patogenicidade , Parede Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Mutação , Transdução de Sinais , Estresse Fisiológico
20.
ACS Chem Neurosci ; 11(9): 1200-1203, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32283006

RESUMO

The novel SARS-CoV-2 virus has very high infectivity, which allows it to spread rapidly around the world. Attempts at slowing the pandemic at this stage depend on the number and quality of diagnostic tests performed. We propose that the olfactory epithelium from the nasal cavity may be a more appropriate tissue for detection of SARS-CoV-2 virus at the earliest stages, prior to onset of symptoms or even in asymptomatic people, as compared to commonly used sputum or nasopharyngeal swabs. Here we emphasize that the nasal cavity olfactory epithelium is the likely site of enhanced binding of SARS-CoV-2. Multiple non-neuronal cell types present in the olfactory epithelium express two host receptors, ACE2 and TMPRSS2 proteases, that facilitate SARS-CoV-2 binding, replication, and accumulation. This may be the underlying mechanism for the recently reported cases of smell dysfunction in patients with COVID-19. Moreover, the possibility of subsequent brain infection should be considered which begins in olfactory neurons. In addition, we discuss the possibility that olfactory receptor neurons may initiate rapid immune responses at early stages of the disease. We emphasize the need to undertake research focused on additional aspects of SARS-CoV-2 actions in the nervous system, especially in the olfactory pathway.


Assuntos
Betacoronavirus/isolamento & purificação , Encéfalo/virologia , Infecções por Coronavirus/diagnóstico , Diagnóstico Precoce , Programas de Rastreamento/métodos , Mucosa Olfatória/virologia , Pneumonia Viral/diagnóstico , Olfato , Animais , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/imunologia , Encéfalo/imunologia , Encéfalo/fisiopatologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/transmissão , Humanos , Imunidade Inata , Programas de Rastreamento/normas , Camundongos , Mucosa Olfatória/citologia , Mucosa Olfatória/imunologia , Mucosa Olfatória/metabolismo , Neurônios Receptores Olfatórios/imunologia , Neurônios Receptores Olfatórios/metabolismo , Neurônios Receptores Olfatórios/virologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/transmissão , Mucosa Respiratória/metabolismo , Mucosa Respiratória/virologia , Serina Endopeptidases/metabolismo , Replicação Viral
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