RESUMEN
Biomolecular condensates have emerged as an important subcellular organizing principle1. Replication of many viruses, including human respiratory syncytial virus (RSV), occurs in virus-induced compartments called inclusion bodies (IBs) or viroplasm2,3. IBs of negative-strand RNA viruses were recently shown to be biomolecular condensates that form through phase separation4,5. Here we report that the steroidal alkaloid cyclopamine and its chemical analogue A3E inhibit RSV replication by disorganizing and hardening IB condensates. The actions of cyclopamine and A3E were blocked by a point mutation in the RSV transcription factor M2-1. IB disorganization occurred within minutes, which suggests that these molecules directly act on the liquid properties of the IBs. A3E and cyclopamine inhibit RSV in the lungs of infected mice and are condensate-targeting drug-like small molecules that have in vivo activity. Our data show that condensate-hardening drugs may enable the pharmacological modulation of not only many previously undruggable targets in viral replication but also transcription factors at cancer-driving super-enhancers6.
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Condensados Biomoleculares/virología , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Alcaloides de Veratrum/farmacología , Replicación Viral/efectos de los fármacos , Animales , Antivirales/farmacología , Línea Celular , Femenino , Humanos , Cuerpos de Inclusión , Pulmón/virología , Ratones , Ratones Endogámicos BALB C , Virus Sincitial Respiratorio Humano/fisiología , Factores de Transcripción , Proteínas ViralesRESUMEN
Elevated temperature (Te ) and drought often co-occur and interactively affect plant carbon (C) metabolism and thus the ecosystem C cycling; however, the magnitude of their interaction is unclear, making the projection of global change impacts challenging. Here, we compiled 107 journal articles in which temperature and water availability were jointly manipulated, and we performed a meta-analysis of interactive effects of Te and drought on leaf photosynthesis (Agrowth ) and respiration (Rgrowth ) at growth temperature, nonstructural carbohydrates and biomass of plants, and their dependencies on experimental and biological moderators (e.g., treatment intensity, plant functional type). Our results showed that, overall, there was no significant interaction of Te and drought on Agrowth . Te accelerated Rgrowth under well-watered conditions rather than under drought conditions. The Te × drought interaction on leaf soluble sugar and starch concentrations were neutral and negative, respectively. The effect of Te and drought on plant biomass displayed a negative interaction, with Te deteriorating the drought impacts. Drought induced an increase in root to shoot ratio at ambient temperature but not at Te . The magnitudes of Te and drought negatively modulated the Te × drought interactions on Agrowth . Root biomass of woody plants was more vulnerable to drought than that of herbaceous plants at ambient temperature, but this difference diminished at Te . Perennial herbs exhibited a stronger amplifying effect of Te on plant biomass in response to drought than did annual herbs. Te exacerbated the responses of Agrowth and stomatal conductance to drought for evergreen broadleaf trees rather than for deciduous broadleaf and evergreen coniferous trees. A negative Te × drought interaction on plant biomass was observed on species-level rather than on community-level. Collectively, our findings provide a mechanistic understanding of the interactive effects of Te and drought on plant C metabolism, which would improve the prediction of climate change impacts.
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Carbono , Ecosistema , Carbono/metabolismo , Temperatura , Sequías , Dióxido de Carbono/análisis , Plantas/metabolismoRESUMEN
The Collagen α1(Ш) chain (COL3A1) is an important structural protein on the surface of human skin. The activity of prolyl 4-hydroxylase (P4H) is crucial to maintaining the stable triple-helix structure and function of human COL3A1. To obtain hydroxylated human COL3A1, virus-derived P4H A085R was co-expressed with human COL3A1 in Pichia pastoris GS115. Colony PCR analysis and sequencing after transfection confirmed that the target gene was successfully inserted. Quantitative reverse transcription PCR (RT-qPCR) indicated that human COL3A1 and P4H A085R were expressed at mRNA levels in the clones. SDS-PAGE and Western blot analysis of supernatant from the recombinant methylotrophic yeast culture showed that recombinant human COL3A1 (rhCOL3A1) was secreted into the culture medium with an apparent molecular mass of approximately 130 kDa. It was observed that the amount of secreted rhCOL3A1 was highest at 120 h after induction. Furthermore, mass spectrometry analysis demonstrated that rhCOL3A1 was successfully expressed in P. pastoris. The His-tagged rhCOL3A1 protein was purified by Ni-affinity column chromatography.
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Pichia , Prolil Hidroxilasas , Colágeno/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Humanos , Pichia/genética , Pichia/metabolismo , Prolil Hidroxilasas/química , Prolil Hidroxilasas/genética , ARN Mensajero/metabolismo , Proteínas Recombinantes/química , SaccharomycetalesRESUMEN
Human metapneumovirus (HMPV) plays an important role in acute respiratory tract infections (ARTIs), especially in children. We investigated the epidemiology of HMPV associated with ARTIs among pediatric inpatients and identified HMPV genetic variations in Qingdao, China, from January 2018 to June 2019. HMPV-positive samples were identified from throat swabs by multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR). The G gene sequences of HMPV were obtained, followed by phylogenetic analysis. As a result, 71 out of 1051 (6.76%) patients were HMPV positive, and the HMPV-positive rate in children under 5 years of age was three times higher than that in those aged 5-17 years. The epidemic season of HMPV was in spring, with a peak mainly in March. Thirty-two nucleotide sequences of the HMPV G gene successfully obtained were clustered into three genotypes, A2c (25/32, 78.13%), B1 (3/32, 9.38%) and B2 (4/32, 12.50%). In addition, 76% (19/25) of A2c viruses were identified as the emerging A2c111nt-dup variants, which were predominantly circulating among pediatric inpatients with ARTIs between January 2018 and June 2019 in Qingdao. The emerging A2c111nt-dup variants have spread between countries and cities and might spread more widely in the future. Further prevalence monitoring of this duplication variant is needed to clarify the potentially expanding transmission and to provide a scientific basis for disease control and vaccine development.
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Metapneumovirus , Infecciones por Paramyxoviridae , Infecciones del Sistema Respiratorio , Niño , Preescolar , China/epidemiología , Genotipo , Humanos , Lactante , Metapneumovirus/genética , Infecciones por Paramyxoviridae/epidemiología , Filogenia , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
The potential security problems of blockchain technology are constantly restricting the development process of related industrial applications. The cost of deploying a blockchain system in a real environment to conduct research on security issues is relatively high, and the related security analysis and verification are also destructive and irreproducible. Therefore, based on the idea of layered design, this paper proposes a blockchain system simulation platform. The blockchain system is divided into four layers in the simulation platform: the consensus layer, network layer, contract layer, and storage layer. In the consensus layer, the problem of computing resource waste is solved. In the network layer, a peer-to-peer network topology simulation is implemented. In the storage layer, the problem of redundant storage is solved. In the contract layer, the contract replay speed is accelerated. Finally, a prototype of an efficient blockchain simulation system is implemented based on the above methods.
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Cadena de Bloques , Simulación por Computador , Consenso , TecnologíaRESUMEN
Roles of environmental factors in transmission of COVID-19 have been highlighted. In this study, we sampled the high-touch environmental surfaces in the quarantine room, aiming to detect the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the environmental surfaces during the incubation period of coronavirus disease 2019 (COVID-19) patients. Fifteen sites were sampled from the quarantine room, distributing in the functional areas such as bedroom, bathroom and living room. All environmental surface samples were collected with sterile polyester-tipped applicator pre-moistened in viral transport medium and tested for SARS-CoV-2. Overall, 34.1% of samples were detected positively for SARS-CoV-2. The positive rates of Patient A, B and C, were 46.2%, 0% and 61.5%, respectively. SARS-CoV-2 was detected positively in bedroom and bathroom, with the positive rate of 50.0% and 46.7%, respectively. In contrast, living room had no positive sample detected. Environmental contamination of SARS-CoV-2 distributes widely during the incubation period of COVID-19, and the positive rates of SARS-CoV-2 on environmental surfaces are relatively high in bathroom and bedroom.
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Aparatos Sanitarios/virología , COVID-19/transmisión , Microbiología Ambiental , Contaminación Ambiental , Periodo de Incubación de Enfermedades Infecciosas , Infección Latente/transmisión , COVID-19/epidemiología , COVID-19/prevención & control , Desinfección , Contaminación Ambiental/análisis , Contaminación Ambiental/prevención & control , Femenino , Humanos , Infección Latente/epidemiología , Infección Latente/prevención & control , Masculino , Cuarentena/normas , SARS-CoV-2 , Propiedades de Superficie , Cuartos de Baño/normasRESUMEN
The odor compound from Periploca sepium Bunge, 2-hydroxy-4-methoxy-benzaldehyde (HMB), is an allelochemical agent and is one of the least investigated isomers of vanillin. In this study, we used label-free quantitative proteomics analysis technology to investigate the effect of HMB on the protein expression of Humulus scandens (Lour.) Merr. leaves in July 2019 on Guiyang. A total of 269 proteins of 624 identified proteins were differentially expressed, among which 21.18% of the proteins were up-regulated and 32.71% down-regulated. These proteins were classified into 11 cell components and more than 20% of differentially expressed proteins were located in cell membrane and chloroplast. Functional classification analysis showed that 12 molecular functions were altered upon HMB treatment, and the ratio of catalytic activity was the highest (19.53%). At least 12 biological functions were affected, which involved small molecule metabolic processes, organic substance metabolic processes, gene expression, and photosynthesis. Our data provide resources and insights into the biochemical mechanism by which HMB kills weeds.
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Humulus/fisiología , Odorantes/análisis , Periploca/fisiología , Hojas de la Planta/química , Benzaldehídos , China , Periploca/química , Fotosíntesis , Proteoma/metabolismo , ProteómicaRESUMEN
Deoxymikanolide (DEO) was isolated from Mikania micrantha Bunge and identified as a novel antibacterial compound previously. However, the mode of antimicrobial mechanism of DEO was not clear but hypothesized to affect the morphology and physiology of Ralstonia solanacearum cells. In this study, we confirmed our hypothesis via transmission electron microscopy (TEM) observation and comprehensive physiological analyses, including electric conductivity, glycan and phosphorus metabolism, activities of antioxidant enzymes (catalase, peroxidase, and superoxide dismutase), intrabacterial reactive oxygen species (ROS), and malondialdehyde (MDA) levels. We found that glycan and phosphorus metabolism, electric conductivity, intracellular ROS and MDA levels of R. solanacearum cells were significantly increased, while the activities of three antioxidant enzymes were significantly inhibited by DEO treatment. Moreover, TEM analysis showed that DEO treatment led to an early-stage of cell shrinkage, intermediate-stages of cytoplasmic damage, and a final-stage of cell disruption. Altogether, our data presented here indicate that DEO could adversely affect the physiology and morphology of R. solanacearum cells and be treated as an alternative antibacterial treatment in the future.
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Ralstonia solanacearum , Catalasa , Lactonas , Sesquiterpenos de GermacranoRESUMEN
We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination in 2 rooms of a quarantine hotel after 2 presymptomatic persons who stayed there were laboratory-confirmed as having coronavirus disease. We detected SARS-CoV-2 RNA on 8 (36%) of 22 surfaces, as well as on the pillow cover, sheet, and duvet cover.
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Ropa de Cama y Ropa Blanca/virología , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/transmisión , Fómites/virología , Neumonía Viral/transmisión , ARN Viral/aislamiento & purificación , Adulto , Betacoronavirus/genética , COVID-19 , China/epidemiología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/virología , Cuarentena , SARS-CoV-2RESUMEN
Natural World Heritage Sites (NWHSs) are invaluable treasure due to the uniqueness of each site. Proper monitoring and management can guarantee their protection from multiple threats. In this study, geographic information system (GIS)-based multi-criteria decision analysis (GIS-MCDA) was used to assess criteria layers acquired from the data available in the literature. A conceptual model for determining the priority area for monitoring in Bogda, China, was created based on outstanding universal values (OUV) and expert knowledge. Weights were assigned to each layer using the analytic hierarchy process (AHP) based on group decisions, encompassing three experts: one being a heritage site expert, another a forest ranger, and the other a heritage site manager. Subsequently, evaluation layers and constraint layers were used to generate a priority map and to determine the feasibility of monitoring in Bogda. Finally, a monitoring suitability map of Bogda was obtained by referencing priority and feasibility maps.The high-priority monitoring area is located in the montane forest belt, which exhibits high biodiversity and is the main tourist area of Bogda. The northern buffer zone of Bogda comprises the concentrated feasible monitoring areas, and the area closest to roads and monitoring facilities is highly feasible for NWHS monitoring. The suitability of an area in terms of monitoring is largely determined by the monitoring priority in that particular area. The majority of planned monitoring facilities are well distributed in both suitable and less suitable areas. Analysis results indicate that the protection of Bogda will be more scientifically based due to its effective and all-around planned monitoring system proposed by the declaration text of Xinjiang Tianshan, which is the essential file submitted to World Heritage Centre to inscribe as a NWHS.
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Conservación de los Recursos Naturales , Técnicas de Apoyo para la Decisión , Monitoreo del Ambiente/métodos , Sistemas de Información Geográfica , China , Bosques , HistoriaRESUMEN
World Natural Heritage Sites (WNHS) are treasures that need human protection and invite appreciation, which makes conservation of WNHS an urgent task. This paper assesses where in the world threats are most pressing and which WNHS require emergency assistance. Using an analysis of "hot spots" and inverse distance weighting, it finds that Africa is the region where WNHS are least secure. Reports of the state of the conservation of WNHS describe the many threats that exist. Of these, management activities and institutional factors are the primary threats. The paper suggests relevant measures to improve the WNHS security.
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Conservación de los Recursos Naturales , Monitoreo del Ambiente , África , Humanos , Análisis Espacio-TemporalRESUMEN
To characterize the genetic properties of coxsackievirus A12 (CVA12) strains isolated from hand, foot and mouth disease (HFMD) patients in Qingdao during 2008-2011, the complete genome and VP1 coding region were sequenced and analyzed. Phylogenetic analysis showed that all strains from China clustered into three different branches, suggesting multiple lineages of CVA12 co-circulating in Asia. Sequence analysis indicated a monophyletic group only when the P1 region was examined, indicating possible recombination between CVA12 and other HEV-A serotypes. The emergence of CVA12 involved in an HFMD outbreak in China is a public-health issue.
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Enfermedades Transmisibles Emergentes/virología , Enterovirus/clasificación , Enterovirus/genética , Enfermedad de Boca, Mano y Pie/virología , ARN Viral/genética , Preescolar , China/epidemiología , Análisis por Conglomerados , Enfermedades Transmisibles Emergentes/epidemiología , Enterovirus/aislamiento & purificación , Femenino , Genotipo , Enfermedad de Boca, Mano y Pie/epidemiología , Humanos , Lactante , Masculino , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , Recombinación Genética , Análisis de Secuencia de ADN , Proteínas Estructurales Virales/genéticaRESUMEN
The temperature sensitivities of photosynthesis and respiration remain a key uncertainty in predicting how forests will respond to climate warming. We grew seedlings of four temperate tree species, including Betula platyphylla, Fraxinus mandshurica, Juglans mandshurica and Tilia amurensis, at three temperature regimes (ambient, +2 °C, and +4 °C in daytime air temperature). We investigated net photosynthesis (Anet25), maximum rate of RuBP-carboxylation (Vcmax25) and RuBP-regeneration (Jmax25), stomatal conductance (gs25), mesophyll conductance (gm25), and leaf respiration (Rleaf) in dark (Rdark25) and in light (Rlight25) at 25 °C in all species. Additionally, we examined the temperature sensitivities of Anet, Vcmax, Jmax, Rdark and Rlight in F. mandshurica. Our findings showed that the warming-induced decreases in Anet25, Vcmax25 and Jmax25 were more prevalent in the late-successional species T. amurensis. Warming had negative impacts on gs25 in all species. Overall, Anet25 was positively correlated with Vcmax25 and Jmax25 across all growth temperatures. However, a positive correlation between Anet25 and gs25 was observed only under warming conditions, and gs25 was negatively associated with vapor pressure deficit. This implies that the vapor pressure deficit-induced decrease in gs25 was responsible for the decline in Anet25 at higher temperatures. The optimum temperature of Anet in F. mandshurica increased by 0.59 °C per 1.0 °C rise in growth temperature. While +2 °C elevated the thermal optima of Jmax, it did not affect the other temperature sensitivity parameters of Vcmax and Jmax. Rdark25 was not affected by warming in any species, and Rlight25 was stimulated in T. amurensis. The temperature response curves of Rdark and Rlight in F. mandshurica were not altered by warming, implying a lack of thermal acclimation. The ratios of Rdark25 and Rlight25 to Anet25 and Vcmax25 in T. amurensis increased with warming. These results suggest that Anet and Rleaf did not acclimate to warming synchronously in these temperate tree species.
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Betula , Fraxinus , Fotosíntesis , Hojas de la Planta , Tilia , Árboles , Fotosíntesis/fisiología , Árboles/fisiología , Árboles/metabolismo , Hojas de la Planta/fisiología , Hojas de la Planta/metabolismo , Fraxinus/fisiología , Fraxinus/metabolismo , Tilia/fisiología , Tilia/metabolismo , Betula/fisiología , Betula/crecimiento & desarrollo , Betula/efectos de la radiación , Betula/metabolismo , Juglans/fisiología , Juglans/crecimiento & desarrollo , Carbono/metabolismo , Temperatura , Respiración de la Célula , Cambio ClimáticoRESUMEN
As an attractive biomaterial for bone reconstruction, injectable biomaterials have many prominent characteristics such as good biocompatibility and bone-filling ability. However, there are weak as load-bearing scaffolds. In this study, polyvinyl alcohol (PVA) and bioactive glass (BAG) were interpenetrated into sodium alginate (SA) network to obtain self-enhanced injectable hydrogel. The optimum ratio of PVA/SA/BAG hydrogel was determined based on injectability, gelation time and chemical characterization. Results showed that the selected ratio had the shortest gelation time of 3.5min, and the hydrogel had a rough surface and good coagulation property. The hydrogel was capable of carrying 1kg of weight by mineralization for 14 d The compressive strength, compressive modulus, and fracture energy of the hydrogel reached 0.12MPa, 0.376MPa and 17.750kJ m-2, respectively. Meanwhile, the hydrogel had high moisture content and dissolution rate, and it was sensitive to temperature and ionic strength. Hydroxyapatite was generated on the hydrogel surface, and the hydrogel pores increased, and the pore size enlarged. The biocompatibility of PVA/SA/BAG hydrogel was analyzed using hemolysis and cytotoxicity assays. Results revealed its good biocompatibility with low hemolysis rate and no cytotoxicity to MC3T3-E1 cells. The hydrogel was also found to promote the differentiation of MC3T3-E1 cells with significantly increased in ALP activity and expression of relevant differentiation factors. In vitro mineralization assay showed an increase in calcium nodules and calcification area, indicating the ability of hydrogel to promote mineralization MC3T3-E1 cells. These findings indicated that PVA/SA/BAG hydrogel had potential uses in the field of irregular bone-defect repair due to its injectability, cytocompatibility, and tailorable functionality.
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Hemólisis , Hidrogeles , Humanos , Hidrogeles/química , Materiales Biocompatibles , Durapatita/química , Diferenciación CelularRESUMEN
OBJECTIVE: To investigate characteristics of the whole-genome of influenza A H1N1 virus circulated in Qingdao from year 2009 to 2011. METHODS: RNA of 35 influenza A H1N1 virus isolates circulated in Qingdao between year 2009 and 2011 was extracted and all segments were amplified by RT-PCR. The sequence was then detected and assembled by software Sequencher.25 HA full-length sequences published on GenBank were selected as reference. While MEGA 5.0 software package was explored for phylogenetic analysis to characterize the molecular feature with reference to the whole-genome sequence and the hemagglutinin (HA).1068 HA sequences of influenza A H1N1 virus isolated worldwide from August 2010 to March 2011 were downloaded for amino acid mutation analysis. RESULTS: On the HA genes phylogenetic tree, the virus were separately divided into 4 clades in 2009-2010 and 2010-2011 surveillance season, each with a preponderant epidemic clade. The homogeneity of nucleotide and amino acids of HA isolates were 99.6%-99.9% and 99.1%-99.8% respectively in 2009-2010 surveillance season; 99.1%-99.6% and 98.2%-99.1% respectively in 2010-2011 surveillance season. The homogeneity of nucleotide and amino acids of the preponderant isolates were separately 98.8%-99.8% and 98.0%-99.6%. Compared with the vaccine strain, there were separately 14 and 12 variant amino acids of virus HA in the two surveillance season, involving 10 antigen sites and 5 positive selected sites. The sequence analysis of neuraminidase protein showed that the positions 247, 274 presented serine and histidine(S247, H274) respectively. The sequence analysis of M2 protein showed that the isolated A H1N1 viruses presented asparagine in amino acid site 31 (N31). CONCLUSION: All the A H1N1 influenza virus circulated in Qingdao from year 2009 to 2011 presented continual variation and therefore caused antigenic drift. All the isolations were adamantane-resistance, but susceptible to inhibitors of neuraminidase.
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Genoma Viral , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/virología , Secuencia de Aminoácidos , China/epidemiología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Neuraminidasa/genética , Filogenia , ARN Viral , Análisis de Secuencia de ProteínaRESUMEN
OBJECTIVE: To investigate the evolution features of whole-genome of influenza virus H3N2 prevalent in Qingdao from year 2007 to 2011. METHODS: The RNA of 58 strains of influenza virus H3N2 prevalent in Qingdao between 2007 and 2011 was extracted and all segments amplified by RT-PCR. The sequence was then detected and assembled by software Sequencer. A total of 589 strains of influenza virus H3N2 with more than 300 amino acid recorded by GenBank were selected. The phylogeny and molecular features of all gene segments were analyzed by software Mega 5.0, referred by the heavy chain of hemagglutinin (HA1). RESULTS: Hemagglutinin (HA) genes of influenza virus H3N2 prevalent in Qingdao between year 2007 and 2011 formed a single trunk of phylogenetic tree. Every prevalent strain originated in last season. The analysis of the evolution of whole genome found that reassortment virus strains were prevalent between year 2009 and 2010, but between 2010 and 2011 there were two series of prevalent strains, which showed complicated reassortment. Compared with the vaccine strains, the variant amino acids of protein of virus HA1 between year 2007 and 2011 were 8, 6, 6, 8 and 11, involving 13 antigenic sites. The sequence analysis of M2 protein showed that the isolated influenza virus H3N2 mutated in amino acid site 31, from serine to asparagine (S31N). HA1 gene of influenza virus H3N2 isolated in Qingdao between 2007 and 2011 shared the similar phylogenetic tree with the globally prevalent strain. The comparison of the sequence and the analysis of the antigenicity found co-infection between H3N2 and A/H1N1 in the strain A/Qingdao/F521/2011. CONCLUSION: The evolution features of all segments of influenza virus H3N2 prevalent in Qingdao between year 2007 and 2011 were complicated.
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Evolución Molecular , Genoma Viral , Subtipo H3N2 del Virus de la Influenza A/genética , China , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Filogenia , ARN Viral , Virus Reordenados/genética , Análisis de Secuencia , Proteínas de la Matriz Viral/genéticaRESUMEN
OBJECTIVE: Miniature pigs are considered ideal organ donors for xenotransplantation in humans, but the mechanism underlying their dwarfism remains to be elucidated. IGF-1R is a crucial factor in body size formation in mammals, including skeletal muscle formation and development. The extracellular domain (ECD) binds to the ligand, a phenomenon that results in the activation of downstream pathways. METHODS: In this study, the coding sequences of two IGF-1R ECD haplotypes of the large Landrace (LP) pig and the small Bama Xiang (BM) pig were cloned into pcDNA3.1 vectors to generate pcDNA3.1-LP and pcDNA3.1-BM. The two recombinant vectors were then transfected into skeletal muscle cells. RESULTS: IGF-1R transcript was found to be expressed at higher levels in the pcDNA3.1-LP group than in the pcDNA3.1-BM group. The IGF-1R ECD from LP promoted cell proliferation and CyclinD1 expression, and promoted the phosphorylation of protein kinase B (to yield p-AKT). Moreover, the IGF-1R ECD from LP increased cell differentiation and the expression of myogenic determination factor (MyoD). CONCLUSION: Our data indicated that the IGF-1R ECD haplotypes between pig breeds with different body sizes affect IGF-1R expression, in turn affecting the proliferation and differentiation of skeletal muscle cells by activating downstream signalling pathways.
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Receptor IGF Tipo 1 , Mutación Silenciosa , Porcinos Enanos , Animales , Humanos , Diferenciación Celular/genética , Proliferación Celular , Factor I del Crecimiento Similar a la Insulina/metabolismo , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor IGF Tipo 1/química , Receptor IGF Tipo 1/genética , Porcinos Enanos/genética , Porcinos Enanos/metabolismoRESUMEN
Insulin-like growth factor (IGF)-1 is a polypeptide hormone with vital biological functions in bone cells. The abnormal expression of IGF-1 has a serious effect on bone growth, particularly bone remodeling. Evidence from animal models and human disease suggested that both IGF-1 deficiency and excess cause changes in bone remodeling equilibrium, resulting in profound alterations in bone mass and development. Here, we first introduced the functions and mechanisms of the members of IGFs in bone. Subsequently, the critical role of IGF-1 in the process of bone remodeling were emphasized from the aspects of bone resorption and bone formation respectively. This review explains the mechanism of IGF-1 in maintaining bone mass and bone homeostasis to a certain extent and provides a theoretical basis for further research.
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Resorción Ósea , Factor I del Crecimiento Similar a la Insulina , Animales , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Huesos/metabolismo , Densidad ÓseaRESUMEN
OBJECTIVE: To explore the differences in DNA methylation associated with age-related hearing loss in a study of 57 twin pairs from China. DESIGN: Monozygotic twins were identified through the Qingdao Twin Registration system. The median age of participants was > 50 years. Their hearing thresholds were measured using a multilevel pure-tone audiometry assessment. The pure-tone audiometry was calculated at low frequencies (0.5, 1.0, and 2.0 kHz), speech frequencies (0.5, 1.0, 2.0, and 4.0 kHz), and high frequencies (4.0 and 8 kHz). The CpG sites were tested using a linear mixed-effects model, and the function of the cis-regulatory regions and ontological enrichments were predicted using the online Genomic Regions Enrichment of Annotations Tool. The differentially methylated regions were identified using a comb-p python library approach. RESULTS: In each of the PTA categories (low-, speech-, high-frequency), age-related hearing loss was detected in 25.9%, 19.3%, and 52.8% of participants. In the low-, speech- and high-frequency categories we identified 18, 42, and 12 individual CpG sites and 6, 11, and 6 differentially methylated regions. The CpG site located near DUSP4 had the strongest association with low- and speech-frequency, while the strongest association with high-frequency was near C21orf58. We identified associations of ALG10 with high-frequency hearing, C3 and LCK with low- and speech-frequency hearing, and GBX2 with low-frequency hearing. Top pathways that may be related to hearing, such as the Notch signaling pathway, were also identified. CONCLUSION: Our study is the first of its kind to identify these genes and their associated with DNA methylation may play essential roles in the hearing process. The results of our epigenome-wide association study on twins clarify the complex mechanisms underlying age-related hearing loss.
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Presbiacusia , Gemelos Monocigóticos , Persona de Mediana Edad , Anciano , Humanos , Gemelos Monocigóticos/genética , Metilación de ADN , Epigénesis Genética , Presbiacusia/genética , China , Audiometría de Tonos PurosRESUMEN
To investigate the effects of algal detritus export on the trophic structure of macrozoobenthic community in the adjacent benthic habitat during the bloom and decline of macroalgae, we collected macrozoobenthos from the adjacent sea area of Dalian Island in the North Yellow Sea in May (the algal bloom period) and August (the algal decay period) of 2020. We quantifyied the seasonal changes in the trophic structure of macrozoobenthic community by using carbon and nitrogen stable isotope techniques. Results showed that δ13C and δ15N values of macrozoo-benthos in May ranged from -23.14 to -14.24, 6.21 to 12.90, respectively, and -22.36 to -14.13, 5.33 to 12.00, respectively in August. Results of PERMANOVA analysis showed that δ13C values of macrozoobenthos differed significantly between the two months, while δ15N values were not significantly different. Based on the Euclidean distance, the macrozoobenthic communities in both months could be classified into five trophic functional groups. The trophic levels of macrozoobenthos ranged from 2.00 (Nitidotellina minuta) to 3.97 (Glycera onomichiensis) in May and from 2.00 (N. minuta) to 3.96 (G. onomichiensis) in August. The δ13C range, δ15N range, mean centroid distance, total area and corrected standard ellipse areas which represented community trophic structure indices in August were higher than those in May. Our results indicated that the trophic diversity level and trophic niche width of the macrozoobenthic community in the adjacent sea area of the seaweed bed were higher in the algal decline season.