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Long noncoding RNAs (lncRNAs) are strongly associated with glucose homeostasis, but their roles remain largely unknown. In this study, the potential role of lncRNA-Snhg3 in glucose metabolism was evaluated both in vitro and in vivo. Here, we found a positive relationship between Snhg3 and hepatic glycogenesis. Glucose tolerance improved in hepatocyte-specific Snhg3 knock-in (Snhg3-HKI) mice, while it worsened in hepatocyte-specific Snhg3 knockout (Snhg3-HKO) mice. Furthermore, hepatic glycogenesis had shown remarkable increase in Snhg3-HKI mice and reduction in Snhg3-HKO mice, respectively. Mechanistically, Snhg3 increased mRNA and protein expression levels of PPP1R3B through inducing chromatin remodeling and promoting the phosphorylation of protein kinase B. Collectively, these results suggested that lncRNA-Snhg3 plays a critical role in hepatic glycogenesis.
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Hígado , ARN Largo no Codificante , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ratones , Hígado/metabolismo , Ratones Noqueados , Glucosa/metabolismo , Masculino , Hepatocitos/metabolismo , Ratones Endogámicos C57BL , Glucógeno Hepático/metabolismoRESUMEN
BACKGROUND: Pulmonary vein (PV) data are commonly measured on multiplanar image reformation (MPR) images and volume rendering (VR) images. PURPOSE: To compared and analyze the advantages and disadvantages of PV data based on VR images and MPR images. MATERIAL AND METHODS: A total of 94 patients with atrial fibrillation (AF) with imaging data were included in the study. The respective image postprocessing time and the three surgical interventionists' preferences for the two images were recorded. A paired t-test or chi-square test was used to compare their difference, and P < 0.05 was considered statistically significant. RESULTS: There was no statistically significant difference between the data values including the maximal and minimal ostial diameters of the left superior PV (LSPV), the left inferior PV (LIPV), the right superior PV (RSPV), and the right inferior PV (RIPV) obtained by VR and MPR images (P > 0.05). Yet, the mean postprocessing time of VR images (15.10 ± 3.05 min) was shorter compared to MPR images (16.54 ± 2.60 min) (t = 22.84, P < 0.05). All three surgical interventionists preferred VR images (accounted for 85.1%, 86.2%, and 84.0%, respectively), and there was no statistical difference in the degree of image preference among the three (chi-square = 0.596, P = 0.963). CONCLUSION: PV data measurement could be performed on both VR and MRP images; however, the data on VR images were more intuitive and more accessible for interventional surgeons.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Humanos , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Ablación por Catéter/métodosRESUMEN
In the shallow eutrophic lakes in cold, arid regions, the phytoplankton functional groups and the factors that drive their spatiotemporal variabilities remain unclear. Samples were collected from Lake Ulansuhai in April, August, and October 2017 (wet season) and January 2018 (dry season). Based on the functional group classification method, 23 phytoplankton functional groups with 5 major ones were identified. During the wet season, high amounts of nutrients, elevated temperatures, and heavy rainfall produced spatiotemporal variabilities in phytoplankton communities, whereas during the dry season, the frozen period was the critical factor that determined the spatiotemporal variabilities in the phytoplankton communities. Through redundancy analyses, total nitrogen and total phosphorus concentrations were observed to directly affect the phytoplankton growth; algal growth affected the chemical oxygen demand, and pH and environmental factors interacted with the phytoplankton growth. These results highlight the complex feedbacks of shallow eutrophic lake ecosystems in arid regions. Group TC (represented by Lyngbya) was correlated with Huangtai algae. In August, a Huangtai algal bloom resulted in a relatively stable water column, which was conducive to group TC growth. Therefore, the presence of certain phytoplankton functional groups can indicate the current lake conditions by identifying the coverage of Huangtai algae, which provides a scientific basis for an early warning of a potential algal bloom.
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Monitoreo del Ambiente , Lagos , Fitoplancton , China , Ecosistema , Eutrofización , FósforoRESUMEN
It is obvious that the majority of cellular transcripts are long noncoding RNAs (lncRNAs). Although studies suggested that lncRNAs participate in many biological processes through diverse mechanisms, however, little is known about their effects on epidermal mechanoreceptors. Here, we identified one novel Drosophila lncRNA, Scutellar Macrochaetes Regulatory Gene (SMRG), which regulates scutellar macrochaetes that act as mechanoreceptors by antagonizing the proneural gene scute (sc), through the repressor Enhancer-of-split mß (E(spl)mß). SMRG deficiency induced supernumerary scutellar macrochaetes and simultaneously a high sc RNA level in the adult thorax. Genetically, sc overexpression enhanced this supernumerary phenotype, while heterozygous sc mutant rescued this phenotype, both of which were mediated by E(spl)mß. At the molecular level, SMRG recruited E(spl)mß to the sc promoter region, which in turn suppressed sc expression. Our work presents a novel function of lncRNA and offers insights into the molecular mechanism underlying mechanoreceptor development.
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Proteínas de Drosophila/genética , Drosophila/genética , ARN Largo no Codificante/genética , Animales , Secuencia de Bases , Regulación de la Expresión Génica , Especificidad de Órganos , Regiones Promotoras Genéticas , ARN Largo no Codificante/químicaRESUMEN
Target leaf spot caused by Corynespora cassiicola is an economically important foliar disease on cucumber. In recent years, this disease has caused a serious problem on greenhouse-cultivated cucumber in China. In this study, to explore the characteristics and possible causes of heavy occurrence of the disease, we monitored the resistance of C. cassiicola strains from different provinces of China to benzimidazole and quinone outside inhibitor (QoI) fungicides. The results from sequence comparison of target genes ß-tubulin and Cytb of 619C. cassiicola strains indicate that resistance frequency to benzimidazoles and QoIs is up to 100%. Furtherly, molecular resistance mechanism of C. cassiicola to benzimidazoles and QoIs was analysed. One single mutation E198A and three double mutations E198A&M163I, E198A&F167Y and E198A&F200S were observed in target gene ß-tubulin, which confers resistance to benzimidazoles. To our knowledge, this is the first report that double mutations of ß-tubulin confer resistance to benzimidazoles in filamentous fungi. Compared with single mutation E198A, three double mutations significantly decreased sensitivity to benzimidazoles. Moreover, significant difference of sensitivity to benzimidazoles was observed among three double mutations. These mutation genotypes of ß-tubulin have different geographical distribution and the mutation E198A&M163I is prevalent, occupying for 63.94%. In addition, strong cross resistance patterns between carbendazim, benomyl and thiabendazole were observed in C. cassiicola strains conferring different ß-tubulin mutations. For QoI resistance, the only mutation G143A of Cytb was detected in tested 619C. cassiicola strains. Strong positive cross resistance was observed when comparing the EC50 values of sensitive and resistant strains of C. cassiicola for six intrinsically different QoIs such as azoxystrobin, fluoxastrobin, pyraclostrobin, fenaminstrobin, picoxystrobin and coumoxystrobin. Taken together, all the results not only provide novel insights into understanding resistance mechanism to benzimidazoles and QoIs in filamentous fungi, but also provide some important references for resistance management of target leaf spot on cucumber.
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Ascomicetos/efectos de los fármacos , Bencimidazoles/toxicidad , Cucumis sativus/microbiología , Farmacorresistencia Fúngica/genética , Fungicidas Industriales/toxicidad , Estrobilurinas/toxicidad , Agricultura , Ascomicetos/genética , China , Citocromos b/genética , Proteínas Fúngicas/genética , Mutación , Tubulina (Proteína)/genéticaRESUMEN
Fusarium graminearum species complex (FGSC), causing Fusarium head blight (FHB) of wheat, has species-specific geographical distributions in wheat-growing regions. In recent years, benzimidazole resistance of FHB pathogens has been largely widespread in China. Although the demethylation inhibitor fungicide metconazole has been used for FHB control in some countries, no information about metconazole sensitivity of Chinese FHB pathogen populations and efficacy of metconazole in FHB control in China is available. In this study, the sensitivity of FGSC to metconazole was measured with 32 carbendazim-sensitive strains and 35 carbendazim-resistant strains based on mycelial growth. The 50% effective concentration values of 67 strains were normally distributed and ranged from 0.0209 to 0.0838 µg ml-1, with a mean of 0.0481 ± 0.0134 µg ml-1. No significant difference in metconazole sensitivity was observed between carbendazim-sensitive and -resistant populations. An interactive effect of metconazole and phenamacril, a novel cyanoacrilate fungicide approved in China against Fusarium spp., in inhibiting mycelial growth showed an additive interaction at different ratios. Furthermore, field trials to evaluate the effect of metconazole and metconazole + phenamacril treatments in FHB control, deoxynivalenol (DON) production, and grain yields were performed. Compared with the fungicides carbendazim and phenamacril currently used in China, metconazole exhibits a better efficacy for FHB control, DON production, and grain yields, and dramatically reduces use dosages of chemical compounds in the field. The mixture of metconazole and phenamacril at ratios of 2:3 and 1:2 showed the greatest efficacy for FHB control, DON production, and grain yields among all the fungicide treatments but its use dosages were higher in comparison with metconazole alone. In addition, FHB control, grain yields, and DON levels were significantly correlated with each other, showing that visual disease indices can be used as an indicator of grain yields and DON contamination. Meanwhile, the frequency of carbendazim-resistant alleles in F. graminearum populations was dramatically reduced after metconazole and phenamacril alone and the mixture of metconazole and phenamacril applications, indicating that metconazole and a mixture of metconazole and phenamacril can be used for carbendazim resistance management of FHB in wheat. Overall, the findings of this study provide important data for resistance management of FHB and reducing DON contamination in wheat grains.
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Farmacorresistencia Fúngica , Fungicidas Industriales , Fusarium , Bencimidazoles/farmacología , Carbamatos/farmacología , China , Farmacorresistencia Fúngica/efectos de los fármacos , Fungicidas Industriales/farmacología , Fusarium/efectos de los fármacos , Triazoles/farmacología , Triticum/microbiologíaRESUMEN
OBJECTIVE: To evaluate the potential of synovial membrane volume measurement by MRI in monitoring the effect of radiation synovectomy on patients of Hemophilic Arthropathy (HA). METHODS: We studied 63 diseased joints of 42 HA patients who received hospitalized services at the Hemophilia Diagnosis and Treatment Center of Henan Provincial People's Hospital from May 2011 to January 2015. Unenhanced and enhanced MR scanning of each diseased joint was performed simultaneously. The volumes of synovial membrane of 21 joints from 16 patients before and after being treated with 32P radiation synovectomy (PRS) were measured and compared using image post-processing software and workstation. Two sample matching t test was conducted to analyze the synovial membrane volumes of the same joint measured by unenhanced and enhanced MR, as well as change of MR enhancement ratio after treatments. RESULTS: The synovial membrane volumes measured by unenhanced versus enhanced MR scanning showed no statistical significance. Significant reduction (tâ=â7.831, pâ<â0.001) of the synovial membrane volume after treatment (2479.45±46.48âmm3 versus 2983.30±42.87âmm3 before treatment) was observed. MR enhancement ratio of synovial membrane decreased after treatment (0.92±0.06 after vs 1.17±0.07 before treatment) with statistical significance. CONCLUSION: The synovial membrane volume and MR enhancement ratio can be used to monitor patient response to PRS treatment.
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Hemofilia A/complicaciones , Artropatías , Imagen por Resonancia Magnética/métodos , Sinovectomía/métodos , Membrana Sinovial/diagnóstico por imagen , Adolescente , Adulto , Niño , Preescolar , Estudios de Seguimiento , Humanos , Artropatías/diagnóstico por imagen , Artropatías/etiología , Artropatías/radioterapia , Masculino , Radioisótopos de Fósforo/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
In this study, treatment of high-fat diet-induced obesity (DIO) C57BL/6J mice with spermidine decreased body weight and subcutaneous and visceral fat content, reversed the apparent hepatosteatosis, and reduced hepatic intracellular and serum triglyceride and total cholesterol concentrations. Moreover, spermidine treatment improved glucose tolerance and insulin sensitivity in DIO mice. The mechanism studies indicated that spermidine indeed increased the phosphorylation of hepatic AMP-activated protein kinase (AMPK), and inhibited the expression of lipogenic genes in vivo and in vitro. Moreover, these spermidine-mediated molecular effects were also abolished by compound C, an inhibitor of AMPK, in primary hepatocytes. In summary, spermidine protected against DIO-induced hepatosteatosis by decreasing lipogenic genes expression through an AMPK-mediated mechanism.
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Proteínas Quinasas Activadas por AMP/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Espermidina/farmacología , Animales , Peso Corporal/efectos de los fármacos , Células Cultivadas , Dieta Alta en Grasa/efectos adversos , Ácido Graso Sintasas/genética , Ácido Graso Sintasas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/etiología , Obesidad/metabolismo , Obesidad/prevención & control , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismoRESUMEN
OBJECTIVE: This study was aimed to explore whether the omentin-1, a novel adipokine marker, could be a biomarker for stroke, as well as its association with stroke severity. METHODS: This study included 239 patients with ischemic stroke. The serum omentin-1 level was determined and the stroke was evaluated when the patients were hospitalized. The control groups consisted of 108 patients with matched age, gender and prior vascular risk factors and 120 health control with matched age and gender. The stroke severity was assessed with National Institutes of Health Stroke Scale (NIHSS) when the patients were hospitalized, and NIHSS scoreâ¯>â¯6 was evaluated as moderate-to-severe stroke. RESULTS: Omentin-1 level in serum samples of 239 stroke patients was determined, with the median value of 109.5â¯ng/ml [Inter Quartile Range (IQR), 78.4-142.9â¯ng/ml]. There was a negative relation between omentin-1 level and the infarct volume (râ¯=â¯-0.289, Pâ¯=â¯0.001). The level of omentin-1 was significantly reduced in stroke patients than that of in control group 1 [125.3 (IQR, 95.8-158.7); Pâ¯=â¯0.002] and control group 2 [146.5 (IQR, 116.2-177.3); Pâ¯<â¯0.001]. With the analysis of multivariate model, omentin-1 as a continuous variable was related to lowered stroke risk (odds ratios [OR] 0.994, 95% confidence interval (CI): 0.990-0.998; Pâ¯=â¯0.006). In addition, omentin-1 was an independent indicator for stroke severity (OR 0.992, 95% CI: 0.989-0.996). Levels of omentin-1 in the Q1 showed a relative risk of 2.66 (95% CI: 1.52-4.18) for moderate-to-severe stroke after adjusting for above possible confounders compared to reference category [Quartile (Q): 2-4]. CONCLUSION: The data indicated a negative relation between omentin-1 level and risk of ischemic stroke. The omentin-1 could be promising indicator of stroke and its severity.
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Isquemia Encefálica/sangre , Citocinas/sangre , Lectinas/sangre , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Anciano , Biomarcadores/sangre , Isquemia Encefálica/diagnóstico , Diagnóstico Precoz , Femenino , Proteínas Ligadas a GPI/sangre , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
In this paper, porous ZnO sheet with an average pore size of 14.7 nm had been successfully prepared via mixed solvent thermal method without any surfactants. The mixed solvents were made up of water and aniline. The effect of calcination temperature on the structure was investigated. The results showed that when the calcination temperature was 350 °C, the porous structure formed and the borders of the as-formed porous structure sheets were heavily regular and straight. The photocatalytic properties of products were studied through detecting the degradation efficiency of RhB under the 500 W mercury lamp irradiation. The effects of calcination temperature and catalyst concentration of the products on photocatalytic efficiency were investigated in detail. When the precursor was calcined at 350 °C for 4 h, the photodegradation efficiency of RhB can be up to 100% after irradiating for 60 min. The morphologies and compositions of the as-prepared products were characterized via transmission electron microscopy (TEM) and X-ray diffraction (XRD).
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The Fusarium graminearum species complex (FGSC), the causal agents of Fusarium head blight (FHB) in wheat, has the different geographically distributed species. Our previous study suggested that a DMI fungicide metconazole exhibits a strong fungicidal activity in mycelial growth of Chinese FHB pathogens and metconazole is currently a most effective compound of commercial fungicides for controlling FHB in China. In the current study, metconazole-resistant F. graminearum mutants were induced by chemical taming and their molecular and biological characteristics were determined. Compared to the corresponding parental strains, three mutation genotypes (two single mutations G443S and D243N, and a combined mutation E103Q&V157â¯L) were observed in the FgCYP51A of metconazole-resistant mutants. In addition to FgCYP51A mutation, all the mutants had no change on sequences of FgCYP51B and FgCYP51C and promotor sequences of FgCYP51s, but expression patterns of FgCYP51s were different. Compared to the corresponding parental strains, overexpression of FgCYP51A, FgCYP51B and FgCYP51C was observed in the mutant conferring D243N mutation, overexpression of FgCYP51A and FgCYP51B was observed in the mutant conferring E103Q&V157L mutations, and overexpression of FgCYP51A was observed in the mutant conferring G443S mutation. Biological fitness of the mutants conferring D243N mutation or E103Q&V157â¯L mutations significantly decreased in comparison to the corresponding parental strains, suggesting a fitness penalty. The mutants conferring G443S mutation had no change in biological fitness as compared with the parental strain, indicating that the G443S mutation may emerge in field resistant populations of F. graminearum in the future. In addition, a positive cross resistance between metconazole and other tested DMI fungicides was observed in the mutants conferring D243N mutation or E103Q&V157L mutations, but no cross resistance between metconazole and ipconazole or prochloraz was observed in the mutants conferring G443S mutation. Therefore, we concluded that the mutation genotype of FgCYP51A may cause the differences of biological fitness, cross-resistance and FgCYP51s overexpression patterns. Such information will increase our understanding of resistance mechanism of F. graminearum to DMIs and could provide new reference data for the management of FHB.
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Familia 51 del Citocromo P450/genética , Proteínas Fúngicas/genética , Fungicidas Industriales/farmacología , Fusarium/efectos de los fármacos , Triazoles/farmacología , Farmacorresistencia Fúngica , Fusarium/genética , Genotipo , MutaciónRESUMEN
Resistance to benzimidazole fungicides in many phytopathogenic fungi is caused by specific point mutations in the ß-tubulin gene (ß-tubulin). However, the mutated locus and genotype of ß-tubulin differ among phytopathogenic fungi. To validate the point mutation in Fusarium asiaticum ß2-tubulin that confers resistance to carbendazim and to analyze the molecular interaction between carbendazim and F. asiaticum ß2-tubulin. In this study, a new point mutation (GAGâGCG, E198A) at codon 198 of ß2-tubulin in a wild-type F. asiaticum strain was constructed by site-directed mutagenesis followed by a split marker strategy. The site-directed mutants were verified and exhibited a high level of resistance to carbendazim. In the absence of fungicide treatment, the biological characteristics did not differ between the site-directed mutants and the wild-type strain. Molecular docking between carbendazim and ß2-tubulin was carried out using the Surflex-Dock program in Sybyl X-2.0 version and the results indicated that the E198A mutation altered the configuration of ß2-tubulin, resulting in the change of the bonding sites and docking scores. We concluded that the point mutation of F. asiaticum ß2-tubulin conferring carbendazim resistance may not always be the bonding site for carbendazim.
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Bencimidazoles/farmacología , Carbamatos/farmacología , Farmacorresistencia Fúngica/genética , Fungicidas Industriales/farmacología , Fusarium/efectos de los fármacos , Mutación Puntual , Tubulina (Proteína)/genética , Sitios de Unión , Fusarium/genética , Genes de Plantas , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Mutagénesis Sitio-Dirigida , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
This study evaluated the use of phenamacril and ipconazole, alone and in mixtures, for the control of rice bakanae disease caused by Fusarium fujikuroi. Mixtures were studied with the goal of reducing the selection of fungicide-resistant field isolates of the fungus. When tested alone, both phenamacril and ipconazole exhibited high antifungal activity against F. fujikuroi mycelial growth; the average EC50 value for 19 field isolates was 0.1544 µg/ml for phenamacril and 0.0472 µg/ml for ipconazole. A 2:1 mixture of phenamacril and ipconazole caused a slightly synergistic (greater than additive) inhibition of mycelial growth. Inhibition of F. fujikuroi sporulation was highest for ipconazole alone, intermediate with the 2:1 mixture, and lowest for phenamacril alone. Inhibition by phenamacril and ipconazole alone or by the 2:1 mixture was substantially lower for spore germination than for mycelial growth or sporulation. When the total fungicide concentration was <24 g of a.i./100 kg of treated rice seeds, the fungicides, whether alone or in the 2:1 mixture, were not phytotoxic to seeds or seedlings of two rice cultivars. In a greenhouse experiment, the 2:1 mixture of phenamacril and ipconazole at 6 g of a.i./100 kg of treated seeds provided 100% control of rice bakanae disease on two cultivars. Overall, the results indicate that the use of a 2:1 mixture of phenamacril and ipconazole should control rice bakanae disease while reducing the occurrence of fungicide resistance in F. fujikuroi.
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Fungicidas Industriales/farmacología , Fusarium/fisiología , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Sinergismo Farmacológico , Fusarium/clasificación , Fusarium/efectos de los fármacos , Interacciones Huésped-Patógeno/efectos de los fármacos , Micelio/efectos de los fármacos , Micelio/fisiología , Plantones/microbiología , Semillas/microbiología , Especificidad de la Especie , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/fisiologíaRESUMEN
BACKGROUND: There are two parts included in traditional imaging diagnosis teaching: theoretical lessons and experimental lessons. Most of the time, the experimental lesson is a review of the theoretical lesson. The teacher is the centre of the course and students are passive learners. Thus, in this study we included the patient problem of the imaging centre in our imaging diagnosis education. The traditional theoretical lessen was used to discuss prior knowledge, the discussion and analysis of patient problems was arranged under class, and the experimental lesson was used to synthesize and test the newly acquired information. The aim of this study is to determine whether or not integration of problem- and lecture-based learning teaching modes in imaging diagnosis education was associated with a good teaching effect. Forty-six of sixty students (76.7%) like integrated problem- and lecture-based learning teaching mode and 53 of 60 students (88.3%) think that integrated problem- and lecture-based learning teaching mode can make their ability of self-study be improved. METHODS: Sixty students participated in a prospective study with a two-phase cross-over design. All of the students were divided into 2 groups of 30 each. In the first term, the first group participated in an integration of the problem- and lecture-based learning teaching mode, whereas students in the second group underwent the lecture-based learning teaching mode alone. During the second term, the teaching modes were exchanged between the two groups. A close-exam and survey were used to evaluate the teaching effect, and the data were analysed means of analysis of variance with a two-phase cross-over design and a χ2 test with a 2-tailed α of 0.05. RESULTS: There was a statistically significant difference in the test scores between the integration of the problem- and lecture-based learning teaching mode and the lecture-based learning teaching mode alone (P < 0.05). The integration of problem- and lecture-based learning teaching mode was well-appraised. CONCLUSION: Integration of the problem- and lecture-based learning teaching modes in teaching imaging diagnosis education resulted in a good teaching effect.
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Diagnóstico por Imagen , Aprendizaje Basado en Problemas , Enseñanza , Estudios Cruzados , Evaluación Educacional , Humanos , Aprendizaje , Proyectos Piloto , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
Correct pathfinding and target recognition of a developing axon are exquisitely regulated processes that require multiple guidance factors. Among these factors, the second messengers, cAMP and cGMP, are known to be involved in establishing the guidance cues for axon growth through different intracellular signaling pathways. However, whether and how cGMP-dependent protein kinase (PKG) regulates axon guidance remains poorly understood. Here, we show that the motor axons of intersegmental nerve b (ISNb) in the Drosophila embryo display targeting defects during axon development in the absence of foraging(for), a gene encoding PKG.In vivo tag expression revealed PKG to be present in the ventral nerve code at late embryonic stages, supporting its function in embryonic axon guidance. Mechanistic studies showed that the transcription factor longitudinal lacking(lola) genetically interacts with for.PKG physically associates with the LolaT isoform via the C-terminal zinc-finger-containing domain. Overexpression of PKG leads to the cytoplasmic retention of LolaT in S2 cells, suggesting a role for PKG in mediating the nucleocytoplasmic trafficking of Lola. Together, these findings reveal a novel function of PKG in regulating the establishment of neuronal connectivity by sequestering Lola in the cytoplasm. SIGNIFICANCE STATEMENT: Axon pathfinding and target recognition are important processes in the formation of specific neuronal connectivity, which rely upon precise coordinated deployment of multiple guidance factors. This paper reveals the role of cGMP-dependent protein kinase (PKG) in regulating the pathfinding and targeting of the developing axons in Drosophila Moreover, our study indicates that PKG regulates the cytoplasmic-nuclear trafficking of the transcription factor LolaT, suggesting a mechanism of PKG in directing motor axon guidance. These findings highlight a new function of PKG in axon guidance by suppressing a transcription factor.
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Axones/metabolismo , Proteínas Quinasas Dependientes de GMP Cíclico/fisiología , Proteínas de Drosophila/metabolismo , Factores de Transcripción/metabolismo , Animales , Animales Modificados Genéticamente , Proteínas Quinasas Dependientes de GMP Cíclico/genética , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Drosophila , Proteínas de Drosophila/genética , Femenino , Masculino , Transporte de Proteínas/fisiología , Factores de Transcripción/genéticaRESUMEN
Streptococcus gallolyticus subsp. pasteurianus is an under-recognized pathogen and zoonotic agent causing opportunistic infections in humans. Despite increasing recognition of this subspecies as a cause for human infectious diseases, limited information is known about its antibiotic resistance mechanism. In this study, we aim to identify the molecular mechanism underlying the high macrolide resistance of six S. gallolyticus subsp. pasteurianus isolates from dead ducklings collected in several natural outbreaks in China during 2010-2013. All isolates exhibited multi-drug resistance including high macrolide resistance (MIC ≥ 1024 mg/L for erythromycin, and 512 mg/L for clarithromycin). Efflux-encoding mefA and mefE genes were not detectable in these isolates. The presence of 23S rRNA mutations in specific isolates did not significantly change macrolide MICs. No nucleotide substitutions were found in genes encoding ribosomal proteins L4 or L22. The ermB and ermT genes were found in the genomes of all isolates. These two genes were acquired independently in one highly virulent isolate AL101002, and clustered with Tn916 and IS1216, respectively. The expression of both ermB and ermT in all isolates was erythromycin inducible and yielded comparable macrolide MICs in all six isolates. Taken together, inducible expression of both ermB and ermT conferred high macrolide resistance in these S. gallolyticus subsp. pasterianus isolates. Our findings reveal new macrolide resistance features in S. gallolyticus subsp. pasteurianus by both ermB and ermT.
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Antibacterianos/farmacología , Proteínas Bacterianas/genética , Macrólidos/farmacología , Streptococcus gallolyticus/efectos de los fármacos , China , Claritromicina/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Eritromicina/farmacología , Proteínas de la Membrana/genética , Pruebas de Sensibilidad Microbiana , ARN Ribosómico 23S/genética , Streptococcus gallolyticus/genética , Streptococcus gallolyticus/aislamiento & purificación , Virulencia/genéticaRESUMEN
BACKGROUND & AIMS: Heme oxygenase 1 (HO-1)-mediated increases in adiponectin, ameliorate the deleterious effects of obesity and metabolic syndrome; however, the effect of HO-1 on hepatic lipid metabolism remains elusive. The aim of this study is to evaluate the role of HO-1 in hepatic lipid metabolism. METHODS: Functional studies were performed using C57BL/6J (WT) mice and Sirt1 liver specific mutant (Sirt1-deficient) mice. The molecular mechanism was explored in primary hepatocytes and mouse liver. RESULTS: Chronic exposure to high-fat diet (HFD) induced hepatic steatosis in WT mice. Treatment of WT mice on HFD with cobalt protoporphyrin (CoPP), an inducer of HO-1 activity, decreased body weight and visceral fat content, reduced intracellular hepatic triglyceride and serum total cholesterol concentrations, and decreased liver lipid droplet formation. Compared with WT mice, the administration of CoPP to Sirt1-deficient mice on HFD increased visceral fat content, and slightly promoted liver lipid droplet formation. CoPP improved glucose tolerance and insulin sensitivity in WT mice on HFD, but compromised insulin sensitivity in Sirt1-deficient mice on HFD. Furthermore, CoPP-induced Sirt1 expression and decreased sterol regulatory element binding protein 1c (SREBP-1c) expression in WT mice on HFD. However, CoPP promoted SREBP-1c expression in Sirt1-deficient hepatocytes, which was reversed by a protein tyrosine phosphatase 1b inhibitor. Additionally, while the administration of CoPP to WT mice on HFD improved antioxidant and anti-inflammatory states, these CoPP-mediated effects were abolished in Sirt1-deficient mice. CONCLUSIONS: Sirt1 mediates the effect of CoPP on ameliorating liver metabolic damage caused by HFD.
Asunto(s)
Hígado Graso/prevención & control , Hemo-Oxigenasa 1/fisiología , Hígado/efectos de los fármacos , Protoporfirinas/farmacología , Sirtuina 1/fisiología , Animales , Células Cultivadas , Dieta Alta en Grasa , Resistencia a la Insulina , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Proteína Tirosina Fosfatasa no Receptora Tipo 1/fisiología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/fisiologíaRESUMEN
Long noncoding RNA (lncRNA) is an emerging category of transcript, and comprises the majority of the transcriptome of various complex organisms. The biological functions of only a handful of lncRNAs have been investigated in detail, showing involvement in a wide range of biological processes through different functional paradigms. However, most lncRNAs remain to be identified. Many lncRNAs are predicted to function, often preferentially, in the nervous system, potentially playing roles in mediating neural functions such as development, behavior, and cognition. To examine the biological significance and potential mechanisms of the remaining unknown neural lncRNAs, certain tractable model organisms, such as Drosophila, can provide advantages including the use of numerous genetic tools. Herein, we summarize recent progress on the in vivo or potential functions of Drosophila lncRNAs, in particular, behavior and development-related lncRNAs.
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Drosophila/fisiología , Neuronas/fisiología , ARN Largo no Codificante/metabolismo , Animales , Drosophila/genética , Locomoción/genética , Locomoción/fisiología , Sueño/genética , Sueño/fisiologíaRESUMEN
Infections of pigeons with herpesviruses have been described in several species of domestic and wild birds. In July 2012, increased mortality was observed in a hybrid meat-type pigeon flock in Beijing, China. Diagnostic tests led to the isolation of a virus designated columbid herpesvirus 1 BJ strain (CoHV-1BJ). Sequence analysis of the viral DNA polymerase catalytic subunit gene revealed a single open reading frame of 3753 nt encoding 1250 amino acids. Phylogenetic analysis revealed that the CoHV-1BJ is closely related to the members of the genus Mardivirus within the subfamily Alphaherpesvirinae. An experimental infection demonstrated that CoHV-1BJ is pathogenic to young pigeons, resulting in systemic infection with scattered focal necrosis in the liver and spleen. The results provide an initial assessment of herpesvirus infection in domestic pigeons in China.
Asunto(s)
Enfermedades de las Aves/epidemiología , Columbidae/virología , ADN Polimerasa Dirigida por ADN/genética , Infecciones por Herpesviridae/veterinaria , Mardivirus/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Enfermedades de las Aves/virología , China , ADN Viral/genética , Infecciones por Herpesviridae/virología , Mardivirus/aislamiento & purificación , Datos de Secuencia Molecular , Filogenia , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
Carboxylesterases are mainly involved in the mediation of metabolic resistance of many insects to organophosphate (OP) insecticides. Carboxylesterases underwent two divergent evolutionary events: (1) quantitative mechanism characterized by the overproduction of carboxylesterase protein; and (2) qualitative mechanism caused by changes in enzymatic properties because of mutation from glycine/alanine to aspartate at the 151 site (G/A151D) or from tryptophan to leucine at the 271 site (W271L), following the numbering of Drosophila melanogaster AChE. Qualitative mechanism has been observed in few species. However, whether this carboxylesterase mutation mechanism is prevalent in insects remains unclear. In this study, wild-type, G/A151D and W271L mutant carboxylesterases from Culex pipiens and Aphis gossypii were subjected to germline transformation and then transferred to D. melanogaster. These germlines were ubiquitously expressed as induced by tub-Gal4. In carboxylesterase activity assay, the introduced mutant carboxylesterase did not enhance the overall carboxylesterase activity of flies. This result indicated that G/A151D or W271L mutation disrupted the original activities of the enzyme. Less than 1.5-fold OP resistance was only observed in flies expressing A. gossypii mutant carboxylesterases compared with those expressing A. gossypii wild-type carboxylesterase. However, transgenic flies universally showed low resistance to OP insecticides compared with non-transgenic flies. The flies expressing A. gossypii W271L mutant esterase exhibited 1.5-fold resistance to deltamethrin, a pyrethroid insecticide compared with non-transgenic flies. The present transgenic Drosophila system potentially showed that a quantitative increase in carboxylesterases induced broader resistance of insects to insecticides than a qualitative change.