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1.
Phytopathology ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31799899

RESUMO

Colletotrichum species isolates contain two paralogous CYP51 genes that encode sterol 14-demethylase enzymes, but their role in sensitivity to DMI fungicides is yet to be determined. In this study, each of the two genes from C. fioriniae and C. nymphaeae was able to rescue the function of CYP51 in the yeast Saccharomyces cerevisiae, demonstrating their independent function. Deletion of CYP51A led to increased sensitivity to propiconazole, diniconazole, prothioconazole, cyproconazole, epoxiconazole, flutriafol, prochloraz, and difenoconazole in C. fioriniae, and to the same fungicides and tebuconazole in C. nymphaeae with the exception of prochloraz. Deletion of CYP51B in C. fioriniae and CYP51B in C. nymphaeae made mutants increasingly sensitive to five of nine DMI fungicides tested. The results suggest species-specific, differential binding of DMI fungicides onto the two CYP51 enzymes. Pairing DMIs with different effects on CYP51A and B deletion mutants resulted in synergistic effects as determined in mycelial growth inhibition experiments. Deletion mutants showed no fitness penalty, in terms of mycelial growth, sporulation, and virulence. Our study elucidates the effect of the CYP51A and CYP51B of Colletotrichum spp. on DMI sensitivity, suggesting using mixture of DMIs may improve the efficacy for anthracnose management.

2.
Front Oncol ; 9: 1304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824864

RESUMO

Background: Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement is a rare kind of hematological malignant disease. Case presentation: A 37-year-old male patient experienced three distinct disease stages from myeloproliferative neoplasm (MPN), T-cell lymphoblastic lymphoma (T-LBL) to a much more complexed phage of a mixed phenotype acute leukemia (MPAL). Both genetic and genomic alternations were detected including chromosomal abnormality and genic mutations. Result: Karyotyping and fluorescence in situ hybridization (FISH) analysis of either bone marrow or lymph node sample confirmed the presence of the FGFR1 rearrangement. Amplifications of RUNX1, ERG, and U2AF1 genes were identified by next generation sequencing. Furthermore, a frame-shift variant of F330fs*>149 in the RUNX1 gene and a missense mutation of R2263Q in NOTCH1 were also detected. Conclusion: The FGFR1 rearrangement functions as a trigging oncogenic event. Then other genetic events such as RUNX1 and/or NOTCH1 alternations further lead to progression of disease with trilineage blasts assignment.

3.
DNA Res ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31883002

RESUMO

Hybridization and polyploidy are pervasive evolutionary features of flowering plants and frequent among some animal groups, such as fish. These processes always lead to novel genotypes and various phenotypes, including growth heterosis. However, its genetic basis in lower vertebrate is still poorly understood. Here, we conducted transcriptome-level analyses of the allopolyploid complex of Carassius auratus red var. (R) (♀) × Cyprinus carpio L. (C) (♂), including the allodiploid and allotetraploid with symmetric subgenomes, and the two allotriploids with asymmetric subgenomes. The gradual changes of gene silencing and novel gene expression suggested the weakening of the constraint of polymorphic expression in genotypic changes. Then, analyses of the direction and magnitude of homoeolog expression exhibited various asymmetric expression patterns, which supported that R incomplete dominance and dosage compensation were co-regulated in the two triploids. Under these effects, various magnitudes of R-homoeolog expression bias were observed in growth-regulated genes, suggesting that they might contribute to growth heterosis in the two triploids. The determination of R incomplete dominance and dosage compensation, which might be led by asymmetric subgenomes and multiple sets of homologous chromosomes, explained why various expression patterns were shaped and their potential contribution to growth heterosis in the two triploids.

4.
Genome Res ; 29(11): 1805-1815, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31649058

RESUMO

Hybridization drives rapid speciation by shaping novel genotypic and phenotypic profiles. Genomic incompatibility and transcriptome shock have been observed in hybrids, although this is rarer in animals than in plants. Using the newly sequenced genomes of the blunt snout bream (Megalobrama amblycephala [BSB]) and the topmouth culter (Culter alburnus [TC]), we focused on the sequence variation and gene expression changes in the reciprocal intergeneric hybrid lineages (F1-F3) of BSB × TC. A genome-wide transcriptional analysis identified 145-974 expressed recombinant genes in the successive generations of hybrid fish, suggesting the rapid emergence of allelic variation following hybridization. Some gradual changes of gene expression with additive and dominance effects and various cis and trans regulations were observed from F1 to F3 in the two hybrid lineages. These asymmetric patterns of gene expression represent the alternative strategies for counteracting deleterious effects of the subgenomes and improving adaptability of novel hybrids. Furthermore, we identified positive selection and additive expression patterns in transforming growth factor, beta 1b (tgfb1b), which may account for the morphological variations of the pharyngeal jaw in the two hybrid lineages. Our current findings provide insights into the evolution of vertebrate genomes immediately following hybridization.

5.
Oncol Lett ; 18(2): 1521-1529, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423219

RESUMO

Forkhead box protein N3 (FOXN3) is a transcriptional repressor involved in cell cycle regulation and tumorigenesis. Abnormalities in gene structure and epigenetics of FOXN3 are closely associated with the occurrence of hematological malignancies; however, its involvement in the pathogenesis of acute myeloid leukemia (AML) remains unknown. The present study aimed to examine the potential significance of FOXN3 in AML. FOXN3 expression levels were examined in patients with AML and AML cell lines, and its clinical significance in AML was evaluated. FOXN3-overexpressing AML cell lines were established, and the biological function of FOXN3 was detected by flow cytometry and a Cell Counting Kit-8 assay. A significant decrease in FOXN3 expression levels was observed in patients with AML and in the AML cell lines in vitro. FOXN3 expression levels were associated with the number of leukocytes in patients. FOXN3 overexpression may inhibit cell proliferation in AML cell lines, induce cell cycle S-phase arrest and promote apoptosis in OCI-AML3 and THP-AML cells. The present study provided insight into how FOXN3 may serve as a novel tumor suppressor in AML.

6.
Bioorg Med Chem ; 27(19): 115048, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31439387

RESUMO

Pyrazole constitutes an important heterocyclic family covering a broad range of synthetic as well as natural products that exhibit numerous chemical, biological, agrochemical and pharmacological properties. In order to explore compounds with good fungicidal activity, a series of new pyrazole derivatives containing 5-phenyl-2-furan were designed and synthesized. In vitro and in vivo fungicidal activities were evaluated and the compound ethyl-1-(5-phenylfuran-2-carbonyl)-5-propyl-1H-pyrazole-3-carboxylate (I8) displayed significant fungicidal activity against various fungi, especially against P. infestans. The structures of the novel pyrazole derivatives were confirmed by 1H NMR, 13C NMR, MS, elemental analysis and X-ray single crystal diffraction. Further study showed that compound I8 might act on the synthesis of cell walls from morphological and ultrastructural studies by SEM and TEM. The results also revealed that compound I8 could block the nutritional transportation leading to cells senescence and death. These results suggested that the novel pyrazole derivatives proved to be promising lead compounds.

7.
Plant Physiol ; 181(1): 249-261, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31331996

RESUMO

DNA methylation and histone modification are important epigenetic marks that coregulate gene expression and genome stability. To identify factors involved in chromatin silencing, we carried out a forward genetic screen for mutants that release the silenced Pro-35S:LUCIFERASE (35SP-LUC) in Arabidopsis (Arabidopsis thaliana). We identified an epigenetic regulator, METHIONINE SYNTHASE1 (ATMS1), which catalyzes the synthesis of methionine (Met) in the one-carbon metabolism pathway. The ATMS1 mutation releases the silenced 35SP-LUC and the majority of endogenous genes and transposons. The effect of ATMS1 on chromatin silencing is related to decreased levels of DNA methylation (CG, CHG, and CHH) and histone-3 lysine-9 dimethylation. The ATMS1 mutation caused a significant decrease in the ratio of S-adenosylmethionine to S-adenosylhomocysteine. Exogenous application of Met rescued the phenotype of atms1-1 ATMS1 plays a predominant role in DNA and histone methylations among the three Met synthetase homologs. These results suggest that ATMS1 is required for DNA and histone methylations through its function in the one-carbon metabolism pathway, indicating the complex interplay between metabolism and epigenetic regulation.

8.
Tree Physiol ; 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31211386

RESUMO

Cellulose synthase A genes (CesAs) are responsible for cellulose biosynthesis in plant cell walls. In this study, functions of secondary wall cellulose synthases PtrCesA4, PtrCesA7-A/B and PtrCesA8-A/B were characterized during wood formation in Populus trichocarpa (Torr. & Gray). CesA RNAi knockdown transgenic plants exhibited stunted growth, narrow leaves, early necrosis, reduced stature, collapsed vessels, thinner fiber cell walls and extended fiber lumen diameters. In the RNAi knockdown transgenics, stems exhibited reduced mechanical strength, with reduced modulus of rupture (MOR) and modulus of elasticity (MOE). The reduced mechanical strength may be due to thinner fiber cell walls. Vessels in the xylem of the transgenics were collapsed, indicating that water transport in xylem may be affected and thus causing early necrosis in leaves. A dramatic decrease in cellulose content was observed in the RNAi knockdown transgenics. Compared with wildtype, the cellulose content was significantly decreased in the PtrCesA4, PtrCesA7 and PtrCesA8 RNAi knockdown transgenics. As a result, lignin and xylem contents were proportionally increased. The wood composition changes were confirmed by solid-state NMR, two-dimensional solution-state NMR and sum-frequency-generation vibration (SFG) analyses. Both solid-state nuclear magnetic resonance (NMR) and SFG analyses demonstrated that knockdown of PtrCesAs did not affect cellulose crystallinity index. Our results provided the evidence for the involvement of PtrCesA4, PtrCesA7-A/B and PtrCesA8-A/B in secondary cell wall formation in wood and demonstrated the pleiotropic effects of their perturbations on wood formation.

9.
Oncol Rep ; 42(2): 785-796, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31233189

RESUMO

Sorafenib is the first­line drug used in the treatment of liver cancer; however, drug resistance seriously limits the clinical response to sorafenib. The present study investigated the molecular mechanisms of sorafenib resistance in liver cancer cells. The data indicated that forkhead box M1 (FoxM1) was significantly overexpressed in sorafenib­resistant cells, at the mRNA and protein levels. Knockdown of FoxM1 rendered drug­tolerant cells sensitive to sorafenib. Furthermore, FoxM1 was upregulated at the transcriptional level. Overexpression of c­jun was associated with the upregulation of FoxM1. The results of a reporter gene assay, electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that there is an activator protein­1 (AP1) binding site in the promoter of FoxM1, located at ­608 to ­618. Knockdown of c­jun significantly decreased the levels of FoxM1, accompanied by enhanced cell sensitivity to sorafenib. Furthermore, the activation of AKT contributed to the upregulation of c­jun and FoxM1. Inhibition of AKT using BEZ­235 markedly suppressed the upregulation of c­jun and FoxM1, and increased the sensitivity of drug­resistant cells to sorafenib in vitro and in vivo. The data indicated that the activation of the AKT/AP1/FoxM1 signaling axis is an important determinant of sorafenib tolerance.

10.
Chin J Integr Med ; 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31065990

RESUMO

OBJECTIVE: To investigate the mechanism of Radix Kansui (RK) stir-fried with vinegar (VRK) decreased hepatotoxicity in mice. METHODS: According to a random number table, 40 mice were randomly divided into negative control group (0.5% carboxymethylcellulose sodium, 20 mL/kg), positive control group (0.1% mixture of carbon tetrachloride in soybean oil, 20 mL/kg), RK group (the ethyl acetate extracts of RK, 250 g crude drug/kg) and VRK group (the ethyl acetate extracts of VRK, 250 g crude drug/kg) with 10 mice per group. All mice were administered orally by gavage daily for 7 continuous days. The morphology of liver tissues was examined to assess the liver injury by a transmission electron microscope. Hepatocyte apoptosis in vivo was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nickend labeling (TUNEL) assay. Immunohistochemical technique was adopted to detect the expression of particular antiapoptotic and proapoptotic proteins in the mitochondrial pathways, including B-cell lymphoma (Bcl-2) and caspase-3, as well as the expression of inflammatory mediators, including nuclear factor kappa B (NF- κ B) and intercellular adhesion molecule-1 (ICAM-1). RESULTS: Liver injury and hepatocyte apoptosis were observed in RK mice, and the liver injury were significantly reduced in VRK-treated mice. In immunohistochemistry study, compared with the negative control group, RK inhibited dramatically the Bcl-2 protein expression and significantly increased the expression of caspase-3, NF- κ B and ICAM-1 (all P<0.01). Compared with the RK group, VRK group induced significant increase on Bcl-2 protein expression, and decreased the caspase-3, NF- κ B and ICAM-1 protein expression (P<0.05 or P<0.01). CONCLUSION: The mechanism of reduced hepatotoxicity of VRK may be associated with the reduced inflammation, regulation of antiapoptotic and proapoptotic mediators in the mitochondrial pathway.

11.
Medicine (Baltimore) ; 98(21): e15743, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31124956

RESUMO

BACKGROUND: Gene mutations with important prognostic role have been identified in patients with myelodysplastic syndrome (MDS). We performed a meta-analysis to investigate the effects of RNA splicing machinery gene mutations on prognosis of MDS patients. METHODS: We searched English database including PubMed, Embase, Cochrane Library for literatures published within recent 10 years on the effect of RNA splicing machinery genes in MDS. Revman version 5.2 software was used for all the statistical processing. We calculated risk ratio and 95% confidence interval (CI) of continuous variables, and find hazard ratio (HR) and 95% CI of time-to-event data. RESULTS: We included 19 studies enrolling 4320 patients. There is a significant superior overall survival (OS) in splicing factor 3b, subunit 1 (SF3B1)-mutation group compared to unmutated group (HR = 0.58, 95% CI: 0.5-0.67, P < .00001); OS decreased significantly in serine/arginine-rich splicing factor 2/ U2 auxiliary factor protein 1 (SRSF2/U2AF1) mutation group compared to unmutated group, (HR = 1.62, 95% CI: 1.34-1.97, P < .00001 and HR = 1.61, 95% CI: 1.35-1.9, P < .00001, respectively). In terms of leukemia-free survival (LFS), the group with SF3B1 mutation had better outcome than unmutated group, HR = 0.63 (95% CI: 0.53-0.75, P < .00001). Other RNA splicing gene mutation group showed significant poor LFS than unmutated groups, (HR = 1.89, 95% CI: 1.6-2.23, P < .00001; HR = 2.77, 95% CI: 2.24-3.44, P < .00001; HR = 1.48, 95% CI: 1.08-2.03, P < .00001; for SRSF2, U2AF1, and zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2 [ZRSR2], respectively). As for subgroup of low- or intermediate-1-IPSS risk MDS, SRSF2, and U2AF1 mutations were related to poor OS. (HR = 1.83, 95% CI: 1.43-2.35, P < .00001; HR = 2.11, 95% CI: 1.59-2.79, P < .00001 for SRSF2 and U2AF1, respectively). SRSF2 and U2AF1 mutations were strongly associated with male patients. SF3B1 mutation was strongly associated with disease staging. CONCLUSION: This meta-analysis indicates a positive effect of SF3B1 and an adverse prognostic effect of SRSF2, U2AF1, and ZRSR2 mutations in patients with MDS. Mutations of RNA splicing genes have important effects on the prognosis of MDS.


Assuntos
Síndromes Mielodisplásicas/genética , Processamento de RNA/genética , Humanos , Proteínas Nucleares/genética , Fosfoproteínas/genética , Prognóstico , Fatores de Processamento de RNA/genética , Ribonucleoproteínas/genética , Fatores de Processamento de Serina-Arginina/genética , Índice de Gravidade de Doença , Fatores Sexuais , Fator de Processamento U2AF/genética , Análise de Sobrevida
12.
J Nat Prod ; 82(4): 980-989, 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-30892884

RESUMO

Aconitum carmichaelii is a traditional Chinese herbal medicine used for the treatment of pain and inflammation in the joints. However, the strong cardiotoxicity hinders its use. Although diester- and monoester-type diterpenoids, e.g., aconitine, mesaconitine, and hypacaonitine, are commonly considered as the toxic components, the toxicity of A. carmichaelii cannot be completely explained by the compounds reported. To investigate further the cardiotoxic compounds and their potential mechanism, the chemical constituents were first isolated by column chromatography and identified using mass spectrometry and NMR spectroscopy. Two new hetisine-type (1 and 2) and four new aconitine-type alkaloids (3-6) were assigned. The cardiac cytotoxicity assessed on H9c2 cells indicated that the new compound 4 as well as six known alkaloids (7 and 9-13) exhibited significant toxicities. A preliminary structure-toxicity relationship study suggested that substitution at C-8 and C-10 both have a significant influence on cardiotoxicity, and such toxicity decreased in the order OBz-8, OBu-8, and OMe-8. The presence of an OH-10 group abolished the toxicity. Finally, it was found that ion channel disorder and induction of mitochondrial-mediated cell apoptosis are the possible mechanisms of cardiotoxicity among the compounds studied.

13.
Pest Manag Sci ; 75(10): 2592-2597, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30927304

RESUMO

BACKGROUND: Quantification of spray deposition on a target crop is of vital importance to optimize pesticide application. In traditional determinations of spray deposition, a large amount of organic solvent is used to extract pesticides from the target crops. In this study, a water-soluble food dye of Allura Red was developed as a tracer to determine pesticide spray deposition on a rice target crop. RESULTS: The addition of Allura Red does not obviously alter the physicochemical properties of pesticides (viscosity, density and surface tension) and droplet spectra. An ultra-performance liquid chromatography (UPLC) analytical method was developed and validated to determine the deposition amount of Allura Red on rice plants. Method accuracy and precision for Allura Red were found to be satisfactory with recoveries of 96.07% to 107.48%. To validate the method, comparative deposition analyses were carried out using representative systematic and non-systematic pesticides (nitenpyram and chlorothalonil) under the same spraying scenarios using a Potter spray tower. Allura Red and pesticides showed comparable deposition under the same application conditions with ratios from 0.98 to 1.21. A field trial using an unmanned aerial vehicle sprayer further indicated that the deposition rates for Allura Red and nitenpyram on rice seedling were 13.04% and 11.07%, with corresponding relative standard deviation values (n = 5) of 16.39% and 18.79%. CONCLUSION: A laboratory test and field trial confirmed that the developed method of using Allura Red as a tracer for spray deposition assessment is feasible and practicable. © 2019 Society of Chemical Industry.

14.
Chem Res Toxicol ; 32(4): 668-680, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30848893

RESUMO

Toosendanin (TSN), a compound from Melia toosendan, exhibits severe hepatotoxicity, which restricts its clinical application. However, the mechanism is not clear. Our previous research found that covalent modification of TSN for proteins might be a possible reason using human liver microsomes, and the glycolytic enzymes, triosephosphate isomerase 1 (TPIS) and α-enolase (ENOA), were responsible for the hepatotoxicity. In this study, we tried to prove these findings in cell and animal models by integration of proteomics, metabolomics, and biological methods. Proteomics analysis in rats showed that TPIS and ENOA were covalently modified by TSN reactive metabolites. The biological functional assessments revealed that the modifications inhibited the activity of TPIS and induced the activity of ENOA, in vitro and in vivo, followed by an increase in the level of cellular methylglyoxal, advanced glycation end products, and reactive oxygen species/superoxide, and the induction of mitochondrial dysfunction, which further inhibited oxidative phosphorylation and stimulated glycolysis. Furthermore, metabolomics demonstrated the decrease in the level of metabolites in the tricarboxylic acid cycle, fatty acid ß-oxidation, and amino acid metabolism; i.e., TSN induced hepatocyte energy metabolism disorder. In conclusion, these data suggest novel mechanistic insights into TSN-induced liver injury on the upstream level and provide valuable proteins and energy metabolic targets for diagnosis and therapy in the clinic.

15.
Int J Mol Sci ; 20(4)2019 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-30813400

RESUMO

The initiative strategy for the development of novel anti-microbial agents usually uses the virulence factors of bacteria as a target, without affecting their growth and survival. The type III secretion system (T3SS), one of the essential virulence factors in most Gram-negative pathogenic bacteria because of its highly conserved construct, has been regarded as an effective target that developed new anti-microbial drugs. Xanthomonas oryzae pv. oryzae (Xoo) causes leaf blight diseases and is one of the most important pathogens on rice. To find potential anti-virulence agents against this pathogen, a number of natural compounds were screened for their effects on the T3SS of Xoo. Three of 34 compounds significantly inhibited the promoter activity of the harpin gene, hpa1, and were further checked for their impact on bacterial growth and on the hypersensitive response (HR) caused by Xoo on non-host tobacco plants. The results indicated that treatment of Xoo with CZ-1, CZ-4 and CZ-9 resulted in an obviously attenuated HR without affecting bacterial growth and survival. Moreover, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis showed that the expression of the Xoo T3SS was suppressed by treatment with the three inhibitors. The mRNA levels of representative genes in the hypersensitive response and pathogenicity (hrp) cluster, as well as the regulatory genes hrpG and hrpX, were reduced. Finally, the in vivo test demonstrated that the compounds could reduce the disease symptoms of Xoo on the rice cultivar (Oryza sativa) IR24.


Assuntos
Oryza/microbiologia , Bibliotecas de Moléculas Pequenas/farmacologia , Sistemas de Secreção Tipo III/metabolismo , Xanthomonas/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genes de Plantas , Oryza/efeitos dos fármacos , Oryza/genética , Doenças das Plantas/microbiologia , Regiões Promotoras Genéticas , Bibliotecas de Moléculas Pequenas/análise , Bibliotecas de Moléculas Pequenas/química , Tabaco/microbiologia , Xanthomonas/efeitos dos fármacos , Xanthomonas/crescimento & desenvolvimento
16.
Sci Rep ; 9(1): 1452, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30723218

RESUMO

Cellulose synthase-like D (CSLD) family was characterized for their expression and functions in Populus trichocarpa. Ten members, PtrCslD1-10, were identified in the P. trichocarpa genome, and they belong to 4 clades by phylogenetic tree analysis. qRT-PCR and promoter:GUS assays in Arabidopsis and P. trichocarpa displayed divergent expression patterns of these 10 PtrCSLD genes in root hairs, root tips, leaves, vascular tissues, xylem and flowers. Among PtrCslD2, PtrCslD4, PtrCslD5, PtrCslD6, and PtrCslD8 that all exhibited expression in root hairs, only PtrCslD5 could restore the root hairless phenotype of the atcsld3 mutant, demonstrating that PtrCslD5 is the functional ortholog of AtCslD3 for root hair formation. Our results suggest more possible functions for other PtrCslD genes in poplar.

17.
New Phytol ; 222(1): 244-260, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30276825

RESUMO

Lignin is the major phenolic polymer in plant secondary cell walls and is polymerized from monomeric subunits, the monolignols. Eleven enzyme families are implicated in monolignol biosynthesis. Here, we studied the functions of members of the cinnamyl alcohol dehydrogenase (CAD) and cinnamoyl-CoA reductase (CCR) families in wood formation in Populus trichocarpa, including the regulatory effects of their transcripts and protein activities on monolignol biosynthesis. Enzyme activity assays from stem-differentiating xylem (SDX) proteins showed that RNAi suppression of PtrCAD1 in P. trichocarpa transgenics caused a reduction in SDX CCR activity. RNAi suppression of PtrCCR2, the only CCR member highly expressed in SDX, caused a reciprocal reduction in SDX protein CAD activities. The enzyme assays of mixed and coexpressed recombinant proteins supported physical interactions between PtrCAD1 and PtrCCR2. Biomolecular fluorescence complementation and pull-down/co-immunoprecipitation experiments supported a hypothesis of PtrCAD1/PtrCCR2 heterodimer formation. These results provide evidence for the formation of PtrCAD1/PtrCCR2 protein complexes in monolignol biosynthesis in planta.

18.
PLoS One ; 13(11): e0205598, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30408038

RESUMO

Spraying insecticide is a common practice in the control against pest insects. However, little attention has been paid to the biocidal radius of droplets. Therefore, in this study, we investigated the biocidal radiuses of abamectin, thiamethoxam and sulfoxaflor droplets controlling against wheat aphid (Sitobion avenae). The mortality of S. avenae showed a droplet density dependent process that can be described by an exponential model. Calculated mortality limit (A2) varied with the concentration of insecticides. Although similar LD50 values were observed in abamectin (13.77 ng aphid-1) and sulfoxaflor (14.52 ng aphid-1) against S. avenae, sulfoxaflor had a larger biocidal radius (r50) than abamectin due to its translocation ability at the same concentration. And sulfoxaflor had a relatively larger biocidal radius than thiamethoxam (LD50 = 68.42 ng aphid-1) because it is more toxic to S. avenae. The ratio of r50/VMD was introduced to estimate the potential of droplets. Droplets generated by the air atomizing nozzle (VMD = 43 µm) had higher value of r50/VMD than the centrifugal atomizing nozzle (VMD = 153 µm). Our results indicated that the mortality limit can be reached at a concentration of an insecticide. The biocidal radius of a droplet is different from its actual size. The LD50 and translocation ability of insecticides contributed to their biocidal radius. Ratio of r50/VMD is an indicator of droplets' insecticidal potential. Smaller droplets generated by the air atomizing nozzle have higher insecticidal potential.


Assuntos
Afídeos/efeitos dos fármacos , Inseticidas/farmacologia , Controle de Pragas , Triticum/crescimento & desenvolvimento , Animais , Afídeos/patogenicidade , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Piridinas/farmacologia , Compostos de Enxofre/farmacologia , Tiametoxam/farmacologia , Triticum/parasitologia
19.
BMC Infect Dis ; 18(1): 528, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30348099

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus named SFTS virus (SFTSV), which is classified into the genus Phlebovirus and family Phenuiviridae. Reactive plasmacytosis mimicking multiple myeloma is a very rare condition in association with SFTS. Here, we describe two SFTS cases who presented with hyperimmunoglobulinemia, as well as extensive bone marrow and peripheral blood plasmacytosis, which mimicked multiple myeloma (MM). CASE PRESENTATION: We report two cases who presented with fever and blood routine abnormity which were conformed as SFTS eventually. They were performed bone marrow aspiration and were admitted to the department of hematology with a preliminary diagnosis of MM. They all had hyperimmunoglobulinemia, extensive bone marrow and peripheral blood plasma cells, prolonged activated partial thromboplastin time (APTT), elevated hepatic enzyme. The two patients recovered with treatment of doxycycline, human immunoglobulins, plasma transfusion, and other supporting treatments. But case 1 occurred lymphoma 8 months later and died. CONCLUSION: SFTS might be one of differential diagnosis of MM in certain endemic area. We also conclude that SFTSV is a pantropic virus that could injure most tissues and cells of the human body.


Assuntos
Febre por Flebótomos/diagnóstico , Phlebovirus/isolamento & purificação , Adulto , Antibacterianos/uso terapêutico , Anticorpos Antivirais/sangue , Medula Óssea/patologia , Diagnóstico Diferencial , Doxiciclina/uso terapêutico , Feminino , Humanos , Imunoglobulinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Febre por Flebótomos/tratamento farmacológico , Febre por Flebótomos/virologia , Phlebovirus/genética , Phlebovirus/imunologia , RNA Viral/metabolismo , Trombocitopenia/etiologia
20.
Theranostics ; 8(16): 4359-4371, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214626

RESUMO

Acute myeloid leukemia (AML) with an NPM1 mutation (NPMc+) has a distinct gene expression signature and displays molecular abnormalities similar to mixed lineage leukemia (MLL), including aberrant expression of the PBX3 and HOXA gene cluster. However, it is unclear if the aberrant expression of PBX3 and HOXA is essential for the survival of NPM1-mutated leukemic cells. Methods: Using the gene expression profiling of TCGA and E-MTAB-3444 datasets, we screened for high co-expression of PBX3 and HOXA9 in NPMc+ leukemia patients. We performed NPMc+ depletion and overexpression experiments to examine aberrant H3K79 methylation through epigenetic regulation. Through RNA interference technology and small-molecule inhibitor treatment, we evaluated the effect of methyl-modified H3K79 on cell survival and explored the possible underlying mechanism. Results: We showed that NPMc+ increased the expression of PBX3 and HOXA9, which are both poor prognosis indicators in AML. High PBX3 and HOXA9 expression was accompanied by increased dimethylated and trimethylated H3K79 in transgenic murine Lin-Sca-1+c-Kit+ cells and human NPMc+ leukemia cells. Using chromatin immunoprecipitation sequencing (ChIP-seq) assays of NPMc+ cells, we determined that hypermethylated H3K79 was present at the expressed HOXA9 gene but not the PBX3 gene. PBX3 expression was positively regulated by HOXA9, and a reduction in either PBX3 or HOXA9 resulted in NPMc+ cell apoptosis. Importantly, an inhibitor of DOT1L, EPZ5676, effectively and selectively promoted NPMc+ human leukemic cell apoptosis by reducing HOXA9 and PBX3 expression. Conclusion: Our data indicate that NPMc+ leukemic cell survival requires upregulation of PBX3 and HOXA9, and this action can be largely attenuated by a DOT1L inhibitor.


Assuntos
Sobrevivência Celular , Histonas/metabolismo , Proteínas de Homeodomínio/antagonistas & inibidores , Leucemia Mieloide Aguda/patologia , Células Mieloides/fisiologia , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Histona-Lisina N-Metiltransferase , Humanos , Metilação , Metiltransferases/antagonistas & inibidores , Camundongos Transgênicos , Proteínas Nucleares/genética
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