RESUMEN
Powerful relativistic jets are one of the ubiquitous features of accreting black holes in all scales1-3. GRS 1915 + 105 is a well-known fast-spinning black-hole X-ray binary4 with a relativistic jet, termed a 'microquasar', as indicated by its superluminal motion of radio emission5,6. It has exhibited persistent X-ray activity over the last 30 years, with quasiperiodic oscillations of approximately 1-10 Hz (refs. 7-9) and 34 and 67 Hz in the X-ray band10. These oscillations probably originate in the inner accretion disk, but other origins have been considered11. Radio observations found variable light curves with quasiperiodic flares or oscillations with periods of approximately 20-50 min (refs. 12-14). Here we report two instances of approximately 5-Hz transient periodic oscillation features from the source detected in the 1.05- to 1.45-GHz radio band that occurred in January 2021 and June 2022. Circular polarization was also observed during the oscillation phase.
RESUMEN
All stellar-mass black holes have hitherto been identified by X-rays emitted from gas that is accreting onto the black hole from a companion star. These systems are all binaries with a black-hole mass that is less than 30 times that of the Sun1-4. Theory predicts, however, that X-ray-emitting systems form a minority of the total population of star-black-hole binaries5,6. When the black hole is not accreting gas, it can be found through radial-velocity measurements of the motion of the companion star. Here we report radial-velocity measurements taken over two years of the Galactic B-type star, LB-1. We find that the motion of the B star and an accompanying Hα emission line require the presence of a dark companion with a mass of [Formula: see text] solar masses, which can only be a black hole. The long orbital period of 78.9 days shows that this is a wide binary system. Gravitational-wave experiments have detected black holes of similar mass, but the formation of such massive ones in a high-metallicity environment would be extremely challenging within current stellar evolution theories.
RESUMEN
BACKGROUND: Long-term treatment with trimethoprim-sulfamethoxazole (SXT) can lead to the formation of small-colony variants (SCVs) of Staphylococcus aureus. However, the mechanism behind SCVs formation remains poorly understood. In this study, we explored the phenotype and omics-based characterization of S. aureus SCVs induced by SXT and shed light on the potential causes of SCV formation. METHODS: Stable SCVs were obtained by continuously treating S. aureus isolates using 12/238 µg/ml of SXT, characterized by growth kinetics, antibiotic susceptibility testing, and auxotrophism test. Subsequently, a pair of representative strains (SCV and its parental strain) were selected for genomic, transcriptomic and metabolomic analysis. RESULTS: Three stable S. aureus SCVs were successfully screened and proven to be homologous to their corresponding parental strains. Phenotypic tests showed that all SCVs were non-classical mechanisms associated with impaired utilization of menadione, heme and thymine, and exhibited slower growth and higher antibiotic minimum inhibitory concentrations (MICs), compared to their corresponding parental strains. Genomic data revealed 15 missense mutations in 13 genes in the representative SCV, which were involved in adhesion, intramolecular phosphate transfer on ribose, transport pathways, and phage-encoded proteins. The combination analysis of transcriptome and metabolome identified 35 overlapping pathways possible associated with the phenotype switching of S. aureus. These pathways mainly included changes in metabolism, such as purine metabolism, pyruvate metabolism, amino acid metabolism, and ABC transporters, which could play a crucial role in promoting SCVs development by affecting nucleic acid synthesis and energy metabolism in bacteria. CONCLUSION: This study provides profound insights into the causes of S. aureus SCV formation induced by SXT. The findings may offer valuable clues for developing new strategies to combat S. aureus SCV infections.
Asunto(s)
Antibacterianos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Combinación Trimetoprim y Sulfametoxazol , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Perfilación de la Expresión Génica , Genómica , Metabolómica , Multiómica , Fenotipo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Transcriptoma , Combinación Trimetoprim y Sulfametoxazol/farmacologíaRESUMEN
Infections caused by Staphylococcus aureus pose a significant global public problem. Therefore, new antibiotics and therapeutic strategies are needed to combat this pathogen. This investigation delves into the effects of iclaprim, a newly discovered inhibitor of folic acid synthesis, on S. aureus virulence. The phenotypic and genotypic effects of iclaprim were thoroughly examined in relation to virulence factors, biofilm formation, and dispersal, as well as partial virulence-encoding genes associated with exoproteins, adherence, and regulation in S. aureus MW2, N315, and ATCC 25923. Then, the in vivo effectiveness of iclaprim on S. aureus pathogenicity was explored by a Galleria mellonella larvae infection model. The use of iclaprim at sub-inhibitory concentrations (sub-MICs) resulted in a reduction of α-hemolysin (Hla) production and a differential effect on the activity of coagulase in S. aureus strains. The results of biofilm formation and eradication assay showed that iclaprim was highly effective in depolymerizing the mature biofilm of S. aureus strains at concentrations of 1 MIC or greater, however, inhibited the biofilm-forming ability of only strains N315 and ATCC 25923 at sub-MICs. Interestingly, treatment of strains with sub-MICs of iclaprim resulted in significant stimulation or suppression of most virulence-encoding genes expression. Iclaprim did not affect the production of δ-hemolysin or staphylococcal protein A (SpA), nor did it impact the total activity of proteases, nucleases, and lipases. In vivo testing showed that sub-MICs of iclaprim significantly improves infected larvae survival. The present study offered valuable insights towards a better understating of the influence of iclaprim on different strains of S. aureus. The findings suggest that iclaprim may have potential as an anti-virulence and antibiofilm agent, thus potentially mitigating the pathogenicity of S. aureus and improving clinical outcomes associated with infections caused by this pathogen. KEY POINTS: ⢠Iclaprim effectively inhibits α-hemolysin production and biofilm formation in a strain-dependent manner and was an excellent depolymerizing agent of mature biofilm ⢠Iclaprim affected the mRNA expression of virulence-encoding genes associated with exoproteins, adherence, and regulation ⢠In vivo study in G. mellonella larvae challenged with S. aureus exhibited that iclaprim improves larvae survival.
Asunto(s)
Antibacterianos , Biopelículas , Larva , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Staphylococcus aureus , Factores de Virulencia , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/patogenicidad , Staphylococcus aureus/genética , Biopelículas/efectos de los fármacos , Animales , Factores de Virulencia/genética , Antibacterianos/farmacología , Virulencia/efectos de los fármacos , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Larva/microbiología , Mariposas Nocturnas/microbiología , Proteínas Hemolisinas/genética , Ácido Fólico/farmacología , Ácido Fólico/biosíntesis , Antagonistas del Ácido Fólico/farmacología , Coagulasa/metabolismo , Modelos Animales de Enfermedad , PirimidinasRESUMEN
The development of a versatile and sensitive analytical biomarker detection platform is important for both early diagnosis and treatment of diseases. In the present study, we propose a novel fluorescence-based, ultrasensitive, and label-free biomarker detection platform. This platform relies on a flexible probe design compatible for multiple biomarker identification and Exo-III enzyme-triggered cascade signal amplification. We have validated that this label-free platform exhibits high sensitivity and specificity. Indeed, this platform exhibited brilliant analytical performance in qualifying a carcinoembryonic antigen and small extracellular vesicles (sEVs). It also shows excellent capability in multiplexing mapping of surface proteins of various cancer-derived sEVs. Therefore, we believe that the proposed sensing platform has great potential for clinical diagnosis and anticancer drug development.
Asunto(s)
Técnicas Biosensibles , Exodesoxirribonucleasas , Exodesoxirribonucleasas/metabolismo , Límite de Detección , Técnicas de Amplificación de Ácido NucleicoRESUMEN
In nature, many different factors cause plants to develop variegated leaves. To explore the mechanism of variegated leaf formation in Pteroceltis tatarinowii, a mutant variety ('Jinyuyuan'), which was induced by ethylmethylsulfone, was selected, and its morphological structure, physiology, biochemistry, transcription and metabolism were analysed. According to differences in colour values, the colours were divided into two regions: a green region and a yellow-green region. The chlorophyll content of the two regions was significantly different. Moreover, the yellow-green regions of the leaves were significantly thinner than the green regions. The chloroplast ultrastructure in the yellow-green region revealed small chloroplasts, large vacuoles, small starch grains, obviously increased numbers of osmophilic grains, loose lamellae of the inner capsule and thin lamellae. Moreover, the yellow-green region was accompanied by oxidative stress, and the activity of the oxidative phosphorylation pathway related to oxidative activity in the transcriptome showed an upward trend. Vitamin B6 and proline contents also increased, indicating that the antioxidant activity of cells in the yellow-green region increased. Transcriptomic and metabolomic analysis showed that the differentially expressed genes (DEGs) related to chlorophyll synthesis and metabolism led to a decrease in the photosynthesis and then a decrease in the assimilation ability and contents of sucrose, starch and other assimilates. Amino acid synthesis and metabolism, lipid synthesis and the activity of metabolic pathways were obviously downregulated, and the contents of differentially accumulated metabolites associated with amino acids and lipids were also reduced. At the same time, 31 out of 32 DEGs involved in the flavonoid synthesis pathway were downregulated, which affected leaf colour. We hypothesized that the variegated leaves of P. tatarinowii 'Jinyuyuan' are caused by transcriptional and post-transcriptional regulation. Mutations in pigment and flavonoid synthesis pathway genes and transcription factor genes directly affect both pigment and flavonoid synthesis and degradation rate, which in turn affect carbon assimilation, carbon fixation, related protein synthesis and enzyme activity, lipid synthesis and degradation and the activity of other metabolic pathways, eventually leading to the formation of different colour regions.
Asunto(s)
Transcriptoma , Árboles , Clorofila/metabolismo , Flavonoides/metabolismo , Regulación de la Expresión Génica de las Plantas , Metaboloma , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Almidón/metabolismo , Árboles/genéticaRESUMEN
The formation of relativistic jets by an accreting compact object is one of the fundamental mysteries of astrophysics. Although the theory is poorly understood, observations of relativistic jets from systems known as microquasars (compact binary stars) have led to a well established phenomenology. Relativistic jets are not expected to be produced by sources with soft or supersoft X-ray spectra, although two such systems are known to produce relatively low-velocity bipolar outflows. Here we report the optical spectra of an ultraluminous supersoft X-ray source (ULS) in the nearby galaxy M81 (M81 ULS-1; refs 9, 10). Unexpectedly, the spectra show blueshifted, broad Hα emission lines, characteristic of baryonic jets with relativistic speeds. These time-variable emission lines have projected velocities of about 17 per cent of the speed of light, and seem to be similar to those from the prototype microquasar SS 433 (refs 11, 12). Such relativistic jets are not expected to be launched from white dwarfs, and an origin from a black hole or a neutron star is hard to reconcile with the persistence of M81 ULS-1's soft X-rays. Thus the unexpected presence of relativistic jets in a ULS challenges canonical theories of jet formation, but might be explained by a long-speculated, supercritically accreting black hole with optically thick outflows.
RESUMEN
BACKGROUND: The data on the prevalence of resistance to mupirocin (MUP), fusidic acid (FA) and retapamulin (RET) in methicillin-resistant Staphylococcus aureus (MRSA) from China are still limited. This study aimed to examine these three antibiotics resistance in 1206 MRSA clinical isolates from Eastern China. Phenotypic MUP, FA and RET resistance was determined by minimum inhibitory concentrations (MICs), and genotypic by PCR and DNA sequencing of the mupA/B, fusB-D, cfr, vgaA/Av/ALC/B/C/E, lsaA-C/E and salA and mutations in ileS, fusA/E, rplC, and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). RESULTS: Overall MRSA MUP, FA and RET resistance was low (5.1, 1.0 and 0.3%, respectively). MupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS; of these, 2 reported an additional V588F mutation with an impact on the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I were the primary FA mechanisms among high-level resistance isolates, most of which also contained fusC; however, all low-level resistance strains carried fusB. Except lsaE gene detected in one isolate, no other resistance mechanisms tested were found among RET-resistant isolates. Additionally, sixteen PFGE types (A-P) were observed, among which type B was the most common (49/76, 64.5%), followed by types E and G (4/76, 5.3% each) and types C and M (3/76, 3.9% each). All resistant strains were divided into 15 ST types by MLST. ST764 (24/76, 31.6%), ST630 (11/76, 14.5%), ST239 (9/76, 11.8%) and ST5 (7/76, 9.2%) were the major types. PFGE type B isolates with the aforementioned STs were mainly found in mupirocin resistant isolates. CONCLUSIONS: MUP, FA and RET exhibited highly activity against the MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance; however, the mechanism for some RET-resistant isolates remains to be further elucidated. Also, the surveillance to MUP in MRSA should be strengthened to prevent elevated resistance due to the expansion of clones.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Staphylococcus aureus Resistente a Meticilina/clasificación , Infecciones Estafilocócicas/epidemiología , Técnicas de Tipificación Bacteriana , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , China/epidemiología , ADN Bacteriano/genética , Diterpenos/farmacología , Electroforesis en Gel de Campo Pulsado , Ácido Fusídico/farmacología , Humanos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Mupirocina/farmacología , Mutación , Prevalencia , Análisis de Secuencia de ADNRESUMEN
Gene- and pathway-based variant association tests are important tools in finding genetic variants that are associated with phenotypes of interest. Although some methods have been proposed in the literature, powerful and robust statistical tests are still desirable in this area. In this study, we propose a statistical test based on decomposing the genotype data into orthogonal parts from which powerful and robust independent p-value combination approaches can be utilized. Through a comprehensive simulation study, we compare the proposed test with some existing popular ones. Our simulation results show that the new test has great performance in terms of controlling type I error rate and statistical power. Real data applications are also conducted to illustrate the performance and usefulness of the proposed test.
Asunto(s)
Estudio de Asociación del Genoma Completo/métodos , Simulación por Computador , Estudio de Asociación del Genoma Completo/normas , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: It has been reported that infectious agents contribute to the atherosclerotic process. However, it is unclear whether Staphylococcus aureus superantigen (SAg) toxic shock syndrome toxin-1 (TSST-1) has an effect on atherosclerosis progression. The present study was designed to investigate the pathogenic role of TSST-1 exposure in the atherosclerotic process in rabbits. METHODS: New Zealand White rabbits were exposed to TSST-1 through Alzet miniosmotic pumps with a constant pumping rate. Aortic atherosclerosis was evaluated by histological and morphometric methods. Using a biochemical analyzer/enzyme-linked immunosorbent assay/immunostaining, we further analyzed various atherosclerosis-related factors. RESULTS: The gross atherosclerotic lesion area in the aortic arch increased by 15.3% in high-fat-diet rabbits exposed to TSST-1 compared to that in the control group. In the atherosclerotic lesions, TSST-1 exposure increased the content of smooth muscle cells. Moreover, TSST-1 treatment up-regulated serum tumor necrosis factor alpha (TNF-α) level, but did not affect serum lipids (except for triglycerides) and endotoxin in the rabbits. CONCLUSIONS: Our data validated that chronic stimulation with TSST-1 facilitates the progression of atherosclerosis in rabbits independently of endotoxins, indicating that S. aureus and its SAgs may be targets to prevent and treat atherosclerosis.
RESUMEN
It is well known that using proper weights for genetic variants is crucial in enhancing the power of gene- or pathway-based association tests. To increase the power, we propose a general approach that adaptively selects weights among a class of weight families and apply it to the popular sequencing kernel association test. Through comprehensive simulation studies, we demonstrate that the proposed method can substantially increase power under some conditions. Applications to real data are also presented. This general approach can be extended to all current set-based rare variant association tests whose performances depend on variant's weight assignment.
Asunto(s)
Estudios de Asociación Genética/métodos , Variación Genética/genética , Modelos Genéticos , Factores de Edad , Simulación por Computador , Humanos , Factores SexualesRESUMEN
BACKGROUND: The bicomponent leukotoxins and the pyrogenic toxin superantigens (PTSAgs) are important virulence factors of Staphylococcus aureus. It is necessary to survey the prevalence and expression of these toxin-encoding genes for understanding the possible pathogenic capacity of S. aureus to cause disease. METHODS: Five leukotoxin genes and thirteen PTSAg determinants were detected for 177 S. aureus isolates from blood (n = 88) and wound (n = 89) infections by Polymerase Chain Reaction (PCR). The expression of leukotoxin ED (lukED) was determined by quantitative real-time PCR (qRT-PCR). The genetic backgrounds of isolates were analyzed by Staphylococcal Cassette Chromosome mec (SCCmec) typing (for methicillin-resistant S. aureus isolates), Pulsed-Field Gel Electrophoresis (PFGE), accessory gene regulator (agr) typing and Multilocus Sequence Typing (MLST, for representative isolates based on PFGE type) methods. RESULTS: 99.4% (176/177) isolates contained at least one of leukotoxin genes. Among them, 94.9% (168/177), 81.4% (144/177) and 67.8% (120/177) isolates harbored hlgBC, lukED and lukAB, respectively. Compared to leukotoxin genes, there was a relatively lower overall prevalence of PTSAg genes [99.4% versus 72.9% (129/177), P < 0.001], and they were organized in 59 patterns, with the most common combination of the egc cluster with or without other PTSAg genes. Genetic analysis showed the distributions of certain toxin genes were associated with the genetic backgrounds of isolates. The egc cluster was a common feature of CC5 isolates, among which ST5 and ST764 isolates harbored more PTSAg genes. The lukED was not present in ST398 isolates, and its expression was quite different among isolates. No significant correlations were observed between the lukED expression levels of strains and the ST or agr types. CONCLUSIONS: The present study elucidated the distribution of leukotoxin and PTSAg genes and the expression of lukED in blood and wound isolates, and analyzed the relationship between them with genetic characteristics of isolates. These data improve the current understanding of the possible pathogenicity of S. aureus.
Asunto(s)
Toxinas Bacterianas/genética , Exotoxinas/genética , Staphylococcus aureus/genética , Superantígenos/genética , Heridas y Lesiones/microbiología , China , Electroforesis en Gel de Campo Pulsado , Antecedentes Genéticos , Humanos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Tipificación de Secuencias Multilocus , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/inmunología , Staphylococcus aureus/aislamiento & purificación , Factores de Virulencia/genéticaRESUMEN
The increasing prevalence of antibiotic resistance has created an urgent need for alternative drugs with new mechanisms of action. Antimicrobial peptides (AMPs) are promising candidates that could address the spread of multidrug-resistant bacteria, either alone or in combination with conventional antibiotics. We studied the antimicrobial efficacy and bactericidal mechanism of cecropin A2, a 36-residue α-helical cationic peptide derived from Aedes aegypti cecropin A, focusing on the common pathogen Pseudomonas aeruginosa The peptide showed little hemolytic activity and toxicity toward mammalian cells, and the MICs against most clinical P. aeruginosa isolates were 32 to 64 µg/ml, and its MICs versus other Gram-negative bacteria were 2 to 32 µg/ml. Importantly, cecropin A2 demonstrated synergistic activity against P. aeruginosa when combined with tetracycline, reducing the MICs of both agents by 8-fold. The combination was also effective in vivo in the P. aeruginosa/Galleria mellonella model (P < 0.001). We found that cecropin A2 bound to P. aeruginosa lipopolysaccharides, permeabilized the membrane, and interacted with the bacterial genomic DNA, thus facilitating the translocation of tetracycline into the cytoplasm. In summary, the combination of cecropin A2 and tetracycline demonstrated synergistic antibacterial activity against P. aeruginosain vitro and in vivo, offering an alternative approach for the treatment of P. aeruginosa infections.
Asunto(s)
Antibacterianos/farmacología , Cecropinas/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Tetraciclina/farmacología , Aedes , Animales , Sinergismo Farmacológico , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Bacterias Gramnegativas/efectos de los fármacos , Células Hep G2 , Humanos , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/genéticaRESUMEN
Little cherry virus 1 (LChV-1), associated with little cherry disease (LCD), has a significant impact on fruit quality of infected sweet cherry trees. We report the full genome sequence of an isolate of LChV-1 from Taian, China (LChV-1-TA), detected by small-RNA deep sequencing and amplified by overlapping RT-PCR. The LChV-1-TA genome was 16,932 nt in length and contained nine open reading frames (ORFs), with sequence identity at the overall genome level of 76%, 76%, and 78% to LChV-1 isolates Y10237 (UW2 isolate), EU715989 (ITMAR isolate) and JX669615 (V2356 isolate), respectively. Based on the phylogenetic analysis of HSP70h amino acid sequences of Closteroviridae family members, LChV-1-TA was grouped into a well-supported cluster with the members of the genus Velarivirus and was also closely related to other LChV-1 isolates. This is the first report of the complete nucleotide sequence of LChV-1 infecting sweet cherry in China.
Asunto(s)
Closteroviridae/genética , Closteroviridae/aislamiento & purificación , Genoma Viral , Enfermedades de las Plantas/virología , Prunus avium/virología , ARN Viral/genética , Análisis de Secuencia de ADN , China , Closteroviridae/clasificación , Análisis por Conglomerados , Secuenciación de Nucleótidos de Alto Rendimiento , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Filogenia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de SecuenciaRESUMEN
BACKGROUND: Because of its important effects, as an epigenetic factor, on gene expression and disease development, DNA methylation has drawn much attention from researchers. Detecting differentially methylated loci is an important but challenging step in studying the regulatory roles of DNA methylation in a broad range of biological processes and diseases. Several statistical approaches have been proposed to detect significant methylated loci; however, most of them were designed specifically for case-control studies. RESULTS: Noticing that the age is associated with methylation level and the methylation data are not normally distributed, in this paper, we propose a nonparametric method to detect differentially methylated loci under multiple conditions with trend for Illumina Array Methylation data. The nonparametric method, Cuzick test is used to detect the differences among treatment groups with trend for each age group; then an overall p-value is calculated based on the method of combining those independent p-values each from one age group. CONCLUSIONS: We compare the new approach with other methods using simulated and real data. Our study shows that the proposed method outperforms other methods considered in this paper in term of power: it detected more biological meaningful differentially methylated loci than others.
Asunto(s)
Metilación de ADN , Estudios de Casos y Controles , Femenino , Sitios Genéticos , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Ováricas/genética , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Combining information from different studies is an important and useful practice in bioinformatics, including genome-wide association study, rare variant data analysis and other set-based analyses. Many statistical methods have been proposed to combine p-values from independent studies. However, it is known that there is no uniformly most powerful test under all conditions; therefore, finding a powerful test in specific situation is important and desirable. RESULTS: In this paper, we propose a new statistical approach to combining p-values based on gamma distribution, which uses the inverse of the p-value as the shape parameter in the gamma distribution. CONCLUSIONS: Simulation study and real data application demonstrate that the proposed method has good performance under some situations.
Asunto(s)
Estudio de Asociación del Genoma Completo , Modelos Estadísticos , Estudios de Casos y Controles , Simulación por Computador , HumanosRESUMEN
BACKGROUND: Shigellae have become increasingly resistant to the extended-spectrum cephalosporin (ESC) worldwide and pose a great challenge to anti-infection treatment options. The purpose of this study was to determine the resistance, cephalosporin resistance mechanisms, virulence characteristic and genotype of ESC-resistant Shigella. METHODS: From 2008 to 2012, Shigella isolates collected from diarrhea patients were detected for antibiotics sensitivity by disk diffusion, cephalosporin resistance determinants and virulence genes using polymerase chain reaction (PCR) and genotyping through enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR). RESULTS: A total of 356 Shigella isolates were gathered, and 198 (55.6%, 58 S. flexneri and 140 S. sonnei) were resistant to ESC. All ESC-resistant isolates were susceptible to imipenem, and only 0.5% isolate was resistant to piperacillin/tazobactam. ESC-resistant S. flexneri showed high degrees of resistance to ampicillin (100%), ampicillin/sulbactam (96.6%), piperacillin (100%), trimethoprim/sulfamethoxazole (74.1%), ciprofloxacin (74.1%), levofloxacin (53.4%), ceftazidime (58.6%) and cefepime (58.6%). ESC-resistant S. sonnei exhibited high resistance rates to ampicillin (100%), piperacillin (100%) and trimethoprim/sulfamethoxazole (96.4%). Cephalosporin resistance genes were confirmed in 184 ESC-resistant isolates. bla(CTX-M) types (91.8%, mainly bla(CTX-M-14), bla(CTX-M-15) and bla(CTX-M-57)) were most prevalent, followed by bla(OXA-30) (26.3%). Over 99.0% ESC-resistant isolates harbored virulence genes ial, ipaH, virA and sen. However, set1 were more prevalent in ESC-resistant S. flexneri isolates than in S. sonnei isolates. ERIC-PCR results showed that 2 and 3 main genotypes were detected in ESC-resistant S. flexneri and S. sonnei, respectively. CONCLUSION: Our findings indicated that a high prevalence of ESC-resistant Shigella mediated mainly by bla(CTX-M) with stronger resistance and virulence, and the existence of specific clones responsible for these Shigella infection in the region studied.
Asunto(s)
Resistencia a las Cefalosporinas/genética , Disentería Bacilar/microbiología , Shigella/genética , Adolescente , Adulto , Antibacterianos , Cefepima , Cefalosporinas , Niño , Preescolar , China , Ciprofloxacina , Femenino , Galanina/análogos & derivados , Genes Bacterianos , Genotipo , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Ácido Penicilánico/análogos & derivados , Piperacilina , Combinación Piperacilina y Tazobactam , Reacción en Cadena de la Polimerasa , Shigella/patogenicidad , Sustancia P/análogos & derivados , Virulencia , beta-Lactamasas/genéticaRESUMEN
The spines of Chinese red chestnut are red and the depth of their color gradually increases with maturity. To identify the anthocyanin types and synthesis pathways in red chestnut and to identify the key genes regulating the anthocyanin biosynthesis pathway, we obtained and analyzed the transcriptome and anthocyanin metabolism of red chestnut and its control variety with green spines at 3 different periods. GO and KEGG analyses revealed that photosynthesis was more highly enriched in green spines compared with red spines, while processes related to defense and metabolism regulation were more highly enriched in red spines. The analysis showed that the change in spine color promoted photoprotection in red chestnut, especially at the early growth stage, which resulted in the accumulation of differentially expressed genes involved in the defense metabolic pathway. The metabolome results revealed 6 anthocyanins in red spines. Moreover, red spines exhibited high levels of cyanidin, peonidin and pelargonidin and low levels of delphinidin, petunidin and malvidin. Compared with those in the control group, the levels of cyanidin, peonidin, pelargonidin and malvidin in red spines were significantly increased, indicating that the cyanidin and pelargonidin pathways were enriched in the synthesis of anthocyanins in red spines, whereas the delphinidin pathways were inhibited and mostly transformed into malvidin. During the process of flower pigment synthesis, the expression of the CHS, CHI, F3H, CYP75A, CYP75B1, DFR and ANS genes clearly increased, that of CYP73A decreased obviously, and that of PAL, 4CL and LAR both increased and decreased. Notably, the findings revealed that the synthesized anthocyanin can be converted into anthocyanidin or epicatechin. In red spines, the upregulation of BZ1 gene expression increases the corresponding anthocyanidin content, and the upregulation of the ANR gene also promotes the conversion of anthocyanin to epicatechin. The transcription factors involved in color formation included 4 WRKYs.
RESUMEN
MOTIVATION: As an epigenetic alteration, DNA methylation plays an important role in epigenetic controls of gene transcription. Recent advances in genome-wide scan of DNA methylation provide great opportunities in studying the impact of DNA methylation on many human diseases including various types of cancer. Due to the unique feature of this type of data, applicable statistical methods are limited and new sophisticated approaches are desirable. RESULTS: In this article, we propose a new statistical test to detect differentially methylated loci for case control methylation data generated by Illumina arrays. This new method utilizes the important finding that DNA methylation is highly correlated with age. The proposed method estimates the overall P-value by combining the P-values from independent individual tests each for one age group. Through real data application and simulation study, we show that the proposed test is robust and usually more powerful than other methods.
Asunto(s)
Metilación de ADN , Modelos Estadísticos , Neoplasias Ováricas/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Simulación por Computador , Femenino , Humanos , Persona de Mediana Edad , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
To fully exploit the economic value of the Chinese endemic species Pteroceltis tatarinowii and provide new resources for forage production, the forage nutritional value of P. tatarinowii leaves from different populations was analyzed and evaluated. The results were as follows: 1) There were significant differences in the forage nutrient indices of leaves from different populations. The crude protein content was 10.77%-18.65%, with an average of 14.58%, and the SDJN population had the highest crude protein content. The average crude fat, crude fiber content was 7.62%; the average neutral detergent fiber content was 25.33%; and the average acid detergent fiber contents were 6.79%, 7.62%, 25.33%, and 17.52%, respectively. The average phosphorus and calcium content in the leaves was 0.785 g·kg-1 and 58.01 g·kg-1, respectively. The tannin content was much lower than the antifeedant standard, at an average of 4.97 g·kg-1. The average total amounts of hydrolyzed and free amino acids in the leaves were 108.20 mg·g-1 and 47.87 mg·g-1, respectively. Thus, P. tatarinowii leaves have high crude protein, crude fat, and calcium contents, and low fiber, tannin contents, and are protein-rich. These results provide evidence that this species can be developed into an excellent woody forage tree. 2) There were significant differences in the forage quality evaluation indices among the populations. The forage indices of NDP, ADP, DMI, DDM, and RFV of 21 populations all met the super standard of the American Grass and Grassland Association (AFGC) for hay, two crude protein indices met the grade 1 standard, and 12 crude protein indices met the grade 2 standard. Four high-protein and high-RFV forage populations (SDJN, SDZZ, SXLQ, and AHXX) were selected. 3) The results of the correlation analysis showed that there was no significant correlation between the forage characteristics of P. tatarinowii leaves and latitude and longitude, indicating no significant geographical variation. However, the forage characteristics were strongly correlated with elevation, average annual temperature, and annual precipitation. Thus, high elevation, low temperatures, and rainy weather can improve the forage value of the leaves. P. tatarinowii can be planted to provide leaf forage in cold and wet areas at a specific elevation. Moreover, the forage value of P. tatarinowii leaves can be further improved by increasing nitrogen fertilizer and reducing K and Ca fertilizers during cultivation. 4) Cluster analysis revealed obvious regionalism. Taking the Yangtze River Basin as the limit, cluster analysis divided the species into four population groups: the Yangtze River Basin and northern, southwestern, and eastern coastal populations.