RESUMEN
Addressing the high false-positive rate of conventional low-dose computed tomography (LDCT) for lung cancer diagnosis, the efficacy of incorporating blood-based noninvasive testing for assisting practicing clinician's decision making in diagnosis of pulmonary nodules (PNs) is investigated. In this prospective observative study, next generation sequencing- (NGS-) based cell-free DNA (cfDNA) mutation profiling, NGS-based cfDNA methylation profiling, and blood-based protein cancer biomarker testing are performed for patients with PNs, who are diagnosed as high-risk patients through LDCT and subsequently undergo surgical resections, with tissue sections pathologically examined and classified. Using pathological classification as the gold standard, statistical and machine learning methods are used to select molecular markers associated with tissue's malignant classification based on a 98-patient discovery cohort (28 benign and 70 malignant), and to construct an integrative multianalytical model for tissue malignancy prediction. Predictive models based on individual testing platforms have shown varying levels of performance, while their final integrative model produces an area under the receiver operating characteristic curve (AUC) of 0.85. The model's performance is further confirmed on a 29-patient independent validation cohort (14 benign and 15 malignant, with power > 0.90), reproducing AUC of 0.86, which translates to an overall sensitivity of 80% and specificity of 85.7%.
Asunto(s)
Metilación de ADN/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Nódulos Pulmonares Múltiples/sangre , Nódulos Pulmonares Múltiples/diagnóstico , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Pulmonares/genética , Aprendizaje Automático , Masculino , Nódulos Pulmonares Múltiples/genética , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
A nitrogen-fixing bacterium, designated strain X19-5(T), was isolated from rhizosphere soil of Sonchus oleraceus. Phylogenetic analysis based on a fragment of the nifH gene and the full-length 16S rRNA gene sequence revealed that strain X19-5(T) was a member of the genus Paenibacillus. Strain X19-5(T) showed the highest 16S rRNA gene sequence similarity (98.8 %) with Paenibacillus graminis RSA19(T) and below 97 % similarity with other recognized members of the genus. The level of DNA-DNA relatedness between strain X19-5(T) and P. graminis RSA19(T) was 45.7 %. The DNA G+C content of strain X19-5(T) was 46.8 mol%. The major fatty acids were anteiso-C(15 : 0), C(16 : 0) and iso-C(16 : 0). On the basis of its phenotypic characteristics and the level of DNA-DNA hybridization, strain X19-5(T) is considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus sonchi sp. nov. is proposed. The type strain is X19-5(T) (=CCBAU 83901(T)=LMG 24727(T)).
Asunto(s)
Fijación del Nitrógeno , Paenibacillus/aislamiento & purificación , Microbiología del Suelo , Sonchus/microbiología , ADN Bacteriano/genética , ADN Ribosómico/genética , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Datos de Secuencia Molecular , Paenibacillus/clasificación , Paenibacillus/genética , Paenibacillus/metabolismo , Filogenia , Raíces de Plantas/microbiología , ARN Ribosómico 16S/genéticaRESUMEN
Drought is one of the most important environmental constraints limiting plant growth and agricultural productivity. To understand the underlying mechanism of drought tolerance and to identify genes for improving this important trait, we conducted a gain-of-function genetic screen for improved drought tolerance in Arabidopsis thaliana. One mutant with improved drought tolerance was isolated and designated as enhanced drought tolerance1. The mutant has a more extensive root system than the wild type, with deeper roots and more lateral roots, and shows a reduced leaf stomatal density. The mutant had higher levels of abscisic acid and Pro than the wild type and demonstrated an increased resistance to oxidative stress and high levels of superoxide dismutase. Molecular genetic analysis and recapitulation experiments showed that the enhanced drought tolerance is caused by the activated expression of a T-DNA tagged gene that encodes a putative homeodomain-START transcription factor. Moreover, overexpressing the cDNA of the transcription factor in transgenic tobacco also conferred drought tolerance associated with improved root architecture and reduced leaf stomatal density. Therefore, we have revealed functions of the homeodomain-START factor that were gained upon altering its expression pattern by activation tagging and provide a key regulator that may be used to improve drought tolerance in plants.
