Jumbo Bacteriophages Are Represented Within an Increasing Diversity of Environmental Viruses Infecting the Emerging Phytopathogen, Dickeya solani

Dickeya species are economically important phytopathogens widespread in mainland Europe that can reduce crop yields by 25%. There are no effective environmentally-acceptable chemical systems available for diseases caused by Dickeya. Bacteriophages have been suggested for use in biocontrol of these pathogens in the field, and limited field trials have been conducted. To date the majority of bacteriophages capable of infecting Dickeya solani, one of the more aggressive species, are from the same family, the Ackermannviridae, many representatives of which have been shown to be unsuitable for use in the field due to their capacity for generalized transduction. Members of this family are also only capable of forming individual plaques on D. solani. Here we describe novel bacteriophages from environmental sources isolated on D. solani, including members of two other viral families; Myoviridae and Podoviridae, most of which are capable of forming plaques on multiple Dickeya species. Full genomic sequencing revealed that the Myoviridae family members form two novel clusters of jumbo bacteriophages with genomes over 250 kbp, with one cluster containing phages of another phytopathogen Erwinia amylovora. Transduction experiments showed that the majority of the new environmental bacteriophages are also capable of facilitating efficient horizontal gene transfer, however the single Podoviridae family member is not. This particular phage therefore has potential for use as a biocontrol agent against multiple species of Dickeya

Low Frequency and Variability of FLT3 Mutations in Korean Patients with Acute Myeloid Leukemia

FLT3 mutations are common genetic changes, and are reported to have prognostic significance in acute myeloid leukemia (AML). The FLT3 internal tandem duplication (ITD) and the D835 activating mutation in the tyrosine kinase domain (TKD) were analyzed by polymerase chain reaction (PCR) in the genomic DNA of Korean patients with AML at diagnosis and during follow-up. There were 226 patients with AML enrolled between March 1996 and August 2005. The incidence of ITD and TKD at diagnosis was 13% (29/226) and 3% (6/226). When compared to Western and other Asian patients with AML, Korean patients had a lower frequency by about two-thirds of ITD and TKD. Among the non-M3 cases (N=203), the patients with an ITD had a significantly shorter event-free survival when compared with those without an ITD (p=0.0079). Among 54 relapsed patients, 9 patients had the FLT3 ITD at diagnosis. Six patients demonstrated a reappearance of the ITD and 3 patients remained negative at relapse. One patient, among 45 patients who relapsed, had a negative baseline ITD but acquired a de novo ITD at relapse. There were 101 samples from 93 patients in remission; they were all negative for an ITD. Among 34 patients who failed to achieve a remission, five patients had a persistent ITD and one patient had a de novo ITD. These results support the concept of resistance of FLT3 ITD leukemic clones to chemotherapy. Therefore, effective therapy with FLT3 targeting agents may improve the prognosis of non-M3 AML patients with the FLT3 mutation

Jumbo Bacteriophages Are Represented Within an Increasing Diversity of Environmental Viruses Infecting the Emerging Phytopathogen, Dickeya solani.

Dickeya species are economically important phytopathogens widespread in mainland Europe that can reduce crop yields by 25%. There are no effective environmentally-acceptable chemical systems available for diseases caused by Dickeya. Bacteriophages have been suggested for use in biocontrol of these pathogens in the field, and limited field trials have been conducted. To date the majority of bacteriophages capable of infecting Dickeya solani, one of the more aggressive species, are from the same family, the Ackermannviridae, many representatives of which have been shown to be unsuitable for use in the field due to their capacity for generalized transduction. Members of this family are also only capable of forming individual plaques on D. solani. Here we describe novel bacteriophages from environmental sources isolated on D. solani, including members of two other viral families; Myoviridae and Podoviridae, most of which are capable of forming plaques on multiple Dickeya species. Full genomic sequencing revealed that the Myoviridae family members form two novel clusters of jumbo bacteriophages with genomes over 250 kbp, with one cluster containing phages of another phytopathogen Erwinia amylovora. Transduction experiments showed that the majority of the new environmental bacteriophages are also capable of facilitating efficient horizontal gene transfer, however the single Podoviridae family member is not. This particular phage therefore has potential for use as a biocontrol agent against multiple species of Dickeya

Landscape of epigenetically regulated lncRNAs and DNA methylation in smokers with lung adenocarcinoma.

In this study, we identified long non-coding RNAs (lncRNAs) associated with DNA methylation in lung adenocarcinoma (LUAD) using clinical and methylation/expression data from 184 qualified LUAD tissue samples and 21 normal lung-tissue samples from The Cancer Genome Atlas (TCGA). We identified 1865 differentially expressed genes that correlated negatively with the methylation profiles of normal lung tissues, never-smoker LUAD tissues and smoker LUAD tissues, while 1079 differentially expressed lncRNAs were identified using the same criteria. These transcripts were integrated using ingenuity pathway analysis to determine significant pathways directly related to cancer, suggesting that lncRNAs play a crucial role in carcinogenesis. When comparing normal lung tissues and smoker LUAD tissues, 86 candidate genes were identified, including six lncRNAs. Of the 43 candidate genes revealed by comparing never-smoker LUAD tissues and smoker LUAD tissues, 13 were also different when compared to normal lung tissues. We then investigated the expression of these genes using the Gene Expression of Normal and Tumor Tissues (GENT) and Methylation and Expression Database of Normal and Tumor Tissues (MENT) databases. We observed an inverse correlation between the expression of 13 genes in normal lung tissues and smoker LUAD tissues, and the expression of five genes between the never-smoker and smoker LUAD tissues. These findings were further validated in clinical specimens using bisulfite sequencing, revealing that AGR2, AURKB, FOXP3, and HMGA1 displayed borderline differences in methylation. Finally, we explored the functional connections between DNA methylation, lncRNAs, and gene expression to identify possible targets that may contribute toward the pathogenesis of cigarette smoking-associated LUAD. Together, our findings suggested that differentially expressed lncRNAs and their target transcripts could serve as potential biomarkers for LUAD

Psychological Aspects of Child Maltreatment

In this review, we provide information about the etiology, risk factors, and clinical presentations of maltreatment to help clinicians better understand child abuse and neglect. Child maltreatment is a major global health challenge that can result in severe consequences. Abused and neglected children are likely to develop psychiatric disorders, such as major depressive disorder, anxiety disorder, and posttraumatic stress disorder. Understanding child maltreatment is expected to prevent and reduce victimization in children, adolescents, and their families.N

Automated Hybrid Model for Detecting Perineural Invasion in the Histology of Colorectal Cancer

Perineural invasion (PNI) is a well-established independent prognostic factor for poor outcomes in colorectal cancer (CRC). However, PNI detection in CRC is a cumbersome and time-consuming process, with low inter-and intra-rater agreement. In this study, a deep-learning-based approach was proposed for detecting PNI using histopathological images. We collected 530 regions of histology from 77 whole-slide images (PNI, 100 regions; non-PNI, 430 regions) for training. The proposed hybrid model consists of two components: a segmentation network for tumor and nerve tissues, and a PNI classifier. Unlike a “black-box” model that is unable to account for errors, the proposed approach enables false predictions to be explained and addressed. We presented a high performance, automated PNI detector, with the area under the curve (AUC) for the receiver operating characteristic (ROC) curve of 0.92. Thus, the potential for the use of deep neural networks in PNI screening was proved, and a possible alternative to conventional methods for the pathologic diagnosis of CRC was provided

Automated Hybrid Model for Detecting Perineural Invasion in the Histology of Colorectal Cancer

Perineural invasion (PNI) is a well-established independent prognostic factor for poor outcomes in colorectal cancer (CRC). However, PNI detection in CRC is a cumbersome and time-consuming process, with low inter-and intra-rater agreement. In this study, a deep-learning-based approach was proposed for detecting PNI using histopathological images. We collected 530 regions of histology from 77 whole-slide images (PNI, 100 regions; non-PNI, 430 regions) for training. The proposed hybrid model consists of two components: a segmentation network for tumor and nerve tissues, and a PNI classifier. Unlike a “black-box” model that is unable to account for errors, the proposed approach enables false predictions to be explained and addressed. We presented a high performance, automated PNI detector, with the area under the curve (AUC) for the receiver operating characteristic (ROC) curve of 0.92. Thus, the potential for the use of deep neural networks in PNI screening was proved, and a possible alternative to conventional methods for the pathologic diagnosis of CRC was provided