Biological Control of Pythiaceous Fungi Causing Death of Longleaf Pine Seedlings During Cold Storage.

Pythium dimorphum Hendrix & Campbell and other Pythium species were determined to be pathogenic fungi that cause the death of longleaf pine seedlings during cold storage. Pathogenicity of these Pythium isolates as determined by infecting newly-germinated slash pine seedlings in vitro was confirmed in field evaluations. An in vitro dual culture screening system was effectively used for selecting Trichoderma isolates capable of killing P. dimorphum. Selected Trichoderma isolates and Gliocladium virens produced volatile and/or non-volatile antibiotics on solid media and in liquid cultures, but antibiotic production could be affected by medium type, pH, and culture age, depending on species or isolate. Some antibiotic-lacking Trichoderma isolates were able to parasitize and kill hyphae of P. dimorphum, but did not kill whole colonies. Antibiotics produced by the Trichoderma spp., rather than parasitism, were responsible for killing and/or inhibition of Pythium in vitro. After being delivered to the root systems of longleaf pine seedlings, both Pythium and Trichoderma could develop populations rapidly during cold storage. Seedling mortality was only correlated with high Pythium populations, where as seedling survival percentage was not always associated with high populations of Trichoderma. All cold-tolerant Trichoderma isolates were effective in biocontrol of Pythium in field experiments where Trichoderma wheat bran inoculum (400 mls) in clay slurry was applied to roots 1 week before the Pythium, regardless of their ability to kill or inhibit Pythium in vitro. These results suggested that the mechanisms involved in killing or inhibition of P. dimorphum in vitro were not useful for predicting biocontrol efficacy in the field. Survival data from 3 years of field experiments provides strong evidence that time and method of application were critical to obtain a successful biological control of P. dimorphum in longleaf pine seedling roots during cold storage

Application of TBSS-based machine learning models in the diagnosis of pediatric autism

ObjectiveTo explore the microstructural changes of white matter in children with pediatric autism by using diffusion kurtosis imaging (DKI), and evaluate whether the combination of tract-based spatial statistics (TBSS) and back-propagation neural network (BPNN)/support vector machine (SVM)/logistic regression (LR) was feasible for the classification of pediatric autism.MethodsDKI data were retrospectively collected from 32 children with autism and 27 healthy controls (HCs). Kurtosis fractional anisotropy (FAK), mean kurtosis (MK), axial kurtosis (KA), radial kurtosis (RK), fractional anisotropy (FA), axial diffusivity (DA), mean diffusivity (MD) and Radial diffusivity (DR) were generated by iQuant workstation. TBSS was used to detect the regions of parameters values abnormalities and for the comparison between these two groups. In addition, we also introduced the lateralization indices (LI) to study brain lateralization in children with pediatric autism, using TBSS for additional analysis. The parameters values of the differentiated regions from TBSS were then calculated for each participant and used as the features in SVM/BPNN/LR. All models were trained and tested with leave-one-out cross validation (LOOCV).ResultsCompared to the HCs group, the FAK, DA, and KA values of multi-fibers [such as the bilateral superior longitudinal fasciculus (SLF), corticospinal tract (CST) and anterior thalamic radiation (ATR)] were lower in pediatric autism group (p < 0.05, TFCE corrected). And we also found DA lateralization abnormality in Superior longitudinal fasciculus (SLF) (the LI in HCs group was higher than that in pediatric autism group). However, there were no significant differences in FA, MD, MK, DR, and KR values between HCs and pediatric autism group (P > 0.05, TFCE corrected). After performing LOOCV to train and test three model (SVM/BPNN/LR), we found the accuracy of BPNN (accuracy = 86.44%) was higher than that of LR (accuracy = 76.27%), but no different from SVM (RBF, accuracy = 81.36%; linear, accuracy = 84.75%).ConclusionOur proposed method combining TBSS findings with machine learning (LR/SVM/BPNN), was applicable in the classification of pediatric autism with high accuracy. Furthermore, the FAK, DA, and KA values and Lateralization index (LI) value could be used as neuroimaging biomarkers to discriminate the children with pediatric autism or not

Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods

Natural products are widely used for treating mitochondrial dysfunction-related diseases and cancers. Curcumin, a well-known natural product, can be potentially used to treat cancer. Human salt-induced kinase 3 (SIK3) is one of the target proteins for curcumin. However, the interactions between curcumin and human SIK3 have not yet been investigated in detail. In this study, we studied the binding models for the interactions between curcumin and human SIK3 using computational tools such as homology modeling, molecular docking, molecular dynamics simulations, and binding free energy calculations. The open activity loop conformation of SIK3 with the ketoenol form of curcumin was the optimal binding model. The I72, V80, A93, Y144, A145, and L195 residues played a key role for curcumin binding with human SIK3. The interactions between curcumin and human SIK3 were also investigated using the kinase assay. Moreover, curcumin exhibited an IC50 (half-maximal inhibitory concentration) value of 131 nM, and it showed significant antiproliferative activities of 9.62 ± 0.33 µM and 72.37 ± 0.37 µM against the MCF-7 and MDA-MB-23 cell lines, respectively. This study provides detailed information on the binding of curcumin with human SIK3 and may facilitate the design of novel salt-inducible kinases inhibitors

Radiogenomics analysis reveals the associations of dynamic contrast-enhanced–MRI features with gene expression characteristics, PAM50 subtypes, and prognosis of breast cancer

BackgroundTo investigate reliable associations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) features and gene expression characteristics in breast cancer (BC) and to develop and validate classifiers for predicting PAM50 subtypes and prognosis from DCE-MRI non-invasively.MethodsTwo radiogenomics cohorts with paired DCE-MRI and RNA-sequencing (RNA-seq) data were collected from local and public databases and divided into discovery (n = 174) and validation cohorts (n = 72). Six external datasets (n = 1,443) were used for prognostic validation. Spatial–temporal features of DCE-MRI were extracted, normalized properly, and associated with gene expression to identify the imaging features that can indicate subtypes and prognosis.ResultsExpression of genes including RBP4, MYBL2, and LINC00993 correlated significantly with DCE-MRI features (q-value < 0.05). Importantly, genes in the cell cycle pathway exhibited a significant association with imaging features (p-value < 0.001). With eight imaging-associated genes (CHEK1, TTK, CDC45, BUB1B, PLK1, E2F1, CDC20, and CDC25A), we developed a radiogenomics prognostic signature that can distinguish BC outcomes in multiple datasets well. High expression of the signature indicated a poor prognosis (p-values < 0.01). Based on DCE-MRI features, we established classifiers to predict BC clinical receptors, PAM50 subtypes, and prognostic gene sets. The imaging-based machine learning classifiers performed well in the independent dataset (areas under the receiver operating characteristic curve (AUCs) of 0.8361, 0.809, 0.7742, and 0.7277 for estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2)-enriched, basal-like, and obtained radiogenomics signature). Furthermore, we developed a prognostic model directly using DCE-MRI features (p-value < 0.0001).ConclusionsOur results identified the DCE-MRI features that are robust and associated with the gene expression in BC and displayed the possibility of using the features to predict clinical receptors and PAM50 subtypes and to indicate BC prognosis

Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation

Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIAPET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells

Current developments in pharmacological therapeutics for chronic constipation

Chronic constipation is a common gastrointestinal disease severely affecting the patient׳s quality of life. The traditional treatment of constipation is the use of laxatives. Recently, several new drugs including lubiprostone, linaclotide and prucalopride have been approved for treatment of chronic constipation. However, a significant unmet medical need still remains, particularly among those patients achieving poor results by current therapies. The 5-HT4 receptor modulators velusetrag and naronapride, the guanylate cyclase C agonist plecanatide and the ileal bile acid transporter inhibitor elobixibat are recognized as the most promising drugs under investigation. Herein, we give a comprehensive review on the pharmacological therapeutics for the treatment of chronic constipation, with the purpose of reflecting the drug development trends in this field

Research on Identification of LVRT Characteristics of Photovoltaic Inverters Based on Data Testing and PSO Algorithm

With the continuous increment of photovoltaic (PV) energy connection into a power grid, the accuracy of control parameters of PV power generation systems becomes the key to the stable operation of the power grid. At present, parameter identification based on an intelligent algorithm is a common means to obtain control parameters. However, most of the data used for identification are simulation data and the identified parameters are difficult to use in practical engineering. Therefore, aiming at the acquisition of low voltage ride through (LVRT) control parameters of PV unit, a method of identification of LVRT parameters of the PV unit is proposed, which combines sensitivity analysis with field measurement. In this paper, the test scheme of the required data is put forward through sensitivity analysis of the identified parameters, and the intelligent algorithm is used to identify the low voltage traverse parameters of the data. Finally, the optimal value is extracted from the identification results and substituted into the model. The accuracy of the parameter identification results is verified by calculating the error between the output of the model and the real operation data. The method considers the errors caused by different power levels of the inverters with highly accurate and consistent identification results, which is applicable to practical engineering calculation

A Fast Point Cloud Recognition Algorithm Based on Keypoint Pair Feature

At present, PPF-based point cloud recognition algorithms can perform better matching than competitors and be verified in the case of severe occlusion and stacking. However, including certain superfluous feature point pairs in the global model description would significantly lower the algorithm’s efficiency. As a result, this paper delves into the Point Pair Feature (PPF) algorithm and proposes a 6D pose estimation method based on Keypoint Pair Feature (K-PPF) voting. The K-PPF algorithm is based on the PPF algorithm and proposes an improved algorithm for the sampling point part. The sample points are retrieved using a combination of curvature-adaptive and grid ISS, and the angle-adaptive judgment is performed on the sampling points to extract the keypoints, therefore improving the point pair feature difference and matching accuracy. To verify the effectiveness of the method, we analyze the experimental results in scenes with different occlusion and complexity levels under the evaluation metrics of ADD-S, Recall, Precision, and Overlap rate. The results show that the algorithm in this paper reduces redundant point pairs and improves recognition efficiency and robustness compared with PPF. Compared with FPFH, CSHOT, SHOT and SI algorithms, this paper improves the recall rate by more than 12.5%