RES-Scanner:a software package for genome-wide identification of RNA-editing sites

BACKGROUND: High-throughput sequencing (HTS) provides a powerful solution for the genome-wide identification of RNA-editing sites. However, it remains a great challenge to distinguish RNA-editing sites from genetic variants and technical artifacts caused by sequencing or read-mapping errors. RESULTS: Here we present RES-Scanner, a flexible and efficient software package that detects and annotates RNA-editing sites using matching RNA-seq and DNA-seq data from the same individuals or samples. RES-Scanner allows the use of both raw HTS reads and pre-aligned reads in BAM format as inputs. When inputs are HTS reads, RES-Scanner can invoke the BWA mapper to align reads to the reference genome automatically. To rigorously identify potential false positives resulting from genetic variants, we have equipped RES-Scanner with sophisticated statistical models to infer the reliability of homozygous genotypes called from DNA-seq data. These models are applicable to samples from either single individuals or a pool of multiple individuals if the ploidy information is known. In addition, RES-Scanner implements statistical tests to distinguish genuine RNA-editing sites from sequencing errors, and provides a series of sophisticated filtering options to remove false positives resulting from mapping errors. Finally, RES-Scanner can improve the completeness and accuracy of editing site identification when the data of multiple samples are available. CONCLUSION: RES-Scanner, as a software package written in the Perl programming language, provides a comprehensive solution that addresses read mapping, homozygous genotype calling, de novo RNA-editing site identification and annotation for any species with matching RNA-seq and DNA-seq data. The package is freely available. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13742-016-0143-4) contains supplementary material, which is available to authorized users

Benefits of laboratory personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials

   Background: The preventive effects of laboratory personalized antiplatelet therapy (PAPT) strategy in­cluding genetic detection and platelet function testing (PFT) on major adverse cardiac events (MACEs) and bleeding events in coronary artery disease (CAD) patients undergoing stenting has been extensively studied. Despite that, no clear conclusion can be drawn. In this study, a meta-analysis was performed to explore a more precise estimation of the benefits of laboratory PAPT. Methods: Randomized controlled trials were identified by the use of search databases such as PubMed, Embase, and Cochrane Controlled Trials Register up to May 2017, and the estimates were pooled. Results: Fourteen studies including 9497 patients met the inclusion criteria. The laboratory PAPT reduced MACEs risk (risk ratio [RR] 0.58, 95% confidence interval [CI] 0.42–0.80, p = 0.001), stent thrombosis (RR 0.60, 95% CI 0.41–0.87, p = 0.008) and myocardial infarctions (RR 0.43, 95% CI 0.21–0.88, p = 0.02) compared to the non-PAPT group. No statistically significant difference was observed between the two groups regarding cardiovascular death (RR 0.77, 95% CI 0.51–1.16, p = 0.21), bleeding events (RR 0.96, 95% CI 0.81–1.13, p = 0.59) and ischemic stroke (RR 0.81; 95% CI 0.39–1.66, p = 0.57). The preventive effect on MACEs was more significant in patients with high on-treatment platelet reactivity (RR 0.46; 95% CI 0.27–0.80, p = 0.006). Conclusions: Coronary artery disease patients after stenting could obtain benefits from laboratory PAPT. (Cardiol J 2018; 25, 1: 128–141

K-Domain Splicing Factor OsMADS1 Regulates Open Hull Male Sterility in Rice

AbstractWe identified the rice floral organ development mutant, termed as open hull and male sterile 1 (ohms1), from the progeny of the indica restorer line Zhonghui 8015 treated with 60Co γ-ray irradiation. The ohms1 mutant exhibited an open hull and lemma- and palea-like structure conversion between the anthers and stigma, which resulted in the ohms1 mutant spikelet showing ‘tridentate lemma’. The ohms1 mutant was entirely sterile but had 60%–70% fertile pollen. Genetic analysis and gene mapping showed that ohms1 was controlled by a single recessive gene, and the mutant gene was fine-mapped to a 42-kb interval on the short arm of chromosome 3 between markers KY2 and KY29. Sequence analysis of the four open reading frames in this region revealed that the mutant carried a single nucleotide transformation (A to G) at the last base of the fifth intron, which was likely corresponded to ohms1 phynotype, in an MIKC type MADS-box gene OsMADS1 (LOC_Os03g11614). Enzyme digestion and cDNA sequencing further indicated that the variable splicing was responsible for the deletion of the sixth exon in ohms1, but no structural changes in the MADS domain or amino acid frame shifts appeared. Additionally, real-time fluorescent quantitative PCR analysis showed that the OsMADS1 expression level decreased significantly in the ohms1 mutant. The expression levels of rice flowering factors and floral glume development-related genes also changed significantly. These results demonstrate that OsMADS1 may play an important role in rice floral organ development, particularly in floral glume development and floret primordium differentiation

A giant hemolymphangioma of the pancreas in a 20-year-old girl: a report of one case and review of the literature

<p>Abstract</p> <p>Background</p> <p>Hemolymphangioma of the pancreas is a very rare benign tumor. There were only six reports of this disease until December 2008. Herein, we report a case of giant hemolymphangioma of the pancreas in a 20-year-old girl.</p> <p>Case presentation</p> <p>We describe a 20-year-old girl who presented with a mass in abdominal cavity and epigastric discomfort about a week. Physical examination showed a great abdominal mass. Abdominal computed tomography showed extrinsic duodenal compression due to a large retroperitoneal tumor possibly arising from pancreas. The tumor enucleation was performed and a diagnosis of hemolymphangioma of the pancreas was made. The patient had a complication of chylous leakage, which was successfully managed. The patient is alive and well, after 26 months of follow-up, with no complaints or recurrence.</p> <p>Conclusion</p> <p>From this case and literature, we can conclude that hemolymphangioma of the pancreas in adult is a rare benign tumor, and accurate diagnosis can not be preoperatively established. Tumor resection should be performed whenever possible. The risk of recurrence seems very low.</p

A Short Review of U. S. Naval Ship Concept Design Technology Development Features

In present study, a history analysis and review of last 30 years for U.S. naval ship concept design development trend is proposed. Based on the development of naval ship concept design model history, the three features of development process are further summarized. The first is that model-based system engineering (MBSE) becomes the basic of naval ship concept design, while the second one is that the multi-discipline crossing and combination becomes a general innovation model. And the third one is that systematization oriented naval system integration is the developing goal. Some detailed examples are presented to illustrate these three characteristics. Finally, the technology difficulties in naval ship concept design are also presented

Eplerenone Reverses Cardiac Fibrosis via the Suppression of Tregs by Inhibition of Kv1.3 Channel

Background: Fibroblast proliferation is a critical feature during heart failure development. Previous studies reported regulatory T-lymphocytes (Tregs)’ protective role against myocardial fibrosis. However, notably, Tregs also secrete fibrogenic cytokine TGF-β when activated. This study aimed to clarify the intriguing link between Tregs and fibrosis, the role of Tregs Kv1.3 potassium channel (regulating T-lymphocytes activation) in the fibrosis process, and how selective aldosterone receptor antagonist Eplerenone affects Tregs and fibrosis through its action on Kv1.3 channel.Methods and Results: After co-incubation with Tregs, cardiac fibroblast proliferation (CCK-8 assay) and levels of collagen I, III, and Matrix metalloproteinase2 (ELISA) significantly elevated. Cell viability assays, Kv1.3 channel mRNA (RT-qPCR), and protein expression (In-Cell Western Blotting) revealed Tregs were activated/proliferated when co-cultured with fibroblasts. Treg intracellular TGF-β level increased by 5.8-fold, far more than that of intracellular IL-10, extracellular TGF-β and IL-10 (ELISA). And 30 μM eplerenone suppressed Tregs proliferation by 82.77% and furthermore, suppressed intracellular TGF-β level to a significantly greater extent than that of intracellular IL-10, extracellular TGF-β and IL-10. Moreover, the Kv1.3 current (whole-cell patch clamp) of Tregs in congestive heart failure patients and rats (induced by coronary artery ligation and exhaustive exercise) elevated by &gt;4-fold than that of healthy volunteers and control rats, whereas 30 μM eplerenone suppressed the current by &gt;60% in control Tregs. In addition, docking calculations (AutoDock software 4.0 suite) showed eplerenone has higher H-bond energy with Kv1.3 channel than other selective blockers.Conclusion: Immuno-regulation in the late stage of CHF activates Tregs proliferation via the upregulation of Kv1.3 channels, which promotes cardiac fibrosis by primarily secreting TGF-β. Taken together, eplerenone’s high affinity to Kv1.3 channel enables it to antagonize the Kv1.3 channels directly to suppress Tregs proliferation, which in turn may play an immuno-regulatory role during CHF

Screening immune adjuvants for an inactivated vaccine against Erysipelothrix rhusiopathiae

In this study, we screened adjuvants for an inactivated vaccine against Erysipelothrix rhusiopathiae (E. rhusiopathiae). Inactivated cells of E. rhusiopathiae strain HG-1 were prepared as the antigen in five adjuvanted inactivated vaccines, including a mineral-oil-adjuvanted vaccine (Oli vaccine), aluminum-hydroxide-gel-adjuvanted vaccine (Alh vaccine), ISA201-biphasic-oil-emulsion-adjuvanted vaccine (ISA201 vaccine), GEL02-water-soluble-polymer-adjuvanted vaccine (GEL vaccine), and IMS1313-water-soluble-nanoparticle-adjuvanted vaccine (IMS1313 vaccine). The safety test results of subcutaneous inoculation in mice showed that Oli vaccine had the most severe side effects, with a combined score of 35, followed by the ISA201 vaccine (25 points), Alh vaccine (20 points), GEL vaccine (10 points), and IMS1313 vaccine (10 points). A dose of 1.5LD50 of strain HG-1 was used to challenge the mice intraperitoneally, 14 days after their second immunization. The protective efficacy of Oli vaccine and Alh vaccine was 100% (8/8), whereas that of the other three adjuvanted vaccines was 88% (7/8). Challenge with 2.5LD50 of strain HG-1 resulted in a 100% survival rate, demonstrating the 100% protective efficacy of the Oli vaccine, followed by the GEL vaccine (71%, 5/7), IMS1313 vaccine (57%, 4/7), ISA201 vaccine (43%, 3/7), and Alh vaccine (29%, 2/7). Challenge with 4LD50 of strain HG-1 showed 100% (7/7) protective efficacy of the Oli vaccine and 71% (5/7) protective efficacy of the GEL vaccine, whereas the protective efficacy of other three adjuvanted vaccine was 14% (1/7). The Alh and GEL vaccines were selected for comparative tests in piglets, and both caused minor side effects. A second immunization with these two adjuvanted vaccines conferred 60 and 100% protective efficacy, respectively, after the piglets were challenged via an ear vein with 8LD100 of strain HG-1. After challenge with 16LD100 of strain HG-1, the Alh and GEL vaccines showed 40% and 100% protective efficacy, respectively. Our results suggested that GEL is the optimal adjuvant for an inactivated vaccine against E. rhusiopathiae

Transcutaneous Vagus Nerve Stimulation for the Treatment of Depression: A Study Protocol for a Double Blinded Randomized Clinical Trial

Background: Depressive disorders are the most common form of mental disorders in community and health care settings. Unfortunately, the treatment of Major Depressive Disorder (MDD) is far from satisfactory. Vagus nerve stimulation (VNS) is a relatively new and promising physical treatment for depressive disorders. One particularly appealing element of VNS is the long-term benefit in mood regulation. However, because this intervention involves surgery, perioperative risks, and potentially significant side effects, this treatment has been limited to those patients with treatment-resistant depression who have failed medication trials and exhausted established somatic treatments for major depression, due to intolerance or lack of response. This double-blinded randomized clinical trial aims to overcome these limitations by introducing a novel method of stimulating superficial branches of the vagus nerve on the ear to treat MDD. The rationale is that direct stimulation of the afferent nerve fibers on the ear area with afferent vagus nerve distribution should produce a similar effect as classic VNS in reducing depressive symptoms without the burden of surgical intervention. Design: One hundred twenty cases (60 males) of volunteer patients with mild and moderate depression will be randomly divided into transcutaneous vagus nerve stimulation group (tVNS) and sham tVNS group. The treatment period lasts 4 months and all clinical and physiological measurements are acquired at the beginning and the end of the treatment period. Discussion: This study has the potential to significantly extend the application of VNS treatment for MDD and other disorders (including epilepsy, bipolar disorder, and morbid obesity), resulting in direct benefit to the patients suffering from these highly prevalent disorders. In addition, the results of this double-blinded clinical trial will shed new light on our understanding of acupuncture point specificity, and development of methodologies in clinical trials of acupuncture treatment

Radiomic Features From Multi-Parameter MRI Combined With Clinical Parameters Predict Molecular Subgroups in Patients With Medulloblastoma

The 2016 WHO classification of central nervous system tumors has included four molecular subgroups under medulloblastoma (MB) as sonic hedgehog (SHH), wingless (WNT), Grade 3, and Group 4. We aimed to develop machine learning models for predicting MB molecular subgroups based on multi-parameter magnetic resonance imaging (MRI) radiomics, tumor locations, and clinical factors. A total of 122 MB patients were enrolled retrospectively. After selecting robust, non-redundant, and relevant features from 5,529 extracted radiomics features, a random forest model was constructed based on a training cohort (n= 92) and evaluated on a testing cohort (n= 30). By combining radiographic features and clinical parameters, two combined prediction models were also built. The subgroup can be classified using an 11-feature radiomics model with a high area under the curve (AUC) of 0.8264 for WNT and modest AUCs of 0.6683, 0.6004, and 0.6979 for SHH, Group 3, and Group 4 in the testing cohort, respectively. Incorporating location and hydrocephalus into the radiomics model resulted in improved AUCs of 0.8403 and 0.8317 for WNT and SHH, respectively. After adding gender and age, the AUCs for WNT and SHH were further improved to 0.9097 and 0.8654, while the accuracies were 70 and 86.67% for Group 3 and Group 4, respectively. Prediction performance was excellent for WNT and SHH, while that for Group 3 and Group 4 needs further improvements. Machine learning algorithms offer potentials to non-invasively predict the molecular subgroups of MB.</p