BMP4 inhibits myogenic differentiation of bone marrow–derived mesenchymal stromal cells in mdx mice

AbstractBackground aimsBone marrow–derived mesenchymal stromal cells (BMSCs) are a promising therapeutic option for treating Duchenne muscular dystrophy (DMD). Myogenic differentiation occurs in the skeletal muscle of the mdx mouse (a mouse model of DMD) after BMSC transplantation. The transcription factor bone morphogenic protein 4 (BMP4) plays a crucial role in growth regulation, differentiation and survival of many cell types, including BMSCs. We treated BMSCs with BMP4 or the BMP antagonist noggin to examine the effects of BMP signaling on the myogenic potential of BMSCs in mdx mice.MethodsWe added BMP4 or noggin to cultured BMSCs under myogenic differentiation conditions. We then injected BMP4- or noggin-treated BMSCs into the muscles of mdx mice to determine their myogenic potential.ResultsWe found that the expression levels of desmin and myosin heavy chain decreased after treating BMSCs with BMP4, whereas the expression levels of phosphorylated Smad, a downstream target of BMP4, were higher in these BMSCs than in the controls. Mdx mouse muscles injected with BMSCs pretreated with BMP4 showed decreased dystrophin expression and increased phosphorylated Smad levels compared with muscles injected with non-treated BMSCs. The opposite effects were seen after pretreatment with noggin, as expected.ConclusionsOur results identified BMP/Smad signaling as an essential negative regulator of promyogenic BMSC activity; inhibition of this pathway improved the efficiency of BMSC myogenic differentiation, which suggests that this pathway might serve as a target to regulate BMSC function for better myogenic differentiation during treatment of DMD and degenerative skeletal muscle diseases

Microbial diversity of intestinal contents and mucus in yellow catfish (Pelteobagrus fulvidraco)

In this study, traditional culture-based techniques and the 16S rDNA sequencing method were used to investigate the microbial community of the intestinal contents and mucosal layer in the intestine of yellow catfish (Pelteobagrus fulvidraco). Eleven phylotypes were detected from culturable microbiota, and their closest relatives were Plesiomonas, Yersinia, Enterobacter, Shewanella, Aeromonas, Vibrio, and Myroides. Forty-four phylotypes were retrieved from 100 positive clones from intestinal contents (library C), and 21 phylotypes were detected in the 57 positive clones from intestinal mucus (library M), most of which were affiliated with Proteobacteria (>50% of the total). However, the bacterial groups OP10 and Actinobacteria detected in library C were not found in library M, suggesting that the abundance and diversity of bacterial populations in mucus might be different from the microbiota in gut contents, and that some microbial species poorly colonized the gut mucosal layer. (C) 2010 Published by Elsevier B.V

Serum Creatinine Level: A Supplemental Index to Distinguish Duchenne Muscular Dystrophy from Becker Muscular Dystrophy

Background. To improve assessment of dystrophinopathy, the aim of this study was to identify whether serum creatinine (Crn) level reflects disease severity. Methods. Biochemical, Vignos score, and genetic data were collected on 212 boys with dystrophinopathy. Results. Serum Crn level had a strong inverse correlation with Vignos score by simple correlation ( = −0.793) and partial correlation analysis after adjustment for age, height, and weight ( = −0.791; both < 0.01). Serum Crn level was significantly higher in patients with in-frame than out-of-frame mutations ( = −4.716, < 0.01) and in Becker muscular dystrophy (BMD) patients than Duchenne muscular dystrophy (DMD) patients at ages 4, 5, 7, and 9 yr (all < 0.0125). After adjusting for age, height, and weight, BMD patients still had a significantly higher serum Crn level than DMD patients ( = 7.140, = 6.277, < 0.01). Conclusions. Serum Crn level reflected disease severity and may serve as a supplemental index to distinguish DMD from BMD in clinical practice

Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition

Many coronaviruses are capable of interspecies transmission. Some of them have caused worldwide panic as emerging human pathogens in recent years, e.g., severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In order to assess their threat to humans, we explored to infer the potential hosts of coronaviruses using a dual-model approach based on nineteen parameters computed from spike genes of coronaviruses. Both the support vector machine (SVM) model and the Mahalanobis distance (MD) discriminant model achieved high accuracies in leave-one-out cross-validation of training data consisting of 730 representative coronaviruses (99.86% and 98.08% respectively). Predictions on 47 additional coronaviruses precisely conformed to conclusions or speculations by other researchers. Our approach is implemented as a web server that can be accessed at http://bioinfo.ihb.ac.cn/seq2hosts.</p

The Grass Carp Genome Database (GCGD): an online platform for genome features and annotations

As one of the four major Chinese carps of important economic value, the grass carp (Ctenopharyngodon idellus) has attracted increasing attention from the scientific community. Recently, the draft genome has been released as a milestone in research of grass carp. In order to facilitate the utilization of these genome data, we developed the grass carp genome database (GCGD). GCGD provides visual presentation of the grass carp genome along with annotations and amino acid sequences of predicted protein-coding genes. Other related genetic and genomic data available in this database include the genetic linkage maps, microsatellite genetic markers (i.e. Short Sequence Repeats, SSRs), and some selected transcriptomic datasets. A series of tools have been integrated into GCGD for visualization, analysis and retrieval of data, e.g. JBrowse for navigation of genome annotations, BLAST for sequence alignment, EC2KEGG for comparison of metabolic pathways, IDConvert for conversion of terms across databases and ReadContigs for extraction of sequences from the grass carp genome

FVD: The fish-associated virus database

With the expanding of marine and freshwater aquaculture, the outbreaks of aquatic animal diseases have increasingly become the major threats to the healthy development of aquaculture industries. Notably, viral infections lead to massive fish deaths and result in great economic loss every year across the world. Hence, it is meaningful to clarify the biodiversity, geographical distribution and host specificity of fish-associated viruses. In this study, viral sequences detected in fish samples were manually collected from public resources, along with the related metadata, such as sampling time, location, specimen type and fish species. Moreover, the information regarding the host fish, including aliases, diet type and geographic distribution were also integrated into a database (FVD). To date, FVD covers the information of 4860 fish-associated viruses belonging to 15 viral families, which were detected from 306 fish species in 57 countries. Meanwhile, sequence alignment, live data statistics and download function are available. Through the user-friendly interface, FVD provides a practical platform that would not only benefit virologists who want to disclose the spread of fish-associated viruses, but also zoologists who focus on the health of domestic and wild animals. Furthermore, it may facilitate the surveillance and prevention of fish viral diseases.</p

PMSeeker: A Scheme Based on the Greedy Algorithm and the Exhaustive Algorithm to Screen Low-Redundancy Marker Sets for Large-Scale Parentage Assignment with Full Parental Genotyping

Parentage assignment is a genetic test that utilizes genetic characteristics, such as molecular markers, to identify the parental relationships within populations, which, in commercial fish farming, are almost always large and where full information on potential parents is known. To accurately find the true parents, the genotypes of all loci in the parentage marker set (PMS) are required for each individual being tested. With the same accuracy, a PMS containing a smaller number of markers will undoubtedly save experimental costs. Thus, this study established a scheme to screen low-redundancy PMSs using the exhaustive algorithm and greedy algorithm. When screening PMSs, the greedy algorithm selects markers based on the parental dispersity index (PDI), a uniquely defined metric that outperforms the probability of exclusion (PE). With the conjunctive use of the two algorithms, non-redundant PMSs were found for more than 99.7% of solvable cases in three groups of random sample experiments in this study. Then, a low-redundancy PMS can be composed using two or more of these non-redundant PMSs. This scheme effectively reduces the number of markers in PMSs, thus conserving human and experimental resources and laying the groundwork for the widespread implementation of parentage assignment technology in economic species breeding

Passionfruit Genomic Database (PGD): a comprehensive resource for passionfruit genomics

Abstract Passionfruit (Passiflora edulis) is a significant fruit crop in the commercial sector, owing to its high nutritional and medicinal value. The advent of high-throughput genomics sequencing technology has led to the publication of a vast amount of passionfruit omics data, encompassing complete genome sequences and transcriptome data under diverse stress conditions. To facilitate the efficient integration, storage, and analysis of these large-scale datasets, and to enable researchers to effectively utilize these omics data, we developed the first passionfruit genome database (PGD). The PGD platform comprises a diverse range of functional modules, including a genome browser, search function, heatmap, gene expression patterns, various tools, sequence alignment, and batch download, thereby providing a user-friendly interface. Additionally, supplementary practical tools have been developed for the PGD, such as gene family analysis tools, gene ontology (GO) terms, a pathway enrichment analysis, and other data analysis and mining tools, which enhance the data’s utilization value. By leveraging the database’s robust scalability, the intention is to continue to collect and integrate passionfruit omics data in the PGD, providing comprehensive and in-depth support for passionfruit research. The PGD is freely accessible via http://passionfruit.com.cn

Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies

The aim of our study was to determine the role of dystrophin hydrophobic regions in the pathogenesis of Duchenne (DMD) and Becker (BMD) muscular dystrophies, by the Kyte-Doolittle scale mean hydrophobicity profile and 3D molecular models. A total of 1038 cases diagnosed with DMD or BMD with the in-frame mutation were collected in our hospital and the Leiden DMD information database in the period 2002-2013. Correlation between clinical types and genotypes were determined on the basis of these two sources. In addition, the Kyte-Doolittle scale mean hydrophobicity of dystrophin was analyzed using BioEdit software and the models of the hydrophobic domains of dystrophin were constructed. The presence of four hydrophobic regions is confirmed. They include the calponin homology CH2 domain on the actin-binding domain (ABD), spectrin-type repeat 16, hinge III and the EF Hand domain. The severe symptoms of DMD usually develop as a result of the mutational disruption in the hydrophobic regions I, II and IV of dystrophin – those that bind associated proteins of the dystrophin-glycoprotein complex (DGC). On the other hand, when the hydrophobic region III is deleted, the connection of the ordered repeat domains of the central rod domain remains intact, resulting in the less severe clinical presentation. We conclude that mutational changes in the structure of hydrophobic regions of dystrophin play an important role in the pathogenesis of DMD