Uncovering the relationship and mechanisms of Tartary buckwheat (Fagopyrum tataricum) and Type II diabetes, hypertension, and hyperlipidemia using a network pharmacology approach
Background Tartary buckwheat (TB), a crop rich in protein, dietary fiber, and flavonoids, has been reported to have an effect on Type II diabetes (T2D), hypertension (HT), and hyperlipidemia (HL). However, limited information is available about the relationship between Tartary buckwheat and these three diseases. The mechanisms of how TB impacts these diseases are still unclear. Methods In this study, network pharmacology was used to investigate the relationship between the herb as well as the diseases and the mechanisms of how TB might impact these diseases. Results A total of 97 putative targets of 20 compounds found in TB were obtained. Then, an interaction network of 97 putative targets for these compounds and known therapeutic targets for the treatment of the three diseases was constructed. Based on the constructed network, 28 major nodes were identified as the key targets of TB due to their importance in network topology. The targets of ATK2, IKBKB, RAF1, CHUK, TNF, JUN, and PRKCA were mainly involved in fluid shear stress and the atherosclerosis and PI3K-Akt signaling pathways. Finally, molecular docking simulation showed that 174 pairs of chemical components and the corresponding key targets had strong binding efficiencies. Conclusion For the first time, a comprehensive systemic approach integrating drug target prediction, network analysis, and molecular docking simulation was developed to reveal the relationships and mechanisms between the putative targets in TB and T2D, HT, and HL.
Lu et al. (2017) Uncovering the relationship and mechanisms of Tartary buckwheat (Fagopyrum tataricum) and Type II diabetes, hypertension, and hyperlipidemia using a network pharmacology approach. PeerJ 5:e4042 https://doi.org/10.7717/peerj.4042
Transcriptome sequencing reveals high isoform diversity in the ant Formica exsecta
Transcriptome resources for social insects have the potential to provide new insight into polyphenism, i.e., how divergent phenotypes arise from the same genome. Here we present a transcriptome based on paired-end RNA sequencing data for the ant Formica exsecta (Formicidae, Hymenoptera). The RNA sequencing libraries were constructed from samples of several life stages of both sexes and female castes of queens and workers, in order to maximize representation of expressed genes. We first compare the performance of common assembly and scaffolding software (Trinity, Velvet-Oases, and SOAPdenovo-trans), in producing de novo assemblies. Second, we annotate the resulting expressed contigs to the currently published genomes of ants, and other insects, including the honeybee, to filter genes that have annotation evidence of being true genes. Our pipeline resulted in a final assembly of altogether 39,262 mRNA transcripts, with an average coverage of >300X, belonging to 17,496 unique genes with annotation in the related ant species. From these genes, 536 genes were unique to one caste or sex only, highlighting the importance of comprehensive sampling. Our final assembly also showed expression of several splice variants in 6,975 genes, and we show that accounting for splice variants affects the outcome of downstream analyses such as gene ontologies. Our transcriptome provides an outstanding resource for future genetic studies on F. exsecta and other ant species, and the presented transcriptome assembly can be adapted to any non-model species that has genomic resources available from a related taxon.
Dhaygude et al. (2017) Transcriptome sequencing reveals high isoform diversity in the ant Formica exsecta. PeerJ 5:e3998 https://doi.org/10.7717/peerj.3998
The reanalysis of biogeography of the Asian tree frog, Rhacophorus (Anura: Rhacophoridae): geographic shifts and climatic change influenced the dispersal process and diversification
Rapid uplifts of the Tibetan Plateau and climate change in Asia are thought to have profoundly modulated the diversification of most of the species distributed throughout Asia. The ranoid tree frog genus Rhacophorus, the largest genus in the Rhacophoridae, is widely distributed in Asia and especially speciose in the areas south and east of the Tibetan Plateau. Here, we infer phylogenetic relationships among species and estimate divergence times, asking whether the spatiotemporal characteristics of diversification within Rhacophorus were related to rapid uplifts of the Tibetan Plateau and concomitant climate change. Phylogenetic analysis recovered distinct lineage structures in Rhacophorus, which indicated a clear distribution pattern from Southeast Asia toward East Asia and India. Molecular dating suggests that the first split within the genus date back to the Middle Oligocene (approx. 30 Ma). The Rhacophorus lineage through time (LTT) showed that there were periods of increased speciation rate: 14–12 Ma and 10–4 Ma. In addition, ancestral area reconstructions supported Southeast Asia as the ancestral area of Rhacophorus. According to the results of molecular dating, ancestral area reconstructions and LTT we think the geographic shifts, the staged rapid rises of the Tibetan Plateau with parallel climatic changes and reinforcement of the Asian monsoons (15 Ma, 8 Ma and 4–3 Ma), possibly prompted a burst of diversification in Rhacophorus.
Pan et al. (2017) The reanalysis of biogeography of the Asian tree frog, Rhacophorus (Anura: Rhacophoridae): geographic shifts and climatic change influenced the dispersal process and diversification. PeerJ 5:e3995 https://doi.org/10.7717/peerj.3995
PBxplore: a tool to analyze local protein structure and deformability with Protein Blocks
This paper describes the development and application of a suite of tools, called PBxplore, to analyze the dynamics and deformability of protein structures using Protein Blocks (PBs). Proteins are highly dynamic macromolecules, and a classical way to analyze their inherent flexibility is to perform molecular dynamics simulations. The advantage of using small structural prototypes such as PBs is to give a good approximation of the local structure of the protein backbone. More importantly, by reducing the conformational complexity of protein structures, PBs allow analysis of local protein deformability which cannot be done with other methods and had been used efficiently in different applications. PBxplore is able to process large amounts of data such as those produced by molecular dynamics simulations. It produces frequencies, entropy and information logo outputs as text and graphics. PBxplore is available at https://github.com/pierrepo/PBxplore and is released under the open-source MIT license.
Barnoud et al. (2017) PBxplore: a tool to analyze local protein structure and deformability with Protein Blocks. PeerJ 5:e4013 https://doi.org/10.7717/peerj.4013
Anterior-posterior gene expression differences in three Lake Malawi cichlid fishes with variation in body stripe orientation
Morphological differentiation among closely related species provides opportunities to study mechanisms shaping natural phenotypic variation. Here, we address variation in the orientation of melanin-colored body stripes in three cichlid species of the tribe Haplochromini. Melanochromis auratus displays a common pattern of dark, straight horizontal body stripes, whereas in Aristochromis christyi and Buccochromis rhoadesii, oblique stripes extend from the anterior dorsal to the posterior mid-lateral trunk. We first validated a stably reference gene, and then, investigated the chromatophore distribution in the skin by assessing the expression levels of the iridophore and melanophore marker genes, ltk and slc24a5, respectively, as well as pmel, a melanophore pigmentation marker gene. We found anterior-posterior differences in the expression levels of the three genes in the oblique-striped species. The higher anterior expression of ltk, indicates increased iridophore density in the anterior region, i.e., uneven horizontal distribution of iridophores, which coincides with the anterior dorsalization of melanophore stripe in these species. The obliqueness of the horizontal body stripes might be a result of distinct migratory or patterning abilities of melanophores in anterior and posterior stripe regions which could be reflected by variation in the expression of genes involved in melanophore patterning. To address this, we investigated anterior-posterior expression levels of a primary set of candidate target genes with known functions in melanophore migration and stripe patterning in the adult zebrafish, and their related gene regulatory network. Among these genes, those with differences in anterior-posterior expression showed only species-specific differential expression, e.g., sdf1a, col14a1a, ifitm5, and agpat3, with the exception of fbxw4/hagoromo (differentially expressed in an oblique-and the straight-striped species). In summary, distinct anterior-posterior gradients in iridophore density found to be more similar characteristic between the two oblique-striped species. Furthermore, the species-specific differential expression of genes involved in stripe patterning might also implicate distinct molecular processes underlying the obliqueness of body stripe in two closely related cichlid species.
Ahi et al. (2017) Anterior-posterior gene expression differences in three Lake Malawi cichlid fishes with variation in body stripe orientation. PeerJ 5:e4080 https://doi.org/10.7717/peerj.4080
The role of biomaterials in the treatment of meniscal tears
Extensive investigations over the recent decades have established the anatomical, biomechanical and functional importance of the meniscus in the knee joint. As a functioning part of the joint, it serves to prevent the deterioration of articular cartilage and subsequent osteoarthritis. To this end, meniscus repair and regeneration is of particular interest from the biomaterial, bioengineering and orthopaedic research community. Even though meniscal research is previously of a considerable volume, the research community with evolving material science, biology and medical advances are all pushing toward emerging novel solutions and approaches to the successful treatment of meniscal difficulties. This review presents a tactical evaluation of the latest biomaterials, experiments to simulate meniscal tears and the state-of-the-art materials and strategies currently used to treat tears.
Kean et al. (2017) The role of biomaterials in the treatment of meniscal tears. PeerJ 5:e4076 https://doi.org/10.7717/peerj.4076
Detection of bacterial contaminants and hybrid sequences in the genome of the kelp Saccharina japonica using Taxoblast
Modern genome sequencing strategies are highly sensitive to contamination making the detection of foreign DNA sequences an important part of analysis pipelines. Here we use Taxoblast, a simple pipeline with a graphical user interface, for the post-assembly detection of contaminating sequences in the published genome of the kelp Saccharina japonica. Analyses were based on multiple blastn searches with short sequence fragments. They revealed a number of probable bacterial contaminations as well as hybrid scaffolds that contain both bacterial and algal sequences. This or similar types of analysis, in combination with manual curation, may thus constitute a useful complement to standard bioinformatics analyses prior to submission of genomic data to public repositories. Our analysis pipeline is open-source and freely available at http://sdittami.altervista.org/taxoblast and via SourceForge (https://sourceforge.net/projects/taxoblast).
Dittami et al. (2017) Detection of bacterial contaminants and hybrid sequences in the genome of the kelp Saccharina japonica using Taxoblast. PeerJ 5:e4073 https://doi.org/10.7717/peerj.4073
NDUFA4L2 is associated with clear cell renal cell carcinoma malignancy and is regulated by ELK1
Background Clear cell renal cell carcinoma (ccRCC) is the most common and lethal cancer of the adult kidney. However, its pathogenesis has not been fully understood till now, which hinders the therapeutic development of ccRCC. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) was found to be upregulated and play an important role in ccRCC. We aimed to further investigate the underlying mechanisms by which NDUFA4L2 exerted function and its expression level was upregulated. Methods The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data were mined to verify the change of NDUFA4L2 expression level in ccRCC tissues. The correlation between expression level of NDUFA4L2 and cell proliferation/apoptosis was explored by Gene Set Enrichment Analysis (GSEA). Protein-protein interaction (PPI) network of NDUFA4L2 was constructed. Biological process and involved pathways of NDUFA4L2 were analyzed by gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The transcription factors (TFs) which can induce the expression of NDUFA4L2 were explored in clinical samples by correlation analysis and its regulation on the expression of NDUFA4L2 was verified by knockdown experiment. Results NDUFA4L2 was verified to be overexpressed in ccRCC tissues and its expression level was increased accordingly as the American Joint Committee on Cancer (AJCC) stage progressed. A high NDUFA4L2 level predicted the poor prognosis of ccRCC patients and correlated with enhanced cell proliferation and anti-apoptosis. NDUFA4L2 may interact with 14 tumor-related proteins, participate in growth and death processes and be involved in ccRCC-related pathways, such as insulin-like growth factor 1 (IGF-1), mammalian target of Rapamycin (mTOR) and phosphoinositide 3 kinase serine/threonine protein kinase (PI3K/AKT). ETS domain-containing protein ELK1 level positively correlated with the level of NDUFA4L2 in ccRCC tissues and ELK1 could regulate the expression of NDUFA4L2 in ccRCC cells. Discussion NDUFA4L2 upregulation was associated with ccRCC malignancy. NDUFA4L2 expression was regulated by ELK1 in ccRCC cells. Our study provided potential mechanisms by which NDUFA4L2 affected ccRCC occurrence and progression.
Wang et al. (2017) NDUFA4L2 is associated with clear cell renal cell carcinoma malignancy and is regulated by ELK1. PeerJ 5:e4065 https://doi.org/10.7717/peerj.4065
A 16-gene signature predicting prognosis of patients with oral tongue squamous cell carcinoma
Background Oral tongue squamous cell carcinoma (OTSCC) is the most common subtype of oral cancer. A predictive gene signature is necessary for prognosis of OTSCC. Methods Five microarray data sets of OTSCC from the Gene Expression Omnibus (GEO) and one data set from The Cancer Genome Atlas (TCGA) were obtained. Differentially expressed genes (DEGs) of GEO data sets were identified by integrated analysis. The DEGs associated with prognosis were screened in the TCGA data set by univariate survival analysis to obtain a gene signature. A risk score was calculated as the summation of weighted expression levels with coefficients by Cox analysis. The signature was used to distinguish carcinoma, estimated by receiver operator characteristic curves and the area under the curve (AUC). All were validated in the GEO and TCGA data sets. Results Integrated analysis of GEO data sets revealed 300 DEGs. A 16-gene signature and a risk score were developed after survival analysis. The risk score was effective to stratify patients into high-risk and low-risk groups in the TCGA data set (P < 0.001). The 16-gene signature was valid to distinguish the carcinoma from normal samples (AUC 0.872, P < 0.001). Discussion We identified a useful 16-gene signature for prognosis of OTSCC patients, which could be applied to clinical practice. Further studies were needed to prove the findings.
Qiu et al. (2017) A 16-gene signature predicting prognosis of patients with oral tongue squamous cell carcinoma. PeerJ 5:e4062 https://doi.org/10.7717/peerj.4062
Comparative analysis of prophages in Streptococcus mutans genomes
Prophages have been considered genetic units that have an intimate association with novel phenotypic properties of bacterial hosts, such as pathogenicity and genomic variation. Little is known about the genetic information of prophages in the genome of Streptococcus mutans, a major pathogen of human dental caries. In this study, we identified 35 prophage-like elements in S. mutans genomes and performed a comparative genomic analysis. Comparative genomic and phylogenetic analyses of prophage sequences revealed that the prophages could be classified into three main large clusters: Cluster A, Cluster B, and Cluster C. The S. mutans prophages in each cluster were compared. The genomic sequences of phismuN66-1, phismuNLML9-1, and phismu24-1 all shared similarities with the previously reported S. mutans phages M102, M102AD, and ϕAPCM01. The genomes were organized into seven major gene clusters according to the putative functions of the predicted open reading frames: packaging and structural modules, integrase, host lysis modules, DNA replication/recombination modules, transcriptional regulatory modules, other protein modules, and hypothetical protein modules. Moreover, an integrase gene was only identified in phismuNLML9-1 prophages.
Fu et al. (2017) Comparative analysis of prophages in Streptococcus mutans genomes. PeerJ 5:e4057 https://doi.org/10.7717/peerj.4057