cRegulome: an R package for accessing microRNA and transcription factor-gene expression correlations in cancer
Background Transcription factors and microRNAs play a critical role in regulating the gene expression in normal physiology and pathological conditions. Many bioinformatics tools were built to predict and identify transcription factor and microRNA targets and their role in the development of diseases including cancers. The availability of public access high-throughput data allows researchers to make data-driven predictions. Implementation Here, we developed an R package called cRegulome to access, manage and visualize data from open source databases. The package provides a programmatic access to the regulome (transcription factor and microRNA) expression correlations with target genes of different cancer types. It obtains a local instance of Cistrome Cancer and miRCancerdb databases and provides classes and methods to query, interact with and visualize the correlation data. Availability cRegulome is available on the comprehensive R archive network (CRAN) and the source code is hosted on GitHub as part of the ROpenSci on-boarding collection, https://github.com/ropensci/cRegulome.
Ahmed et al. (2019) cRegulome: an R package for accessing microRNA and transcription factor-gene expression correlations in cancer. PeerJ 7:e6509 https://doi.org/10.7717/peerj.6509
Comparison of laboratory indices of non-alcoholic fatty liver disease for the detection of incipient kidney dysfunction
Non-alcoholic fatty liver disease (NAFLD) is closely linked to insulin resistance and related adverse health outcomes. We investigated the non-invasive index of NAFLD that has the best performance in estimating the renal manifestations of metabolic disturbances. This nation-wide, cross-sectional study included 11,836 subjects, using various non-invasive assessments comprising routinely measured clinical and laboratory variables. The subjects were native Koreans aged 20 years or older and had no diabetes, history of liver or kidney disease. All participants were divided into quintiles according to their fibrosis-4 (FIB-4) results. Participants in the highest quintile were more hypertensive and obese with greater glycemic exposure, poor lipid profiles, and impaired kidney function, than those in the other quintiles. Multiple logistic regression, adjusted for age, sex, smoking, systolic blood pressure, white blood cell, platelet, fasting plasma glucose, and triglyceride, demonstrated that FIB-4, the hepatic steatosis index, the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, Gholam’s model for non-alcoholic steatohepatitis, and the BARD score were independently associated with kidney dysfunction. ROC curve analysis revealed that FIB-4 (AUC = 0.6227, 95% CI [0.5929–0.6526], p = 0.0258) was the most precise in predicting kidney dysfunction. Our findings suggest that FIB-4 may be a favorable screening tool for the renal manifestation of hepatic metabolic disturbances.
Choi et al. (2019) Comparison of laboratory indices of non-alcoholic fatty liver disease for the detection of incipient kidney dysfunction. PeerJ 7:e6524 https://doi.org/10.7717/peerj.6524
Transcriptome sequencing and comparative analysis of adult ovary and testis identify potential gonadal maintenance-related genes in Mauremys reevesii with temperature-dependent sex determination
Mauremys reevesii is a classical organism with temperature-dependent sex determination (TSD). Gonad development in early life has recently received considerable attention but gonadal maintenance after sex differentiation in turtles with TSD remains a mystery. In this study, we sequenced the transcriptomes for the adult testis and ovary using RNA-seq, and 36,221 transcripts were identified. In total, 1,594 differentially expressed genes (DEGs) were identified where 756 DEGs were upregulated in the testis and 838 DEGs were upregulated in the ovary. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that the TGF-beta signaling pathway and Hedgehog signaling pathway have important roles in testis maintenance and spermatogenesis, whereas the Hippo signaling pathway and Wnt signaling pathway are likely to participate in ovary maintenance. We determined the existence of antagonistic networks containing significant specific-expressed genes and pathways related to gonadal maintenance and gametogenesis in the adult gonads of M. reevesii. The candidate gene Fibronectin type 3 and ankyrin repeat domains 1 (FANK1) might be involved with the regulation of testis spermatogenesis.
Xiong et al. (2019) Transcriptome sequencing and comparative analysis of adult ovary and testis identify potential gonadal maintenance-related genes in Mauremys reevesii with temperature-dependent sex determination. PeerJ 7:e6557 https://doi.org/10.7717/peerj.6557
Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan
Background Hepatitis B virus (HBV) is an important infectious cause of morbidity and mortality in Jordan. HBV genotype D is the most prevalent in the country. Virus escape mutants in the HBV S region is an important public health problem halting preventive efforts. The aim of the current study was to investigate patterns of HBV escape and resistance mutations and to assess domestic transmission of the virus. Methods Patients infected with HBV were recruited at Jordan University Hospital (n = 56) and were diagnosed during (1984–2012). A total of 37 partial HBV S sequences were generated using Sanger’s method. Mutation analysis was done using the HIV grade HBV drug resistance interpretation online tool and Geno2pheno (HBV) online tools. Domestic transmission of HBV was assessed using maximum likelihood phylogenetic inference with similar GenBank sequences. Results Genotyping revealed an exclusive presence of sub-genotype D1. Typical HBV escape mutants were identified in seven patients. These mutations included: L109R, Q129R, M133L, S143L and D144E with overall prevalence of 18.9% (95% CI [9.5–34.2]). Reverse transcriptase (RT) sequence analysis showed mutations in three patients with overall prevalence of 8.1% (95% CI [2.8–21.3]). RT mutations included: V173L, S202I, L180M, M204V and T184A. Transmission cluster analysis revealed a relatively high proportion of infections taking place as a result of domestic spread (29.7%). Conclusions Based on our findings, RT mutation analysis appears to be of high value before the initiation of therapy in patients with chronic HBV infection in Jordan. Phylogenetic analyses revealed a considerable proportion of local spread in the country which should be considered in the preventive infection control efforts.
Ababneh et al. (2019) Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. PeerJ 7:e6583 https://doi.org/10.7717/peerj.6583
Osteogenic capacity and cytotherapeutic potential of periodontal ligament cells for periodontal regeneration in vitro and in vivo
Background The periodontal ligament cells (PDLCs) contain heterogeneous cell populations and possess stem-cell-like properties. PDLCs have attracted considerable attention as an option for periodontal regeneration. However, the osteogenic differentiation of PDLCs remains obscure owing to variable osteo-inductive methods and whether PDLCs could be directly used for periodontal regeneration without stem cell enrichment is uncertain. The aim of the present study was to clarify the osteogenic differentiation capacity of PDLCs and test PDLCs as an alternative to stem cells for periodontal regeneration. Methods We tested the performance of human PDLCs in osteo-inductive culture and transplantation in vivo while taking human bone marrow derived mesenchymal stem cells (hMSCs) as positive control. Proliferation of PDLCs and hMSCs in osteo-inductive condition were examined by MTT assay and colony formation assay. The osteogenic differentiations of PDLCs and hMSCs were assessed by Alkaline phosphatase (ALP) activity measurement, von Kossa staining, Alizarin red S staining and quantitative RT-PCR of osteogenic marker gene including RUNX2, ALP, OCN, Col I, BSP, OPN. We transplanted osteo-inductive PDLCs and hMSCs with hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds to immunodeficient mice to explore their biological behaviors in vivo by histological staining and immunohistochemical evaluation. Results After 14 days of osteo-induction, PDLCs exhibited significantly higher proliferation rate but lower colony-forming ability comparing with hMSCs. PDLCs demonstrated lower ALP activity and generated fewer mineralized nodules than hMSCs. PDLCs showed overall up-regulated expression of RUNX2, ALP, OCN, Col I, BSP, OPN after osteo-induction. Col I level of PDLCs in osteo-inductive group was significantly higher while RUNX2, ALP, OCN were lower than that of hMSCs. Massive fiber bundles were produced linking or circling the scaffold while the bone-like structures were limited in the PDLCs-loaded HA/TCP samples. The fiber bundles displayed strong positive Col I, but weak OCN and OPN staining. The in vivo results were consistent with the in vitro data, which confirmed strong collagen forming ability and considerable osteogenic potential of PDLCs. Conclusion It is encouraging to find that PDLCs exhibit higher proliferation, stronger collagen fiber formation capacity, but lower osteogenic differentiation ability in comparison with hMSCs. This characteristic is essential for the successful periodontal reconstruction which is based on the synchronization of fiber formation and bone deposition. Moreover, PDLCs have advantages such as good accessibility, abundant source, vigorous proliferation and evident osteogenic differentiation capacity when triggered properly. They can independently form PDL-like structure in vivo without specific stem cell enrichment procedure. The application of PDLCs may offer a novel cytotherapeutic option for future clinical periodontal reconstruction.
Li et al. (2019) Osteogenic capacity and cytotherapeutic potential of periodontal ligament cells for periodontal regeneration in vitro and in vivo. PeerJ 7:e6589 https://doi.org/10.7717/peerj.6589
Environmental inactivation and irrigation-mediated regrowth of Escherichia coli O157:H7 on romaine lettuce when inoculated in a fecal slurry matrix
Field trials were conducted in July–August and October 2012 to quantify the inactivation rate of Escherichia coli O157:H7 when mixed with fecal slurry and applied to romaine lettuce leaves. Lettuce was grown under commercial conditions in Salinas Valley, California. One-half milliliter of rabbit, chicken, or pig fecal slurry, containing an average of 4.05 × 107 CFU E. coli O157:H7 (C0), was inoculated onto the upper (adaxial) surface of a lower leaf on 288 heads of lettuce per trial immediately following a 2.5 h irrigation event. To estimate the bacterial inactivation rate as a function of time, fecal matrix, irrigation and seasonal climate effects, sets of lettuce heads (n = 28) were sampled each day over 10 days and the concentration of E. coli O157:H7 (Ct) determined. E. coli O157:H7 was detected on 100% of heads during the 10-day duration, with concentrations ranging from ≤340 MPN/head (∼5-log reduction) to >3.45 × 1012 MPN/head (∼5-log growth). Relative to C0, on day 10 (Ct = 12) we observed an overall 2.6-log and 3.2-log mean reduction of E. coli O157:H7 in July and October, respectively. However, we observed relative maximum concentrations due to bacterial growth on day 6 (maximum Ct = 8) apparently stimulated by foliar irrigation on day 5. From this maximum there was a mean 5.3-log and 5.1-log reduction by day 10 (Ct = 12) for the July and October trials, respectively. This study provides insight into the inactivation and growth kinetics of E. coli O157:H7 on romaine lettuce leaves under natural field conditions. This study provides evidence that harvesting within 24 h post irrigation has the potential to increase the concentration of E. coli O157:H7 contamination, if present on heads of romaine lettuce; foliar irrigation can temporarily stimulate substantial regrowth of E. coli O157:H7.
Chase et al. (2019) Environmental inactivation and irrigation-mediated regrowth of Escherichia coli O157:H7 on romaine lettuce when inoculated in a fecal slurry matrix. PeerJ 7:e6591 https://doi.org/10.7717/peerj.6591
Exotic urban trees conserve similar natural enemy communities to native congeners but have fewer pests
Urban trees serve a critical conservation function by supporting arthropod and vertebrate communities but are often subject to arthropod pest infestations. Native trees are thought to support richer arthropod communities than exotic trees but may also be more susceptible to herbivorous pests. Exotic trees may be less susceptible to herbivores but provide less conservation value as a consequence. We tested the hypotheses that native species in Acer and Quercus would have more herbivorous pests than exotic congeners and different communities of arthropod natural enemies. The density of scale insects, common urban tree pests, was greatest on a native Acer and a native Quercus than exotic congeners in both years of our research (2012 and 2016) and sometimes reached damaging levels. However, differences in predator and parasitoid abundance, diversity, and communities were not consistent between native and exotic species in either genus and were generally similar. For example, in 2012 neither predator nor parasitoid abundance differed among native and exotic Acer congeners but in 2016 a native species, A. saccharum, had the least of both groups. A native, Q. phellos, had significantly more predators and parasitoids in 2012 than its native and exotic congeners but no differences in 2016. Parasitoid communities were significantly different among Acer species and Quercus species due in each case to greater abundance of a single family on one native tree species. These native and exotic tree species could help conserve arthropod natural enemies and achieve pest management goals.
Frank et al. (2019) Exotic urban trees conserve similar natural enemy communities to native congeners but have fewer pests. PeerJ 7:e6531 https://doi.org/10.7717/peerj.6531
Experimental mechanical strain measurement of tissues
Strain, an important biomechanical factor, occurs at different scales from molecules and cells to tissues and organs in physiological conditions. Under mechanical strain, the strength of tissues and their micro- and nanocomponents, the structure, proliferation, differentiation and apoptosis of cells and even the cytokines expressed by cells probably shift. Thus, the measurement of mechanical strain (i.e., relative displacement or deformation) is critical to understand functional changes in tissues, and to elucidate basic relationships between mechanical loading and tissue response. In the last decades, a great number of methods have been developed and applied to measure the deformations and mechanical strains in tissues comprising bone, tendon, ligament, muscle and brain as well as blood vessels. In this article, we have reviewed the mechanical strain measurement from six aspects: electro-based, light-based, ultrasound-based, magnetic resonance-based and computed tomography-based techniques, and the texture correlation-based image processing method. The review may help solving the problems of experimental and mechanical strain measurement of tissues under different measurement environments.
Huang et al. (2019) Experimental mechanical strain measurement of tissues. PeerJ 7:e6545 https://doi.org/10.7717/peerj.6545
Identification of differentially expressed key genes between glioblastoma and low-grade glioma by bioinformatics analysis
Gliomas are a very diverse group of brain tumors that are most commonly primary tumor and difficult to cure in central nervous system. It’s necessary to distinguish low-grade tumors from high-grade tumors by understanding the molecular basis of different grades of glioma, which is an important step in defining new biomarkers and therapeutic strategies. We have chosen the gene expression profile GSE52009 from gene expression omnibus (GEO) database to detect important differential genes. GSE52009 contains 120 samples, including 60 WHO II samples and 24 WHO IV samples that were selected in our analysis. We used the GEO2R tool to pick out differently expressed genes (DEGs) between low-grade glioma and high-grade glioma, and then we used the database for annotation, visualization and integrated discovery to perform gene ontology analysis and Kyoto encyclopedia of gene and genome pathway analysis. Furthermore, we used the Cytoscape search tool for the retrieval of interacting genes with molecular complex detection plug-in applied to achieve the visualization of protein–protein interaction (PPI). We selected 15 hub genes with higher degrees of connectivity, including tissue inhibitors metalloproteinases-1 and serum amyloid A1; additionally, we used GSE53733 containing 70 glioblastoma samples to conduct Gene Set Enrichment Analysis. In conclusion, our bioinformatics analysis showed that DEGs and hub genes may be defined as new biomarkers for diagnosis and for guiding the therapeutic strategies of glioblastoma.
Xu et al. (2019) Identification of differentially expressed key genes between glioblastoma and low-grade glioma by bioinformatics analysis. PeerJ 7:e6560 https://doi.org/10.7717/peerj.6560
The explosion in volumes and types of data has led to substantial challenges in data management. These challenges are often faced by front-line researchers who are already dealing with rapidly changing technologies and have limited time to devote to data management. There are good high-level guidelines for managing and processing scientific data. However, there is a lack of simple, practical tools to implement these guidelines. This is particularly problematic in a highly distributed research environment where needs differ substantially from group to group and centralised solutions are difficult to implement and storage technologies change rapidly. To meet these challenges we have developed dtool, a command line tool for managing data. The tool packages data and metadata into a unified whole, which we call a dataset. The dataset provides consistency checking and the ability to access metadata for both the whole dataset and individual files. The tool can store these datasets on several different storage systems, including a traditional file system, object store (S3 and Azure) and iRODS. It includes an application programming interface that can be used to incorporate it into existing pipelines and workflows. The tool has provided substantial process, cost, and peace-of-mind benefits to our data management practices and we want to share these benefits. The tool is open source and available freely online at http://dtool.readthedocs.io.
Olsson et al. (2019) Lightweight data management with dtool. PeerJ 7:e6562 https://doi.org/10.7717/peerj.6562