Large-scale gene expression analysis reveals robust gene signatures for prognosis prediction in lung adenocarcinoma
Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide. High mortality in LUAD motivates us to stratify the patients into high- and low-risk groups, which is beneficial for the clinicians to design a personalized therapeutic regimen. To robustly predict the risk, we identified a set of robust prognostic gene signatures and critical pathways based on ten gene expression datasets by the meta-analysis-based Cox regression model, 25 of which were selected as predictors of multivariable Cox regression model by MMPC algorithm. Gene set enrichment analysis (GSEA) identified the Aurora-A pathway, the Aurora-B pathway, and the FOXM1 transcription factor network as prognostic pathways in LUAD. Moreover, the three prognostic pathways were also the biological processes of G2-M transition, suggesting that hyperactive G2-M transition in cell cycle was an indicator of poor prognosis in LUAD. The validation in the independent datasets suggested that overall survival differences were observed not only in all LUAD patients, but also in those with a specific TNM stage, gender, and age group. The comprehensive analysis demonstrated that prognostic signatures and the prognostic model by the large-scale gene expression analysis were more robust than models built by single data based gene signatures in LUAD overall survival prediction.
Songyang et al. (2019) Large-scale gene expression analysis reveals robust gene signatures for prognosis prediction in lung adenocarcinoma. PeerJ 7:e6980 https://doi.org/10.7717/peerj.6980
Comparison of therapeutic effects of different mesenchymal stem cells on rheumatoid arthritis in mice
Background Rheumatoid arthritis (RA) is a chronic and nonspecific autoimmune disease, which leads to joint destruction and deformity. To investigate the potential of human mesenchymal stem cells (MSCs) as a new therapeutic strategy for patients with RA, we compared the therapeutic effects of bone marrow derived MSCs (BMSCs), umbilical cord derived MSCs (UCs), and stem cells derived from human exfoliated deciduous teeth (SHED) on collagen-induced arthritis (CIA) in mice. Methods A total of 24 DBA/1 mice were infused with type II collagen to induce RA in the experimental model. MSC-treated mice were infused with UCs, BMSCs, and SHED, respectively. Bone erosion and joint destruction were measured by micro-computed tomographic (micro-CT) analysis and hematoxylin and eosin staining. The levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were measured by immunohistochemistry and Enzyme-Linked Immunosorbent Assay (ELISA). Results Systemic delivery of MSCs significantly improved the severity of the symptoms related to CIA to greater extent compared with the untreated control group. Micro-CT revealed reduced bone erosions in the metatarsophalangeal joints upon treatment with MSCs. Additionally, according to histologic evaluation, reduced synovitis and articular destruction were observed in MSC-treated groups. The levels of TNF-α and IL-1β in the serum and joints decreased with treatment by MSCs. Conclusion Our findings suggest that systemic infusion of UCs, BMSCs, and SHED may significantly alleviate the effects of RA. The therapeutic effect of BMSCs was greater than that of SHED, while the UCs were shown to have the best therapeutic effect on CIA mice. In conclusion, compared with BMSCs and SHED, UCs may be a more suitable source of MSCs for the treatment of patients with RA.
Zhang et al. (2019) Comparison of therapeutic effects of different mesenchymal stem cells on rheumatoid arthritis in mice. PeerJ 7:e7023 https://doi.org/10.7717/peerj.7023
Associations between cortisol awakening response and resting electroencephalograph asymmetry
The cortisol awakening response (CAR), a rapid cortisol rise in the morning after awakening, has been proposed to provide energy to cope with daily demands and suggested to be associated with brain functions. Electroencephalogram (EEG) asymmetry studies have implicated asymmetric cortical activation, especially in frontal cortex, in approach-withdrawal motivation. In this study, we examined the relationship between the CAR and lateralized cortical activity under rest in 55 university male students. Saliva samples were collected at 0, 15, 30 and 60 min after awakening on the two consecutive workdays. The lateralized cortical activity at frontocentral sites was examined by alpha asymmetry score. The results showed that a higher CAR was positively associated with alpha asymmetry score, which indicated that the higher CAR is linked with more left-sided cortical activity at frontocentral sites under resting state. This association still existed even after controlling psychological and sleep quality variables. These results suggested that appropriately mobilizing energy resource storage after awakening revealed as CAR might be associated with goal-directed approach tendencies before any eventual stressful situation, characteristic of more left than right resting-state frontocentral cortical activity.
Duan et al. (2019) Associations between cortisol awakening response and resting electroencephalograph asymmetry. PeerJ 7:e7059 https://doi.org/10.7717/peerj.7059
Spray-dried immobilized lipase from Geobacillus sp. strain ARM in sago
Sago starch is traditionally used as food especially in Southeast Asia. Generally, sago is safe for consumption, biodegradable, easily available and inexpensive. Therefore, this research was done to expand the potential of sago by using it as a support for enzyme immobilization. In this study, ARM lipase, which was isolated from Geobacillus sp. strain ARM, was overexpressed in Escherichia coli system and then purified using affinity chromatography. The specific activity of the pure enzyme was 650 U/mg, increased 7 folds from the cell lysate. The purified enzyme was immobilized in gelatinized sago and spray-dried by entrapment technique in order to enhance the enzyme operational stability for handling at high temperature and also for storage. The morphology of the gelatinized sago and immobilized enzyme was studied by scanning electron microscopy. The results showed that the spray-dried gelatinized sago was shrunken and became irregular in structure as compared to untreated sago powder. The surface areas and porosities of spray-dried gelatinized sago with and without the enzyme were analyzed using BET and BJH method and have shown an increase in surface area and decrease in pore size. The immobilized ARM lipase showed good performance at 60–80 °C, with a half-life of 4 h and in a pH range 6–9. The immobilized enzyme could be stored at 10 °C with the half-life for 9 months. Collectively, the spray-dried immobilized lipase shows promising capability for industrial uses, especially in food processing.
Mohtar et al. (2019) Spray-dried immobilized lipase from Geobacillus sp. strain ARM in sago. PeerJ 7:e6880 https://doi.org/10.7717/peerj.6880
This paper presents the CellCycler, a model of a growing tumour which aims to simulate and predict the effect of treatment on xenograft studies or in the clinic. The model, which is freely available as a web application, uses ordinary differential equations (ODEs) to simulate cells as they pass through the phases of the cell cycle. However the guiding philosophy of the model is that it should only use parameters that can be observed or reasonably well approximated. There is no representation of the complex internal dynamics of each cell; instead the level of analysis is limited to cell state observables such as cell phase, apoptosis, and damage. We show that this approach, while limited in many respects, still naturally accounts for a heteregenous cell population with varying doubling time, and closely captures the dynamics of a growing tumour as it is exposed to treatment. The program is demonstrated using three case studies.
Orrell et al. (2019) A simple model of a growing tumour. PeerJ 7:e6983 https://doi.org/10.7717/peerj.6983
ConFindr: rapid detection of intraspecies and cross-species contamination in bacterial whole-genome sequence data
Whole-genome sequencing (WGS) of bacterial pathogens is currently widely used to support public-health investigations. The ability to assess WGS data quality is critical to underpin the reliability of downstream analyses. Sequence contamination is a quality issue that could potentially impact WGS-based findings; however, existing tools do not readily identify contamination from closely-related organisms. To address this gap, we have developed a computational pipeline, ConFindr, for detection of intraspecies contamination. ConFindr determines the presence of contaminating sequences based on the identification of multiple alleles of core, single-copy, ribosomal-protein genes in raw sequencing reads. The performance of this tool was assessed using simulated and lab-generated Illumina short-read WGS data with varying levels of contamination (0–20% of reads) and varying genetic distance between the designated target and contaminant strains. Intraspecies and cross-species contamination was reliably detected in datasets containing 5% or more reads from a second, unrelated strain. ConFindr detected intraspecies contamination with higher sensitivity than existing tools, while also being able to automatically detect cross-species contamination with similar sensitivity. The implementation of ConFindr in quality-control pipelines will help to improve the reliability of WGS databases as well as the accuracy of downstream analyses. ConFindr is written in Python, and is freely available under the MIT License at github.com/OLC-Bioinformatics/ConFindr.
Low et al. (2019) ConFindr: rapid detection of intraspecies and cross-species contamination in bacterial whole-genome sequence data. PeerJ 7:e6995 https://doi.org/10.7717/peerj.6995
Recommendations for dietary level of micro-minerals and vitamin D3 to Atlantic salmon (Salmo salar) parr and post-smolt when fed low fish meal diets
Atlantic salmon (Salmo salar) feeds have changed drastically in their composition from being predominantly marine-based to plant-based. This has altered the dietary supply and availability of micro-nutrients to Atlantic salmon. The impact of graded inclusion levels of a nutrient package (NP) comprising of 25 different micro-nutrients were studied in Atlantic salmon parr in freshwater (Trial 1) and post-smolts in seawater (Trial 2). In brief, the NP was included from 0 to 400%, where 100% corresponded to the recommendation by the National Research Council, 2011. Micro-nutrients, namely Zn, Mn, Se, Cu, Fe, Co, I and vitamin D3 were included in the NP with the objective of (re)evaluating the dietary need to meet the requirement of Atlantic salmon parr and post-smolt, when fed low fish meal, plant ingredient-based diets. Responses in apparent availability coefficient (AAC), whole body and vertebrae mineral concentrations, and retention were analysed. AAC of Cu, Mn, Se and Zn responded in a quadratic fashion with an increase in NP from 0 to 400% in freshwater parr; AAC could not be measured in post-smolt salmon. The whole-body concentration of Zn, Se, Co and I in Atlantic salmon parr were significantly affected by increasing NP inclusion; the same was observed for Zn, Se and Co in post-smolt Atlantic salmon. Vertebrae mineral concentration as the response criterion was non-responsive in parr; whereas, in post-smolt, Co had a linear increase, while Zn and Se showed a non-linear increase upon 0 to 400 NP inclusion. Zinc concentration and activities of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) in vertebrae indicated increased bone resorption in post-smolt Atlantic salmon; TRAP activity increased linearly with NP inclusion in post-smolt, but not in parr. Significant correlations between Zn and Se were observed in AAC and vertebral concentrations, indicating an interaction in intestinal uptake and vertebral deposition. Overall, Atlantic salmon parr held in freshwater were able to satisfy the requirement for the trace minerals Zn, Mn, Se, Cu, and Fe through supply from 100–150 NP, corresponding to 101–132, 47–63, 0.6–0.8, 12–16 and 150–166 mg kg −1, respectively; for iodine, dietary supply from 150–200 NP, corresponding to 0.7–1.6 mg kg−1, was required. In the seawater, Atlantic salmon post-smolt, in general, required micro-minerals and vitamin D3 levels as supplied through 150–200 NP, corresponding to 140–177, Zn; 61–67, Mn; 0.9–1, Se; 14–16, Cu; and vitamin D3, 0.06–0.09 mg kg −1 to fulfil the requirement, except for Cu which was satisfied at 100–150 NP, equivalent to 13–14 mg kg −1 diet.
Antony Jesu Prabhu et al. (2019) Recommendations for dietary level of micro-minerals and vitamin D3 to Atlantic salmon (Salmo salar) parr and post-smolt when fed low fish meal diets. PeerJ 7:e6996 https://doi.org/10.7717/peerj.6996
Prevalence and contributing factors of dental caries of 6-year-old children in four regions of China
Background From 2005 to 2015, the prevalence of dental caries in both primary and permanent dentitions was significantly increased in China. Previous studies have shown that the prevalence of permanent dental caries in school-aged children had already reached 19.7%–54.0%, 97.5% affecting first permanent molars. This study aimed to investigate the prevalence and contributing factors of dental caries in 6-year-old children in four regions of China to provide information for oral health promotion programs. Methods A randomized cluster sampling method was employed in the study. All 6-year-old first grade children from the selected schools were invited to receive a clinical oral examination. Dental caries were diagnosed according to the World Health Organization criteria. The erupting first permanent molars were recorded using the modified International Caries Detection Assessment System. Questionnaires assessing children’s oral health-related behaviors and their caretakers’ oral health awareness and attitudes were completed by the children’s parents or guardians. Results Overall, 4,936 6-year-old school children participated in the survey. The prevalence of caries among these children was 87.7%, with a mean number of decayed, missing and filled teeth of 6.04 (SD, 4.24). In primary dentition, the caries prevalence was 87.7%, and the mean dmft score was 6.01 (SD, 4.22). In permanent dentition, the caries prevalence was 2.0%, the mean DFS score was 0.04 (SD, 0.31). All permanent dental caries occurred on the first permanent molars. Carious tooth surfaces were identified as modified ICDAS code “A” to indicate initial caries and distinct visual change in enamel. The mean DAS score of non-cavitated caries in the first permanent molars was 0.18 (SD, 0.67). Logistic regression analysis showed that regional and gender factors were significantly related to the caries experience of these children. Conclusions The 6-year-old children from four regions of China had sever primary dental caries and the first permanent molars were at high risk for dental caries. It is critical to protect permanent teeth from caries as early as the eruption of the first permanent molars.
Wang et al. (2019) Prevalence and contributing factors of dental caries of 6-year-old children in four regions of China. PeerJ 7:e6997 https://doi.org/10.7717/peerj.6997
Funmap2: an R package for QTL mapping using longitudinal phenotypes
Quantitative trait locus (QTL) mapping has been used as a powerful tool for inferring the complexity of the genetic architecture that underlies phenotypic traits. This approach has shown its unique power to map the developmental genetic architecture of complex traits by implementing longitudinal data analysis. Here, we introduce the R package Funmap2 based on the functional mapping framework, which integrates prior biological knowledge into the statistical model. Specifically, the functional mapping framework is engineered to include longitudinal curves that describe the genetic effects and the covariance matrix of the trait of interest. Funmap2 chooses the type of longitudinal curve and covariance matrix automatically using information criteria. Funmap2 is available for download at https://github.com/wzhy2000/Funmap2.
Wang et al. (2019) Funmap2: an R package for QTL mapping using longitudinal phenotypes. PeerJ 7:e7008 https://doi.org/10.7717/peerj.7008
Integrating species and interactions into similarity metrics: a graph theory-based approach to understanding community similarity
Community similarity is often assessed through similarities in species occurrences and abundances (i.e., compositional similarity) or through the distribution of species interactions (i.e., interaction similarity). Unfortunately, the joint empirical evaluation of both is still a challenge. Here, we analyze community similarity in ecological systems in order to evaluate the extent to which indices based exclusively on species composition differ from those that incorporate species interactions. Borrowing tools from graph theory, we compared the classic Jaccard index with the graph edit distance (GED), a metric that allowed us to combine species composition and interactions. We found that similarity measures computed using only taxonomic composition could differ strongly from those that include composition and interactions. We conclude that new indices that incorporate community features beyond composition will be more robust for assessing similitude between natural systems than those purely based on species occurrences. Our results have therefore important conceptual and practical consequences for the analysis of ecological communities.
López et al. (2019) Integrating species and interactions into similarity metrics: a graph theory-based approach to understanding community similarity. PeerJ 7:e7013 https://doi.org/10.7717/peerj.7013