title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=1206 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Upregulated expression of pyruvate kinase M2 mRNA predicts poor prognosis in lung adenocarcinoma link: https://peerj.com/articles/8625 last-modified: 2020-02-20 description: BackgroundPyruvate kinase M2 (PKM2) is critical regulator contributing to Warburg effect. However, the expression pattern and prognostic value of PKM2 remain unknown in lung adenocarcinoma (LUAD). The aim of this study is to clarify the prognostic value of PKM2 via intergrated bioinformatics analysis.MethodsFirstly, mRNA expression levels of PKM2 in LUAD were systematically analyzed using the ONCOMINE and TCGA databases. Then, the association between PKM2 expression and clinical parameters was investigated by UALCAN. The Kaplan–Meier Plotter was used to assess the prognostic significance of PKM2. Finally, the relationship between PKM2 expression and its genetic and epigenetic changes was evaluated with MEXPRESS and MethHC database.ResultsPooled analysis showed that PKM2 is frequently upregulated expression in LUAD. Subsequently, PKM2 expression was identified to be positively associated with tumor stage and lymph node metastasis and also strongly correlated with worse OS (P = 2.80e−14), PPS (P = 0.022), FP (P = 1.30e−6) and RFS (P = 3.41e−8). Importantly, our results demonstrated that over-expressed PKM2 is associated with PKM2 hypomethylation and copy number variations (CNVs).ConclusionThis study confirms that over-expressed PKM2 in LUAD is associated with poor prognosis, suggesting that PKM2 might act as a promising prognostic biomarker and novel therapeutic target for LUAD. creator: Guiping Wang creator: Yingying Zhong creator: Jiecong Liang creator: Zhibin Li creator: Yun Ye uri: https://doi.org/10.7717/peerj.8625 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Wang et al. title: Single nucleotide polymorphism of MTHFR rs1801133 associated with elevated Hcy levels affects susceptibility to cerebral small vessel disease link: https://peerj.com/articles/8627 last-modified: 2020-02-20 description: BackgroundMethylenetetrahydrofolate reductase (MTHFR) is indispensable for the conversion of homocysteine (Hcy) to methionine. The single nucleotide polymorphism (SNP) of MTHFR gene (rs1801133, C667T) is correlated with decreased enzyme activity that eventually results in elevated plasma Hcy levels. Hyperhomocysteinemia has been confirmed to be involved in the pathogenesis of stroke, cerebral small vessel disease (CSVD), various metabolic disorders and so on. However, the relationship between the MTHFR gene polymorphisms, Hcy, and CSVD has not been investigated. In this study, the relationship between SNPs of MTHFR gene and CSVD was determined after adjusting for cardiovascular risk factors, and the potential mechanism based on Hcy levels was explored.MethodsA total of 163 consecutive CSVD patients were collected as the case group. In the corresponding period, 326 healthy people were selected as the control group, who were matched to these cases according to age (±2 years) and gender at a ratio of 2:1. SNPs of MTHFR rs1801133, rs1801131, rs2274976, rs4846048, rs4846049, rs13306561 and rs3737964, were genotyped with TaqMan Pre-Designed SNP Genotyping Assays. Plasma Hcy levels were detected using Hcy reagent through enzymatic cycling assay. Multivariate analysis was used to identify the SNPs associated with CSVD susceptibility. Plasma Hcy levels were compared between different genotypes.ResultsThe MTHFR rs1801133 TT and CT genotype had increased risk for CSVD, and the OR was higher in the TT genotype than in the CT genotype (2.307 vs 1.473). The plasma Hcy levels of different genotypes showed the tendency of the TT genotype > CT genotype > CC genotype (19.91 ± 8.73 pg/ml vs 17.04 ± 5.68 pg/ml vs 14.96 ± 4.85 pg/ml).ConclusionsThe SNP of MTHFR rs1801133 was correlated with CSVD, and the TT and CT genotypes had increased risk for CSVD compared to the CC genotype. The potential mechanism was associated with elevated Hcy levels. creator: Hongyu Yuan creator: Man Fu creator: Xianzhang Yang creator: Kun Huang creator: Xiaoyan Ren uri: https://doi.org/10.7717/peerj.8627 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Yuan et al. title: Endoplasmic reticulum stress and the protein degradation system in ophthalmic diseases link: https://peerj.com/articles/8638 last-modified: 2020-02-20 description: ObjectiveEndoplasmic reticulum (ER) stress is involved in the pathogenesis of various ophthalmic diseases, and ER stress-mediated degradation systems play an important role in maintaining ER homeostasis during ER stress. The purpose of this review is to explore the potential relationship between them and to find their equilibrium sites.DesignThis review illustrates the important role of reasonable regulation of the protein degradation system in ER stress-mediated ophthalmic diseases. There were 128 articles chosen for review in this study, and the keywords used for article research are ER stress, autophagy, UPS, ophthalmic disease, and ocular.Data sourcesThe data are from Web of Science, PubMed, with no language restrictions from inception until 2019 Jul.ResultsThe ubiquitin proteasome system (UPS) and autophagy are important degradation systems in ER stress. They can restore ER homeostasis, but if ER stress cannot be relieved in time, cell death may occur. However, they are not independent of each other, and the relationship between them is complementary. Therefore, we propose that ER stability can be achieved by adjusting the balance between them.ConclusionThe degradation system of ER stress, UPS and autophagy are interrelated. Because an imbalance between the UPS and autophagy can cause cell death, regulating that balance may suppress ER stress and protect cells against pathological stress damage. creator: Jing-Yao Song creator: Xue-Guang Wang creator: Zi-Yuan Zhang creator: Lin Che creator: Bin Fan creator: Guang-Yu Li uri: https://doi.org/10.7717/peerj.8638 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Song et al. title: Engrailed-2 promotes a malignant phenotype of esophageal squamous cell carcinoma through upregulating the expression of pro-oncogenic genes link: https://peerj.com/articles/8662 last-modified: 2020-02-20 description: BackgroundA number of homeobox genes have been implicated in the development of various cancers. However, the role of engrailed 2 (EN2), a member of the homeobox gene superfamily, in esophageal squamous cell carcinoma (ESCC) remains unknown.MethodsThe expression of EN2 was examined using quantitative real-time PCR and immunohistochemistry. A stable cell line was established to express exogenous EN2 using a lentivirus system. The malignant phenotype was analyzed with proliferation, clonogenicity, wound-healing and invasion assays. The CRISPR/Cas9 system was adopted to deplete endogenous EN2. RNA profiling was performed using gene expression microarray. The ShRNA-mediated method was used to knock down the expression of SPARC. The structure-function relationship was determined using site-directed mutagenesis.ResultsEN2 is highly expressed in ESCC. The malignant phenotype of the ESCC cell line was amplified by an overexpression of EN2 but was attenuated by a disruption of EN2. RNA profiling analysis revealed that distinct sets of genes were modulated by the expression of EN2 in various ESCC cell lines and oncogenes were among these. EN2 greatly increased the expression of SPARC in Eca109. Site-directed mutagenesis revealed that the induction of SPARC was closely correlated with the protumor function of EN2. ShRNA-mediated knockdown of SPARC attenuated the malignant phenotype of EN2-infected cells. These data suggest that SPARC is crucial for mediating the protumor function of EN2.DiscussionEN2 has an oncogenic function in ESCC that is mediated by upregulating the expression of pro-oncogenic genes downstream. EN2 may potentially act as a diagnostic marker or therapeutic target for ESCC treatment in the future. creator: Yong Cao creator: Xiaoyan Wang creator: Li Tang creator: Yan Li creator: Xueqin Song creator: Xu Liu creator: Mingying Li creator: Feng Chen creator: Haisu Wan uri: https://doi.org/10.7717/peerj.8662 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Cao et al. title: Reassessment of the Triassic archosauriform Scleromochlus taylori: neither runner nor biped, but hopper link: https://peerj.com/articles/8418 last-modified: 2020-02-19 description: The six known specimens of Scleromochlus taylori and casts made from their negative impressions were examined to reassess the osteological evidence that has been used to interpret Scleromochlus’s locomotion and phylogenetic relationships. It was found that the trunk was dorsoventrally compressed. The upper temporal fenestra was on the lateral surface of skull and two-thirds the size of the lower, the jaw joint posteriorly placed with short retroarticular process, and teeth short and subconical, but no evidence of external nares or antorbital fossae was found. The posterior trunk was covered with ~20 rows of closely spaced transversely elongate dorsal osteoderms. The coracoid was robust and elongate. The acetabulum was imperforate and the femoral head hemispherical and only weakly inturned such that the hip joint was unsuited to swinging in a parasagittal plane. The presence of four distal tarsals is confirmed. The marked disparity of tibial and fibular shaft diameters and of proximal tarsal dimensions indicates that the larger proximal tarsal is the astragalus and the significantly smaller tarsal is the calcaneum. The astragalus and calcaneum bear little resemblance to those of Lagosuchus, and the prominent calcaneal tuber confirms that the ankle was crurotarsal. There is no evidence that preserved body and limb postures are unnatural, and most specimens are preserved in what is interpreted as a typical sprawling resting pose. A principal component analysis of skeletal measurements of Scleromochlus and other vertebrates of known locomotor type found Scleromochlus to plot with frogs, and that finding combined with skeletal morphology suggests Scleromochlus was a sprawling quadrupedal hopper. Phylogenetic analyses found that Scleromochlus was not an ornithodiran, but was either within the Doswelliidae or outside the clade consisting of the most recent common ancestor of the Erythrosuchidae and Archosauria and all its descendants. creator: S. Christopher Bennett uri: https://doi.org/10.7717/peerj.8418 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Bennett title: Mutant dlx3b disturbs normal tooth mineralization and bone formation in zebrafish link: https://peerj.com/articles/8515 last-modified: 2020-02-19 description: BackgroundTricho-dento-osseous (TDO) syndrome is an autosomal dominant disorder characterized by anomalies in hair, teeth and bone (OMIM190320). Various mutations of Distal-Less 3 (DLX3) gene are found to be responsible for human TDO. The aim of this study was to investigate effects of DLX3 on tooth and bone development using a zebrafish model.MethodsThe dlx3b mutant zebrafish lines were established using the gene targeting tool transcription activator-like effector nuclease (TALEN). Micro-computed tomography was used to render the three-dimensional skeletal structures of mutant fishes. The pharyngeal bone along with connected teeth was isolated and stained by Alizarine Red S, then observed under stereomicroscope. Scanning electron microscopy (SEM) and energy dispersive spectrometer (EDS) were used to examine the tooth surface morphology and mineral composition. Quantitative real-time PCR was used to analyze gene expression.ResultsA moderate curvature of the spine toward the dorsal side was found at the early larval stages, appearing in 86 out of 100 larvae in dlx3b-/- group as compared to 3 out of 99 in the dlx3b+/+ group. At the adult stage, three of the thirty dlx3b-/- homozygotes exhibited prominent abnormal curvature in the spine. SEM revealed morphological surface changes in pharyngeal teeth enameloid, accompanied by a decrease in the mineral content detected by EDS. Furthermore, specific secretory calcium-binding phosphoprotein (SCPP) genes, including odam, scpp9, spp1, scpp1, and scpp5 were significantly downregulated in dlx3b mutants.ConclusionThe findings of this study suggest that dlx3b is critical for enamel mineralization and bone formation in zebrafish. Moreover, the discovery of the downregulation of SCPP genes in dlx3b mutants sheds new light on the molecular mechanisms underlying TDO syndrome. creator: Liping Pang creator: Zhichun Zhang creator: Yan Shen creator: Zhenchao Cheng creator: Xuejun Gao creator: Bo Zhang creator: Xiaoyan Wang creator: Hua Tian uri: https://doi.org/10.7717/peerj.8515 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Pang et al. title: Invasive vegetation affects amphibian skin microbiota and body condition link: https://peerj.com/articles/8549 last-modified: 2020-02-19 description: Invasive plants are major drivers of habitat modification and the scale of their impact is increasing globally as anthropogenic activities facilitate their spread. In California, an invasive plant genus of great concern is Eucalyptus. Eucalyptus leaves can alter soil chemistry and negatively affect underground macro- and microbial communities. Amphibians serve as excellent models to evaluate the effect of Eucalyptus invasion on ground-dwelling species as they predate on soil arthropods and incorporate soil microbes into their microbiotas. The skin microbiota is particularly important to amphibian health, suggesting that invasive plant species could ultimately affect amphibian populations. To investigate the potential for invasive vegetation to induce changes in microbial communities, we sampled microbial communities in the soil and on the skin of local amphibians. Specifically, we compared Batrachoseps attenuatus skin microbiomes in both Eucalyptus globulus (Myrtaceae) and native Quercus agriflolia (Fagaceae) dominated forests in the San Francisco Bay Area. We determined whether changes in microbial diversity and composition in both soil and Batrachoseps attenuatus skin were associated with dominant vegetation type. To evaluate animal health across vegetation types, we compared Batrachoseps attenuatus body condition and the presence/absence of the amphibian skin pathogen Batrachochytrium dendrobatidis. We found that Eucalyptus invasion had no measurable effect on soil microbial community diversity and a relatively small effect (compared to the effect of site identity) on community structure in the microhabitats sampled. In contrast, our results show that Batrachoseps attenuatus skin microbiota diversity was greater in Quercus dominated habitats. One amplicon sequence variant identified in the family Chlamydiaceae was observed in higher relative abundance among salamanders sampled in Eucalyptus dominated habitats. We also observed that Batrachoseps attenuatus body condition was higher in Quercus dominated habitats. Incidence of Batrachochytrium dendrobatidis across all individuals was very low (only one Batrachochytrium dendrobatidis positive individual). The effect on body condition demonstrates that although Eucalyptus may not always decrease amphibian abundance or diversity, it can potentially have cryptic negative effects. Our findings prompt further work to determine the mechanisms that lead to changes in the health and microbiome of native species post-plant invasion. creator: Obed Hernández-Gómez creator: Allison Q. Byrne creator: Alex R. Gunderson creator: Thomas S. Jenkinson creator: Clay F. Noss creator: Andrew P. Rothstein creator: Molly C. Womack creator: Erica B. Rosenblum uri: https://doi.org/10.7717/peerj.8549 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Hernández-Gómez et al. title: The E2F family as potential biomarkers and therapeutic targets in colon cancer link: https://peerj.com/articles/8562 last-modified: 2020-02-19 description: BackgroundThe E2F family is a group of genes encoding a series of transcription factors in higher eukaryotes and participating in the regulation of cell cycle and DNA synthesis in mammals. This study was designed to investigate the role of E2F family in colon cancer.MethodsIn this study, the transcriptional levels of E2F1-8 in patients with colon cancer from GEPIA was examined. Meanwhile, the immunohistochemical data of the eight genes were also obtained in the The Human Protein Atlas website. Additionally, we re-identified the mRNA expression levels of these genes via real time PCR. Furthermore, the association between the levels of E2F family and stage plot as wells overall survival of patients with colon cancer were analyzed.ResultsWe found that the mRNA and protein levels of E2F1, E2F2, E3F3, E2F5, E2F7 and E2F8 were significantly higher in colon cancer tissues than in normal colon tissues while the expression levels of E2F4 and E2F6 displayed no significant difference between colon cancer tissues and normal tissues. Additionally, E2F3, E2F4, E2F7 and E2F8 were significantly associated with the stages of colon cancer. The Kaplan-Meier Plotter showed that the high levels of E2F3 conferred a worse overall survival and disease free survival of patients with colon cancer. Also, high levels of E2F4 resulted in a worse overall survival.ConclusionOur study implied that E2F3, E2F4, E2F7 and E2F8 are potential targets of precision therapy for patients with colon cancer while E2F1, E2F2, E3F3, E2F5, E2F7 and E2F8 are potential biomarkers for the diagnosis of colon cancer. creator: Haibo Yao creator: Fang Lu creator: Yanfei Shao uri: https://doi.org/10.7717/peerj.8562 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Yao et al. title: Facilitating open-science with realistic fMRI simulation: validation and application link: https://peerj.com/articles/8564 last-modified: 2020-02-19 description: With advances in methods for collecting and analyzing fMRI data, there is a concurrent need to understand how to reliably evaluate and optimally use these methods. Simulations of fMRI data can aid in both the evaluation of complex designs and the analysis of data. We present fmrisim, a new Python package for standardized, realistic simulation of fMRI data. This package is part of BrainIAK: a recently released open-source Python toolbox for advanced neuroimaging analyses. We describe how to use fmrisim to extract noise properties from real fMRI data and then create a synthetic dataset with matched noise properties and a user-specified signal. We validate the noise generated by fmrisim to show that it can approximate the noise properties of real data. We further show how fmrisim can help researchers find the optimal design in terms of power. The fmrisim package holds promise for improving the design of fMRI experiments, which may facilitate both the pre-registration of such experiments as well as the analysis of fMRI data. creator: Cameron T. Ellis creator: Christopher Baldassano creator: Anna C. Schapiro creator: Ming Bo Cai creator: Jonathan D. Cohen uri: https://doi.org/10.7717/peerj.8564 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Ellis et al. title: A high Mn(II)-tolerance strain, Bacillus thuringiensis HM7, isolated from manganese ore and its biosorption characteristics link: https://peerj.com/articles/8589 last-modified: 2020-02-19 description: Microorganisms play a significant part in detoxifying and immobilizing excessive metals. The present research isolated a strain (HM7) with high Mn(II) tolerance from Mn(II)-contaminated soil samples. The 16S rDNA sequence analysis showed that HM7 had a 99% similarity to Bacillus thuringiensis, which can survive under a high concentration 4,000 mg/L of Mn(II), and the highest removal rate was up to 95.04% at the concentration of 400 mg/L. The highest Mn(II) removal rate was detected at the contact time 72 h, temperature 30 °C, and pH 5.0, while the differences in strain growth and Mn(II) removal rate among different inoculation doses were insignificant. Scanning electron microscopy indicated B. thuringiensis HM7 cells appeared irregular and cracked under Mn(II) stress. Fourier transform infrared exhibited that functional groups like carboxyl, hydroxyl, amino, sulfhydryl groups, and amide bands might take part in the complexation of Mn(II). In addition, HM7 suggested the ability of indoleacetic acid production, siderophore production, and P’ solubilization potential. Therefore, HM7 might have a potential to promote metal absorption by changing the form of heavy metals, and the experiments supported the application of B. thuringiensis HM7 as a biological adsorbent in Mn(II) contaminated environment remediation. creator: Huimin Huang creator: Yunlin Zhao creator: Zhenggang Xu creator: Yi Ding creator: Xiaomei Zhou creator: Meng Dong uri: https://doi.org/10.7717/peerj.8589 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Huang et al.