title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=920 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Long non-coding RNA taurine upregulated gene 1 is downregulated in osteoporosis and influences the osteogenic differentiation of bone marrow mesenchymal stem cells link: https://peerj.com/articles/11251 last-modified: 2021-04-20 description: BackgroundWith aging, an imbalance in bone remodeling leading to increased bone resorption and decreased bone formation is thought to contribute to osteoporosis. Osteoblastic differentiation of bone marrow mesenchymal stem cells (BMMSCs) plays a vital role in the pathogenesis of osteoporosis. However, the detailed molecular mechanisms of osteoporosis remain incompletely understood. Given that long non-coding RNA taurine upregulated gene 1 (lnc TUG1) plays a critical role in the osteogenic differentiation, and microRNA-23b (miR-23b) as a putative sponge for lnc TUG1 has upregulated expression in osteoporosis. Therefore, this study investigated the roles of TUG1/miR-23b in osteoporotic pathology.Material and MethodsTUG1 and miR-23b expression in the plasma of osteoporotic patients were evaluated by quantitative real-time PCR (qRT-PCR). The osteogenic differentiation in human BMMSCs was evaluated by qRT-PCR, western blot, Alizarin red staining after knockdown of TUG1 by small interfering RNA (siRNA) treatment.ResultsDecreased expression of TUG1 and increased expression of miR-23b evident in the plasma of patients with osteoporosis than in that of age- and sex-matched healthy controls. Additionally, increased miR-23b expression inhibited runt-related transcription factor 2 (RUNX2), osteocalcin, and osteopontin expression and reduced calcified nodule formation based on the results of qRT-PCR, western blot, and Alizarin Red S staining.ConclusionThe study for the first time reported that silence of lncRNA TUG1 significantly suppressed the osteogenic differentiation of BMMSCs possibly by targeting the miR-23b/RUNX2 signaling pathway. This mechanism of TUG1/miR-23b/RUNX2 signaling within the osteogenic differentiation of BMMSCs might provide new insight for the development of lncRNA-directed diagnostic and therapeutic strategies for osteoporosis. creator: Zhaowei Teng creator: Yun Zhu creator: Qinggang Hao creator: Xiaochao Yu creator: Yirong Teng creator: Qiaoning Yue creator: Xiguang Zhang creator: Sheng Lu uri: https://doi.org/10.7717/peerj.11251 license: https://creativecommons.org/licenses/by-nc/4.0 rights: ©2021 Teng et al. title: Development and validation of an oxidative stress—associated prognostic risk model for melanoma link: https://peerj.com/articles/11258 last-modified: 2021-04-20 description: BackgroundOxidative stress (OS) is key to various diseases and is implicated in cancer progression and oncogenesis. However, the potential diagnostic value of OS-related genes in skin cutaneous melanoma (SKCM) remains unclear.MethodsWe used data of RNA sequencing from 471 tumor tissues and one healthy tissue acquired from The Cancer Genome Atlas (TCGA)-SKCM cohort. The Genome Tissue Expression database was used to acquire transcriptome data from 812 healthy samples. OS-related genes that were differentially expressed between SKCM and healthy samples were investigated and 16 prognosis-associated OS genes were identified. The prognostic risk model was built using univariate and Cox multivariate regressions. The prognostic value of the hub genes was validated in the GSE65904 cohort, which included 214 SKCM patients.ResultsThe overall survival rate of SKCM patients in the high-risk group was decreased compared to the low-risk group. In both TCGA and GSE65904 cohorts, the ROC curves suggested that our prognostic risk model was more accurate than other clinicopathological characteristics to diagnose SKCM. Moreover, risk score and nomograms associated with the expression of hub genes were developed. These presented reiterated our prognostic risk model. Altogether, this study provides novel insights with regards to the pathogenesis of SKCM. The 16 hub genes identified may help in SKCM prognosis and individualized clinical treatment. creator: Yu Yang creator: Xuan Long creator: Kun Li creator: Guiyun Li creator: Xiaohong Yu creator: Ping Wen creator: Jun Luo creator: Xiaobin Tian creator: Jinmin Zhao uri: https://doi.org/10.7717/peerj.11258 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Yang et al. title: Prediction and analysis of novel key genes ITGAX, LAPTM5, SERPINE1 in clear cell renal cell carcinoma through bioinformatics analysis link: https://peerj.com/articles/11272 last-modified: 2021-04-20 description: BackgroundClear Cell Renal Cell Carcinoma (CCRCC) is the most aggressive subtype of Renal Cell Carcinoma (RCC) with high metastasis and recurrence rates. This study aims to find new potential key genes of CCRCC.MethodsFour gene expression profiles (GSE12606, GSE53000, GSE68417, and GSE66272) were downloaded from the Gene Expression Omnibus (GEO) database. The TCGA KIRC data was downloaded from The Cancer Genome Atlas (TCGA). Using GEO2R, the differentially expressed genes (DEG) in CCRCC tissues and normal samples were analyzed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed in DAVID database. A protein-protein interaction (PPI) network was constructed and the hub gene was predicted by STRING and Cytoscape. GEPIA and Kaplan-Meier plotter databases were used for further screening of Key genes. Expression verification and survival analysis of key genes were performed using TCGA database, GEPIA database, and Kaplan-Meier plotter. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of key genes in CCRCC, which is plotted by R software based on TCGA database. UALCAN database was used to analyze the relationship between key genes and clinical pathology in CCRCC and the methylation level of the promoter of key genes in CCRCC.ResultsA total of 289 up-regulated and 449 down-regulated genes were identified based on GSE12606, GSE53000, GSE68417, and GSE66272 profiles in CCRCC. The upregulated DEGs were mainly enriched with protein binding and PI3K-Akt signaling pathway, whereas down-regulated genes were enriched with the integral component of the membrane and metabolic pathways. Next, the top 35 genes were screened out from the PPI network according to Degree, and three new key genes ITGAX, LAPTM5 and SERPINE1 were further screened out through survival and prognosis analysis. Further results showed that the ITGAX, LAPTM5, and SERPINE1 levels in CCRCC tumor tissues were significantly higher than those in normal tissues and were associated with poor prognosis. ROC curve shows that ITGAX, LAPTM5, and SERPINE1 have good diagnostic value with good specificity and sensitivity. The promoter methylation levels of ITGAX, LAPTM5 and SERPINE1 in CCRCC tumor tissues were significantly lower than those in normal tissues. We also found that key genes were associated with clinical pathology in CCRCC.ConclusionITGAX, LAPTM5, and SERPINE1 were identified as novel key candidate genes that could be used as prognostic biomarkers and potential therapeutic targets for CCRCC. creator: Yingli Sui creator: Kun Lu creator: Lin Fu uri: https://doi.org/10.7717/peerj.11272 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Sui et al. title: The impact of functional excess of footwear on the foot shape of 7-year-old girls and boys link: https://peerj.com/articles/11277 last-modified: 2021-04-20 description: BackgroundProperly fitted shoes can support the development of growing feet and prevent problems and pathologies, not only in childhood, but also in adulthood. This points to the need to conduct research on the impact of shoe fitting on the structure of the foot in order to raise awareness and importance of this problem, to enable proper decisions regarding the purchase and use of shoes. The aim of this study was to analyze indoor footwear fit and its impact on foot structure in 7-year-old schoolchildren.MethodsThe CQ-ST podoscope and the Clevermess device were used for measurements. The analysis was carried out using the Mann Whitney U test, Wilcoxon signed-rank test, Chi-square test, regression analysis.ResultsAbout 40% of girls and boys had shoes that were incorrectly fitted in length, while as many as 74% of girls and 66% of boys wore shoes that were incorrectly fitted in width. Regression analysis demonstrated a statistically significant influence of the footwear length on longitudinal arch of the right and left foot and the transverse arch of the right foot. In boys, the length of the shoes shows associations with the right and left hallux valgus angle.ConclusionA significant percentage of the studied 7-year-olds, regardless of gender, wears inappropriately fitted shoes. In both sexes, the length of the footwear influenced the longitudinal arch of the right and left foot and the transverse arch of the right foot. Due to the deformity of the first metatarsophalangeal joint, the boys with hallux valgus require footwear which is wider and therefore their shoes need to be bigger in size. creator: Ewa Puszczalowska-Lizis creator: Aleksandra Lukasiewicz creator: Sabina Lizis creator: Jaroslaw Omorczyk uri: https://doi.org/10.7717/peerj.11277 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Puszczalowska-Lizis et al. title: Anti-atherosclerotic vaccination against Porphyromonas gingivalis as a potential comparator of statin in mice link: https://peerj.com/articles/11293 last-modified: 2021-04-20 description: BackgroundPorphyromonas gingivalis (Pg) is an oral anaerobe which damages teeth and periodontal tissues. Its body infection is known to cause chronic inflammation, thereby inducing an early stage of atherosclerosis through humoral immune actions. Hence, vaccination by immunizing the proteins of P. gingivalis (Pg) post sonication with heating may prevent atherosclerosis. This study aimed to compare the effect of its vaccination with statin, which effectively prevents atherosclerosis by lowering lipids.MethodsThe vaccine was produced by sonicating P. gingivalis through heating, and a total of 32 male APOE-/-mice (8-week old) were subjected Western diet for 8 weeks, in order to induce atherosclerosis in a physiological manner. Then, the mice were grouped to undergo four treatment conditions (i.e., no treatment, pitavastatin, vaccine, or pitavastatin with vaccine). Vaccination was conducted through nasal immunization and confirmed by a Pg-specific humoral immune reaction. Then, half of the mice in each group were orally injected with P. gingivalis for the next 5 weeks while the other half remained uninfected, generating a total of eight groups (n = 4/group). The mice were sacrificed at 3 weeks after the last injection. After harvesting the aorta, Oil Red O staining of en face was conducted with imaging and image analysis, and plaque formation was quantitatively determined.ResultsCompared to no treatment, the vaccination through nasal immunization significantly reduced the atherosclerotic plaque sizes in APOE -/- mice under Western diet to the comparable level of statin group. When both vaccine and statin were used, no clear synergistic effect was observed as opposed to expectation.ConclusionsThis study revealed that nasal immunization of heat shock P. gingivalis has a significant impact on the prevention of arteriosclerosis and acts as a potential comparator of statin. creator: Hyun-Su Ha creator: Tae Young Kim creator: Soo Jung Han creator: Hak-Joon Sung creator: Kyoung Yul Seo creator: Jong-Won Ha uri: https://doi.org/10.7717/peerj.11293 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Ha et al. title: Characteristics of craniofacial morphology and factors affecting them in patients with isolated cleft palate link: https://peerj.com/articles/11297 last-modified: 2021-04-20 description: BackgroundMyriad maxillo-mandibular occlusal relationships are observed in patients with isolated cleft palate (ICP), unlike in patients with other cleft types, such as cleft lip and palate.ObjectivesThis study aimed to categorise the characteristics of craniofacial morphology in patients with ICP, and investigate the clinical factors affecting these categorised morphological characteristics.MethodsThirty-six girls with ICP (age (mean ± SD): 5.36 ± 0.36 years) underwent cephalometric measurement. Their craniofacial morphology was categorised using cluster analysis. Profilograms were created and superimposed onto the standard Japanese profilograms to visualise the morphological characteristics of each group (cluster). The mean values and variations in the linear and angular measurements of each group were compared with the Japanese standards and statistically analysed using Dunnett’s test after the analysis of variance. Fisher’s exact test was used to analyse the differences between the cleft types (cleft in the hard and/or soft palate) and skills of the operating surgeons in the groups.ResultsCluster analysis of craniofacial morphologies in patients with ICP resulted in the formation of three categories: the first cluster exhibited a relatively harmonious anteroposterior relationship between the maxilla and the mandible (22.2%); the second cluster exhibited crossbite owing to a significantly smaller maxilla (33.3%); and the third cluster exhibited a smaller mandible with posterior rotation showing skeletal class II malocclusion (44.4%). Differences in cleft types and surgeons were not associated with the distribution of patients in each cluster.ConclusionsPatients with ICP exhibited characteristic morphological patterns, such as bimaxillary retrusion or severe mandibular retrusion, besides the anterior crossbite frequently found in patients with cleft lip and palate . Understanding the typical morphological characteristics could enable better diagnostic categorisation of patients with ICP, which may eventually improve orthodontic treatment planning. creator: Kyoko Tsuji creator: Naoto Haruyama creator: Shunsuke Nomura creator: Naohisa Murata creator: Keigo Yoshizaki creator: Takeshi Mitsuyasu creator: Hiroyuki Nakano creator: Seiji Nakamura creator: Yoshihide Mori creator: Ichiro Takahashi uri: https://doi.org/10.7717/peerj.11297 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Tsuji et al. title: Identification and comparison of circular RNAs in preeclampsia link: https://peerj.com/articles/11299 last-modified: 2021-04-20 description: BackgroundPreeclampsia (PE) is a pregnancy-specific syndrome, belongs to the gestational hypertension diseases category and is considered among the causes of maternal and perinatal mortality and morbidity. However, the pathogenesis of PE is still vague.MethodsIn the present study, the circular RNA (circRNA) expression patterns of normal pregnant women and PE patients were investigated using whole RNA sequencing.ResultsA total of 151 differential expressed circRNAs were identified including 121 upregulated and 30 downregulated ones. Functional and pathway enrichment analysis was conducted on the differentially expressed circRNAs using Gene Ontology and KEGG databases. The results of this analysis indicated that several crucial biological processes and pathways were enriched in PE patients. circRNA–microRNA (miRNA) interaction analysis indicated that the reported differentially expresse circRNAs may be associated with some regulatory functions through miRNAs in PE patients. Two ceRNAs networks were constructed according to the targeting relationship between circRNAs/miRNAs and miRNAs/mRNAs. One sub-network contained one upregulated circRNA, four downregulated miRNAs and five upregulated mRNAs, and another sub-network contained 10 downregulated circRNAs, 21 upregulated miRNAs and 15 downregulated mRNAs.ConclusionCircRNA expression patterns have been investigated and this analysis revealed their potential regulatory mechanisms in PE patients. We constructed the ceRNAs (competing endogenous RNA) to reveal the potential molecular roles of dysregulated circRNAs in the PE patients using RNA sequencing data. circRNA_13301 was the only one upregulated circRNA in ceRNA being targeted by four miRNAs. creator: Zepeng Ping creator: Ling Ai creator: Huaxiang Shen creator: Xing Zhang creator: Huling Jiang creator: Ye Song uri: https://doi.org/10.7717/peerj.11299 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Ping et al. title: Sexual dimorphism and skull size and shape in the highly specialized snake species, Aipysurus eydouxii (Elapidae: Hydrophiinae) link: https://peerj.com/articles/11311 last-modified: 2021-04-20 description: BackgroundSnakes exhibit sexual dimorphism in both head size and shape. Such differences are often attributed to different reproductive roles and feeding habits. We aim to investigate how sexual dimorphism is displayed in the highly specialised fish-egg-eating snake, Aipysurus eydouxii, by analysing two complementary features: body size and skull morphology.MethodsWe used data on body length, weight, and skull shape from 27 measurements of 116 males and females of A. eydouxii. We investigated both sexual dimorphism and allometric (multivariate and bi-variate) properties of skull growth in the analysed data set.ResultsWe found that although there was female-biased sexual size dimorphism in body length, females were not heavier than males, contrary to what is commonly observed pattern among snakes. Moreover, females tend to possess relatively smaller heads than males. However, we only found very subtle differences in skull shape reflected in nasal width, mandibular fossa, quadrate crest and quadrate length.DiscussionWe suggest that the feeding specialisation in A. eydouxii does not allow for an increase in body thickness and the size of the head above a certain threshold. Our results may be interpreted as support for prey-size divergence as a factor driving skull dimorphism since such species in which the sexes do not differ in prey size also shows very subtle or no differences in skull morphology. creator: Bartosz Borczyk creator: Łukasz Paśko creator: Jan Kusznierz creator: Stanisław Bury uri: https://doi.org/10.7717/peerj.11311 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Borczyk et al. title: Naturally-occurring tooth wear, tooth fracture, and cranial injuries in large carnivores from Zambia link: https://peerj.com/articles/11313 last-modified: 2021-04-20 description: Determining the incidence and causes of craniodental damage in wild carnivores is often constrained by limited access to specimens with associated ecological data, such as prey type and abundance. We assessed dental condition and cranial injuries in lion, leopard, and spotted hyena in relation to prey and predator populations in Zambia’s Luangwa Valley, where large prey are more abundant and lion and leopard more numerous, and the Greater Kafue Ecosystem, where smaller prey species are more prevalent and lion and leopard less common. In Luangwa, lions had significantly higher rates of tooth fracture, and blunt trauma injuries attributable to prey-handling, compared to Kafue lions. In contrast, leopards in both regions had similar rates of tooth wear and breakage. Overall, lions showed a significantly higher tooth fracture rate than leopards on a per tooth basis. Spotted hyenas had the highest rates of tooth wear and fracture among all three carnivores, and greatly exceeded previously recorded rates based on historical samples. Despite larger numbers of lion and leopard in Luangwa, there was no difference in incidence of intraspecific injuries between regions. These results are consistent with a greater abundance of large prey species, especially buffalo, in the diets of Luangwa lions, and previous work showing a reliance on smaller prey species in Kafue throughout the large carnivore guild. creator: Blaire Van Valkenburgh creator: Paula A. White uri: https://doi.org/10.7717/peerj.11313 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Van Valkenburgh and White title: Geology and taphonomy of a unique tyrannosaurid bonebed from the upper Campanian Kaiparowits Formation of southern Utah: implications for tyrannosaurid gregariousness link: https://peerj.com/articles/11013 last-modified: 2021-04-19 description: Tyrannosaurids are hypothesized to be gregarious, possibly parasocial carnivores engaging in cooperative hunting and extended parental care. A tyrannosaurid (cf. Teratophoneus curriei) bonebed in the late Campanian age Kaiparowits Formation of southern Utah, nicknamed the Rainbows and Unicorns Quarry (RUQ), provides the first opportunity to investigate possible tyrannosaurid gregariousness in a taxon unique to southern Laramidia. Analyses of the site’s sedimentology, fauna, flora, stable isotopes, rare earth elements (REE), charcoal content and taphonomy suggest a complex history starting with the deaths and transport of tyrannosaurids into a peri-fluvial, low-energy lacustrine setting. Isotopic and REE analyses of the fossil material yields a relatively homogeneous signature indicating the assemblage was derived from the same source and represents a fauna living in a single ecospace. Subsequent drying of the lake and fluctuating water tables simultaneously overprinted the bones with pedogenic carbonate and structurally weakened them through wet-dry cycling. Abundant charcoal recovered from the primary bone layer indicate a low temperature fire played a role in the site history, possibly triggering an avulsion that exhumed and reburied skeletal material on the margin of a new channel with minimal transport. Possible causes of mortality and concentration of the tyrannosaurids include cyanobacterial toxicosis, fire, and flooding, the latter being the preferred hypothesis. Comparisons of the RUQ site with other North American tyrannosaur bonebeds (Dry Island-Alberta; Daspletosaurus horneri-Montana) suggest all formed through similar processes. Combined with ichnological evidence, these tyrannosaur mass-burial sites could be part of an emerging pattern throughout Laramidia reflecting innate tyrannosaurid behavior such as habitual gregariousness. creator: Alan L. Titus creator: Katja Knoll creator: Joseph J.W. Sertich creator: Daigo Yamamura creator: Celina A. Suarez creator: Ian J. Glasspool creator: Jonathan E. Ginouves creator: Abigail K. Lukacic creator: Eric M. Roberts uri: https://doi.org/10.7717/peerj.11013 license: https://creativecommons.org/publicdomain/zero/1.0/ rights: