title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=797 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Frequent, quantitative bone planar scintigraphy for determination of bone anabolism in growing mice link: https://peerj.com/articles/12355 last-modified: 2021-12-09 description: BackgroundTo provide insight into bone turnover, quantitative measurements of bone remodeling are required. Radionuclide studies are widely used in clinical care, but have been rarely used in the exploration of the bone in preclinical studies. We describe a bone planar scintigraphy method for frequent assessment of bone activity in mice across the growing period. Since repeated venous radiotracer injections are hardly feasible in mice, we investigated the subcutaneous route.MethodsRepeated 99mTc-hydroxymethylene diphosphonate (HMDP) tracer bone planar scintigraphy studies of the knee region and µCT to measure femur growth rate were performed in eight mice between week 6 and week 27 of life, i.e., during their growth period. Three independent investigators assessed the regions of interest (ROI). An index was calculated based on the counts in knees ROI (normalized by pixels and seconds), corrected for the activity administered, the decay between administration and imaging, and individual weights.ResultsA total of 93 scintigraphy studies and 85 µCT were performed. Repeated subcutaneous tracer injections were well tolerated and allowed for adequate radionuclide studies. Mean scintigraphic indexes in the knees ROI decreased from 87.4 ± 2.6 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 6 to 15.0 ± 3.3 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 27. The time constant of the fitted exponential decay was equal to 23.5 days. As control mean femur length assessed by µCT increased from 12.2 ± 0.8 mm at week 6 to 15.8 ± 0.2 mm at week 22. The time constant of the fitted Gompertz law was equal to 26.7 days. A correlation index of −0.97 was found between femur growth and decrease of bone tracer activity count between week 6 and 24.ConclusionThis methodological study demonstrates the potential of repeated bone planar scintigraphy in growing mice, with subcutaneous route for tracer administration, for quantitative assessment of bone remodeling. creator: Ariane Zaloszyc creator: Claus Peter Schmitt creator: Amira Sayeh creator: Laetitia Higel creator: Catherine-Isabelle Gros creator: Fabien Bornert creator: Gaëlle Aubertin-Kirch creator: Jean-Philippe Dillenseger creator: Christian Goetz creator: André Constantinesco creator: Michel Fischbach creator: Seiamak Bahram creator: Philippe Choquet uri: https://doi.org/10.7717/peerj.12355 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Zaloszyc et al. title: The phylogenetic nomenclature of ornithischian dinosaurs link: https://peerj.com/articles/12362 last-modified: 2021-12-09 description: Ornithischians form a large clade of globally distributed Mesozoic dinosaurs, and represent one of their three major radiations. Throughout their evolutionary history, exceeding 134 million years, ornithischians evolved considerable morphological disparity, expressed especially through the cranial and osteodermal features of their most distinguishable representatives. The nearly two-century-long research history on ornithischians has resulted in the recognition of numerous diverse lineages, many of which have been named. Following the formative publications establishing the theoretical foundation of phylogenetic nomenclature throughout the 1980s and 1990s, many of the proposed names of ornithischian clades were provided with phylogenetic definitions. Some of these definitions have proven useful and have not been changed, beyond the way they were formulated, since their introduction. Some names, however, have multiple definitions, making their application ambiguous. Recent implementation of the International Code of Phylogenetic Nomenclature (ICPN, or PhyloCode) offers the opportunity to explore the utility of previously proposed definitions of established taxon names. Since the Articles of the ICPN are not to be applied retroactively, all phylogenetic definitions published prior to its implementation remain informal (and ineffective) in the light of the Code. Here, we revise the nomenclature of ornithischian dinosaur clades; we revisit 76 preexisting ornithischian clade names, review their recent and historical use, and formally establish their phylogenetic definitions. Additionally, we introduce five new clade names: two for robustly supported clades of later-diverging hadrosaurids and ceratopsians, one uniting heterodontosaurids and genasaurs, and two for clades of nodosaurids. Our study marks a key step towards a formal phylogenetic nomenclature of ornithischian dinosaurs. creator: Daniel Madzia creator: Victoria M. Arbour creator: Clint A. Boyd creator: Andrew A. Farke creator: Penélope Cruzado-Caballero creator: David C. Evans uri: https://doi.org/10.7717/peerj.12362 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Madzia et al. title: Overexpression of fucosyltransferase 8 reverses the inhibitory effect of high-dose dexamethasone on osteogenic response of MC3T3-E1 preosteoblasts link: https://peerj.com/articles/12380 last-modified: 2021-12-09 description: BackgroundCore fucosylation catalyzed by FUT8 is essential for TGF-β binding to TGF-β receptors.MethodsIndirect TGF-β1 binding assay was used to evaluate the ability of TGF-β1 to bind to TGFBRs, Alizarin red and alkaline phosphatase staining were used to detect osteogenic differentiation and mineralization ability , western blot and quantitative RT-PCR were used to measure the differential expression of osteogenesis-related proteins and genes. Plasmid-mediated gain-of-function study. The scale of core fucosylation modification was detected by Lectin-blot and LCA laser confocal.ResultsOur results showed that compared with vehicle treatment, high-dose (10−6 and 10−5 M) dexamethasone significantly inhibited cell proliferation, osteogenic differentiation, and FUT8 mRNA expression while promoting mRNA expression of adipogenesis-related genes in MC3T3-E1 cells, suggesting that downregulation of FUT8 is involved in the inhibitory effect of high-dose dexamethasone on osteogenesis. Overexpression of FUT8 significantly promoted osteogenic differentiation and activated TGF-β/Smad signaling in MC3T3-E1 cells in the presence of high-dose dexamethasone, suggesting that FUT8 reverses the inhibitory effect of high-dose dexamethasone on osteogenesis. In addition, lectin fluorescent staining and blotting showed that overexpression of FUT8 significantly reversed the inhibitory effects of high-dose dexamethasone on core fucosylation of TGFBR1 and TGFBR2. Furthermore, indirect TGF-β1 binding assay showed that overexpression of FUT8 remarkably promoted TGF-β1 binding to TGFBRs in MC3T3-E1 cells in the presence of high-dose dexamethasone.ConclusionsTaken together, these results suggest that overexpression of FUT8 facilitates counteracting the inhibitory effect of dexamethasone on TGF-β signaling and osteogenesis. creator: Zhiming Wu creator: Tianye Lin creator: Pan Kang creator: Zhikun Zhuang creator: Haibin Wang creator: Wei He creator: Qiushi Wei creator: Ziqi Li uri: https://doi.org/10.7717/peerj.12380 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Wu et al. title: A transcription factor signature predicts the survival of patients with adrenocortical carcinoma link: https://peerj.com/articles/12433 last-modified: 2021-12-09 description: BackgroundAdrenocortical carcinoma (ACC) is a rare endocrine cancer that manifests as abdominal masses and excessive steroid hormone levels and is associated with poor clinical outcomes. Transcription factors (TFs) deregulation is found to be involved in adrenocortical tumorigenesis and cancer progression. This study aimed to construct a TF-based prognostic signature for the prediction of survival of ACC patients.MethodsThe gene expression profile and clinical information for ACC patients were downloaded from The Cancer Genome Atlas (TCGA, training set) and Gene Expression Omnibus (GEO, validation set) datasets after obtained 1,639 human TFs from a previously published study. The univariate Cox regression analysis was applied to identify the survival-related TFs and the LASSO Cox regression was conducted to construct the TF signature based on these survival-associated TFs candidates. Then, multivariate analysis was used to reveal the independent prognostic factors. Furthermore, Gene Set Enrichment Analysis (GSEA) was performed to analyze the significance of the TFs constituting the prognostic signature.ResultsLASSO Cox regression and multivariate Cox regression identified a 13-TF prognostic signature comprised of CREB3L3, NR0B1, CENPA, FOXM1, E2F2, MYBL2, HOXC11, ZIC2, ZNF282, DNMT1, TCF3, ELK4, and KLF6. The risk score based on the TF signature could classify patients into low- and high-risk groups. Kaplan-Meier analyses showed that patients in the high-risk group had significantly shorter overall survival (OS) compared to the low-risk patients. Receiver operating characteristic (ROC) curves showed that the prognostic signature predicted the OS of ACC patients with good sensitivity and specificity both in the training set (AUC > 0.9) and the validation set (AUC > 0.7). Furthermore, the TF-risk score was an independent prognostic factor.ConclusionsTaken together, we identified a 13-TF prognostic marker to predict OS in ACC patients. creator: Jianyu Zhao creator: Bo Liu creator: Xiaoping Li uri: https://doi.org/10.7717/peerj.12433 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Zhao et al. title: Characterization and expression analysis of the SPL gene family during floral development and abiotic stress in pecan (Carya illinoinensis) link: https://peerj.com/articles/12490 last-modified: 2021-12-09 description: SQUAMOSA promoter binding protein-like (SPL) genes are a type of plant-specific transcription factors that play crucial roles in the regulation of phase transition, floral transformation, fruit development, and various stresses. Although SPLs have been characterized in several model species, no systematic analysis has been studied in pecans, an important woody oil tree species. In this study, a total of 32 SPL genes (CiSPLs) were identified in the pecan genome. After conducting phylogenetic analysis of the conserved SBP proteins from Arabidopsis, rice, and poplar, the CiSPLs were separated into eight subgroups. The CiSPL genes within the same subgroup contained very similar exon-intron structures and conserved motifs. Nine segmentally duplicated gene pairs in the pecan genome and 16 collinear gene pairs between the CiSPL and AtSPL genes were identified. Cis-element analysis showed that CiSPL genes may regulate plant meristem differentiation and seed development, participate in various biological processes, and respond to plant hormones and environmental stresses. Therefore, we focused our study on the expression profiles of CiSPL genes during flower and fruit development. Most of the CiSPL genes were predominantly expressed in buds and/or female flowers. Additionally, quantitative real time PCR (qRT-PCR) analyses confirmed that CiSPL genes showed distinct spatiotemporal expression patterns in response to drought and salt treatments. The study provides foundation for the further exploration of the function and evolution of SPL genes in pecan. creator: Min Wang creator: Zhenghai Mo creator: Ruozhu Lin creator: Cancan Zhu uri: https://doi.org/10.7717/peerj.12490 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Wang et al. title: Prognostic values of the core components of the mammalian circadian clock in prostate cancer link: https://peerj.com/articles/12539 last-modified: 2021-12-09 description: BackgroundProstate cancer (PC) is one of the most common malignancies in males. Extensive and complex connections between circadian rhythm and cancer were found. Nonetheless, in PC, the potential role of the core components of the mammalian circadian clock (CCMCCs) in prognosis prediction has not been fully clarified.MethodsWe firstly collected 605 patients with PC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Survival analysis was carried out for each CCMCC. Then, we investigated the prognostic ability of CCMCCs by Cox regression analysis. Independent prognostic signatures were extracted for the establishment of the circadian clock-based risk score model. We explored the predictive performance of the risk score model in the TCGA training cohort and the independent GEO dataset. Finally, the relationships between risk score and clinicopathological parameters, biological processes, and signaling pathways were evaluated.ResultsThe expression levels of CCMCCs were widely correlated with age, tumor status, lymph node status, disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). Nine circadian clock genes, including CSNK1D, BTRC, CLOCK, CSNK1E, FBXL3, PRKAA2, DBP, NR1D2, and RORB, were identified as vital prognostic factors in PC and were used to construct the circadian clock-based risk score model. For DFS, the area under the 3-year or 5-year receiver operating characteristic curves ranged from 0.728 to 0.821, suggesting better predictive performance. When compared with T3-4N1 stage, PC patients at T2N0 stage might be benefited more from the circadian clock-based risk score model. Furthermore, a high circadian clock-based risk score indicated shorter DFS (p < 0.0001), early progression (p < 0.0001), and higher 5-year death rate (p = 0.007) in PC. The risk score was related to tumor status (p < 0.001), lymph node status (p < 0.001), and ribosome-related biogenesis and pathways.ConclusionsThe vital roles of circadian clock genes in clinical outcomes were fully depicted. The circadian clock-based risk score model could reflect and predict the prognosis of patients with PC. creator: Wenchang Yue creator: Xiao Du creator: Xuhong Wang creator: Niu Gui creator: Weijie Zhang creator: Jiale Sun creator: Jiawei You creator: Dong He creator: Xinyu Geng creator: Yuhua Huang creator: Jianquan Hou uri: https://doi.org/10.7717/peerj.12539 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Yue et al. title: Distributions of extinction times from fossil ages and tree topologies: the example of mid-Permian synapsid extinctions link: https://peerj.com/articles/12577 last-modified: 2021-12-09 description: Given a phylogenetic tree that includes only extinct, or a mix of extinct and extant taxa, where at least some fossil data are available, we present a method to compute the distribution of the extinction time of a given set of taxa under the Fossilized-Birth-Death model. Our approach differs from the previous ones in that it takes into account (i) the possibility that the taxa or the clade considered may diversify before going extinct and (ii) the whole phylogenetic tree to estimate extinction times, whilst previous methods do not consider the diversification process and deal with each branch independently. Because of this, our method can estimate extinction times of lineages represented by a single fossil, provided that they belong to a clade that includes other fossil occurrences. We assess and compare our new approach with a standard previous one using simulated data. Results show that our method provides more accurate confidence intervals. This new approach is applied to the study of the extinction time of three Permo-Carboniferous synapsid taxa (Ophiacodontidae, Edaphosauridae, and Sphenacodontidae) that are thought to have disappeared toward the end of the Cisuralian (early Permian), or possibly shortly thereafter. The timing of extinctions of these three taxa and of their component lineages supports the idea that the biological crisis in the late Kungurian/early Roadian consisted of a progressive decline in biodiversity throughout the Kungurian. creator: Gilles Didier creator: Michel Laurin uri: https://doi.org/10.7717/peerj.12577 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Didier and Laurin title: Preclinical models of acute liver failure: a comprehensive review link: https://peerj.com/articles/12579 last-modified: 2021-12-09 description: Acute liver failure is marked by the rapid deterioration of liver function in a previously well patient over period of days to weeks. Though relatively rare, it is associated with high morbidity and mortality. This makes it a challenging disease to study clinically, necessitating reliance on preclinical models as means to explore pathophysiology and novel therapies. Preclinical models of acute liver failure are artificial by nature, and generally fall into one of three categories: surgical, pharmacologic or immunogenic. This article reviews preclinical models of acute liver failure and considers their relevance in modeling clinical disease. creator: Joshua Hefler creator: Braulio A. Marfil-Garza creator: Rena L. Pawlick creator: Darren H. Freed creator: Constantine J. Karvellas creator: David L. Bigam creator: A. M. James Shapiro uri: https://doi.org/10.7717/peerj.12579 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Hefler et al. title: Change in alcohol consumption and physical activity during the COVID-19 pandemic amongst 76 medical students link: https://peerj.com/articles/12580 last-modified: 2021-12-09 description: ObjectiveTo investigate whether the COVID-19 pandemic has affected physical activity and alcohol consumption among medical students.MethodsCross-sectional survey study among 76 students in their second year of medical school. The Wilcoxon sign-rank test and Kruskal-Wallis H test were used to assess the difference between groups.ResultsOf 76 respondents, 68% were women, 66% were single and 34% were co-habiting. The median age was 21 years. Overall alcohol consumption decreased during the pandemic year by 12 g/week. Overall physical activity did not significantly change. The decrease in alcohol consumption was mostly caused by a change seen in a high tertile, change was −96 g/week. Alcohol consumption decreased more in women than in men, p = 0.0001.ConclusionsIt seems that alcohol consumption among medical students has decreased during the COVID-19 pandemic probably due to reduced social contacts and negative effect of social isolation. This decrease was seen especially among women and among students with higher alcohol consumption before the pandemic. Also, it seems that students had found their ways to remain active during the pandemic since the amount of leisure-time physical activity had not changed significantly. creator: Christina Sandell creator: Mikhail Saltychev uri: https://doi.org/10.7717/peerj.12580 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Sandell and Saltychev title: The carbon and nitrogen budget of Desmophyllum dianthus—a voracious cold-water coral thriving in an acidified Patagonian fjord link: https://peerj.com/articles/12609 last-modified: 2021-12-09 description: In the North Patagonian fjord region, the cold-water coral (CWC) Desmophyllum dianthus occurs in high densities, in spite of low pH and aragonite saturation. If and how these conditions affect the energy demand of the corals is so far unknown. In a laboratory experiment, we investigated the carbon and nitrogen (C, N) budget of D. dianthus from Comau Fjord under three feeding scenarios: (1) live fjord zooplankton (100–2,300 µm), (2) live fjord zooplankton plus krill (>7 mm), and (3) four-day food deprivation. In closed incubations, C and N budgets were derived from the difference between C and N uptake during feeding and subsequent C and N loss through respiration, ammonium excretion, release of particulate organic carbon and nitrogen (POC, PON). Additional feeding with krill significantly increased coral respiration (35%), excretion (131%), and POC release (67%) compared to feeding on zooplankton only. Nevertheless, the higher C and N losses were overcompensated by the threefold higher C and N uptake, indicating a high assimilation and growth efficiency for the krill plus zooplankton diet. In contrast, short food deprivation caused a substantial reduction in respiration (59%), excretion (54%), release of POC (73%) and PON (87%) compared to feeding on zooplankton, suggesting a high potential to acclimatize to food scarcity (e.g., in winter). Notwithstanding, unfed corals ‘lost’ 2% of their tissue-C and 1.2% of their tissue-N per day in terms of metabolism and released particulate organic matter (likely mucus). To balance the C (N) losses, each D. dianthus polyp has to consume around 700 (400) zooplankters per day. The capture of a single, large krill individual, however, provides enough C and N to compensate daily C and N losses and grow tissue reserves, suggesting that krill plays an important nutritional role for the fjord corals. Efficient krill and zooplankton capture, as well as dietary and metabolic flexibility, may enable D. dianthus to thrive under adverse environmental conditions in its fjord habitat; however, it is not known how combined anthropogenic warming, acidification and eutrophication jeopardize the energy balance of this important habitat-building species. creator: Sandra R. Maier creator: Carin Jantzen creator: Jürgen Laudien creator: Verena Häussermann creator: Günter Försterra creator: Astrid Cornils creator: Jutta Niggemann creator: Thorsten Dittmar creator: Claudio Richter uri: https://doi.org/10.7717/peerj.12609 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Maier et al.