CELSR3 mRNA expression is increased in hepatocellular carcinoma and indicates poor prognosis
Objective Hepatocellular carcinoma (HCC) is a disease that is associated with high mortality; currently, there is no curative and reliable treatment. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) is the key signaling molecule in the wingless and INT-1/planar cell polarity (WNT/PCP) pathway. This study aimed to elucidate the prognostic significance of CELSR3 in HCC patients. Methods The Cancer Genome Atlas (TCGA) database, the Cancer Cell Line Encyclopedia (CCLE) database and the Gene Expression Omnibus (GEO) database were used to analyze the expression of CELSR3 mRNA in HCC samples and cells. The relationship between CELSR3 mRNA and clinical features was assessed by the chi-square test. the diagnostic and predictive value of CELSR3 mRNA expression were analyzed using the receiver operating characteristic (ROC) curve. Kaplan–Meier curve and Cox regression analyses were performed to assess the prognostic value of CELSR3 mRNA in HCC patients. Finally, all three cohorts database was used for gene set enrichment analysis(GSEA) and the identification of CELSR3-related signal transduction pathways. Results The expression of CELSR3 mRNA was upregulated in HCC, and its expression was correlated with age (P = 0.025), tumor status (P = 0.022), clinical stage (P = 0.003), T classification (P = 0.010), vital status (P = 0.001), and relapse (P = 0.005). The ROC curve assessment indicated that CELSR3 mRNA expression has high diagnostic value in HCC and in the subgroup analysis of stage. In addition, the Kaplan-Meier curve and Cox analyses suggested that patients with high CELSR3 mRNA expression have a poor prognosis, indicating that CELSR3 mRNA is an independent prognostic factor for the overall survival of HCC patients. GSEA showed that GO somatic diversification of immune receptors, GO endonuclease activity, GO DNA repair complex and GO somatic cell DNA recombination, were differentially enriched in the meta-GEO cohort, the HCC cell line cohort and the TCGA cohort of the high CELSR3 mRNA expression phenotype. Conclusion Our results indicate that CELSR3 mRNA is involved in the progression of cancer and can be used as a biomarker for the prognosis of HCC patients.
Gu et al. (2019) CELSR3 mRNA expression is increased in hepatocellular carcinoma and indicates poor prognosis. PeerJ 7:e7816 https://doi.org/10.7717/peerj.7816
Social Motor Priming: when offline interference facilitates motor execution
Many daily activities involve synchronizing with other people’s actions. Previous literature has revealed that a slowdown of performance occurs whenever the action to be carried out is different to the one observed (i.e., visuomotor interference). However, action execution can be facilitated by observing a different action if it calls for an interactive gesture (i.e., social motor priming). The aim of this study is to investigate the costs and benefits of spontaneously processing a social response and then executing the same or a different action. Participants performed two different types of grips, which could be either congruent or not with the socially appropriate response and with the observed action. In particular, participants performed a precision grip (PG; thumb-index fingers opposition) or a whole-hand grasp (WHG; fingers-palm opposition) after observing videos showing an actor performing a PG and addressing them (interactive condition) or not (non-interactive condition). Crucially, in the interactive condition, the most appropriate response was a WHG, but in 50 percent of trials participants were asked to perform a PG. This procedure allowed us to measure both the facilitator effect of performing an action appropriate to the social context (WHG)—but different with respect to the observed one (PG)—and the cost of inhibiting it. These effects were measured by means of 3-D kinematical analysis of movement. Results show that, in terms of reaction time and movement time, the interactive request facilitated (i.e., speeded) the socially appropriate action (WHG), whereas interfered with (i.e., delayed) a different action (PG), although observed actions were always PGs. This interference also manifested with an increase of maximum grip aperture, which seemingly reflects the concurrent representation of the socially appropriate response. Overall, these findings extend previous research by revealing that physically incongruent action representations can be integrated into a single action plan even during an offline task and without any training.
Betti et al. (2019) Social Motor Priming: when offline interference facilitates motor execution. PeerJ 7:e7796 https://doi.org/10.7717/peerj.7796
Validation of COI metabarcoding primers for terrestrial arthropods
Metabarcoding can rapidly determine the species composition of bulk samples and thus aids biodiversity and ecosystem assessment. However, it is essential to use primer sets that minimize amplification bias among taxa to maximize species recovery. Despite this fact, the performance of primer sets employed for metabarcoding terrestrial arthropods has not been sufficiently evaluated. This study tests the performance of 36 primer sets on a mock community containing 374 insect species. Amplification success was assessed with gradient PCRs and the 21 most promising primer sets selected for metabarcoding. These 21 primer sets were also tested by metabarcoding a Malaise trap sample. We identified eight primer sets, mainly those including inosine and/or high degeneracy, that recovered more than 95% of the species in the mock community. Results from the Malaise trap sample were congruent with the mock community, but primer sets generating short amplicons produced potential false positives. Taxon recovery from both mock community and Malaise trap sample metabarcoding were used to select four primer sets for additional evaluation at different annealing temperatures (40–60 °C) using the mock community. The effect of temperature varied by primer pair but overall it only had a minor effect on taxon recovery. This study reveals the weak performance of some primer sets employed in past studies. It also demonstrates that certain primer sets can recover most taxa in a diverse species assemblage. Thus, based our experimental set up, there is no need to employ several primer sets targeting the same gene region. We identify several suitable primer sets for arthropod metabarcoding, and specifically recommend BF3 + BR2, as it is not affected by primer slippage and provides maximal taxonomic resolution. The fwhF2 + fwhR2n primer set amplifies a shorter fragment and is therefore ideal when targeting degraded DNA (e.g., from gut contents).
Elbrecht et al. (2019) Validation of COI metabarcoding primers for terrestrial arthropods. PeerJ 7:e7745 https://doi.org/10.7717/peerj.7745
In vivo acute toxicity evaluation and in vitro molecular mechanism study of antiproliferative activity of a novel indole Schiff base β-diiminato manganeseIII complex in hormone-dependent and triple negative breast cancer cells
Breast cancer is the most frequently diagnosed cancer among women worldwide. Recently, increasing attention has been paid to the anticancer effects of transition metal complexes of indole Schiff bases. β-diiminato ManganeseIII complex has shown promising cell cycle arrest and apoptosis induction against MCF-7 and MDA-MB-231 breast cancer cells. In this study, time- and dose- dependent inhibitory activity were evaluated using MTT assay after 48 h and 72 h exposure time. In addition, median effect analysis was conducted according to Chou–Talalay method to investigate whether MnIII complex has synergistic effect in combination with chemotherapeutic drugs on inhibiting breast cancer cell growth. The molecular mechanisms underlying its potent antiproliferative effect was determined through bioluminescent caspase-3/7, -8 and -9 activity assays and quantitative expression analysis of cell cycle- and apoptosis-related genes. Furthermore, safety evaluation of MnIII complex was assessed through the acute oral toxicity test in in vivo model. The MTT assay results revealed that it potently reduced the viability of MCF-7 (IC50 of 0.63 ± 0.07 µg/mL for 48 h and 0.39 ± 0.08 µg/mL for 72 h) and MDA-MB-231 (1.17 ± 0.06 µg/mL for 48 h, 1.03 ± 0.15 µg/mL for 72 h) cells in dose- and time-dependent manner. Combination treatment also enhanced the cytotoxic effects of doxorubicin but not tamoxifen on inhibiting breast cancer cell growth. The involvement of intrinsic and extrinsic pathway in apoptosis induction was exhibited through the increased activity of caspase-9 and caspase-8, respectively, leading to enhanced downstream executioner caspase-3/7 activity in treated MCF-7 and MDA-MB-231 cells. In addition, gene expression analysis revealed that MnIII complex exerts its antiproliferative effect via up-and down-regulation of p21 and cyclin D1, respectively, along with increased expression of Bax/Bcl-2 ratio, TNF-α, initiator caspase-8 and -10 and effector caspase-3 in MCF-7 and MDA-MB-231 cells. However, the results did not show increased caspase-8 activity in treated MCF-7 cells. Furthermore, in vivo acute oral toxicity test revealed no signs of toxicity and mortality in treated animal models compared to the control group. Collectively, the promising inhibitory effect and molecular and mechanistic evidence of antiproliferative activity of MnIII complex and its safety characterization have demonstrated that it may have therapeutic value in breast cancer treatment worthy of further investigation and development.
Farghadani et al. (2019) In vivo acute toxicity evaluation and in vitro molecular mechanism study of antiproliferative activity of a novel indole Schiff base β-diiminato manganeseIII complex in hormone-dependent and triple negative breast cancer cells. PeerJ 7:e7686 https://doi.org/10.7717/peerj.7686
Plastome sequences help to improve the systematic position of trinerved Lindera species in the family Lauraceae
Lindera is a genus (c. 100 spp.) of trees belonging to the “core Laureae” group in the family Lauraceae. It is often confused with Litsea, and the systematics of the genus is unclear. Here, total 10 complete plastomes from nine trinerved Lindera species and another species Lindera obtusiloba (sect. Palminerviae Meissn.) were sequenced. Nine highly variable regions, trnH-GUG/psbA, psbM/trnD-GUC, petA/psbL, ndhF, trnL-UAG/ndhD, and ycf1, were identified among the 10 Lindera species. In addition, a total of 1,836 mutation events including six micro-inversions, 156 indels, and 1,674 substitutions, were also summarized. Comparing our sequences with other available plastomes in the “core Laureae,” we put forward that six hypervariable loci, trnH-GUG/psbA, ndhF, ndhF/rpl32, trl32/trnL-UAG, ndhD, and ycf1, could potentially be used as plastid barcode candidates for species identification. Further phylogenetic analyses were conducted using 49 complete Lauraceae plastomes. The results supported a close relationship among trinerved Lindera species and suggested an improved trinerved group comprising species of trinerved Lindera species and Iteadaphne caudate.
Tian et al. (2019) Plastome sequences help to improve the systematic position of trinerved Lindera species in the family Lauraceae. PeerJ 7:e7662 https://doi.org/10.7717/peerj.7662
Analyzing the interpretative ability of landscape pattern to explain thermal environmental effects in the Beijing-Tianjin-Hebei urban agglomeration
The development of the urban agglomeration has caused drastic changes in landscape pattern and increased anthropogenic heat emission and lead to the urban heat island (UHI) effect more serious. Therefore, understanding the interpretation ability of landscape pattern on the thermal environment has gradually become an important focus. In the study, the spatial heterogeneity of the surface temperature was analyzed using the hot-spot analysis method which was improved by changing the calculation of space weight. Then the interpretation ability of a single landscape and a combination of landscapes to explain surface temperature was explored using the Pearson correlation coefficient and ordinary least squares regression from different spatial levels, and the spatial heterogeneity of the interpretation ability was explored using geographical weighted regression under the optimal granularity (5 × 5 km). The results showed that: (1) The hot spots of surface temperature were distributed mainly in the plains and on the southeast hills, where the landscapes primarily include artificial landscape (ArtLS) and farmland landscape (FarmLS). The cold spots were distributed mainly in the northern hills, which are dominated by forest landscape (ForLS). (2) On the whole, the interpretative ability of ForLS, FarmLS, ArtLS, green space landscape pattern, and ecological landscape pattern to explain surface temperature was stronger, whereas the interpretative ability of grassland landscape and wetland landscape to explain surface temperature was weaker. The interpretation ability of landscape pattern to explain surface temperature was obviously different in different areas. Specifically, the ability was stronger in the hills than in the plain and plateau. The results are intended to provide a scientific basis for adjusting landscape structural, optimizing landscape patterns, alleviating the UHI effect, and coordinating the balance among cities within the urban agglomeration.
Spatial and Geographic Information Science
Wang et al. (2019) Analyzing the interpretative ability of landscape pattern to explain thermal environmental effects in the Beijing-Tianjin-Hebei urban agglomeration. PeerJ 7:e7874 https://doi.org/10.7717/peerj.7874
Different expression pattern of flowering pathway genes contribute to male or female organ development during floral transition in the monoecious weed Ambrosia artemisiifolia L. (Asteraceae)
The highly allergenic and invasive weed Ambrosia artemisiifolia L. is a monoecius plant with separated male and female flowers. The genetic regulation of floral morphogenesis is a less understood field in the reproduction biology of this species. Therefore the objective of this work was to investigate the genetic control of sex determination during floral organogenesis. To this end, we performed a genome-wide transcriptional profiling of vegetative and generative tissues during the plant development comparing wild-growing and in vitro cultivated plants. RNA-seq on Illumina NextSeq 500 platform with an integrative bioinformatics analysis indicated differences in 80 floral gene expressions depending on photoperiodic and endogenous initial signals. Sex specificity of genes was validated based on RT-qPCR experiments. We found 11 and 16 uniquely expressed genes in female and male transcriptomes that were responsible particularly to maintain fertility and against abiotic stress. High gene expression of homologous such as FD, FT, TFL1 and CAL, SOC1, AP1 were characteristic to male and female floral meristems during organogenesis. Homologues transcripts of LFY and FLC were not found in the investigated generative and vegetative tissues. The repression of AP1 by TFL1 homolog was demonstrated in male flowers resulting exclusive expression of AP2 and PI that controlled stamen and carpel formation in the generative phase. Alterations of male and female floral meristem differentiation were demonstrated under photoperiodic and hormonal condition changes by applying in vitro treatments.
Mátyás et al. (2019) Different expression pattern of flowering pathway genes contribute to male or female organ development during floral transition in the monoecious weed Ambrosia artemisiifolia L. (Asteraceae). PeerJ 7:e7421 https://doi.org/10.7717/peerj.7421
The impact of artificial intelligence in medicine on the future role of the physician
The practice of medicine is changing with the development of new Artificial Intelligence (AI) methods of machine learning. Coupled with rapid improvements in computer processing, these AI-based systems are already improving the accuracy and efficiency of diagnosis and treatment across various specializations. The increasing focus of AI in radiology has led to some experts suggesting that someday AI may even replace radiologists. These suggestions raise the question of whether AI-based systems will eventually replace physicians in some specializations or will augment the role of physicians without actually replacing them. To assess the impact on physicians this research seeks to better understand this technology and how it is transforming medicine. To that end this paper researches the role of AI-based systems in performing medical work in specializations including radiology, pathology, ophthalmology, and cardiology. It concludes that AI-based systems will augment physicians and are unlikely to replace the traditional physician–patient relationship.
Ahuja (2019) The impact of artificial intelligence in medicine on the future role of the physician. PeerJ 7:e7702 https://doi.org/10.7717/peerj.7702
The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma
Background Esophageal squamous cell carcinoma (ESCC) is a subtype of esophageal cancer with high incidence and mortality. Due to the poor 5-year survival rates of patients with ESCC, exploring novel diagnostic markers for early ESCC is emergent. Collagen, the abundant constituent of extracellular matrix, plays a critical role in tumor growth and epithelial-mesenchymal transition. However, the clinical significance of collagen genes in ESCC has been rarely studied. In this work, we systematically analyzed the gene expression of whole collagen family in ESCC, aiming to search for ideal biomarkers. Methods Clinical data and gene expression profiles of ESCC patients were collected from The Cancer Genome Atlas and the gene expression omnibus databases. Bioinformatics methods, including differential expression analysis, survival analysis, gene sets enrichment analysis (GSEA) and co-expression network analysis, were performed to investigate the correlation between the expression patterns of 44 collagen family genes and the development of ESCC. Results A total of 22 genes of collagen family were identified as differentially expressed genes in both the two datasets. Among them, COL1A1, COL10A1 and COL11A1 were particularly up-regulated in ESCC tissues compared to normal controls, while COL4A4, COL6A5 and COL14A1 were notably down-regulated. Besides, patients with low COL6A5 expression or high COL18A1 expression showed poor survival. In addition, a 7-gene prediction model was established based on collagen gene expression to predict patient survival, which had better predictive accuracy than the tumor-node-metastasis staging based model. Finally, GSEA results suggested that collagen genes might be tightly associated with PI3K/Akt/mTOR pathway, p53 pathway, apoptosis, cell cycle, etc. Conclusion Several collagen genes could be potential diagnostic and prognostic biomarkers for ESCC. Moreover, a novel 7-gene prediction model is probably useful for predicting survival outcomes of ESCC patients. These findings may facilitate early detection of ESCC and help improves prognosis of the patients.
Li et al. (2019) The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma. PeerJ 7:e7705 https://doi.org/10.7717/peerj.7705
Multiplexed ISSR genotyping by sequencing distinguishes two precious coral species (Anthozoa: Octocorallia: Coralliidae) that share a mitochondrial haplotype
Background Precious corals known as coralliid corals (Anthozoa: Octocorallia) play an important role in increasing the biodiversity of the deep sea. Currently, these corals are highly threatened because of overfishing that has been brought on by an increased demand and elevated prices for them.The deep sea precious corals Pleurocorallium elatius and P. konojoi are distributed in Japanese waters and have distinct morphological features: (1) the terminal branches of the colony form of P. elatius are very fine, while those of P. konojoi are blunt and rounded, (2) the autozooids of P. elatius are arranged in approximately four rows, while those of P. konojoi are clustered in groups. However, previous genetic analysis using mtDNA and nuclear DNA did not indicate monophyly. Therefore, it is important to clarify their species status to allow for their conservation. Methodology We collected a total of 87 samples (60 of Corallium japonicum and 27 of P. konojoi) from around the Ryukyu Islands and Shikoku Island, which are geographically separated by approximately 1,300 km. We used a multiplexed inter-simple sequence repeat (ISSR) genotyping by sequencing (MIG-seq) and obtained 223 SNPs with which to perform STRUCTURE analysis and principle coordinate analysis (PCoA). In addition, two relatively polymorphic mtDNA regions were sequenced and compared. Results P. elatius and P. konojoi share a same mtDNA haplotype, which has been previously reported. However, MIG-seq analysis clearly distinguished the two species based on PCoA and STRUCTURE analysis, including 5% of species-specific fixed SNPs. Conclusion This study indicated that P. elatius and P. konojoi are different species and therefore both species should be conserved separately. Our findings highlight the importance of the conservation of these two species, especially P. elatius, whose population has been dramatically depleted over the last 100 years. The study also demonstrated the effectiveness and robustness of MIG-seq for defining closely related octocoral species that were otherwise indistinguishable using traditional genetic markers (mtDNA and EF).
Takata et al. (2019) Multiplexed ISSR genotyping by sequencing distinguishes two precious coral species (Anthozoa: Octocorallia: Coralliidae) that share a mitochondrial haplotype. PeerJ 7:e7769 https://doi.org/10.7717/peerj.7769