title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=828 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Significant correlation between HSPA4 and prognosis and immune regulation in hepatocellular carcinoma link: https://peerj.com/articles/12315 last-modified: 2021-10-26 description: BackgroundHepatocellular carcinoma (HCC) is an inflammation-associated tumor involved in immune tolerance and evasion in the immune microenvironment. Heat shock proteins (HSPs) are involved in the occurrence, progression, and immune regulation of tumors. Therefore, HSPs have been considered potential therapeutic targets. Here, we aimed to elucidate the value of HSP family A (Hsp70) member 4 (HSPA4) in the diagnosis and predicting prognosis of HCC, and its relationship with immune cell infiltration, immune cell biomarkers, and immune checkpoints. Gene mutation, DNA methylation, and the pathway involved in HCC were also analyzed.MethodsThe gene expression omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to compare HSPA4 expression, and the results were confirmed by immunohistochemical staining of clinical samples. R package was used to analyze the correlation between HSPA4 and cancer stage, and to establish receiver operating characteristic (ROC) curve of diagnosis, time-dependent survival ROC curve, and a nomogram model. cBioPortal and MethSurv were used to identify genetic alterations and DNA methylation, and their effect on prognosis. The Tumor Immune Estimation Resource (TIMER) was used to analyze immune cell infiltration, immune cell biomarkers, and immune checkpoints. The STRING database was used to analyze protein–protein interaction network information. Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the functions of HSPA4 and its functional partner genes.ResultsOverexpression of HSPA4 was identified in 25 cancers. Overexpression of HSPA4 considerably correlated with cancer stage and alpha-fetoprotein (AFP) level in HCC. Patients with higher HSPA4 expression showed poorer prognosis. HSPA4 expression can accurately identify tumor from normal tissue (AUC = 0.957). The area under 1-, 3-, and 5-year survival ROCs were above 0.6. The HSPA4 genetic alteration rate was 1.3%. Among the 14 DNA methylation CpG sites, seven were related to the prognosis of HCC. HSPA4 was positively related to immune cell infiltration and immune checkpoints (PD-1 and CTLA-4) in HCC. The KEGG pathway enrichment analysis revealed HSPA4 enrichment in antigen processing and presentation together with HSPA8 and HSP90AA1. We verified the value of HSPA4 in the diagnosis and predicting prognosis of HCC. HSPA4 may not only participate in the occurrence and progression but also the immune regulation of HCC. Therefore, HSPA4 can be a potential diagnostic and prognostic biomarker and a therapeutic target for HCC. creator: Bing-Bing Shang creator: Jun Chen creator: Zhi-Guo Wang creator: Hui Liu uri: https://doi.org/10.7717/peerj.12315 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Shang et al. title: Removal or component reversal of local geomagnetic field affects foraging orientation preference in migratory insect brown planthopper Nilaparvata lugens link: https://peerj.com/articles/12351 last-modified: 2021-10-26 description: BackgroundMigratory brown planthopper Nilaparvata lugens (N. lugens) annually migrates to Northeast Asia in spring and returns to Southeast Asia in autumn. However, mechanisms for orientation and navigation during their flight remain largely unknown. The geomagnetic field (GMF) is an important source of directional information for animals (including N. lugens), yet the magnetic compass involved has not been fully identified.MethodsHere we assessed the influences of GMF on the foraging orientation preference of N. lugens by removing or component reversal of local GMF. At the same time, we examined the role of iron-sulfur cluster assembly1 (IscA1), a putative component of magnetoreceptor, in the foraging orientation preference of N. lugens under the controlled magnetic fields by RNA silencing (RNAi).ResultsWe found that the near-zero magnetic field (NZMF) or vertical reversal of GMF could lead to N. lugens losing the foraging orientation preference, suggesting that a normal level of GMF, in the way of either intensity or inclination, was essential for the foraging orientation of N. lugens. Moreover, the gene knockdown of IscA1, also affected the foraging orientation preference of N. lugens, pointing out a potential role of IscA1 in the insects’ sensing of variation in the GMF.DiscussionThese results suggested a foraging orientation preference is associated with the GMF and revealed new insights into the relationship between the IscA1 and magnetosensitivity mechanism in N. lugens. creator: Yingchao Zhang creator: Weidong Pan uri: https://doi.org/10.7717/peerj.12351 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Zhang and Pan title: Identification of hub genes and transcription factor-miRNA-mRNA pathways in mice and human renal ischemia-reperfusion injury link: https://peerj.com/articles/12375 last-modified: 2021-10-26 description: BackgroundRenal ischemia-reperfusion injury (IRI) is a disease with high incidence rate in kidney related surgery. Micro RNA (miRNA) and transcription factors (TFs) are widely involved in the process of renal IRI through regulation of their target genes. However, the regulatory relationships and functional roles of TFs, miRNAs and mRNAs in the progression of renal IRI are insufficiently understood. The present study aimed to clarify the underlying mechanism of regulatory relationships in renal IRI.MethodsSix gene expression profiles were downloaded from Gene Expression Omnibus (GEO). Differently expressed genes (DEGs) and differently expressed miRNAs (DEMs) were identified through RRA integrated analysis of mRNA datasets (GSE39548, GSE87025, GSE52004, GSE71647, and GSE131288) and miRNA datasets (GSE29495). miRDB and TransmiR v2.0 database were applied to predict target genes of miRNA and TFs, respectively. DEGs were applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, followed with construction of protein-protein interaction (PPI) network. Then, the TF-miRNA-mRNA network was constructed. Correlation coefficient and ROC analysis were used to verify regulatory relationship between genes and their diagnostic value in GSE52004. Furthermore, in independent mouse RNA-seq datasets GSE98622, human RNA-seq GSE134386 and in vitro, the expression of hub genes and genes from the network were observed and correlation coefficient and ROC analysis were validated.ResultsA total of 21 DEMs and 187 DEGs were identified in renal IRI group compared to control group. The results of PPI analysis showed 15 hub genes. The TF-miRNA-mRNA regulatory network was constructed and several important pathways were identified and further verified, including Junb-miR-223-Ranbp3l, Cebpb-miR-223-Ranbp3l, Cebpb-miR-21-Ranbp3l and Cebpb-miR-181b-Bsnd. Four regulatory loops were identified, including Fosl2-miR-155, Fosl2-miR-146a, Cebpb-miR-155 and Mafk-miR-25. The hub genes and genes in the network showed good diagnostic value in mice and human.ConclusionsIn this study, we found 15 hub genes and several TF-miRNA-mRNA pathways, which are helpful for understanding the molecular and regulatory mechanisms in renal IRI. Junb-miR-223-Ranbp3l, Cebpb-miR-223-Ranbp3l, Cebpb-miR-21-Ranbp3l and Cebpb-miR-181b-Bsnd were the most important pathways, while Spp1, Fos, Timp1, Tnc, Fosl2 and Junb were the most important hub genes. Fosl2-miR-155, Fosl2-miR-146a, Cebpb-miR-155 and Mafk-miR-25 might be the negative feedback loops in renal IRI. creator: Peng Ke creator: Lin Qian creator: Yi Zhou creator: Liu Feng creator: Zhentao Zhang creator: Chengjie Zheng creator: Mengnan Chen creator: Xinlei Huang creator: Xiaodan Wu uri: https://doi.org/10.7717/peerj.12375 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Ke et al. title: Identification of genes and gene expression associated with dispersal capacity in the mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae) link: https://peerj.com/articles/12382 last-modified: 2021-10-26 description: Dispersal flights by the mountain pine beetle have allowed range expansion and major damage to pine stands in western Canada. We asked what the genetic and transcriptional basis of mountain pine beetle dispersal capacity is. Using flight mills, RNA-seq and a targeted association study, we compared strong-flying, weak-flying, and non-flying female beetles from the recently colonized northern end of their range. Nearly 3,000 genes were differentially expressed between strong and weak flying beetles, while weak fliers and nonfliers did not significantly differ. The differentially expressed genes were mainly associated with lipid metabolism, muscle maintenance, oxidative stress response, detoxification, endocrine function, and flight behavior. Three variant loci, two in the coding region of genes, were significantly associated with flight capacity but these genes had no known functional link to flight. Several differentially expressed gene systems may be important for sustained flight, while other systems are downregulated during dispersal and likely to conserve energy before host colonization. The candidate genes and SNPs identified here will inform further studies and management of mountain pine beetle, as well as contribute to understanding the mechanisms of insect dispersal flights. creator: Victor A. Shegelski creator: Maya L. Evenden creator: Dezene P.W. Huber creator: Felix A.H. Sperling uri: https://doi.org/10.7717/peerj.12382 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Shegelski et al. title: Assessment of antimycobacterial activities of pure compounds extracted from Thai medicinal plants against clarithromycin-resistant Mycobacterium abscessus link: https://peerj.com/articles/12391 last-modified: 2021-10-26 description: BackgroundInfection with Mycobacterium abscessus is usually chronic and is associated with clarithromycin resistance. Increasing drug resistance is a major public-health problem and has led to the search for new antimycobacterial agents. We evaluated the antimycobacterial activity, toxicity, and synergistic effects of several plant secondary metabolites against M. abscessus.MethodsTwenty-three compounds were evaluated for antimycobacterial activity against thirty M. abscessus clinical isolates by broth microdilution to determine their minimum inhibitory concentration (MIC) values. Toxicity was evaluated using red and white blood cells (RBCs and WBCs). The compounds were used in combination with clarithromycin to investigate the possibility of synergistic activity.ResultsFive out of twenty-three compounds (RL008, RL009, RL011, RL012 and RL013) exhibited interesting antimycobacterial activity against M. abscessus, with MIC values ranging from <1 to >128 μg/mL. These extracts did not induce hemolytic effect on RBCs and displayed low toxicity against WBCs. The five least-toxic compounds were tested for synergism with clarithromycin against seven isolates with inducible clarithromycin resistance and seven with acquired clarithromycin resistance. The best synergistic results against these isolates were observed for RL008 and RL009 (8/14 isolates; 57%).ConclusionsThis study demonstrated antimycobacterial and synergistic activities of pure compounds extracted from medicinal plants against clarithromycin-resistant M. abscessus. This synergistic action, together with clarithromycin, may be effective for treating infections and should be further studied for the development of novel antimicrobial agents. creator: Auttawit Sirichoat creator: Irin Kham-ngam creator: Orawee Kaewprasert creator: Pimjai Ananta creator: Awat Wisetsai creator: Ratsami Lekphrom creator: Kiatichai Faksri uri: https://doi.org/10.7717/peerj.12391 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Sirichoat et al. title: Blood cells and hematological parameters of the mountain dragon, Diploderma micangshanensis (Squamata: Lacertilia: Agamidae) link: https://peerj.com/articles/12397 last-modified: 2021-10-26 description: Hematological characteristics reflect the health status of animals and their physiological adaptation to the environment. However, few studies focused on the species of Diploderma. In this study, the blood cells and the hematological parameters of Diploderma micangshanensis, a species endemic to China, were examined based on 48 healthy adult (32 males and 16 females). The blood cells and hematological parameters of D. micangshanensis were similar to those of other lizard species. Although the values of erythrocyte morphometric characters and hematological parameters varied between males and females, the differences were only significant in the case of the hematocrit and erythrocyte size, which may allow for higher oxygen availability in males. Hemoglobin, mean corpuscular hemoglobin concentration, and mean corpuscle volume were strongly affected by the snout-vent length and/or body mass, which reflect the physiological adaptation to the oxygen requirement of different individuals. This is the first report of hematological data from a species of Diploderma, and the results will provide data for research on the adaptive evolution and health assessment in this species and other congeners. creator: Yinlong Bai creator: Guanglu Li creator: Shuaichao Lin creator: Jianli Xiong uri: https://doi.org/10.7717/peerj.12397 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Bai et al. title: Phylogeny of Crataegus (Rosaceae) based on 257 nuclear loci and chloroplast genomes: evaluating the impact of hybridization link: https://peerj.com/articles/12418 last-modified: 2021-10-26 description: BackgroundHawthorn species (Crataegus L.; Rosaceae tribe Maleae) form a well-defined clade comprising five subgeneric groups readily distinguished using either molecular or morphological data. While multiple subsidiary groups (taxonomic sections, series) are recognized within some subgenera, the number of and relationships among species in these groups are subject to disagreement. Gametophytic apomixis and polyploidy are prevalent in the genus, and disagreement concerns whether and how apomictic genotypes should be recognized taxonomically. Recent studies suggest that many polyploids arise from hybridization between members of different infrageneric groups.MethodsWe used target capture and high throughput sequencing to obtain nucleotide sequences for 257 nuclear loci and nearly complete chloroplast genomes from a sample of hawthorns representing all five currently recognized subgenera. Our sample is structured to include two examples of intersubgeneric hybrids and their putative diploid and tetraploid parents. We queried the alignment of nuclear loci directly for evidence of hybridization, and compared individual gene trees with each other, and with both the maximum likelihood plastome tree and the nuclear concatenated and multilocus coalescent-based trees. Tree comparisons provided a promising, if challenging (because of the number of comparisons involved) method for visualizing variation in tree topology. We found it useful to deploy comparisons based not only on tree-tree distances but also on a metric of tree-tree concordance that uses extrinsic information about the relatedness of the terminals in comparing tree topologies.ResultsWe obtained well-supported phylogenies from plastome sequences and from a minimum of 244 low copy-number nuclear loci. These are consistent with a previous morphology-based subgeneric classification of the genus. Despite the high heterogeneity of individual gene trees, we corroborate earlier evidence for the importance of hybridization in the evolution of Crataegus. Hybridization between subgenus Americanae and subgenus Sanguineae was documented for the origin of Sanguineae tetraploids, but not for a tetraploid Americanae species. This is also the first application of target capture probes designed with apple genome sequence. We successfully assembled 95% of 257 loci in Crataegus, indicating their potential utility across the genera of the apple tribe. creator: Aaron Liston creator: Kevin A. Weitemier creator: Lucas Letelier creator: János Podani creator: Yu Zong creator: Lang Liu creator: Timothy A. Dickinson uri: https://doi.org/10.7717/peerj.12418 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Liston et al. title: Modernising tactile acuity assessment; clinimetrics of semi-automated tests and effects of age, sex and anthropometry on performance link: https://peerj.com/articles/12192 last-modified: 2021-10-25 description: BackgroundReduced tactile acuity has been observed in several chronic pain conditions and has been proposed as a clinical indicator of somatosensory impairments related to the condition. As some interventions targeting these impairments have resulted in pain reduction, assessing tactile acuity may have significant clinical potential. While two-point discrimination threshold (TPDT) is a popular method of assessing tactile acuity, large measurement error has been observed (impeding responsiveness) and its validity has been questioned. The recently developed semi-automated ‘imprint Tactile Acuity Device’ (iTAD) may improve tactile acuity assessment, but clinimetric properties of its scores (accuracy score, response time and rate correct score) need further examination.AimsExperiment 1: To determine inter-rater reliability and measurement error of TPDT and iTAD assessments. Experiment 2: To determine internal consistencies and floor or ceiling effects of iTAD scores, and investigate effects of age, sex, and anthropometry on performance.MethodsExperiment 1: To assess inter-rater reliability (ICC(2,1)) and measurement error (coefficient of variation (CoV)), three assessors each performed TPDT and iTAD assessments at the neck in forty healthy participants. Experiment 2: To assess internal consistency (ICC(2,k)) and floor or ceiling effects (skewness z-scores), one hundred healthy participants performed the iTAD’s localisation and orientation tests. Balanced for sex, participants were equally divided over five age brackets (18–30, 31–40, 41–50, 51–60 and 61–70). Age, sex, body mass index (BMI) and neck surface area were assessed to examine their direct (using multiple linear regression analysis) and indirect (using sequential mediation analysis) relationship with iTAD scores.ResultsMean ICC(2,1) was moderate for TPDT (0.70) and moderate-to-good for the various iTAD scores (0.65–0.86). The CoV was 25.3% for TPDT and ranged from 6.1% to 16.5% for iTAD scores. Internal consistency was high for both iTAD accuracy scores (ICC(2,6) = 0.84; ICC(2,4) = 0.86). No overt floor or ceiling effects were detected (all skewness z-scores < 3.29). Accuracy scores were only directly related to age (decreasing with increasing age) and sex (higher for men).DiscussionAlthough reliability was similar, iTAD scores demonstrated less measurement error than TPDT indicating a potential for better responsiveness to treatment effects. Further, unlike previously reported for TPDT, iTAD scores appeared independent of anthropometry, which simplifies interpretation. Additionally, the iTAD assesses multiple aspects of tactile processing which may provide a more comprehensive evaluation of tactile acuity. Taken together, the iTAD shows promise in measuring tactile acuity, but patient studies are needed to verify clinical relevance. creator: Nick A. Olthof creator: Michel W. Coppieters creator: G Lorimer Moseley creator: Michele Sterling creator: Dylan J. Chippindall creator: Daniel S. Harvie uri: https://doi.org/10.7717/peerj.12192 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Olthof et al. title: Salinity effects on water potential and the normalized difference vegetation index in four species of a saline semi-arid ecosystem link: https://peerj.com/articles/12297 last-modified: 2021-10-25 description: This study was carried out during January 2020–December 2020 in a semi-desert ecosystem in southern Sonora, Mexico, to determine the annual and daily variations in water potential and the normalized difference vegetation index (NDVI) of Bursera fagaroides Engl., Monogr. Phan., Parkinsonia aculeata L., Sp. Pl.; Prosopis laevigata (Humb. & Bonpl. ex Willd.), and Atriplex canescens (Pursh) Nutt. Soil electrical conductivity, cation content, and physical characteristics were determined at two depths, and water potential (ψ) was measured in roots, stems, and leaves. The daily leaf ψ was measured every 15 days each month to determine the duration of stress (hours) and the stress intensity (SI). The electrical conductivity determinations classified the soil in the experimental area as strongly saline. A significant difference was noted in electrical conductivity between soil depths. The four studied species showed significant gradients of ψ in their organs. In this soil, all four species remained in a stressed condition for approximately 11 h per day. The mean SI was 27%, and B. fagaroides Engl., Monogr. Phan. showed the lowest value. The four species showed increased NDVI values during the rainy months, with P. laevigata (Humb. & Bonpl. ex Willd.) and Parkinsonia aculeata L., Sp. Pl. showing the highest values. The capacity for ψ decrease under saline conditions identified A. canescens (Pursh) Nutt., B. fagaroides Engl., Monogr. Phan. and P. aculeata L., Sp. Pl. as practical and feasible alternatives for establishment in saline soils in southern Sonora for purposes of soil recovery and reforestation. creator: Hebert Hernán Soto Gonzáles creator: Ofelda Peñuelas-Rubio creator: Leandris Argentel-Martínez creator: Aurelio Leyva Ponce creator: María Hermelinda Herrera Andrade creator: Mirza Hasanuzzaman creator: Jorge González Aguilera creator: Paulo Eduardo Teodoro uri: https://doi.org/10.7717/peerj.12297 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Soto Gonzáles et al. title: Comparative transcriptomic analysis provides insight into carpel petaloidy in lotus (Nelumbo nucifera) link: https://peerj.com/articles/12322 last-modified: 2021-10-25 description: Lotus (Nelumbo nucifera) is a highly recognized flower with high ornamental value. Flower color and flower morphology are two main factors for flower lotus breeding. Petaloidy is a universal phenomenon in lotus flowers. However, the genetic regulation of floral organ petaloidy in lotus remains elusive. In this study, the transcriptomic analysis was performed among three organs, including petal, carpel petaloidy, and carpel in lotus. A total of 1,568 DEGs related to carpel petaloidy were identified. Our study identified one floral homeotic gene encoded by the MADS-box transcription factor, AGAMOUS (AG) as the candidate gene for petaloid in lotus. Meanwhile, a predicted labile boundary in floral organs of N. nucifera was hypothesized. In summary, our results explored the candidate genes related to carpel petaloidy, setting a theoretical basis for the molecular regulation of petaloid phenotype. creator: Zhongyuan Lin creator: Dingding Cao creator: Rebecca Njeri Damaris creator: Pingfang Yang uri: https://doi.org/10.7717/peerj.12322 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Lin et al.