title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=1005 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Identification and characterization of critical genes associated with tamoxifen resistance in breast cancer link: https://peerj.com/articles/10468 last-modified: 2020-12-04 description: BackgroundTamoxifen resistance in breast cancer is an unsolved problem in clinical practice. The aim of this study was to determine the potential mechanisms of tamoxifen resistance through bioinformatics analysis.MethodsGene expression profiles of tamoxifen-resistant MCF-7/TR and MCF-7 cells were acquired from the Gene Expression Omnibus dataset GSE26459, and differentially expressed genes (DEGs) were detected with R software. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using Database for Annotation, Visualization and Integrated Discovery. A protein–protein interaction (PPI) network was generated, and we analyzed hub genes in the network with the Search Tool for the Retrieval of Interacting Genes database. Finally, we used siRNAs to silence the target genes and conducted the MTS assay.ResultsWe identified 865 DEGs, 399 of which were upregulated. GO analysis indicated that most genes are related to telomere organization, extracellular exosomes, and binding-related items for protein heterodimerization. PPI network construction revealed that the top 10 hub genes—ACLY, HSPD1, PFAS, GART, TXN, HSPH1, HSPE1, IRAS, TRAP1, and ATIC—might be associated with tamoxifen resistance. Consistently, RT-qPCR analysis indicated that the expression of these 10 genes was increased in MCF-7/TR cells comparing with MCF-7 cells. Four hub genes (TXN, HSPD1, HSPH1 and ATIC) were related to overall survival in patients who accepted tamoxifen. In addition, knockdown of HSPH1 by siRNA may lead to reduced growth of MCF-7/TR cell with a trend close to significance (P = 0.07), indicating that upregulation of HSPH1 may play a role in tamoxifen resistance.ConclusionThis study revealed a number of critical hub genes that might serve as therapeutic targets in breast cancer resistant to tamoxifen and provided potential directions for uncovering the mechanisms of tamoxifen resistance. creator: Kai Zhang creator: Kuikui Jiang creator: Ruoxi Hong creator: Fei Xu creator: Wen Xia creator: Ge Qin creator: Kaping Lee creator: Qiufan Zheng creator: Qianyi Lu creator: Qinglian Zhai creator: Shusen Wang uri: https://doi.org/10.7717/peerj.10468 license: https://creativecommons.org/licenses/by-nc/4.0 rights: © 2020 Zhang et al. title: Patterns of telomere length with age in African mole-rats: New insights from quantitative fluorescence in situ hybridisation (qFISH) link: https://peerj.com/articles/10498 last-modified: 2020-12-04 description: Naked mole-rats Heterocephalus glaber (NMRs) are the longest-lived rodent and also resist the normal signs of senescence. In a number of species, cellular ageing has been correlated with a reduction in telomere length, yet relatively little is known about telomeres and their age-related dynamics in NMRs and other African mole-rats. Here, we apply fluorescence in situ hybridisation (FISH) to quantify telomeric repeat sequences in the NMR, the Damaraland mole-rat, Fukomys damarensis (DMR) and the Mahali mole-rat, Cryptomys hottentotus mahali (MMR). Both terminal and non-terminal telomeric sequences were identified in chromosomes of the NMR and DMR, whilst the MMR displayed only terminal telomeric repeats. Measurements of tooth wear and eruption patterns in wild caught DMRs and MMRs, and known ages in captive bred NMRs, were used to place individuals into relative age classes and compared with a quantitative measure of telomeric fluorescence (as a proxy for telomere size). While NMRs and MMRs failed to show an age-related decline in telomeric fluorescence, the DMR had a significant decrease in fluorescence with age, suggesting a decrease in telomere size in older animals. Our results suggest that among African mole-rats there is variation between species with respect to the role of telomere shortening in ageing, and the replicative theory of cellular senescence. creator: Stephanie R.L. Leonida creator: Nigel C. Bennett creator: Andrew R. Leitch creator: Chris G. Faulkes uri: https://doi.org/10.7717/peerj.10498 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Leonida et al. title: Comprehensive analysis of circRNA expression profiles and circRNA-associated competing endogenous RNA networks in IgA nephropathy link: https://peerj.com/articles/10395 last-modified: 2020-12-03 description: BackgroundImmunoglobulin A nephropathy (IgAN) is immune-mediated primary glomerulonephritis, which is the most common reason leading to renal failure worldwide. The exact pathogenesis of IgAN is not well defined. Accumulating evidence indicates that circular RNAs (circRNAs) play crucial roles in the immune disease by involving in the competing endogenous RNA (ceRNA) network mechanism. At present, the studies of the circRNA profiles and circRNA-associated ceRNA networks in the IgAN are still scarce. This study aimed to elucidate the potential roles of circRNA-associated ceRNA networks of peripheral blood mononuclear cells (PBMCs) in IgAN patientsMethodCircRNA sequencing was used to identify the differential expressed circRNAs (DEcircRNAs) of PBMCs in IgAN and healthy controls; limma packages from data sets GSE25590 and GSE73953 in the Gene Expression Omnibus (GEO) database, were used to identify differentially expressed micro RNAs (miRNAs) and message RNAs (mRNAs). A circRNA-miRNA-mRNA ceRNA network was constructed to further investigate the mechanisms of IgAN. Then, GO analysis and KEGG enrichment analyses were used to annotate the genes involved in the circRNA-associated ceRNA network. Further, Protein-protein interaction (PPI) networks were established to screen potential hub genes, by using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Last, a quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify the hub genes in the ceRNA network.ResultA total of 145 circRNAs, 22 miRNAs, and 1,117 mRNAs were differentially expressed in IgAN compared with controls (P < 0.05). A ceRNA network was constructed which contained 16 DEcircRNAs, 72 differential expressed mRNAs (DEmRNAs) and 11 differential expressed miRNAs (DEmiRNAs). KEGG pathway enrichment analysis illustrated the underlying biological functions of the ceRNA-associated genes, such as Nitrogen compound metabolic process, COPII-coated ER to Golgi transport vesicle, CAMP response element protein binding process (P < 0.01); meanwhile, Hepatitis B, GnRH signaling, and Prion disease were the most significant enrichment GO terms (P < 0.01). PPI network based on STRING analysis identified 4 potentially hub genes. Finally, Ankyrin repeat and SOCS box containing 16 (ASB16), SEC24 homolog C, COPII coat complex component (SEC24C) were confirmed by qRT-PCR (P < 0.05) and were identified as the hub genes of the ceRNA network in our study.ConclusionOur study identified a novel circRNA-mediated ceRNA regulatory network mechanisms in the pathogenesis of IgAN. creator: Haiyang Liu creator: Di Liu creator: Yexin Liu creator: Ming Xia creator: Yan Li creator: Mei Li creator: Hong Liu uri: https://doi.org/10.7717/peerj.10395 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Liu et al. title: Effects of monofilament nylon versus braided multifilament nylon gangions on catch rates of Greenland shark (Somniosus microcephalus) in bottom set longlines link: https://peerj.com/articles/10407 last-modified: 2020-12-03 description: The Greenland shark (Somniosus microcephalus) is the main bycatch species in established and exploratory inshore longline fisheries for Greenland halibut (Reinhardtius hippoglossoides) on the east coast of Baffin Island, Canada. Bycatch and entanglement in longline gear has at times been substantial and post-release survival is questionable when Greenland sharks are released with trailing fishing gear. This study investigated the effect of the type of fishing line used in the gangion and gangion breaking strength on catch rates of Greenland shark and Greenland halibut in bottom set longlines. Circle (size 14/0, 0° offset) hooks were used throughout the study. Behavior of captured sharks, mode of capture (i.e., jaw hook and/or entanglement), level of entanglement in longline gear, time required to disentangle sharks and biological information (sex, body length and health status) were recorded. Catch rates of Greenland shark were independent of monofilament nylon gangion breaking strength and monofilament gangions captured significantly fewer Greenland sharks than the traditional braided multifilament nylon gangion. Catch rates and body size of Greenland halibut did not differ significantly between gangion treatments. Although most (84%) of the Greenland sharks were hooked by the jaw, a high percentage (76%) were entangled in the mainline. The mean length of mainline entangled around the body and/or caudal peduncle and caudal fin was 28.7 m. Greenland sharks exhibited cannibalistic behavior with 15% of captured sharks cannibalized. All remaining sharks were alive and survived the disentanglement process which can be attributed to their lethargic behavior and lack of resistance when hauled to the surface. Thus, as a conservation measure fishers should be encouraged to remove trailing fishing gear prior to release. Our results are used to demonstrate benefits to the fishing industry with regard to an overall reduction in the period of time to disentangle sharks and damage to fishing gear by switching from braided multifilament to monofilament gangions in Greenland halibut longline fisheries. creator: Scott M. Grant creator: Jenna G. Munden creator: Kevin J. Hedges uri: https://doi.org/10.7717/peerj.10407 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Grant et al. title: Bacterial exposure leads to variable mortality but not a measurable increase in surface antimicrobials across ant species link: https://peerj.com/articles/10412 last-modified: 2020-12-03 description: Social insects have co-existed with microbial species for millions of years and have evolved a diversity of collective defenses, including the use of antimicrobials. While many studies have revealed strategies that ants use against microbial entomopathogens, and several have shown ant-produced compounds inhibit environmental bacterial growth, few studies have tested whether exposure to environmental bacteria represents a health threat to ants. We compare four ant species’ responses to exposure to Escherichia coli and Staphylococcus epidermidis bacteria in order to broaden our understanding of microbial health-threats to ants and their ability to defend against them. In a first experiment, we measure worker mortality of Solenopsis invicta, Brachymyrmex chinensis, Aphaenogaster rudis, and Dorymyrmex bureni in response to exposure to E. coli and S. epidermidis. We found that exposure to E. coli was lethal for S. invicta and D. bureni, while all other effects of exposure were not different from experimental controls. In a second experiment, we compared the antimicrobial ability of surface extracts from bacteria-exposed and non-exposed S. invicta and B. chinensis worker ants, to see if exposure to E. coli or S. epidermidis led to an increase in antimicrobial compounds. We found no difference in the inhibitory effects from either treatment group in either species. Our results demonstrate the susceptibility to bacteria is varied across ant species. This variation may correlate with an ant species’ use of surface antimicrobials, as we found significant mortality effects in species which also were producing antimicrobials. Further exploration of a wide range of both bacteria and ant species is likely to reveal unique and nuanced antimicrobial strategies and deepen our understanding of how ant societies respond to microbial health threats. creator: Omar Halawani creator: Robert R. Dunn creator: Amy M. Grunden creator: Adrian A. Smith uri: https://doi.org/10.7717/peerj.10412 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Halawani et al. title: Moderately low nitrogen application mitigate the negative effects of salt stress on annual ryegrass seedlings link: https://peerj.com/articles/10427 last-modified: 2020-12-03 description: Appropriate application of nitrogen (N) can alleviate the salt stress-induced damage on plants. This study explores the changes of nitrogen requirement in feeding annual ryegrass seedlings under mild salt concentrations (50 mM, 100 mM) plus its underlying mitigation mechanism. Results showed that low salt concentration decreased N requirement as observed from the increment in plant height and biomass at a relative low N level (2.0 mM not 5.0 mM). Under salt treatment, especially at 50 mM NaCl, the OJIP (Chl a fluorescence induction transient) curve and a series of performance indexes (PIABS, RC/CS0, ET0/CS0, ϕE0, ϕ0) peaked whereas DI0/RC, Vj and M0 were the lowest under moderately low N level (2.0 mM). In addition, under salt stress, moderately low N application could maintain the expression of NR (nitrate reductase) and GS (glutamine synthetase) encoding genes at a relatively stable level but had no effect on the expression of detected NRT (nitrate transporter) gene. The seedlings cultured at 2.0 mM N also exhibited the highest activity of CAT and POD antioxidant enzymes and the lowest MDA content and EL under relative low level of salt treatment. These results indicated that mild salt treatment of annual ryegrass seedlings might reduce N requirement while moderately low N application could promote their growth via regulating photosynthesis, alleviating ROS-induced (reactive oxygen species) damage and maintenance of N metabolism. These results also can provide useful reference for nitrogen application in moderation rather than in excess on annual ryegrass in mild or medium salinity areas through understanding the underlying response mechanisms. creator: An Shao creator: Zhichao Sun creator: Shugao Fan creator: Xiao Xu creator: Wei Wang creator: Erick Amombo creator: Yanling Yin creator: Xiaoning Li creator: Guangyang Wang creator: Hongli Wang creator: Jinmin Fu uri: https://doi.org/10.7717/peerj.10427 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Shao et al. title: Analysis of 44 Vibrio anguillarum genomes reveals high genetic diversity link: https://peerj.com/articles/10451 last-modified: 2020-12-03 description: Vibriosis, a hemorrhagic septicemic disease caused by the bacterium Vibrio anguillarum, is an important bacterial infection in Danish sea-reared rainbow trout. Despite of vaccination, outbreaks still occur, likely because the vaccine is based on V. anguillarum strains from abroad/other hosts than rainbow trout. Information about the genetic diversity of V. anguillarum specifically in Danish rainbow trout, is required to investigate this claim. Consequently, the aim of the present investigation was to sequence and to characterize a collection of 44 V. anguillarum strains obtained primarily from vibriosis outbreaks in Danish rainbow trout. The strains were sequenced, de novo assembled, and the genomes examined for the presence of plasmids, virulence, and acquired antibiotic resistance genes. To investigate the phylogeny, single nucleotide polymorphisms were identified, and the pan-genome was calculated. All strains carried tet(34) encoding tetracycline resistance, and 36 strains also contained qnrVC6 for increased fluoroquinolone/quinolone resistance. But interestingly, all strains were phenotypic sensitive to both oxytetracycline and oxolinic acid. Almost all serotype O1 strains contained a pJM1-like plasmid and nine serotype O2A strains carried the plasmid p15. The distribution of virulence genes was rather similar across the strains, although evident variance among serotypes was observed. Most significant, almost all serotype O2 and O3 strains, as well as the serotype O1 strain without a pJM1-like plasmid, carried genes encoding piscibactin biosynthesis. Hence supporting the hypothesis, that piscibactin plays a crucial role in virulence for pathogenic strains lacking the anguibactin system. The phylogenetic analysis and pan-genome calculations revealed great diversity within V. anguillarum. Serotype O1 strains were in general very similar, whereas considerable variation was found among serotype O2A strains. The great diversity within the V. anguillarum serotype O2A genomes is most likely the reason why vaccines provide good protection from some strains, but not from others. Hopefully, the new genomic data and knowledge provided in this study might help develop an optimized vaccine against V. anguillarum in the future to reduce the use of antibiotics, minimize economic losses and improve the welfare of the fish. creator: Mie Johanne Hansen creator: Egle Kudirkiene creator: Inger Dalsgaard uri: https://doi.org/10.7717/peerj.10451 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Hansen et al. title: ARID1A alterations and their clinical significance in cholangiocarcinoma link: https://peerj.com/articles/10464 last-modified: 2020-12-03 description: BackgroundARID1A is a member of the SWI/SNF chromatin remodeling complex. It functions as a tumor suppressor and several therapeutic targets in ARID1A-mutated cancers are currently under development, including EZH2. A synthetic lethal relationship between ARID1A and EZH2 has been revealed in several tumor entities. Although genomic alterations of ARID1A have been described in various cancers, no study has examined correlations between ARID1A gene mutation and protein expression with clinicopathologic parameters and prognosis, particularly in liver fluke-related cholangiocarcinoma (Ov-CCA). Here, we investigated the clinical significance of ARID1A mutations and protein expression in CCA tissues and determined whether there is a correlation with EZH2 protein expression.MethodsWe evaluated ARID1A and EZH2 immunoreactivity using immunohistochemistry in 98 Ov-CCA with a wide range of clinicopathological features. Somatic mutations of ARID1A were analyzed using the ICGC sequencing data in 489 of Ov and non Ov-CCA and assessed prognostic values.ResultsWhile detecting a loss or reduction of ARID1A expression in 54 cases (55%) in Ov-CCA, ARID1A expression was associated with ARID1A mutations (p < 0.001, adjusted p-value < 0.001). We observed that 12 of 13 tumors (92%) with loss of ARID1A expression had truncating mutations. There were nine of 13 tumors (69%) with loss of ARID1A expression and 25 of 41 tumors (61%) with low ARID1A expression exhibited distant metastasis (p = 0.028, adjusted p-value = 0.168). ARID1A was predominantly mutated in Ov-CCA compared to non Ov-CCA (24% and 14% in Ov-CCA and non Ov-CCA, respectively, p = 0.027). There were 36 of 72 (50%) and 52 of 79 (66%) tumors with ARID1A mutation showed tumor stage IV and T3/T4, respectively. The significant mutual exclusivity and co-occurrence between ARID1A and TP53/KRAS mutations were not found in ICGC cohort. In addition, high EZH2 expression, a potential synthetic lethal target in ARID1A-mutated tumors, was detected in 49 of 98 Ov-CCA (50%). Importantly, neither ARID1A expression nor ARID1A mutations correlated with EZH2 expression in this cohort.ConclusionWe found that ARID1A inactivation, by somatic mutation or by loss of expression, frequently occurs in Ov-CCA. Reduction of ARID1A expression and/or somatic mutation was shown to be associated with CCA progression. These findings suggest that ARID1A may serve as a prognostic biomarker, and thus may be a promising therapeutic target for CCA. creator: Achira Namjan creator: Anchalee Techasen creator: Watcharin Loilome creator: Prakasit Sa-ngaimwibool creator: Apinya Jusakul uri: https://doi.org/10.7717/peerj.10464 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Namjan et al. title: Foliar mycoendophytome of an endemic plant of the Mediterranean biome (Myrtus communis) reveals the dominance of basidiomycete woody saprotrophs link: https://peerj.com/articles/10487 last-modified: 2020-12-03 description: The true myrtle, Myrtus communis, is a small perennial evergreen tree that occurs in Europe, Africa, and Asia with a circum-Mediterranean geographic distribution. Unfortunately, the Mediterranean Forests, where M. communis occurs, are critically endangered and are currently restricted to small fragmented areas in protected conservation units. In the present work, we performed, for the first time, a metabarcoding study on the spatial variation of fungal community structure in the foliar endophytome of this endemic plant of the Mediterranean biome, using bipartite network analysis as a model. The local bipartite network of Myrtus communis individuals and their foliar endophytic fungi is very low connected, with low nestedness, and moderately high specialization and modularity. Similar network patterns were also retrieved in both culture-dependent and amplicon metagenomics of foliar endophytes in distinct arboreal hosts in varied biomes. Furthermore, the majority of putative fungal endophytes species were basidiomycete woody saprotrophs of the orders Polyporales, Agaricales, and Hymenochaetales. Altogether, these findings suggest a possible adaptation of these wood-decaying fungi to cope with moisture limitation and spatial scarcity of their primary substrate (dead wood), which are totally consistent with the predictions of the viaphytism hypothesis that wood-decomposing fungi inhabit the internal leaf tissue of forest trees in order to enhance dispersal to substrates on the forest floor, by using leaves as vectors and as refugia, during periods of environmental stress. creator: Aline Bruna M. Vaz creator: Paula Luize C. Fonseca creator: Felipe F. Silva creator: Gabriel Quintanilha-Peixoto creator: Inmaculada Sampedro creator: Jose A. Siles creator: Anderson Carmo creator: Rodrigo B. Kato creator: Vasco Azevedo creator: Fernanda Badotti creator: Juan A. Ocampo creator: Carlos A. Rosa creator: Aristóteles Góes-Neto uri: https://doi.org/10.7717/peerj.10487 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Vaz et al. title: Identification of a six-gene metabolic signature predicting overall survival for patients with lung adenocarcinoma link: https://peerj.com/articles/10320 last-modified: 2020-12-02 description: BackgroundLung cancer is the leading cause of cancer-related deaths worldwide. Lung adenocarcinoma (LUAD) is one of the main subtypes of lung cancer. Hundreds of metabolic genes are altered consistently in LUAD; however, their prognostic role remains to be explored. This study aimed to establish a molecular signature that can predict the prognosis in patients with LUAD based on metabolic gene expression.MethodsThe transcriptome expression profiles and corresponding clinical information of LUAD were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. The differentially expressed genes (DEGs) between LUAD and paired non-tumor samples were identified by the Wilcoxon rank sum test. Univariate Cox regression analysis and the lasso Cox regression model were used to construct the best-prognosis molecular signature. A nomogram was established comprising the prognostic model for predicting overall survival. To validate the prognostic ability of the molecular signature and the nomogram, the Kaplan–Meier survival analysis, Cox proportional hazards model, and receiver operating characteristic analysis were used.ResultsThe six-gene molecular signature (PFKP, PKM, TPI1, LDHA, PTGES, and TYMS) from the DEGs was constructed to predict the prognosis. The molecular signature demonstrated a robust independent prognostic ability in the training and validation sets. The nomogram including the prognostic model had a greater predictive accuracy than previous systems. Furthermore, a gene set enrichment analysis revealed several significantly enriched metabolic pathways, which suggests a correlation of the molecular signature with metabolic systems and may help explain the underlying mechanisms.ConclusionsOur study identified a novel six-gene metabolic signature for LUAD prognosis prediction. The molecular signature could reflect the dysregulated metabolic microenvironment, provide potential biomarkers for predicting prognosis, and indicate potential novel metabolic molecular-targeted therapies. creator: Yubo Cao creator: Xiaomei Lu creator: Yue Li creator: Jia Fu creator: Hongyuan Li creator: Xiulin Li creator: Ziyou Chang creator: Sa Liu uri: https://doi.org/10.7717/peerj.10320 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Cao et al.