title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=1552 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Changes in DNA methylation assessed by genomic bisulfite sequencing suggest a role for DNA methylation in cotton fruiting branch development link: https://peerj.com/articles/4945 last-modified: 2018-06-14 description: Cotton plant architecture, including fruit branch formation and flowering pattern, influences plant light exploitation, cotton yield and planting cost. DNA methylation has been widely observed at different developmental stages in both plants and animals and is associated with regulation of gene expression, chromatin remodelling, genome protection and other functions. Here, we investigated the global epigenetic reprogramming during the development of fruiting branches and floral buds at three developmental stages: the seedling stage, the pre-squaring stage and the squaring stage. We first identified 22 cotton genes which potentially encode DNA methyltransferases and demethylases. Among them, the homologous genes of CMT, DRM2 and MET1 were upregulated at pre-squaring and squaring stages, suggesting that DNA methylation is involved in the development of floral buds and fruit branches. Although the global methylation at all of three developmental stages was not changed, the CHG-type methylation of non-expressed genes was higher than those of expressed genes. In addition, we found that the expression of the homologous genes of the key circadian rhythm regulators, including CRY, LHY and CO, was associated with changes of DNA methylation at three developmental stages. creator: Quan Sun creator: Jing Qiao creator: Sai Zhang creator: Shibin He creator: Yuzhen Shi creator: Youlu Yuan creator: Xiao Zhang creator: Yingfan Cai uri: https://doi.org/10.7717/peerj.4945 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2018 Sun et al. title: Establishment of a 12-gene expression signature to predict colon cancer prognosis link: https://peerj.com/articles/4942 last-modified: 2018-06-14 description: A robust and accurate gene expression signature is essential to assist oncologists to determine which subset of patients at similar Tumor-Lymph Node-Metastasis (TNM) stage has high recurrence risk and could benefit from adjuvant therapies. Here we applied a two-step supervised machine-learning method and established a 12-gene expression signature to precisely predict colon adenocarcinoma (COAD) prognosis by using COAD RNA-seq transcriptome data from The Cancer Genome Atlas (TCGA). The predictive performance of the 12-gene signature was validated with two independent gene expression microarray datasets: GSE39582 includes 566 COAD cases for the development of six molecular subtypes with distinct clinical, molecular and survival characteristics; GSE17538 is a dataset containing 232 colon cancer patients for the generation of a metastasis gene expression profile to predict recurrence and death in COAD patients. The signature could effectively separate the poor prognosis patients from good prognosis group (disease specific survival (DSS): Kaplan Meier (KM) Log Rank p = 0.0034; overall survival (OS): KM Log Rank p = 0.0336) in GSE17538. For patients with proficient mismatch repair system (pMMR) in GSE39582, the signature could also effectively distinguish high risk group from low risk group (OS: KM Log Rank p = 0.005; Relapse free survival (RFS): KM Log Rank p = 0.022). Interestingly, advanced stage patients were significantly enriched in high 12-gene score group (Fisher’s exact test p = 0.0003). After stage stratification, the signature could still distinguish poor prognosis patients in GSE17538 from good prognosis within stage II (Log Rank p = 0.01) and stage II & III (Log Rank p = 0.017) in the outcome of DFS. Within stage III or II/III pMMR patients treated with Adjuvant Chemotherapies (ACT) and patients with higher 12-gene score showed poorer prognosis (III, OS: KM Log Rank p = 0.046; III & II, OS: KM Log Rank p = 0.041). Among stage II/III pMMR patients with lower 12-gene scores in GSE39582, the subgroup receiving ACT showed significantly longer OS time compared with those who received no ACT (Log Rank p = 0.021), while there is no obvious difference between counterparts among patients with higher 12-gene scores (Log Rank p = 0.12). Besides COAD, our 12-gene signature is multifunctional in several other cancer types including kidney cancer, lung cancer, uveal and skin melanoma, brain cancer, and pancreatic cancer. Functional classification showed that seven of the twelve genes are involved in immune system function and regulation, so our 12-gene signature could potentially be used to guide decisions about adjuvant therapy for patients with stage II/III and pMMR COAD. creator: Dalong Sun creator: Jing Chen creator: Longzi Liu creator: Guangxi Zhao creator: Pingping Dong creator: Bingrui Wu creator: Jun Wang creator: Ling Dong uri: https://doi.org/10.7717/peerj.4942 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Sun et al. title: Crucial biological functions of CCL7 in cancer link: https://peerj.com/articles/4928 last-modified: 2018-06-14 description: Chemokine (C-C motif) ligand 7 (CCL7), a CC chemokine, is a chemotactic factor and attractant for various kinds of leukocytes, including monocytes and neutrophils. CCL7 is widely expressed in multiple cell types and can participate in anti-inflammatory responses through binding to its receptors to mediate the recruitment of immune cells. Abnormal CCL7 expression is associated with certain immune diseases. Furthermore, CCL7 plays a pivotal role in tumorigenesis. CCL7 promotes tumor progression by supporting the formation of the tumor microenvironment and facilitating tumor invasion and metastasis, although some studies have suggested that CCL7 has tumor suppressor effects. In this review, we summarize the currently available information regarding the influence of CCL7 on tumors. creator: Yangyang Liu creator: Yadi Cai creator: Li Liu creator: Yudong Wu creator: Xiangyang Xiong uri: https://doi.org/10.7717/peerj.4928 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2018 Liu et al. title: What killed Frame Lake? A precautionary tale for urban planners link: https://peerj.com/articles/4850 last-modified: 2018-06-14 description: Frame Lake, located within the city of Yellowknife, Northwest Territories, Canada, has been identified as requiring significant remediation due to its steadily declining water quality and inability to support fish by the 1970s. Former gold mining operations and urbanization around the lake have been suspected as probable causes for the decline in water quality. While these land-use activities are well documented, little information is available regarding their impact on the lake itself. For this reason, Arcellinida, a group of shelled protozoans known to be reliable bioindicators of land-use change, were used to develop a hydroecological history of the lake. The purpose of this study was to use Arcellinida to: (1) document the contamination history of the lake, particularly related to arsenic (As) associated with aerial deposition from mine roaster stacks; (2) track the progress of water quality deterioration in Frame Lake related to mining, urbanization and other activities; and (3) identify any evidence of natural remediation within the lake. Arcellinida assemblages were assessed at 1-cm intervals through the upper 30 cm of a freeze core obtained from Frame Lake. The assemblages were statistically compared to geochemical and loss-on-ignition results from the core to document the contamination and degradation of conditions in the lake. The chronology of limnological changes recorded in the lake sediments were derived from 210Pb, 14C dating and known stratigraphic events. The progress of urbanization near the lake was tracked using aerial photography. Using Spearman correlations, the five most significant environmental variables impacting Arcellinida distribution were identified as minerogenics, organics, As, iron and mercury (p < 0.05; n = 30). Based on CONISS and ANOSIM analysis, three Arcellinida assemblages are identified. These include the Baseline Limnological Conditions Assemblage (BLCA), ranging from 17–30 cm and deposited in the early Holocene >7,000 years before present; the As Contamination Assemblage (ACA), ranging from 7–16 cm, deposited after ∼1962 when sedimentation began in the lake again following a long hiatus that spanned to the early Holocene; and the Eutrophication Assemblage (EA), ranging from 1–6 cm, comprised of sediments deposited after 1990 following the cessation of As and other metal contaminations. The EA developed in response to nutrient-rich waters entering the lake derived from the urbanization of the lake catchment and a reduction in lake circulation associated with the development at the lake outlet of a major road, later replaced by a causeway with rarely open sluiceways. The eutrophic condition currently charactering the lake—as evidenced by a population explosion of eutrophication indicator taxa Cucurbitella tricuspis—likely led to a massive increase in macrophyte growth and winter fish-kills. This ecological shift ultimately led to a system dominated by Hirudinea (leeches) and cessation of the lake as a recreational area. creator: Melody J. Gavel creator: R. Timothy Patterson creator: Nawaf A. Nasser creator: Jennifer M. Galloway creator: Bruce W. Hanna creator: Peter A. Cott creator: Helen M. Roe creator: Hendrik Falck uri: https://doi.org/10.7717/peerj.4850 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Gavel et al. title: Population diversity and relatedness in Sugarbirds (Promeropidae: Promerops spp.) link: https://peerj.com/articles/5000 last-modified: 2018-06-13 description: Sugarbirds are a family of two socially-monogamous passerine species endemic to southern Africa. Cape and Gurney’s Sugarbird (Promerops cafer and P. gurneyi) differ in abundance, dispersion across their range and in the degree of sexual dimorphism in tail length, factors that affect breeding systems and potentially genetic diversity. According to recent data, P. gurneyi are in decline and revision of the species’ IUCN conservation status to a threatened category may be warranted. It is therefore necessary to understand genetic diversity and risk of inbreeding in this species. We used six polymorphic microsatellite markers and one mitochondrial gene (ND2) to compare genetic diversity in P. cafer from Helderberg Nature Reserve and P. gurneyi from Golden Gate Highlands National Park, sites at the core of each species distribution. We describe novel universal avian primers which amplify the entire ND2 coding sequence across a broad range of bird orders. We observed high mitochondrial and microsatellite diversity in both sugarbird populations, with no detectable inbreeding and large effective population sizes. creator: Evan S. Haworth creator: Michael J. Cunningham creator: Kathleen M. Calf Tjorve uri: https://doi.org/10.7717/peerj.5000 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Haworth et al. title: Epidemiology of Haemophilus parasuis isolates from pigs in China using serotyping, antimicrobial susceptibility, biofilm formation and ERIC-PCR genotyping link: https://peerj.com/articles/5040 last-modified: 2018-06-13 description: BackgroundHaemophilus parasuis is a commensal organism of the upper respiratory tract of healthy pigs and causes high morbidity and mortality in piglets. The aim of this study was to investigate the epidemiology of H. parasuis in China from 2014 to 2017.MethodsWe characterized 143 H. parasuis isolates by serotyping, antimicrobial susceptibility, biofilm formation and with enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) assays.ResultsSerotyping revealed serovar 5 as the most prevalent (26.6%) followed by serovars 4 (22.4%), 7 (9.1 %), 13 (6.3%), 12 (5.6 %), and non-typeable (8.4%). In a panel of 23 antimicrobials, the minimum inhibitory concentration 50% (MIC50) were in the range of 0.25–16 μg/mL and MIC90 were 2–>512 μg/mL. A total of 99 isolates of H. parasuis (69.2%) were able to form biofilms and 59.6% (59/99) performed weak biofilm-forming ability. ERIC-PCR revealed a very heterogeneous pattern with 87 clusters.DiscussionThese H. parasuis isolates showed a high serovar and genotypic lineage diversity, different abilities to form biofilms and a high degree of genetic diversity. Biofilm formation was related to antimicrobial susceptibility but there were no statistically significant associations between the antimicrobial susceptibility and either the serovars or the ERIC-PCR clusters. This study showed a high prevalence of high-MIC H. parasuis strains and suggests the need for a continuous surveillance of clinical isolates of H. parasuis. creator: Yongda Zhao creator: Qin Wang creator: Jie Li creator: Xiaohuan Lin creator: Xianhui Huang creator: Binghu Fang uri: https://doi.org/10.7717/peerj.5040 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2018 Zhao et al. title: Increased chronic kidney disease development and progression in diabetic patients after appendectomy: a population-based cohort study link: https://peerj.com/articles/5019 last-modified: 2018-06-13 description: BackgroundThe vermiform appendix serves as a “safe house” for maintaining normal gut bacteria and appendectomy may impair the intestinal microbiota. Appendectomy is expected to profoundly alter the immune system and modulate the pathogenic inflammatory immune responses of the gut. Recent studies have shown that a dysbiotic gut increases the risk of cardiovascular disease and chronic kidney disease (CKD). Therefore, we hypothesized that appendectomy would increase the risk of CKD.MethodsThis nationwide, population-based, propensity-score-matched cohort study included 10,383 patients who underwent appendectomy and 41,532 propensity-score-matched controls. Data were collected by the National Health Insurance Research Database of Taiwan from 2000 to 2013. We examined the associations between appendectomy and CKD and end-stage renal disease (ESRD). The major outcome was a new diagnosis of CKD based on an outpatient diagnosis made at least three times or hospital discharge diagnosis made once during the follow-up period. ESRD was defined as undergoing dialysis therapy for at least 90 days, as in previous studies.ResultsThe incidence rates of CKD and ESRD were higher in the appendectomy group than in the control cohort (CKD: 6.52 vs. 5.93 per 1,000 person-years, respectively; ESRD: 0.49 vs. 0.31 per 1,000 person-years, respectively). Appendectomy patients also had a higher risk of developing CKD (adjusted hazard ratio [aHR] 1.13; 95% CI [1.01–1.26]; P = 0.037) and ESRD (aHR 1.59; 95% CI [1.06–2.37]; P = 0.024) than control group patients. Subgroup analysis showed that appendectomy patients with concomitant diabetes mellitus (aHR 2.08; P = 0.004) were at higher risk of incident ESRD than those without diabetes mellitus. The interaction effects of appendectomy and diabetes mellitus were significant for ESRD risk (P = 0.022); no interaction effect was found for CKD risk (P = 0.555).ConclusionsAppendectomy increases the risk of developing CKD and ESRD, especially in diabetic patients. Physicians should pay close attention to renal function prognosis in appendectomy patients. creator: Chin-Hua Chang creator: Chew-Teng Kor creator: Chia-Lin Wu creator: Ping-Fang Chiu creator: Jhao-Rong Li creator: Chun-Chieh Tsai creator: Teng-Hsiang Chang creator: Chia-Chu Chang uri: https://doi.org/10.7717/peerj.5019 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Chang et al. title: Evaluating the utility of the female-specific mitochondrial f-orf gene for population genetic, phylogeographic and systematic studies in freshwater mussels (Bivalvia: Unionida) link: https://peerj.com/articles/5007 last-modified: 2018-06-13 description: Freshwater mussels (order: Unionida) represent one of the most critically imperilled groups of animals; consequently, there exists a need to establish a variety of molecular markers for population genetics and systematic studies in this group. Recently, two novel mitochondrial protein-coding genes were described in unionoids with doubly uniparental inheritance of mtDNA. These genes are the f-orf in female-transmitted mtDNA and the m-orf in male-transmitted mtDNA. In this study, whole F-type mitochondrial genome sequences of two morphologically similar Lampsilis spp. were compared to identify the most divergent protein-coding regions, including the f-orf gene, and evaluate its utility for population genetic and phylogeographic studies in the subfamily Ambleminae. We also tested whether the f-orf gene is phylogenetically informative at the species level. Our preliminary results indicated that the f-orf gene could represent a viable molecular marker for population- and species-level studies in freshwater mussels. creator: Brent M. Robicheau creator: Emily E. Chase creator: Walter R. Hoeh creator: John L. Harris creator: Donald T. Stewart creator: Sophie Breton uri: https://doi.org/10.7717/peerj.5007 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Robicheau et al. title: Efficient dispersal and substrate acquisition traits in a marine invasive species via transient chimerism and colony mobility link: https://peerj.com/articles/5006 last-modified: 2018-06-13 description: Over the past three decades the colonial ascidian Didemnum vexillum has been expanding its global range, significantly impacting marine habitats and aquaculture facilities. What biological features make D. vexillum so highly invasive? Here, we show that juxtaposed allogeneic D. vexillum colony fragments (‘ramets’) may, initially, form chimeric entities. Subsequently, zooids of the differing genotypes within such chimeras coordinately retreat away from fusion zones. A few days following such post-fusion retreat movements there is further ramet fission and the formation of zooid-depauperate tunic zones. Using polymorphic microsatellite loci to distinguish between genotypes, we found that they were sectorial at the fusion zones and the subsequent ramet movements resulted in further spatial separation of the paired-genotypes indicating that the fusion events observed did not lead to formation of long-term, stable chimeras. Thus, movements of D. vexillum colony ramets from initial fusion zones lead to progressive segregation of genotypes probably minimizing potential somatic/germ-cell competition/parasitism. We speculate that relatively fast (≤10 mm/day) movement of D. vexillum colonies on substrates along with frequent, and perhaps unrestrained, transient allogeneic fusions play significant roles in this species’ striking invasiveness and capacity to colonize new substrates. creator: Andrew E. Fidler creator: Aurelie Bacq-Labreuil creator: Elad Rachmilovitz creator: Baruch Rinkevich uri: https://doi.org/10.7717/peerj.5006 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Fidler et al. title: Synergistic and antagonistic effects of immunomodulatory drugs on the action of antifungals against Candida glabrata and Saccharomyces cerevisiae link: https://peerj.com/articles/4999 last-modified: 2018-06-13 description: Candidemia and other forms of invasive fungal infections caused by Candida glabrata and to a lesser extent Saccharomyces cerevisiae are a serious health problem, especially if their steadily rising resistance to the limited range of antifungal drugs is taken into consideration. Various drug combinations are an attractive solution to the resistance problem, and some drug combinations are already common in the clinical environment due to the nature of diseases or therapies. We tested a few of the common antifungal-immunomodulatory drug combinations and evaluated their effect on selected strains of C. glabrata and S. cerevisiae. The combinations were performed using the checkerboard microdilution assay and interpreted using the Loewe additivity model and a model based on the Bliss independence criterion. A synergistic interaction was confirmed between calcineurin inhibitors (Fk506 and cyclosporine A) and antifungals (fluconazole, itraconazole, and amphotericin B). A new antagonistic interaction between mycophenolic acid (MPA) and azole antifungals was discovered in non-resistant strains. A possible mechanism that explains this is induction of the Cdr1 efflux pump by MPA in C. glabrata ATCC 2001. The Pdr1 regulatory cascade plays a role in overall resistance to fluconazole, but it is not essential for the antagonistic interaction. This was confirmed by the Cgpdr1Δ mutant still displaying the antagonistic interaction between the drugs, although at lower concentrations of fluconazole. This antagonism calls into question the use of simultaneous therapy with MPA and azoles in the clinical environment. creator: Miha Tome creator: Jure Zupan creator: Zorica Tomičić creator: Tadeja Matos creator: Peter Raspor uri: https://doi.org/10.7717/peerj.4999 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Tome et al.