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 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. title: Risk factors for new-onset atrial fibrillation in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis link: https://peerj.com/articles/10376 last-modified: 2020-12-02 description: BackgroundNew-onset atrial fibrillation (AF) in patients with chronic obstructive pulmonary disease (COPD) is associated with an accelerated decline in lung function, and a significant increase in mortality rate. A deeper understanding of the risk factors for new-onset AF during COPD will provide insights into the relationship between COPD and AF and guide clinical practice. This systematic review and meta-analysis is designed to identify risk factors for new-onset AF in patients with COPD, and to formulate recommendations for preventing AF in COPD patients that will assist clinical decision making.MethodsPubMed, Embase, Web of Science and Cochrane Library databases were searched for studies, which reported the results of potential risk factors for new-onset AF in COPD patients.ResultsTwenty studies involving 8,072,043 participants were included. Fifty factors were examined as potential risk factors for new-onset AF during COPD. Risk factors were grouped according to demographics, comorbid conditions, and COPD- and cardiovascular-related factors. In quantitative analysis, cardiovascular- and demographic-related factors with a greater than 50% increase in the odds of new-onset AF included age (over 65 years and over 75 years), acute care encounter, coronary artery disease, heart failure and congestive heart failure. Only one factor is related to the reduction of odds by more than 33.3%, which is black race (vs white). In qualitative analysis, the comparison of the risk factors was conducted between COPD-associated AF and non-COPD-associated AF. Cardiovascular-related factors for non-COPD-associated AF were also considered as risk factors for new-onset AF during COPD; however, the influence tended to be stronger during COPD. In addition, comorbid factors identified in non-COPD-associated AF were not associated with an increased risk of AF during COPD.ConclusionsNew-onset AF in COPD has significant demographic characteristics. Older age (over 65 years), males and white race are at higher risk of developing AF. COPD patients with a history of cardiovascular disease should be carefully monitored for new-onset of AF, and appropriate preventive measures should be implemented. Even patients with mild COPD are at high risk of new-onset AF. This study shows that risk factors for new-onset AF during COPD are mainly those associated with the cardiovascular-related event and are not synonymous with comorbid factors for non-COPD-associated AF. The pathogenesis of COPD-associated AF may be predominantly related to the cardiac dysfunction caused by the chronic duration of COPD, which increases the risk of cardiovascular-related factors and further increases the risk of AF during COPD.PROSPERO registration numberCRD42019137758. creator: Qiangru Huang creator: Huaiyu Xiong creator: Tiankui Shuai creator: Meng Zhang creator: Chuchu Zhang creator: Yalei Wang creator: Lei Zhu creator: Jiaju Lu creator: Jian Liu uri: https://doi.org/10.7717/peerj.10376 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Huang et al. title: Identification of significant genes signatures and prognostic biomarkers in cervical squamous carcinoma via bioinformatic data link: https://peerj.com/articles/10386 last-modified: 2020-12-02 description: BackgroundCervical squamous cancer (CESC) is an intractable gynecological malignancy because of its high mortality rate and difficulty in early diagnosis. Several biomarkers have been found to predict the prognose of CESC using bioinformatics methods, but they still lack clinical effectiveness. Most of the existing bioinformatic studies only focus on the changes of oncogenes but neglect the differences on the protein level and molecular biology validation are rarely conducted.MethodsGene set data from the NCBI-GEO database were used in this study to compare the differences of gene and protein levels between normal and cancer tissues through significant pathway selection and core gene signature analysis to screen potential clinical biomarkers of CESC. Subsequently, the molecular and protein levels of clinical samples were verified by quantitative transcription PCR, western blot and immunohistochemistry.ResultsThree differentially expressed genes (RFC4, MCM2, TOP2A) were found to have a significant survival (P < 0.05) and highly expressed in CESC tissues. Molecular biological verification using quantitative reverse transcribed PCR, western blotting and immunohistochemistry assays exhibited significant differences in the expression of RFC4 between CESC and para-cancerous tissues (P < 0.05).ConclusionThis study identified three potential biomarkers (RFC4, MCM2, TOP2A) of CESC which may be useful to clarify the underlying mechanisms of CESC and predict the prognosis of CESC patients. creator: Yunan He creator: Shunjie Hu creator: Jiaojiao Zhong creator: Anran Cheng creator: Nianchun Shan uri: https://doi.org/10.7717/peerj.10386 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 He et al. title: Ixodes scapularis microbiome correlates with life stage, not the presence of human pathogens, in ticks submitted for diagnostic testing link: https://peerj.com/articles/10424 last-modified: 2020-12-02 description: Ticks are globally distributed arthropods and a public health concern due to the many human pathogens they carry and transmit, including the causative agent of Lyme disease, Borrelia burgdorferi. As tick species’ ranges increase, so do the number of reported tick related illnesses. The microbiome is a critical part of understanding arthropod biology, and the microbiome of pathogen vectors may provide critical insight into disease transmission and management. Yet we lack a comprehensive understanding of the microbiome of wild ticks, including what effect the presence of multiple tick-borne pathogens (TBPs) has on the microbiome. In this study we chose samples based on life stage (adult or nymph) and which TBPs were present. We used DNA from previously extracted Ixodes scapularis ticks that tested positive for zero, one, two or three common TBPs (B. burgdorferi, B. miyamotoi, Anaplasma phagocytophilum, Babesia microti). We produced 16S rRNA amplicon data for the whole tick microbiome and compared samples across TBPs status, single vs multiple coinfections, and life stages. Focusing on samples with a single TBP, we found no significant differences in microbiome diversity in ticks that were infected with B. burgdorferi and ticks with no TBPs. When comparing multiple TBPs, we found no significant difference in both alpha and beta diversity between ticks with a single TBP and ticks with multiple TBPs. Removal of TBPs from the microbiome did not alter alpha or beta diversity results. Life stage significantly correlated to variation in beta diversity and nymphs had higher alpha diversity than adult ticks. Rickettsia, a common tick endosymbiont, was the most abundant genus. This study confirms that the wild tick microbiome is highly influenced by life stage and much less by the presence of human pathogenic bacteria. creator: Joshua C. Gil creator: Zeinab H. Helal creator: Guillermo Risatti creator: Sarah M. Hird uri: https://doi.org/10.7717/peerj.10424 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Gil et al. title: Phospho-islands and the evolution of phosphorylated amino acids in mammals link: https://peerj.com/articles/10436 last-modified: 2020-12-02 description: BackgroundProtein phosphorylation is the best studied post-translational modification strongly influencing protein function. Phosphorylated amino acids not only differ in physico-chemical properties from non-phosphorylated counterparts, but also exhibit different evolutionary patterns, tending to mutate to and originate from negatively charged amino acids (NCAs). The distribution of phosphosites along protein sequences is non-uniform, as phosphosites tend to cluster, forming so-called phospho-islands.MethodsHere, we have developed a hidden Markov model-based procedure for the identification of phospho-islands and studied the properties of the obtained phosphorylation clusters. To check robustness of evolutionary analysis, we consider different models for the reconstructions of ancestral phosphorylation states.ResultsClustered phosphosites differ from individual phosphosites in several functional and evolutionary aspects including underrepresentation of phosphotyrosines, higher conservation, more frequent mutations to NCAs. The spectrum of tissues, frequencies of specific phosphorylation contexts, and mutational patterns observed near clustered sites also are different. creator: Mikhail Moldovan creator: Mikhail S. Gelfand uri: https://doi.org/10.7717/peerj.10436 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Moldovan and Gelfand title: Distribution of phylogenetic groups, adhesin genes, biofilm formation, and antimicrobial resistance of uropathogenic Escherichia coli isolated from hospitalized patients in Thailand link: https://peerj.com/articles/10453 last-modified: 2020-12-02 description: BackgroundUrinary tract infections (UTIs) are the most common bacterial infections and are often caused by uropathogenic Escherichia coli (UPEC). We investigated the distribution of phylogenetic groups, adhesin genes, antimicrobial resistance, and biofilm formation in E. coli isolated from patients with UTIs.MethodsIn the present study, 208 UPEC isolated from Thai patients were classified into phylogenetic groups and adhesin genes were detected using multiplex PCR. Antimicrobial susceptibility testing was performed using agar disk diffusion. The Congo red agar method was used to determine the ability of the UPEC to form biofilm.ResultsThe most prevalent UPEC strains in this study belonged to phylogenetic group B2 (58.7%), followed by group C (12.5%), group E (12.0%), and the other groups (16.8%). Among adhesin genes, the prevalence of fimH (91.8%) was highest, followed by pap (79.3%), sfa (12.0%), and afa (7.7%). The rates of resistance to fluoroquinolones, trimethoprim-sulfamethoxazole, and amoxicillin-clavulanate were  65%, 54.3%, and 36.5%, respectively. The presence of adhesin genes and antibiotic resistance were more frequent in groups B2 and C compared to the other groups. Of the 129 multidrug-resistant UPEC strains, 54% were biofilm producers. Our findings further indicated that biofilm production was significantly correlated with the pap adhesin gene (p ≤ 0.05).ConclusionThese findings provide molecular epidemiologic data, antibiotic resistance profiles, and the potential for biofilm formation among UPEC strains that can inform further development of the appropriate prevention and control strategies for UTIs in this region. creator: Nipaporn Tewawong creator: Siriporn Kowaboot creator: Yaowaluk Pimainog creator: Naiyana Watanagul creator: Thanunrat Thongmee creator: Yong Poovorawan uri: https://doi.org/10.7717/peerj.10453 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Tewawong et al. title: Genome-wide identification and evolution of HECT genes in wheat link: https://peerj.com/articles/10457 last-modified: 2020-12-02 description: BackgroundAs an important class of E3 ubiquitin ligases in the ubiquitin proteasome pathway, proteins containing homologous E6-AP carboxyl terminus (HECT) domains are crucial for growth, development, metabolism, and abiotic and biotic stress responses in plants. However, little is known about HECT genes in wheat (Triticum aestivum L.), one of the most important global crops.MethodsUsing a genome-wide analysis of high-quality wheat genome sequences, we identified 25 HECT genes classified into six groups based on the phylogenetic relationship among wheat, rice, and Arabidopsis thaliana.ResultsThe predicted HECT genes were distributed evenly in 17 of 21 chromosomes of the three wheat subgenomes. Twenty-one of these genes were hypothesized to be segmental duplication genes, indicating that segmental duplication was significantly associated with the expansion of the wheat HECT gene family. The Ka/Ks ratios of the segmental duplication of these genes were less than 1, suggesting purifying selection within the gene family. The expression profile analysis revealed that the 25 wheat HECT genes were differentially expressed in 15 tissues, and genes in Group II, IV, and VI (UPL8, UPL6, UPL3) were highly expressed in roots, stems, and spikes. This study contributes to further the functional analysis of the HECT gene family in wheat. creator: Xianwen Meng creator: Ting Yang creator: Jing Liu creator: Mingde Zhao creator: Jiuli Wang uri: https://doi.org/10.7717/peerj.10457 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Meng et al. title: Comparative genomic analysis of the principal Cryptosporidium species that infect humans link: https://peerj.com/articles/10478 last-modified: 2020-12-02 description: Cryptosporidium parasites are ubiquitous and can infect a broad range of vertebrates and are considered the most frequent protozoa associated with waterborne parasitic outbreaks. The intestine is the target of three of the species most frequently found in humans: C. hominis, C. parvum, and. C. meleagridis. Despite the recent advance in genome sequencing projects for this apicomplexan, a broad genomic comparison including the three species most prevalent in humans have not been published so far. In this work, we downloaded raw NGS data, assembled it under normalized conditions, and compared 23 publicly available genomes of C. hominis, C. parvum, and C. meleagridis. Although few genomes showed highly fragmented assemblies, most of them had less than 500 scaffolds and mean coverage that ranged between 35X and 511X. Synonymous single nucleotide variants were the most common in C. hominis and C. meleagridis, while in C. parvum, they accounted for around 50% of the SNV observed. Furthermore, deleterious nucleotide substitutions common to all three species were more common in genes associated with DNA repair, recombination, and chromosome-associated proteins. Indel events were observed in the 23 studied isolates that spanned up to 500 bases. The highest number of deletions was observed in C. meleagridis, followed by C. hominis, with more than 60 species-specific deletions found in some isolates of these two species. Although several genes with indel events have been partially annotated, most of them remain to encode uncharacterized proteins. creator: Laura M. Arias-Agudelo creator: Gisela Garcia-Montoya creator: Felipe Cabarcas creator: Ana L. Galvan-Diaz creator: Juan F. Alzate uri: https://doi.org/10.7717/peerj.10478 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Arias-Agudelo et al. title: The gut microbiota in the common kestrel (Falco tinnunculus): a report from the Beijing Raptor Rescue Center link: https://peerj.com/articles/9970 last-modified: 2020-12-01 description: As a complex microecological system, the gut microbiota plays crucial roles in many aspects, including immunology, physiology and development. The specific function and mechanism of the gut microbiota in birds are distinct due to their body structure, physiological attributes and life history. Data on the gut microbiota of the common kestrel, a second-class protected animal species in China, are currently scarce. With high-throughput sequencing technology, we characterized the bacterial community of the gut from nine fecal samples from a wounded common kestrel by sequencing the V3-V4 region of the 16S ribosomal RNA gene. Our results showed that Proteobacteria (41.078%), Firmicutes (40.923%) and Actinobacteria (11.191%) were the most predominant phyla. Lactobacillus (20.563%) was the most dominant genus, followed by Escherichia-Shigella (17.588%) and Acinetobacter (5.956%). Our results would offer fundamental data and direction for the wildlife rescue. creator: Yu Guan creator: Hongfang Wang creator: Yinan Gong creator: Jianping Ge creator: Lei Bao uri: https://doi.org/10.7717/peerj.9970 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Guan et al. title: Tracking the dynamics of individual gut microbiome of sea cucumber Apostichopus japonicus during gut regeneration link: https://peerj.com/articles/10260 last-modified: 2020-12-01 description: Sea cucumbers possess the remarkable capacity to regenerate their body parts or organs. Regeneration of host organs and/or body parts involves reconstruction of the host associated microbiota, however, the dynamics and contribution of microbiota to the regeneration process are largely unknown due to a lack of experimental models. To track the dynamics of individual gut microbiomes during gut regeneration, both caged mariculture and laboratory isolator systems of sea cucumbers (Apostichopus japonicus) were developed and longitudinal meta16S analyses were performed. Under natural environmental conditions in the caged mariculture system, both bacterial and eukaryotic communities in sea cucumbers’ guts appeared to be reconstructed within 4 months after evisceration. Using the laboratory isolator, which can trace daily dynamics, we found that fecal microbiota collected before evisceration were clearly different from those collected after evisceration. We also identified eight key bacteria, belonging to Alteromonadaceae, Rhodobacteraceae, Oceanospirillaceae and family-unassigned Gammaproteobacteria, suggesting that these bacteria might interact with the host during the gut regeneration process. Six of the eight key bacteria were isolated for further bioassay using the isolator developed in this study to test whether these isolates affect gut regeneration. creator: Yohei Yamazaki creator: Yuichi Sakai creator: Juanwen Yu creator: Sayaka Mino creator: Tomoo Sawabe uri: https://doi.org/10.7717/peerj.10260 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Yamazaki et al.