PeerJ
type: channel
link: https://peerj.com/articles/
description: Articles published in PeerJ
publisher: PeerJ Inc.
publication name: PeerJ
issn: 2167-8359
items: Development of a gene doping detection method to detect overexpressed human follistatin using an adenovirus vector in mice
items: Comparative transcriptome analyses of different Salvia miltiorrhiza varieties during the accumulation of tanshinones
items: Functional analysis of a dihydroflavonol 4-reductase gene in Ophiorrhiza japonica (OjDFR1) reveals its role in the regulation of anthocyanin
items: DNA barcode reference library construction and genetic diversity and structure analysis of Amomum villosum Lour. (Zingiberaceae) populations in Guangdong Province
items: Transcriptomic analysis reveals candidate genes for male sterility in Prunus sibirica
items: Effect of SARS-CoV-2 infection on host competing endogenous RNA and miRNA network
items: In silico evaluation of molecular virus–virus interactions taking place between Cotton leaf curl Kokhran virus- Burewala strain and Tomato leaf curl New Delhi virus
items: New phiocricetomyine rodents (Hystricognathi) from the Jebel Qatrani Formation, Fayum Depression, Egypt
items: Visual assessment of dynamic knee joint alignment in patients with patellofemoral pain: an agreement study
items: Upright walking has driven unique vascular specialization of the hominin ilium

Development of a gene doping detection method to detect overexpressed human follistatin using an adenovirus vector in mice
type: item
type: AcademicArticle
description: Background Gene doping is the misuse of genome editing and gene therapy technologies for the purpose of manipulating specific genes or gene functions in order to improve athletic performance. However, a non-invasive detection method for gene doping using recombinant adenoviral (rAdV) vectors containing human follistatin (hFST) genes (rAdV<hFST>) has not yet been developed. Therefore, the aim of this study was to develop a method to detect gene doping using rAdV<hFST>. Methods First, we generated rAdV<hFST> and evaluated the overexpression of the hFST gene, FST protein, and muscle protein synthesis signaling using cell lines. Next, rAdV<hFST> was injected intravenously or intramuscularly into mice, and whole blood was collected, and hFST and cytomegalovirus promoter (CMVp) gene fragments were detected using TaqMan-quantitative polymerase chain reaction (qPCR). Finally, to confirm the specificity of the primers and the TaqMan probes, samples from each experiment were pooled, amplified using TaqMan-qPCR, and sequenced using the Sanger sequencing. Results The expression of hFST and FST proteins and muscle protein synthesis signaling significantly increased in C2C12 cells. In long-term, transgene fragments could be detected until 4 days after intravenous injection and 3 days after intramuscular injection. Finally, the Sanger sequencing confirmed that the primers and TaqMan probe specifically amplified the gene sequence of interest. Conclusions These results indicate the possibility of detecting gene doping using rAdV<hFST> using TaqMan-qPCR in blood samples. This study may contribute to the development of detection methods for gene doping using rAdV<hFST>.
format: application/pdf
format: text/html
creator: Koki Yanazawa
creator: Takehito Sugasawa
creator: Kai Aoki
creator: Takuro Nakano
creator: Yasushi Kawakami
creator: Kazuhiro Takekoshi
subject: Biochemistry
subject: Genetics
subject: Molecular Biology
description: doi:10.7717/peerj.12285
publisher: PeerJ Inc.
rights: © 2021 Yanazawa et al.
abstract: Background Gene doping is the misuse of genome editing and gene therapy technologies for the purpose of manipulating specific genes or gene functions in order to improve athletic performance. However, a non-invasive detection method for gene doping using recombinant adenoviral (rAdV) vectors containing human follistatin (hFST) genes (rAdV<hFST>) has not yet been developed. Therefore, the aim of this study was to develop a method to detect gene doping using rAdV<hFST>. Methods First, we generated rAdV<hFST> and evaluated the overexpression of the hFST gene, FST protein, and muscle protein synthesis signaling using cell lines. Next, rAdV<hFST> was injected intravenously or intramuscularly into mice, and whole blood was collected, and hFST and cytomegalovirus promoter (CMVp) gene fragments were detected using TaqMan-quantitative polymerase chain reaction (qPCR). Finally, to confirm the specificity of the primers and the TaqMan probes, samples from each experiment were pooled, amplified using TaqMan-qPCR, and sequenced using the Sanger sequencing. Results The expression of hFST and FST proteins and muscle protein synthesis signaling significantly increased in C2C12 cells. In long-term, transgene fragments could be detected until 4 days after intravenous injection and 3 days after intramuscular injection. Finally, the Sanger sequencing confirmed that the primers and TaqMan probe specifically amplified the gene sequence of interest. Conclusions These results indicate the possibility of detecting gene doping using rAdV<hFST> using TaqMan-qPCR in blood samples. This study may contribute to the development of detection methods for gene doping using rAdV<hFST>.
bibliographic citation: Yanazawa et al. (2021) Development of a gene doping detection method to detect overexpressed human follistatin using an adenovirus vector in mice. PeerJ 9:e12285 https://doi.org/10.7717/peerj.12285
date submitted: 2021-04-17
date accepted: 2021-09-20
issued: 2021-10-20
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Yanazawa
  given name: Koki
author list: Agent
  family name: Sugasawa
  given name: Takehito
author list: Agent
  family name: Aoki
  given name: Kai
author list: Agent
  family name: Nakano
  given name: Takuro
author list: Agent
  family name: Kawakami
  given name: Yasushi
author list: Agent
  family name: Takekoshi
  given name: Kazuhiro
doi: 10.7717/peerj.12285
volume: 9
issn: 2167-8359
publication name: PeerJ
publication date: 2021-10-20
copyright: © 2021 Yanazawa et al.
attribution name: Yanazawa et al.

Comparative transcriptome analyses of different Salvia miltiorrhiza varieties during the accumulation of tanshinones
type: item
type: AcademicArticle
description: Salvia miltiorrhiza (Labiatae) is an important medicinal plant in traditional Chinese medicine. Tanshinones are one of the main active components of S. miltiorrhiza. It has been found that the intraspecific variation of S. miltiorrhiza is relatively large and the content of tanshinones in its roots of different varieties is also relatively different. To investigate the molecular mechanisms that responsible for the differences among these varieties, the tanshinones content was determined and comparative transcriptomics analysis was carried out during the tanshinones accumulation stage. A total of 52,216 unigenes were obtained from the transcriptome by RNA sequencing among which 23,369 genes were differentially expressed among different varieties, and 2,016 genes including 18 diterpenoid biosynthesis-related genes were differentially expressed during the tanshinones accumulation stage. Functional categorization of the differentially expressed genes (DEGs) among these varieties revealed that the pathway related to photosynthesis, oxidative phosphorylation, secondary metabolite biosynthesis, diterpenoid biosynthesis, terpenoid backbone biosynthesis, sesquiterpenoid and triterpenoid biosynthesis are the most differentially regulated processes in these varieties. The six tanshinone components in these varieties showed different dynamic changes in tanshinone accumulation stage. In addition, combined with the analysis of the dynamic changes, 277 DEGs (including one dehydrogenase, three CYP450 and 24 transcription factors belonging to 12 transcription factor families) related to the accumulation of tanshinones components were obtained. Furthermore, the KEGG pathway enrichment analysis of these 277 DEGs suggested that there might be an interconnection between the primary metabolic processes, signaling processes and the accumulation of tanshinones components. This study expands the vision of intraspecific variation and gene regulation mechanism of secondary metabolite biosynth…
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format: text/html
creator: Jingwen Zhou
creator: Rui Liu
creator: Min Shuai
creator: Zhu-Yun Yan
creator: Xin Chen
subject: Biodiversity
subject: Bioinformatics
subject: Ecology
subject: Genetics
subject: Plant Science
description: doi:10.7717/peerj.12300
publisher: PeerJ Inc.
rights: © 2021 Zhou et al.
abstract: Salvia miltiorrhiza (Labiatae) is an important medicinal plant in traditional Chinese medicine. Tanshinones are one of the main active components of S. miltiorrhiza. It has been found that the intraspecific variation of S. miltiorrhiza is relatively large and the content of tanshinones in its roots of different varieties is also relatively different. To investigate the molecular mechanisms that responsible for the differences among these varieties, the tanshinones content was determined and comparative transcriptomics analysis was carried out during the tanshinones accumulation stage. A total of 52,216 unigenes were obtained from the transcriptome by RNA sequencing among which 23,369 genes were differentially expressed among different varieties, and 2,016 genes including 18 diterpenoid biosynthesis-related genes were differentially expressed during the tanshinones accumulation stage. Functional categorization of the differentially expressed genes (DEGs) among these varieties revealed that the pathway related to photosynthesis, oxidative phosphorylation, secondary metabolite biosynthesis, diterpenoid biosynthesis, terpenoid backbone biosynthesis, sesquiterpenoid and triterpenoid biosynthesis are the most differentially regulated processes in these varieties. The six tanshinone components in these varieties showed different dynamic changes in tanshinone accumulation stage. In addition, combined with the analysis of the dynamic changes, 277 DEGs (including one dehydrogenase, three CYP450 and 24 transcription factors belonging to 12 transcription factor families) related to the accumulation of tanshinones components were obtained. Furthermore, the KEGG pathway enrichment analysis of these 277 DEGs suggested that there might be an interconnection between the primary metabolic processes, signaling processes and the accumulation of tanshinones components. This study expands the vision of intraspecific variation and gene regulation mechanism of secondary metabolite biosynth…
bibliographic citation: Zhou et al. (2021) Comparative transcriptome analyses of different Salvia miltiorrhiza varieties during the accumulation of tanshinones. PeerJ 9:e12300 https://doi.org/10.7717/peerj.12300
date submitted: 2021-03-26
date accepted: 2021-09-22
issued: 2021-10-20
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Zhou
  given name: Jingwen
author list: Agent
  family name: Liu
  given name: Rui
author list: Agent
  family name: Shuai
  given name: Min
author list: Agent
  family name: Yan
  given name: Zhu-Yun
author list: Agent
  family name: Chen
  given name: Xin
doi: 10.7717/peerj.12300
volume: 9
issn: 2167-8359
publication name: PeerJ
publication date: 2021-10-20
copyright: © 2021 Zhou et al.
attribution name: Zhou et al.

Functional analysis of a dihydroflavonol 4-reductase gene in Ophiorrhiza japonica (OjDFR1) reveals its role in the regulation of anthocyanin
type: item
type: AcademicArticle
description: Dihydroflavonol 4-reductase (DFR), a key regulatory enzyme, participated in the biosynthesis of anthocyanins, proanthocyanidins and other flavonoids that essential for plant survival and human health. However, the role of this enzyme in Ophiorrhiza japonica is still unknown. Here, three putative DFR-like genes were firstly isolated from O. japonica. Phylogenetic analysis indicated that OjDFR1 was classified into DFR subgroup, while the rest two were clustered into other NADPH-dependent reductases. Then, functions of the three genes were further characterized. Expression analysis showed that OjDFR1 transcripts had strong correlations with the accumulation pattern of anthocyanin during the flower developmental, whereas other two were not, this suggested the potential roles of OjDFR1 in anthocyanin biosynthesis. Subsequently, all three clones were functionally expressed in Escherichia coli, but confirming that only OjDFR1 encode active DFR proteins that catalyzed the reduction of dihydroflavonols to leucoanthocyanidin. Consistant with the biochemical assay results, overexpressing OjDFR1 in Arabidopsis tt3-1 mutant successfully restored the deficiency of anthocyanin and proanthocyanidin, hinting its function as DFR in planta. Additionally, heterologous expression of OjDFR1 in transgenic tobacco contributed to darker flower color via up-regulating the expressions of endogenous NtANS and NtUFGT, which suggested that OjDFR1 was involved in flower color development. In summary, this study validates the functions of OjDFR1 and expands our understanding of anthocyanin biosynthesis in O. japonica.
format: application/pdf
format: text/html
creator: Wei Sun
creator: Nana Zhou
creator: Cai Feng
creator: Shiyu Sun
creator: Ming Tang
creator: Xiaoxin Tang
creator: Zhigang Ju
creator: Yin Yi
subject: Biochemistry
subject: Molecular Biology
subject: Plant Science
description: doi:10.7717/peerj.12323
publisher: PeerJ Inc.
rights: © 2021 Sun et al.
abstract: Dihydroflavonol 4-reductase (DFR), a key regulatory enzyme, participated in the biosynthesis of anthocyanins, proanthocyanidins and other flavonoids that essential for plant survival and human health. However, the role of this enzyme in Ophiorrhiza japonica is still unknown. Here, three putative DFR-like genes were firstly isolated from O. japonica. Phylogenetic analysis indicated that OjDFR1 was classified into DFR subgroup, while the rest two were clustered into other NADPH-dependent reductases. Then, functions of the three genes were further characterized. Expression analysis showed that OjDFR1 transcripts had strong correlations with the accumulation pattern of anthocyanin during the flower developmental, whereas other two were not, this suggested the potential roles of OjDFR1 in anthocyanin biosynthesis. Subsequently, all three clones were functionally expressed in Escherichia coli, but confirming that only OjDFR1 encode active DFR proteins that catalyzed the reduction of dihydroflavonols to leucoanthocyanidin. Consistant with the biochemical assay results, overexpressing OjDFR1 in Arabidopsis tt3-1 mutant successfully restored the deficiency of anthocyanin and proanthocyanidin, hinting its function as DFR in planta. Additionally, heterologous expression of OjDFR1 in transgenic tobacco contributed to darker flower color via up-regulating the expressions of endogenous NtANS and NtUFGT, which suggested that OjDFR1 was involved in flower color development. In summary, this study validates the functions of OjDFR1 and expands our understanding of anthocyanin biosynthesis in O. japonica.
bibliographic citation: Sun et al. (2021) Functional analysis of a dihydroflavonol 4-reductase gene in Ophiorrhiza japonica (OjDFR1) reveals its role in the regulation of anthocyanin. PeerJ 9:e12323 https://doi.org/10.7717/peerj.12323
date submitted: 2021-07-29
date accepted: 2021-09-26
issued: 2021-10-20
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Sun
  given name: Wei
author list: Agent
  family name: Zhou
  given name: Nana
author list: Agent
  family name: Feng
  given name: Cai
author list: Agent
  family name: Sun
  given name: Shiyu
author list: Agent
  family name: Tang
  given name: Ming
author list: Agent
  family name: Tang
  given name: Xiaoxin
author list: Agent
  family name: Ju
  given name: Zhigang
author list: Agent
  family name: Yi
  given name: Yin
doi: 10.7717/peerj.12323
volume: 9
issn: 2167-8359
publication name: PeerJ
publication date: 2021-10-20
copyright: © 2021 Sun et al.
attribution name: Sun et al.

DNA barcode reference library construction and genetic diversity and structure analysis of Amomum villosum Lour. (Zingiberaceae) populations in Guangdong Province
type: item
type: AcademicArticle
description: Background Amomum villosum Lour. is the plant that produces the famous traditional Chinese medicine Amomi Fructus. Frequent habitat destruction seriously threatens A. villosum germplasm resources. Genetic diversity is very important to the optimization of germplasm resources and population protection, but the range of inherited traits within A. villosum is unclear. In this study, we analyzed the genetic diversity and genetic structures of A. villosum populations in Guangdong and constructed a local reference DNA barcode library as a resource for conservation efforts. Methods DNA barcoding and Inter-Simple Sequence Repeat (ISSR) markers were used to investigate the population genetics of A. villosum. Five universal DNA barcodes were amplified and used in the construction of a DNA barcode reference library. Parameters including percentage of polymorphic sites (PPB), number of alleles (Na), effective number of alleles (Ne), Nei’s gene diversity index (H), and Shannon’s polymorphism information index (I) were calculated for the assessment of genetic diversity. Genetic structure was revealed by measuring Nei’s gene differentiation coefficient (Gst), total population genetic diversity (Ht), intra-group genetic diversity (Hs), and gene flow (Nm). Analysis of molecular variance (AMOVA), Mantel tests, unweighted pair-group method with arithmetic mean (UPGMA) dendrogram, and principal co-ordinates (PCoA) analysis were used to elucidate the genetic differentiation and relationship among populations. Results A total of 531 sequences were obtained from the five DNA barcodes with no variable sites from any of the barcode sequences. A total of 66 ISSR bands were generated from A. villosum populations using the selected six ISSR primers; 56 bands, 84.85% for all the seven A. villosum populations were polymorphic. The A. villosum populations showed high genetic diversity (H = 0.3281, I = 0.4895), whereas the gene flow was weak (Nm = 0.6143). Gst (0.4487) and AMOVA analysis indicated…
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format: text/html
creator: Lu Gong
creator: Danchun Zhang
creator: Xiaoxia Ding
creator: Juan Huang
creator: Wan Guan
creator: Xiaohui Qiu
creator: Zhihai Huang
subject: Biodiversity
subject: Molecular Biology
subject: Plant Science
subject: Population Biology
description: doi:10.7717/peerj.12325
publisher: PeerJ Inc.
rights: © 2021 Gong et al.
abstract: Background Amomum villosum Lour. is the plant that produces the famous traditional Chinese medicine Amomi Fructus. Frequent habitat destruction seriously threatens A. villosum germplasm resources. Genetic diversity is very important to the optimization of germplasm resources and population protection, but the range of inherited traits within A. villosum is unclear. In this study, we analyzed the genetic diversity and genetic structures of A. villosum populations in Guangdong and constructed a local reference DNA barcode library as a resource for conservation efforts. Methods DNA barcoding and Inter-Simple Sequence Repeat (ISSR) markers were used to investigate the population genetics of A. villosum. Five universal DNA barcodes were amplified and used in the construction of a DNA barcode reference library. Parameters including percentage of polymorphic sites (PPB), number of alleles (Na), effective number of alleles (Ne), Nei’s gene diversity index (H), and Shannon’s polymorphism information index (I) were calculated for the assessment of genetic diversity. Genetic structure was revealed by measuring Nei’s gene differentiation coefficient (Gst), total population genetic diversity (Ht), intra-group genetic diversity (Hs), and gene flow (Nm). Analysis of molecular variance (AMOVA), Mantel tests, unweighted pair-group method with arithmetic mean (UPGMA) dendrogram, and principal co-ordinates (PCoA) analysis were used to elucidate the genetic differentiation and relationship among populations. Results A total of 531 sequences were obtained from the five DNA barcodes with no variable sites from any of the barcode sequences. A total of 66 ISSR bands were generated from A. villosum populations using the selected six ISSR primers; 56 bands, 84.85% for all the seven A. villosum populations were polymorphic. The A. villosum populations showed high genetic diversity (H = 0.3281, I = 0.4895), whereas the gene flow was weak (Nm = 0.6143). Gst (0.4487) and AMOVA analysis indicated…
bibliographic citation: Gong et al. (2021) DNA barcode reference library construction and genetic diversity and structure analysis of Amomum villosum Lour. (Zingiberaceae) populations in Guangdong Province. PeerJ 9:e12325 https://doi.org/10.7717/peerj.12325
date submitted: 2021-06-08
date accepted: 2021-09-27
issued: 2021-10-20
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Gong
  given name: Lu
author list: Agent
  family name: Zhang
  given name: Danchun
author list: Agent
  family name: Ding
  given name: Xiaoxia
author list: Agent
  family name: Huang
  given name: Juan
author list: Agent
  family name: Guan
  given name: Wan
author list: Agent
  family name: Qiu
  given name: Xiaohui
author list: Agent
  family name: Huang
  given name: Zhihai
doi: 10.7717/peerj.12325
volume: 9
issn: 2167-8359
publication name: PeerJ
publication date: 2021-10-20
copyright: ©2021 Gong et al.
attribution name: Gong et al.

Transcriptomic analysis reveals candidate genes for male sterility in Prunus sibirica
type: item
type: AcademicArticle
description: Background The phenomenon of male sterility widely occurs in Prunus sibirica and has a serious negative impact on yield. We identified the key stage and cause of male sterility and found differentially expressed genes related to male sterility in Prunus sibirica, and we analyzed the expression pattern of these genes. This work aimed to provide valuable reference and theoretical basis for the study of reproductive development and the mechanisms of male sterility in Prunus sibirica. Method The microstructures of male sterile flower buds and male fertile flower buds were observed by paraffin section. Transcriptome sequencing was used to screen genes related to male sterility in Prunus sibirica. Quantitative real-time PCR analysis was performed to verify the transcriptome data. Results Anther development was divided into the sporogenous cell stage, tetrad stage, microspore stage, and pollen maturity stage. Compared with male fertile flower buds, in the microspore stage, the pollen sac wall tissue in the male sterile flower buds showed no signs of degeneration. In the pollen maturity stage, the tapetum and middle layer were not fully degraded, and anther development stopped. Therefore, the microspore stage was the key stage for anther abortion , and the pollen maturity stage was the post stage for anther abortion. A total of 4,108 differentially expressed genes were identified by transcriptome analysis. Among them, 1,899 were up-regulated, and 2,209 were down-regulated in the transcriptome of male sterile flower buds. We found that “protein kinase activity”, “apoptosis process”, “calcium binding”, “cell death”, “cytochrome c oxidase activity”, “aspartate peptidase activity”, “cysteine peptidase activity” and other biological pathways such as “starch and sucrose metabolism” and “proteasome” were closely related to male sterility in Prunus sibirica. A total of 331 key genes were preliminarily screened. Conclusion The occurrence of male sterility in Prunus sibirica involved…
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format: text/html
creator: Jianhua Chen
creator: Hao Xu
creator: Jian Zhang
creator: Shengjun Dong
creator: Quangang Liu
creator: Ruoxi Wang
subject: Developmental Biology
subject: Molecular Biology
subject: Plant Science
subject: Forestry
description: doi:10.7717/peerj.12349
publisher: PeerJ Inc.
rights: © 2021 Chen et al.
abstract: Background The phenomenon of male sterility widely occurs in Prunus sibirica and has a serious negative impact on yield. We identified the key stage and cause of male sterility and found differentially expressed genes related to male sterility in Prunus sibirica, and we analyzed the expression pattern of these genes. This work aimed to provide valuable reference and theoretical basis for the study of reproductive development and the mechanisms of male sterility in Prunus sibirica. Method The microstructures of male sterile flower buds and male fertile flower buds were observed by paraffin section. Transcriptome sequencing was used to screen genes related to male sterility in Prunus sibirica. Quantitative real-time PCR analysis was performed to verify the transcriptome data. Results Anther development was divided into the sporogenous cell stage, tetrad stage, microspore stage, and pollen maturity stage. Compared with male fertile flower buds, in the microspore stage, the pollen sac wall tissue in the male sterile flower buds showed no signs of degeneration. In the pollen maturity stage, the tapetum and middle layer were not fully degraded, and anther development stopped. Therefore, the microspore stage was the key stage for anther abortion , and the pollen maturity stage was the post stage for anther abortion. A total of 4,108 differentially expressed genes were identified by transcriptome analysis. Among them, 1,899 were up-regulated, and 2,209 were down-regulated in the transcriptome of male sterile flower buds. We found that “protein kinase activity”, “apoptosis process”, “calcium binding”, “cell death”, “cytochrome c oxidase activity”, “aspartate peptidase activity”, “cysteine peptidase activity” and other biological pathways such as “starch and sucrose metabolism” and “proteasome” were closely related to male sterility in Prunus sibirica. A total of 331 key genes were preliminarily screened. Conclusion The occurrence of male sterility in Prunus sibirica involved…
bibliographic citation: Chen et al. (2021) Transcriptomic analysis reveals candidate genes for male sterility in Prunus sibirica. PeerJ 9:e12349 https://doi.org/10.7717/peerj.12349
date submitted: 2021-03-23
date accepted: 2021-09-29
issued: 2021-10-20
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Chen
  given name: Jianhua
author list: Agent
  family name: Xu
  given name: Hao
author list: Agent
  family name: Zhang
  given name: Jian
author list: Agent
  family name: Dong
  given name: Shengjun
author list: Agent
  family name: Liu
  given name: Quangang
author list: Agent
  family name: Wang
  given name: Ruoxi
doi: 10.7717/peerj.12349
volume: 9
issn: 2167-8359
publication name: PeerJ
publication date: 2021-10-20
copyright: ©2021 Chen et al.
attribution name: Chen et al.

Effect of SARS-CoV-2 infection on host competing endogenous RNA and miRNA network
type: item
type: AcademicArticle
description: Competing endogenous RNAs (ceRNA) play a crucial role in cell functions. Computational methods that provide large-scale analysis of the interactions between miRNAs and their competitive targets can contribute to the understanding of ceRNA regulations and critical regulatory functions. Recent reports showed that viral RNAs can compete with host RNAs against host miRNAs. Regarding SARS-CoV-2 RNA, no comprehensive study had been reported about its competition with cellular ceRNAs. In this study, for the first time, we used the ceRNAnetsim package to assess ceRNA network effects per individual cell and competitive behavior of SARS-CoV-2 RNA in the infected cells using single-cell sequencing data. Our computations identified 195 genes and 29 miRNAs which vary in competitive behavior specifically in presence of SARS-CoV-2 RNA. We also investigated 18 genes that are affected by genes that lost perturbation ability in presence of SARS-CoV-2 RNA in the human miRNA:ceRNA network. These transcripts have associations with COVID-19-related symptoms as well as many dysfunctions such as metabolic diseases, carcinomas, heart failure. Our results showed that the effects of the SARS-CoV-2 genome on host ceRNA interactions and consequent dysfunctions can be explained by competition among various miRNA targets. Our perturbation ability perspective has the potential to reveal yet to be discovered SARS-CoV-2 induced effects invisible to conventional approaches.
format: application/pdf
format: text/html
creator: Selcen Ari Yuka
creator: Alper Yilmaz
subject: Bioinformatics
subject: Molecular Biology
subject: Virology
subject: COVID-19
description: doi:10.7717/peerj.12370
publisher: PeerJ Inc.
rights: © 2021 Ari Yuka and Yilmaz
abstract: Competing endogenous RNAs (ceRNA) play a crucial role in cell functions. Computational methods that provide large-scale analysis of the interactions between miRNAs and their competitive targets can contribute to the understanding of ceRNA regulations and critical regulatory functions. Recent reports showed that viral RNAs can compete with host RNAs against host miRNAs. Regarding SARS-CoV-2 RNA, no comprehensive study had been reported about its competition with cellular ceRNAs. In this study, for the first time, we used the ceRNAnetsim package to assess ceRNA network effects per individual cell and competitive behavior of SARS-CoV-2 RNA in the infected cells using single-cell sequencing data. Our computations identified 195 genes and 29 miRNAs which vary in competitive behavior specifically in presence of SARS-CoV-2 RNA. We also investigated 18 genes that are affected by genes that lost perturbation ability in presence of SARS-CoV-2 RNA in the human miRNA:ceRNA network. These transcripts have associations with COVID-19-related symptoms as well as many dysfunctions such as metabolic diseases, carcinomas, heart failure. Our results showed that the effects of the SARS-CoV-2 genome on host ceRNA interactions and consequent dysfunctions can be explained by competition among various miRNA targets. Our perturbation ability perspective has the potential to reveal yet to be discovered SARS-CoV-2 induced effects invisible to conventional approaches.
bibliographic citation: Ari Yuka et al. (2021) Effect of SARS-CoV-2 infection on host competing endogenous RNA and miRNA network. PeerJ 9:e12370 https://doi.org/10.7717/peerj.12370
date submitted: 2021-07-21
date accepted: 2021-10-01
issued: 2021-10-20
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Ari Yuka
  given name: Selcen
author list: Agent
  family name: Yilmaz
  given name: Alper
doi: 10.7717/peerj.12370
volume: 9
issn: 2167-8359
publication name: PeerJ
publication date: 2021-10-20
copyright: ©2021 Ari Yuka and Yilmaz
attribution name: Ari Yuka and Yilmaz

In silico evaluation of molecular virus–virus interactions taking place between Cotton leaf curl Kokhran virus- Burewala strain and Tomato leaf curl New Delhi virus
type: item
type: AcademicArticle
description: Background Cotton leaf curl disease (CLCuD) is a disease of cotton caused by begomoviruses, leading to a drastic loss in the annual yield of the crop. Pakistan has suffered two epidemics of this disease leading to the loss of billions in annual exports. The speculation that a third epidemic of CLCuD may result as consequence of the frequent occurrence of Tomato leaf curl New Delhi virus (ToLCNDV) and Cotton leaf curl Kokhran Virus-Burewala Strain (CLCuKoV-Bu) in CLCuD infected samples, demand that the interactions taking between the two viruses be properly evaluated. This study is designed to assess virus-virus interactions at the molecular level and determine the type of co-infection taking place. Methods Based on the amino acid sequences of the gene products of both CLCuKoV-Bu and ToLCNDV, protein structures were generated using different software, i.e., MODELLER, I-TASSER, QUARKS, LOMETS and RAPTORX. A consensus model for each protein was selected after model quality assessment using ERRAT, QMEANDisCo, PROCHECK Z-Score and Ramachandran plot analysis. The active and passive residues in the protein structures were identified using the CPORT server. Protein–Protein Docking was done using the HADDOCK webserver, and 169 Protein–Protein Interaction (PPIs) were performed between the proteins of the two viruses. The docked complexes were submitted to the PRODIGY server to identify the interacting residues between the complexes. The strongest interactions were determined based on the HADDOCK Score, Desolvation energy, Van der Waals Energy, Restraint Violation Energy, Electrostatic Energy, Buried Surface Area and Restraint Violation Energy, Binding Affinity and Dissociation constant (Kd). A total of 50 ns Molecular Dynamic simulations were performed on complexes that exhibited the strongest affinity in order to validate the stability of the complexes, and to remove any steric hindrances that may exist within the structures. Results Our results indicate significant interact…
format: application/pdf
format: text/html
creator: Nida Fatima Ali
creator: Rehan Zafar Paracha
creator: Muhammad Tahir
subject: Agricultural Science
subject: Bioinformatics
subject: Molecular Biology
subject: Plant Science
subject: Virology
description: doi:10.7717/peerj.12018
publisher: PeerJ Inc.
rights: © 2021 Ali et al.
abstract: Background Cotton leaf curl disease (CLCuD) is a disease of cotton caused by begomoviruses, leading to a drastic loss in the annual yield of the crop. Pakistan has suffered two epidemics of this disease leading to the loss of billions in annual exports. The speculation that a third epidemic of CLCuD may result as consequence of the frequent occurrence of Tomato leaf curl New Delhi virus (ToLCNDV) and Cotton leaf curl Kokhran Virus-Burewala Strain (CLCuKoV-Bu) in CLCuD infected samples, demand that the interactions taking between the two viruses be properly evaluated. This study is designed to assess virus-virus interactions at the molecular level and determine the type of co-infection taking place. Methods Based on the amino acid sequences of the gene products of both CLCuKoV-Bu and ToLCNDV, protein structures were generated using different software, i.e., MODELLER, I-TASSER, QUARKS, LOMETS and RAPTORX. A consensus model for each protein was selected after model quality assessment using ERRAT, QMEANDisCo, PROCHECK Z-Score and Ramachandran plot analysis. The active and passive residues in the protein structures were identified using the CPORT server. Protein–Protein Docking was done using the HADDOCK webserver, and 169 Protein–Protein Interaction (PPIs) were performed between the proteins of the two viruses. The docked complexes were submitted to the PRODIGY server to identify the interacting residues between the complexes. The strongest interactions were determined based on the HADDOCK Score, Desolvation energy, Van der Waals Energy, Restraint Violation Energy, Electrostatic Energy, Buried Surface Area and Restraint Violation Energy, Binding Affinity and Dissociation constant (Kd). A total of 50 ns Molecular Dynamic simulations were performed on complexes that exhibited the strongest affinity in order to validate the stability of the complexes, and to remove any steric hindrances that may exist within the structures. Results Our results indicate significant interact…
bibliographic citation: Ali et al. (2021) In silico evaluation of molecular virus–virus interactions taking place between Cotton leaf curl Kokhran virus- Burewala strain and Tomato leaf curl New Delhi virus. PeerJ 9:e12018 https://doi.org/10.7717/peerj.12018
date submitted: 2021-03-17
date accepted: 2021-07-29
issued: 2021-10-19
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Ali
  given name: Nida Fatima
author list: Agent
  family name: Paracha
  given name: Rehan Zafar
author list: Agent
  family name: Tahir
  given name: Muhammad
doi: 10.7717/peerj.12018
volume: 9
issn: 2167-8359
publication name: PeerJ
publication date: 2021-10-19
copyright: ©2021 Ali et al.
attribution name: Ali et al.

New phiocricetomyine rodents (Hystricognathi) from the Jebel Qatrani Formation, Fayum Depression, Egypt
type: item
type: AcademicArticle
description: Background The rich rodent assemblages from the Eocene–Oligocene deposits of the Jebel Qatrani Formation (Fayum Depression, Egypt) have important implications for our understanding of the origin and paleobiogeography of Hystricognathi, a diverse clade that is now represented by the Afro-Asiatic Hystricidae, New World Caviomorpha, and African Phiomorpha. Methods Here we present previously undescribed material of the enigmatic hystricognath clade Phiocricetomyinae, from two stratigraphic levels in the lower sequence of the Jebel Qatrani Formation—a new genus and species (Qatranimys safroutus) from the latest Eocene Locality 41 (~34 Ma, the oldest and most productive quarry in the formation) and additional material of Talahphiomys lavocati from that species’ type locality, early Oligocene Quarry E (~31–33.2 Ma). Results The multiple specimens of Qatranimys safroutus from L-41 document almost the entire lower and upper dentition, as well as mandibular fragments and the first cranial remains known for a derived phiocricetomyine. Specimens from Quarry E allow us to expand comparisons with specimens from Libya (late Eocene of Dur at-Talah and early Oligocene of Zallah Oasis) that have been placed in T. lavocati, and we show that the Dur at-Talah and Zallah specimens do not pertain to this species. These observations leave the Fayum Quarry E as the only locality where T. lavocati occurs.
format: application/pdf
format: text/html
creator: Shorouq F. Al-Ashqar
creator: Erik R. Seiffert
creator: Dorien de Vries
creator: Sanaa El-Sayed
creator: Mohamed S. Antar
creator: Hesham M. Sallam
subject: Biodiversity
subject: Evolutionary Studies
subject: Paleontology
subject: Zoology
description: doi:10.7717/peerj.12074
publisher: PeerJ Inc.
rights: © 2021 Al-Ashqar et al.
abstract: Background The rich rodent assemblages from the Eocene–Oligocene deposits of the Jebel Qatrani Formation (Fayum Depression, Egypt) have important implications for our understanding of the origin and paleobiogeography of Hystricognathi, a diverse clade that is now represented by the Afro-Asiatic Hystricidae, New World Caviomorpha, and African Phiomorpha. Methods Here we present previously undescribed material of the enigmatic hystricognath clade Phiocricetomyinae, from two stratigraphic levels in the lower sequence of the Jebel Qatrani Formation—a new genus and species (Qatranimys safroutus) from the latest Eocene Locality 41 (~34 Ma, the oldest and most productive quarry in the formation) and additional material of Talahphiomys lavocati from that species’ type locality, early Oligocene Quarry E (~31–33.2 Ma). Results The multiple specimens of Qatranimys safroutus from L-41 document almost the entire lower and upper dentition, as well as mandibular fragments and the first cranial remains known for a derived phiocricetomyine. Specimens from Quarry E allow us to expand comparisons with specimens from Libya (late Eocene of Dur at-Talah and early Oligocene of Zallah Oasis) that have been placed in T. lavocati, and we show that the Dur at-Talah and Zallah specimens do not pertain to this species. These observations leave the Fayum Quarry E as the only locality where T. lavocati occurs.
bibliographic citation: Al-Ashqar et al. (2021) New phiocricetomyine rodents (Hystricognathi) from the Jebel Qatrani Formation, Fayum Depression, Egypt. PeerJ 9:e12074 https://doi.org/10.7717/peerj.12074
date submitted: 2021-02-18
date accepted: 2021-08-05
issued: 2021-10-19
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Al-Ashqar
  given name: Shorouq F.
author list: Agent
  family name: Seiffert
  given name: Erik R.
author list: Agent
  family name: de Vries
  given name: Dorien
author list: Agent
  family name: El-Sayed
  given name: Sanaa
author list: Agent
  family name: Antar
  given name: Mohamed S.
author list: Agent
  family name: Sallam
  given name: Hesham M.
doi: 10.7717/peerj.12074
volume: 9
issn: 2167-8359
publication name: PeerJ
publication date: 2021-10-19
copyright: © 2021 Al-Ashqar et al.
attribution name: Al-Ashqar et al.

Visual assessment of dynamic knee joint alignment in patients with patellofemoral pain: an agreement study
type: item
type: AcademicArticle
description: Background Assessment of knee kinematics plays an important role in the clinical examination of patients with patellofemoral pain (PFP). There is evidence that visual assessments are reliable in healthy subjects, but there is a lack of evidence in injured populations. The purpose of this study was to examine the intra- and interrater agreement in the visual assessment of dynamic knee joint alignment in patients with PFP. Methods The study was a cross-sectional agreement study. Sixty participants (42 females) were included. We assessed the intra- and interrater agreement of two functional tests: The single leg squat (SLS) and the forward lunge (FL). One investigator scored the movement according to preset criteria while video recording the movement for retest. Moreover, the performance was scored by another investigator using the video recording. Agreement was assessed using weighted kappa statistics. Results The intrarater agreement ranged from moderate to good (Kappa 0.58 (FL) to 0.70 (SLS)) whereas the interrater agreement ranged from fair to moderate (Kappa 0.22 (SLS) to 0.50 (FL)). Conclusion The agreement within raters was better than between raters, which suggests that assessments should preferably be performed by the same tester in research and in a clinical setting, e.g., to evaluate any treatment effect. We promote FL as a reliable clinical tool for evaluating dynamic knee alignment, since it shows equally good intra- and interrater agreement, and it is an inexpensive and easy method to use.
format: application/pdf
format: text/html
creator: Rudi Hansen
creator: Mathilde Lundgaard-Nielsen
creator: Marius Henriksen
subject: Anesthesiology and Pain Management
subject: Orthopedics
subject: Rheumatology
subject: Biomechanics
description: doi:10.7717/peerj.12203
publisher: PeerJ Inc.
rights: © 2021 Hansen et al.
abstract: Background Assessment of knee kinematics plays an important role in the clinical examination of patients with patellofemoral pain (PFP). There is evidence that visual assessments are reliable in healthy subjects, but there is a lack of evidence in injured populations. The purpose of this study was to examine the intra- and interrater agreement in the visual assessment of dynamic knee joint alignment in patients with PFP. Methods The study was a cross-sectional agreement study. Sixty participants (42 females) were included. We assessed the intra- and interrater agreement of two functional tests: The single leg squat (SLS) and the forward lunge (FL). One investigator scored the movement according to preset criteria while video recording the movement for retest. Moreover, the performance was scored by another investigator using the video recording. Agreement was assessed using weighted kappa statistics. Results The intrarater agreement ranged from moderate to good (Kappa 0.58 (FL) to 0.70 (SLS)) whereas the interrater agreement ranged from fair to moderate (Kappa 0.22 (SLS) to 0.50 (FL)). Conclusion The agreement within raters was better than between raters, which suggests that assessments should preferably be performed by the same tester in research and in a clinical setting, e.g., to evaluate any treatment effect. We promote FL as a reliable clinical tool for evaluating dynamic knee alignment, since it shows equally good intra- and interrater agreement, and it is an inexpensive and easy method to use.
bibliographic citation: Hansen et al. (2021) Visual assessment of dynamic knee joint alignment in patients with patellofemoral pain: an agreement study. PeerJ 9:e12203 https://doi.org/10.7717/peerj.12203
date submitted: 2021-06-17
date accepted: 2021-09-02
issued: 2021-10-19
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Hansen
  given name: Rudi
author list: Agent
  family name: Lundgaard-Nielsen
  given name: Mathilde
author list: Agent
  family name: Henriksen
  given name: Marius
doi: 10.7717/peerj.12203
volume: 9
issn: 2167-8359
publication name: PeerJ
publication date: 2021-10-19
copyright: ©2021 Hansen et al.
attribution name: Hansen et al.

Upright walking has driven unique vascular specialization of the hominin ilium
type: item
type: AcademicArticle
description: Background A novel physis in hominins modulates broadening and shortening of the ilium. We report analysis of a vascular canal system whose origin may be associated with this physis and which appears to be also unique to hominins. Its presence is potentially identifiable in the fossil record by its association with a highly enlarged foramen that is consistently present in modern humans and hominin fossils. Methods We measured the diameter of this foramen in humans, fossil hominins, and African great apes and corrected for body size. Results The mean relative human foramen diameter is significantly greater than those of either Pan or Gorilla. Moreover, eight of the nine values of the Cohen’s d for these differences in ratios are highly significant and support the ordering of magnitudes: Pan < Gorilla < Homo. The relative foramen diameter of A.L. 288-1 is above the 75th percentile of all other hominoids and at the high end of humans. The foramen is also present in ARA-VP-6/500. Conclusions We posit that the presence and significant enlargement of this foramen in fossils can reasonably serve as an indicator that its anterior inferior iliac spine emerged via the unique hominin physis. The foramen can therefore serve as an indicator of hominin iliac ontogenetic specialization for bipedality in fossil taxa.
format: application/pdf
format: text/html
creator: Dexter Zirkle
creator: Richard S. Meindl
creator: C. Owen Lovejoy
subject: Anthropology
subject: Evolutionary Studies
subject: Zoology
subject: Anatomy and Physiology
description: doi:10.7717/peerj.12240
publisher: PeerJ Inc.
rights: © 2021 Zirkle et al.
abstract: Background A novel physis in hominins modulates broadening and shortening of the ilium. We report analysis of a vascular canal system whose origin may be associated with this physis and which appears to be also unique to hominins. Its presence is potentially identifiable in the fossil record by its association with a highly enlarged foramen that is consistently present in modern humans and hominin fossils. Methods We measured the diameter of this foramen in humans, fossil hominins, and African great apes and corrected for body size. Results The mean relative human foramen diameter is significantly greater than those of either Pan or Gorilla. Moreover, eight of the nine values of the Cohen’s d for these differences in ratios are highly significant and support the ordering of magnitudes: Pan < Gorilla < Homo. The relative foramen diameter of A.L. 288-1 is above the 75th percentile of all other hominoids and at the high end of humans. The foramen is also present in ARA-VP-6/500. Conclusions We posit that the presence and significant enlargement of this foramen in fossils can reasonably serve as an indicator that its anterior inferior iliac spine emerged via the unique hominin physis. The foramen can therefore serve as an indicator of hominin iliac ontogenetic specialization for bipedality in fossil taxa.
bibliographic citation: Zirkle et al. (2021) Upright walking has driven unique vascular specialization of the hominin ilium. PeerJ 9:e12240 https://doi.org/10.7717/peerj.12240
date submitted: 2021-07-16
date accepted: 2021-09-12
issued: 2021-10-19
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Zirkle
  given name: Dexter
author list: Agent
  family name: Meindl
  given name: Richard S.
author list: Agent
  family name: Lovejoy
  given name: C. Owen
doi: 10.7717/peerj.12240
volume: 9
issn: 2167-8359
publication name: PeerJ
publication date: 2021-10-19
copyright: © 2021 Zirkle et al.
attribution name: Zirkle et al.

PeerJ
type: Periodical
uri: PeerJ
issn: 2167-8359