title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=1026 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Integrated network pharmacology and molecular docking approaches to reveal the synergistic mechanism of multiple components in Venenum Bufonis for ameliorating heart failure link: https://peerj.com/articles/10107 last-modified: 2020-10-30 description: Venenum Bufonis (VB), also called Chan Su in China, has been extensively used as a traditional Chinese medicine (TCM) for treating heart failure (HF) since ancient time. However, the active components and the potential anti-HF mechanism of VB remain unclear. In the current study, the major absorbed components and metabolites of VB after oral administration in rats were first collected from literatures. A total of 17 prototypes and 25 metabolites were gathered. Next, a feasible network-based pharmacological approach was developed and employed to explore the therapeutic mechanism of VB on HF based on the collected constituents. In total, 158 main targets were screened out and considered as effective players in ameliorating HF. Then, the VB components–main HF putative targets–main pathways network was established, clarifying the underlying biological process of VB on HF. More importantly, the main hubs were found to be highly enriched in adrenergic signalling in cardio-myocytes. After verified by molecular docking studies, four key targets (ATP1A1, GNAS, MAPK1 and PRKCA) and three potential active leading compounds (bufotalin, cinobufaginol and 19-oxo-bufalin) were identified, which may play critical roles in cardiac muscle contraction. This study demonstrated that the integrated strategy based on network pharmacology and molecular docking was helpful to uncover the synergistic mechanism of multiple constituents in TCM. creator: Wei Ren creator: Zhiqiang Luo creator: Fulu Pan creator: Jiali Liu creator: Qin Sun creator: Gang Luo creator: Raoqiong Wang creator: Haiyu Zhao creator: Baolin Bian creator: Xiao Xiao creator: Qingrong Pu creator: Sijin Yang creator: Guohua Yu uri: https://doi.org/10.7717/peerj.10107 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Ren et al. title: Biases in genome reconstruction from metagenomic data link: https://peerj.com/articles/10119 last-modified: 2020-10-30 description: BackgroundAdvances in sequencing, assembly, and assortment of contigs into species-specific bins has enabled the reconstruction of genomes from metagenomic data (MAGs). Though a powerful technique, it is difficult to determine whether assembly and binning techniques are accurate when applied to environmental metagenomes due to a lack of complete reference genome sequences against which to check the resulting MAGs.MethodsWe compared MAGs derived from an enrichment culture containing ~20 organisms to complete genome sequences of 10 organisms isolated from the enrichment culture. Factors commonly considered in binning software—nucleotide composition and sequence repetitiveness—were calculated for both the correctly binned and not-binned regions. This direct comparison revealed biases in sequence characteristics and gene content in the not-binned regions. Additionally, the composition of three public data sets representing MAGs reconstructed from the Tara Oceans metagenomic data was compared to a set of representative genomes available through NCBI RefSeq to verify that the biases identified were observable in more complex data sets and using three contemporary binning software packages.ResultsRepeat sequences were frequently not binned in the genome reconstruction processes, as were sequence regions with variant nucleotide composition. Genes encoded on the not-binned regions were strongly biased towards ribosomal RNAs, transfer RNAs, mobile element functions and genes of unknown function. Our results support genome reconstruction as a robust process and suggest that reconstructions determined to be >90% complete are likely to effectively represent organismal function; however, population-level genotypic heterogeneity in natural populations, such as uneven distribution of plasmids, can lead to incorrect inferences. creator: William C. Nelson creator: Benjamin J. Tully creator: Jennifer M. Mobberley uri: https://doi.org/10.7717/peerj.10119 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Nelson et al. title: Revalidation of morphological characteristics and multiplex PCR for the identification of three congener invasive Liriomyza species (Diptera: Agromyzidae) in China link: https://peerj.com/articles/10138 last-modified: 2020-10-30 description: Due to varietal differences, diminutive size, and similar morphological characters, it is difficult to classify and identify Liriomyza spp., a genus comprised of economically-important, highly-polyphagous insect pests. In this study, we reconfirmed the morphological characteristics of three closely-related invasive leafminers, L. trifolii, L. sativae, and L. huidobrensis. Morphological results showed that characteristics imparted by the male genitalia were the most reliable morphological features for identification. The colors exhibited by vertical setae were variable among species, and the ratio of the length of the ultimate section of vein CuA1 divided by penultimate section also varied within species. Although the patterns of abdominal tergites were diverse among Liriomyza spp., L. trifolii exhibited a unique pattern with a yellow patch at the 5th black visible tergite; this pattern can be profiled as a prominent characteristic for morphological identification. In order to identify the three Liriomyza spp. quickly and accurately, we developed an improved molecular identification method using multiplex PCR based on the gene encoding mitochondrial cytochrome oxidase I (COI); this method enabled direct identification based on the size of amplified products. The results of this study provide a valuable reference for the identification of Liriomyza spp., which will ultimately improve our ability to control individual species. creator: Ya-Wen Chang creator: Jing-Yun Chen creator: Si-Zhu Zheng creator: Yuan Gao creator: Yunfang Chen creator: Yanfeng Deng creator: Yu-Zhou Du uri: https://doi.org/10.7717/peerj.10138 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Chang et al. title: Social cognition and social functioning in people with borderline personality disorder and their first-degree relatives link: https://peerj.com/articles/10212 last-modified: 2020-10-30 description: BackgroundA few papers studying healthy, first-degree relatives of people with borderline personality disorder (BPD) have found that this group presents attention and memory problems. However, current research has not analyzed their social cognition.Materials and MethodsWe designed an age-, gender- and education-level matched case-control study involving 57 people with BPD, 32 of their first-degree relatives, and 57 healthy controls in Spain in 2018–2019. All were assessed for social cognition and functioning using the Movie for Assessment of Social Cognition and the Social Functioning Scale; other potential confounders were also collected (marital status, occupation and household variables).ResultsThere were differences in the social cognition domain of overmentalizing errors, with the BPD group scoring significantly higher than controls; however, there was no significant difference with relatives; in the social functioning domain of family relationships, with the controls showing the highest scores. Social engagement/withdrawal, interpersonal behavior, independence-competence, prosocial activities, full scale and categorization domains showed the same pattern: the BPD group had lower scores than their relatives and the controls. Relatives were significantly different from BPD patients in family relationships, social engagement/withdrawal and interpersonal behavior, as well as on the full Social Functioning Scale (both as a linear and categorical variable). However, only controls showed differences with relatives in family relationships.ConclusionsAll in all, relatives show similar levels of social cognition and functioning compared with controls, and people with BPD show some alterations in different domains of both social cognition and functioning. creator: Esther Ortega-Díaz creator: Jonatan García-Campos creator: José María Rico-Gomis creator: Carlos Cuesta-Moreno creator: Antonio Palazón-Bru creator: Gabriel Estañ-Cerezo creator: José Antonio Piqueras-Rodríguez creator: Jesús Rodríguez-Marín uri: https://doi.org/10.7717/peerj.10212 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Ortega-Díaz et al. title: Genetic variations and dog breed identification using inter-simple sequence repeat markers coupled with high resolution melting analysis link: https://peerj.com/articles/10215 last-modified: 2020-10-30 description: The identification of differing physical characteristics of dogs is an uncomplicated and straightforward way to categorize dog breeds. However, many dog owners and veterinarians still struggle to distinguish between pure breed and mixed variations in certain breeds of dogs. Presently, the absence of the tools and methods needed to confirm a pure breed dog is a significant problem since the only method available to validate pure or mongrel breeds is the official pedigree system. Inter-simple sequence repeat markers have been successfully used to assess genetic variations and differentiations. Notably, inter-simple sequence repeat markers coupled with high resolution melting analysis were effectively used for the breed identification of 43 breeds of dogs (total 463 dogs). The 10 primers chosen for analysis resulted in a range of 31–78.6% of breed discrimination when using one primer, while a combination of two primers was able to successfully discriminate between all of the 43 dog breeds (100%). Shannon’s index information (I = 2.586 ± 0.034) and expected heterozygosity (He = 0.908 ± 0.003) indicated a high level of genetic diversity among breeds. The fixation index (Fst) revealed a value of 10.4%, demonstrating that there was a high level of genetic subdivision between populations. This study showed that inter-simple sequence repeat marker analysis was effective in demonstrating high genetic diversity among varying breeds of dogs, while a combination of Inter-simple sequence repeat marker analysis and high resolution melting analysis could provide an optional technique for researchers to effectively identify breeds through genetic variations. creator: Wannapimol Kriangwanich creator: Korakot Nganvongpanit creator: Kittisak Buddhachat creator: Puntita Siengdee creator: Siriwadee Chomdej creator: Siriluck Ponsuksili creator: Chatchote Thitaram uri: https://doi.org/10.7717/peerj.10215 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Kriangwanich et al. title: Construction of fibronectin conditional gene knock-out mice and the effect of fibronectin gene knockout on hematopoietic, biochemical and immune parameters in mice link: https://peerj.com/articles/10224 last-modified: 2020-10-30 description: Fibronectin (FN) is a multi-functional glycoprotein that primarily acts as a cell adhesion molecule and tethers cells to the extra cellular matrix. In order to clarify the effect of FN deficiency on hematopoiesis, biochemical and immune parameters in mice. We constructed a tamoxifen-induced conditional (cre-loxp system) fibronectin knock-out (FnKO) mouse model on a C57BL/6 background, and monitored their behavior, fertility, histological, hematopoietic, biochemical and immunological indices. We found that the Fn KO mice had reduced fertility, high platelet counts, smaller bone marrow megakaryocytes and looser attachment between the hepatocyte and vascular endothelial junctions compared to the wild type (WT) mice. In contrast, the behavior, hematological counts, serum biochemical indices and vital organ histology were similar in both Fn KO and WT mice. This model will greatly help in elucidating the role of FN in immune-related diseases in future. creator: Xiaohong Yuan creator: Shu Yang creator: Wen Li creator: Jinggang Li creator: Jia Lin creator: Yong Wu creator: Yuanzhong Chen uri: https://doi.org/10.7717/peerj.10224 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Yuan et al. title: Cytological and molecular characterizations of a novel 2A nullisomic line derived from a widely-grown wheat cultivar Zhoumai 18 conferring male sterility link: https://peerj.com/articles/10275 last-modified: 2020-10-30 description: A dwarf, multi-pistil and male sterile dms mutant was previously reported by us. However, the genetic changes in this dms are unclear. To examine the genetic changes, single nucleotide polymorphism (SNP) association, chromosome counting, and high-resolution chromosome fluorescence in situ hybridization (FISH) techniques were employed. By comparing tall plants (T) with dwarf plants (D) in the offspring of dms mutant plants, SNP association analysis indicated that most SNPs were on chromosome 2A. There were three types in offspring of dms plants, with 42, 41 and 40 chromosomes respectively. High-resolution chromosome painting analysis demonstrated that T plants had all 42 wheat chromosomes; the medium plants (M) had 41 chromosomes, lacking one chromosome 2A; while D plants had 40 wheat chromosomes, and lacked both 2A chromosomes. These data demonstrated that dms resulted from a loss of chromosome 2A. We identified 23 genes on chromosome 2A which might be involved in the development of stamens or pollen grains. These results lay a solid foundation for further analysis of the molecular mechanisms of wheat male sterility. Because D plants can be used as a female parent to cross with other wheat genotypes, dms is a unique germplasm for any functional study of chromosome 2A and wheat breeding specifically targeting genes on 2A. creator: Zhixin Jiao creator: Xinxin Zhu creator: Huijuan Li creator: Zhitao Liu creator: Xinyi Huang creator: Nan Wu creator: Junhang An creator: Junchang Li creator: Jing Zhang creator: Yumei Jiang creator: Qiaoyun Li creator: Zengjun Qi creator: Jishan Niu uri: https://doi.org/10.7717/peerj.10275 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Jiao et al. title: On local scouring downstream small water structures link: https://peerj.com/articles/10282 last-modified: 2020-10-30 description: BackgroundIn order to regulate water flow, hydraulic structures such as weirs or checks, frequently equipped with gates, are used. Water can flow below or over the gate or, simultaneously, over and below the gate. Both diversifications of hydraulic gradient, being an effect of damming up a river by the structure and shear stresses at the bed, which exceeds the critical shear stress value, invoke the local scouring downstream the structure. This phenomenon has been studied in laboratory and field conditions for many years, however Researchers do not agree on the parameters that affect the size of the local scour and the intensity of its formation. There are no universal methods for estimating its magnitude However, solutions are sought in the form of calculation formulas typical for the method of flow through the structure, taking into account the parameters that characterize a given structure. These formulas are based on factors that affect the size of the local scours, that is, their dimensions and location. Examples of such formulas are those contained in this article: Franke (1960), Straube (1963), Tarajmovič (1966), Rossinski & Kuzmin (1969) equations. The need to study this phenomenon results from the prevalence of hydrotechnical structures equipped with gates (from small gated checks to large weirs) and from potential damage that may be associated with excessive development of local erosion downstream, including washing of foundations and, consequently, loss of stability of the structure.MethodsThis study verifies empirical formulas applied to estimate the geometry parameters of a scour hole on a laboratory model of a structure where water is conducted downstream the gate with bottom reinforcements of various roughness. A specially designed remote-controlled measuring device, equipped with laser scanner, was applied to determine the shape of the sandy bottom. Then the formula optimization is conducted, using Monte Carlo sampling method, followed by verification of field conditions.ResultsThe suitability of a specially designed device, equipped with laser scanner for measuring the bottom shape in laboratory conditions was demonstrated. Simple formula describing local scour geometry in laboratory conditions was derived basing on the Straube formula. The optimized formula was verified in field conditions giving very good comparative results. Therefore, it can be applied in engineering and designing practices. creator: Marta Kiraga creator: Zbigniew Popek uri: https://doi.org/10.7717/peerj.10282 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Kiraga and Popek title: A review of Euryoryzomys legatus (Rodentia, Sigmodontinae): morphological redescription, cytogenetics, and molecular phylogeny link: https://peerj.com/articles/9884 last-modified: 2020-10-29 description: The taxonomic history of Euryoryzomys legatus has been complex and controversial, being either included in the synonymy of other oryzomyine species or considered as a valid species, as in the most recent review of the genus. Previous phylogenetic analyses segregated E. legatus from E. russatus, its putative senior synonym, but recovered it nested within E. nitidus. A general lack of authoritative evaluation of morphological attributes, details of the chromosome complement, or other data types has hampered the ability to choose among alternative taxonomic hypotheses, and thus reach a general consensus for the status of the taxon. Herein we revisit the status of E. legatus using an integrated approach that includes: (1) a morphological review, especially centered on specimens from northwestern Argentina not examined previously, (2) comparative cytogenetics, and (3) phylogenetic reconstruction, using mitochondrial genes. Euryoryzomys legatus is morphologically and phylogenetically distinct from all other species-level taxa in the genus, but its 2n=80, FN=86 karyotype is shared with E. emmonsae, E. nitidus, and E. russatus. Several morphological and morphometric characters distinguish E. legatus from other species of Euryoryzomys, and we provide an amended diagnosis for the species. Morphological characters useful in distinguishing E. legatus from E. nitidus, its sister taxon following molecular analyses, include: larger overall size, dorsal fur with a strong yellowish brown to orange brown tinge, flanks and cheeks with an orange lateral line, ventral color grayish-white with pure white hairs present only on the chin, presence of a thin blackish eye-ring, tail bicolored, presence of an alisphenoid strut and a well-developed temporal and lambdoid crests in the skull, and a labial cingulum on M3. Molecular phylogenetic analyses recovered E. legatus as a monophyletic group with high support nested within a paraphyletic E. nitidus; genetic distances segregated members of both species, except for an exemplar of E. nitidus. Our integrated analyses reinforce E. legatus as a full species, but highlight that E. macconnelli, E. emmonsae, and E. nitidus each may be a species complex and worthy of systematic attention. Finally, we also evaluated the chromosome evolution of the genus within a phylogenetic context. creator: Mariana D. Guilardi creator: Pablo Jayat creator: Marcelo Weksler creator: James L. Patton creator: Pablo Edmundo Ortiz creator: Keila Almeida creator: Maria José de J. Silva uri: https://doi.org/10.7717/peerj.9884 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Guilardi et al. title: A 14 immune-related gene signature predicts clinical outcomes of kidney renal clear cell carcinoma link: https://peerj.com/articles/10183 last-modified: 2020-10-29 description: Kidney renal clear cell carcinoma (KIRC) is the leading cause of kidney cancer-related deaths. Currently, there are no studies in tumor immunology investigating the use of signatures as a predictor of overall survival in KIRC patients. Our study attempts to establish an immune-related gene risk signature to predict clinical outcomes in KIRC. A total of 528 patients from The Cancer Genome Atlas (TCGA) database were included in our analysis and randomly divided into training (n = 315) and testing sets (n = 213). We collected 1,534 immune-related genes from the Immunology Database and Analysis Portal as candidates to construct our signature. LASSO-COX was used to find gene models with the highest predictive ability. We used survival and Cox analysis to test the model’s independent prognostic ability. Univariate analysis identified 650 immune-related genes with prognostic abilities. After 1,000 iterations, we choose 14 of the most frequent and stable immune-related genes as our signature. We found that the signature was associated with M stage, T stage, and pathological staging. More importantly, the signature can independently predict clinical prognosis in KIRC patients. Gene Set Enrichment Analysis (GSEA) showed an association between our signature and critical metabolism pathways. Our research established a model based upon 14 immune-related genes that predicted the prognosis of KIRC patients based on tumor immune microenvironments. creator: Yong Zou creator: Chuan Hu uri: https://doi.org/10.7717/peerj.10183 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Zou and Hu