title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=720 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Network subgraph-based approach for analyzing and comparing molecular networks link: https://peerj.com/articles/13137 last-modified: 2022-05-03 description: Molecular networks are built up from genetic elements that exhibit feedback interactions. Here, we studied the problem of measuring the similarity of directed networks by proposing a novel alignment-free approach: the network subgraph-based approach. Our approach does not make use of randomized networks to determine modular patterns embedded in a network, and this method differs from the network motif and graphlet methods. Network similarity was quantified by gauging the difference between the subgraph frequency distributions of two networks using Jensen–Shannon entropy. We applied the subgraph approach to study three types of molecular networks, i.e., cancer networks, signal transduction networks, and cellular process networks, which exhibit diverse molecular functions. We compared the performance of our subgraph detection algorithm with other algorithms, and the results were consistent, but other algorithms could not address the issue of subgraphs/motifs embedded within a subgraph/motif. To evaluate the effectiveness of the subgraph-based method, we applied the method along with the Jensen–Shannon entropy to classify six network models, and it achieves a 100% accuracy of classification. The proposed information-theoretic approach allows us to determine the structural similarity of two networks regardless of node identity and network size. We demonstrated the effectiveness of the subgraph approach to cluster molecular networks that exhibit similar regulatory interaction topologies. As an illustration, our method can identify (i) common subgraph-mediated signal transduction and/or cellular processes in AML and pancreatic cancer, and (ii) scaffold proteins in gastric cancer and hepatocellular carcinoma; thus, the results suggested that there are common regulation modules for cancer formation. We also found that the underlying substructures of the molecular networks are dominated by irreducible subgraphs; this feature is valid for the three classes of molecular networks we studied. The subgraph-based approach provides a systematic scenario for analyzing, compare and classifying molecular networks with diverse functionalities. creator: Chien-Hung Huang creator: Efendi Zaenudin creator: Jeffrey J.P. Tsai creator: Nilubon Kurubanjerdjit creator: Ka-Lok Ng uri: https://doi.org/10.7717/peerj.13137 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Huang et al. title: Genome-wide identification of the SWEET gene family mediating the cold stress response in Prunus mume link: https://peerj.com/articles/13273 last-modified: 2022-05-03 description: The Sugars Will Eventually be Exported Transporter (SWEET) gene family encodes a family of sugar transporters that play essential roles in plant growth, reproduction, and biotic and abiotic stresses. Prunus mume is a considerable ornamental wood plant with high edible and medicinal values; however, its lack of tolerance to low temperature has severely limited its geographical distribution. To investigate whether this gene family mediates the response of P. mume to cold stress, we identified that the P. mume gene family consists of 17 members and divided the family members into four groups. Sixteen of these genes were anchored on six chromosomes, and one gene was anchored on the scaffold with four pairs of segmental gene duplications and two pairs of tandem gene duplications. Cis-acting regulatory element analysis indicated that the PmSWEET genes are potentially involved in P. mume development, including potentially regulating roles in procedure, such as circadian control, abscisic acid-response and light-response, and responses to numerous stresses, such as low-temperature and drought. We performed low-temperature treatment in the cold-tolerant cultivar ‘Songchun’ and cold-sensitive cultivar ‘Zaolve’ and found that the expression of four of 17 PmSWEETs was either upregulated or downregulated with prolonged treatment times. This finding indicates that these family members may potentially play a role in cold stress responses in P. mume. Our study provides a basis for further investigation of the role of SWEET proteins in the development of P. mume and its responses to cold stress. creator: Zhenying Wen creator: Mingyu Li creator: Juan Meng creator: Ping Li creator: Tangren Cheng creator: Qixiang Zhang creator: Lidan Sun uri: https://doi.org/10.7717/peerj.13273 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Wen et al. title: Reassessment of Faxinalipterus minimus, a purported Triassic pterosaur from southern Brazil with the description of a new taxon link: https://peerj.com/articles/13276 last-modified: 2022-05-03 description: Faxinalipterus minimus was originally described as a purported pterosaur from the Late Triassic (early Norian) Caturrita Formation of southern Brazil. Its holotype comprises fragmentary postcranial elements, whereas a partial maxilla was referred to the species. The assignment of Faxinalipterus minimus to Pterosauria has been questioned by some studies, but the specimen has never been accessed in detail after its original description. Here we provide a reassessment of Faxinalipterus minimus after additional mechanical preparation of the holotype. Our interpretations on the identity of several bones differ from those of the original description, and we found no support favoring pterosaur affinities for the taxon. The maxilla previously referred to Faxinalipterus minimus is disassociated from this taxon and referred to a new putative pterosauromorph described here from a partial skull and fragmentary postcranial elements. Maehary bonapartei gen. et sp. nov. comes from the same fossiliferous site that yielded Faxinalipterus minimus, but the lack of overlapping bones hampers comparisons between the two taxa. Our phylogenetic analysis places Faxinalipterus minimus within Lagerpetidae and Maehary bonapartei gen. et sp. nov. as the earliest-diverging member of Pterosauromorpha. Furthermore, the peculiar morphology of the new taxon reveals a new dental morphotype for archosaurs, characterized by conical, unserrated crowns, with a pair of apicobasally oriented grooves. These two enigmatic archosaurs expand our knowledge on the Caturrita Formation fauna and reinforce the importance of its beds on the understanding of Late Triassic ecosystems. creator: Alexander W.A. Kellner creator: Borja Holgado creator: Orlando Grillo creator: Flávio Augusto Pretto creator: Leonardo Kerber creator: Felipe Lima Pinheiro creator: Marina Bento Soares creator: Cesar Leandro Schultz creator: Ricardo Tadeu Lopes creator: Olga Araújo creator: Rodrigo Temp Müller uri: https://doi.org/10.7717/peerj.13276 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Kellner et al. title: Climate change influences on the geographic distributional potential of the spotted fever vectors Amblyomma maculatum and Dermacentor andersoni link: https://peerj.com/articles/13279 last-modified: 2022-05-03 description: Amblyomma maculatum (Gulf Coast tick), and Dermacentor andersoni (Rocky Mountain wood tick) are two North American ticks that transmit spotted fevers associated Rickettsia. Amblyomma maculatum transmits Rickettsia parkeri and Francisella tularensis, while D. andersoni transmits R. rickettsii, Anaplasma marginale, Coltivirus (Colorado tick fever virus), and F. tularensis. Increases in temperature causes mild winters and more extreme dry periods during summers, which will affect tick populations in unknown ways. Here, we used ecological niche modeling (ENM) to assess the potential geographic distributions of these two medically important vector species in North America under current condition and then transfer those models to the future under different future climate scenarios with special interest in highlighting new potential expansion areas. Current model predictions for A. maculatum showed suitable areas across the southern and Midwest United States, and east coast, western and southern Mexico. For D. andersoni, our models showed broad suitable areas across northwestern United States. New potential for range expansions was anticipated for both tick species northward in response to climate change, extending across the Midwest and New England for A. maculatum, and still farther north into Canada for D. andersoni. creator: Abdelghafar Alkishe creator: A. Townsend Peterson uri: https://doi.org/10.7717/peerj.13279 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Alkishe and Peterson title: Spatial heterogeneity of soil nutrients in Yili River Valley link: https://peerj.com/articles/13311 last-modified: 2022-05-03 description: Soil nutrients are a vital reference index of soil fertility and are essential in studying spatial variability for the development of land resources. The traditional statistical methods including correlation analysis and geostatistical analysis, were used to explore the spatial variability of nutrients and its influencing factors in the Yili River Valley. The results showed that soil total potassium (STK) had a weak variation, soil organic carbon (SOC), soil total nitrogen (STN) and soil total phosphorus (STP) showed a moderate degree of variation. Correlation analysis showed that SOC had a significant correlation with STN, STP, STK, silt, soil water content (SWC), Cos a and altitude (p < 0.01). In contrast, negative correlations were found between the SOC and sand, soil bulk density (SBD) and pH (p < 0.01), the same as STN. STP had a significant correlation with STK, silt (p < 0.01) and Cos a (p < 0.05), whereas negative correlations were found between the STP, sand and SBD (p < 0.01). STK had a significant correlation with silt, whereas negative correlations were found between the STK, sand and SBD. Ordinary Kriging interpolation showed that the distribution of SOC and STN had a high value in the northeast, northwest and southeast, and a low value in the central and southwest. STP was high in the northwest and southeast and low in the northeast and southwest. STK was high in the northwest and northeast and low in the central and southeast regions. This is helpful for the rational exploitation of land resources in ecological economy development in the Yili River Basin. creator: Guojun Sun creator: Haijun Liu creator: Dong Cui creator: Chunmei Chai uri: https://doi.org/10.7717/peerj.13311 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Sun et al. title: Glucocorticoids induce osteonecrosis of the femoral head in rats via PI3K/AKT/FOXO1 signaling pathway link: https://peerj.com/articles/13319 last-modified: 2022-05-03 description: BackgroundSteroid-induced osteonecrosis of the femoral head (SONFH) is a disorder that causes severe disability in patients and has a high incidence worldwide. Although glucocorticoid (GC)-induced apoptosis of osteoblasts is an important cytological basis of SONFH, the detailed mechanism underlying SONFH pathogenesis remains elusive. PI3K/AKT signaling pathway was reported to involve in cell survival and apoptosis.ObjectiveWe explored the role of PI3K/AKT/FOXO1 signaling pathway and its downstream targets during glucocorticoid -induced osteonecrosis of the femoral head.MethodsWe obtained gene expression profile of osteoblasts subjected to dexamethasone (Dex) treatment from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened out and functional enrichment analysis were conducted by bioinformatics analysis. In vitro, we analyzed Dex-induced apoptosis in MC3T3-E1 cells and explored the role of PI3K/AKT/FOXO1 signaling pathway in this phenomenon by employing siRNA-FOXO1 and IGF-1(PI3K/AKT agonist). Finally, we verified our results in a rat model of SONFH.ResultsIn Dex-treated osteoblasts, DEGs were mainly enriched in the FOXO signaling pathway. Dex inhibited MC3T3-E1 cell viability in a dose-dependent effect and induced apoptosis by increasing the expression levels of FOXO1, Bax, cleaved-Caspase-3, and cleaved-Caspase-9, while reducing the expression of Bcl-2. Notably, these results were reversed by siRNA-FOXO1 treatment. Dex inhibited PI3K/AKT signaling pathway, upregulated FOXO1 expression and increased FOXO1 nuclear translocation, which were reversed by IGF-1. Compared to normal rats, the femoral head of SONFH showed increased expression of FOXO1, increased number of apoptotic cells, and empty osteocytic lacunas, as well as decreased bone tissue content and femoral head integrity. Significantly, the effects of GC-induced SONFH were alleviated following IGF-1 treatment.ConclusionDex induces osteoblast apoptosis via the PI3K/AKT/FOXO1 signaling pathway. Our research offers new insights into the underlying molecular mechanisms of glucocorticoid-induced osteonecrosis in SONFH and proposes FOXO1 as a therapeutic target for this disease. creator: Fei Sun creator: Jian Lin Zhou creator: Si Xing Wei creator: Ze Wen Jiang creator: Hao Peng uri: https://doi.org/10.7717/peerj.13319 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Sun et al. title: The association of plasma osteoprotegerin levels and functional outcomes post endovascular thrombectomy in acute ischemic stroke patients: a retrospective observational study link: https://peerj.com/articles/13327 last-modified: 2022-05-03 description: BackgroundOsteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor, is a tumor necrosis factor receptor superfamily component. There is an established relationship between OPG and cardiovascular disease. We hypothesized that plasma OPG levels are associated with functional outcomes in acute ischemic stroke patients who have undergone endovascular thrombectomy (EVT).MethodsFrom April 2014 through December 2020, a total of 360 acute ischemic stroke patients who underwent EVT were prospectively included in this retrospective observational study. Plasma OPG was measured after fasting for 12 postoperative hours after EVT. A modified Rankin Scale (mRS) was used to assess functional outcomes 3 months after index stroke occurrence. Univariate and multivariate binary logistic regression and ordinal logistic regression analyses were performed to investigate the association of plasma OPG levels with poor functional outcomes.ResultsOverall, 145 (40.2%) patients had poor (mRS > 2) outcomes. The mean ± standard deviation plasma OPG level was 200.2 ± 74.4 pg/mL. Multivariate analysis after adjusting for sex, body mass index, and variables with p < 0.1 in the preceding univariate analysis revealed high plasma OPG levels were independently associated with poor functional outcomes (highest tertile vs. lowest tertile of OPG; odds ratios (OR) 2.121, 95% confidence interval (CI) [1.089–4.191], p = 0.037 in binary logistic regression, OR 2.102, 95% CI [1.301–3.412], p = 0.002 in ordinal logistic regression analysis).ConclusionsThis study demonstrated that higher plasma OPG levels were associated with poor functional outcomes in acute ischemic stroke patients who underwent EVT. creator: Moo-Seok Park creator: Jin-Hee Park creator: Ahran Joo creator: Yoonkyung Chang creator: Tae-Jin Song uri: https://doi.org/10.7717/peerj.13327 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Park et al. title: Feature tuning improves MAXENT predictions of the potential distribution of Pedicularis longiflora Rudolph and its variant link: https://peerj.com/articles/13337 last-modified: 2022-05-03 description: Pedicularis longiflora Rudolph and its variant (P. longiflora var. tubiformis (Klotzsch) Tsoong) are alpine plants and traditional Chinese medicines with important medicinal value, and future climate changes may have an adverse impact on their geographic distribution. The maximum entropy (MAXENT) model has the outstanding ability to predict the potential distribution region of species under climate change. Therefore, given the importance of the parameter settings of feature classes (FCs) and the regularization multiplier (RM) of the MAXENT model and the importance of add indicators to evaluate model performance, we used ENMeval to improve the MAXENT niche model and conducted an in-depth study on the potential distributions of these two alpine medicinal plants. We adjusted the parameters of FC and RM in the MAXENT model, evaluated the adjusted MAXENT model using six indicators, determined the most important ecogeographical factors (EGFs) that affect the potential distributions of these plants, and compared their current potential distributions between the adjusted model and the default model. The adjusted model performed better; thus, we used the improved MAXENT model to predict their future potential distributions. The model predicted that P. longiflora Rudolph and its variant (P. longiflora var. tubiformis (Klotzsch) Tsoong) would move northward and showed a decrease in extent under future climate scenarios. This result is important to predict their potential distribution regions under changing climate scenarios to develop effective long-term resource conservation and management plans for these species. creator: Ru Bao creator: Xiaolong Li creator: Jianghua Zheng uri: https://doi.org/10.7717/peerj.13337 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Bao et al. title: miR-9-5p promotes myogenic differentiation via the Dlx3/Myf5 axis link: https://peerj.com/articles/13360 last-modified: 2022-05-03 description: MicroRNAs play an important role in myogenic differentiation, they bind to target genes and regulate muscle formation. We previously found that miR-9-5p, which is related to bone formation, was increased over time during the process of myogenic differentiation. However, the mechanism by which miR-9-5p regulates myogenic differentiation remains largely unknown. In the present study, we first examined myotube formation and miR-9-5p, myogenesis-related genes including Dlx3, Myod1, Mef2c, Desmin, MyoG and Myf5 expression under myogenic induction. Then, we detected the expression of myogenic transcription factors after overexpression or knockdown of miR-9-5p or Dlx3 in the mouse premyoblast cell line C2C12 by qPCR, western blot and myotube formation under myogenic induction. A luciferase assay was performed to confirm the regulatory relationships between not only miR-9-5p and Dlx3 but also Dlx3 and its downstream gene, Myf5, which is an essential transcription factor of myogenic differentiation. The results showed that miR-9-5p promoted myogenic differentiation by increasing myogenic transcription factor expression and promoting myotube formation, but Dlx3 exerted the opposite effect. Moreover, the luciferase assay showed that miR-9-5p bound to the 3’UTR of Dlx3 and downregulated Dlx3 expression. Dlx3 in turn suppressed Myf5 expression by binding to the Myf5 promoter, ultimately inhibiting the process of myogenic differentiation. In conclusion, the miR-9-5p/Dlx3/Myf5 axis is a novel pathway for the regulation of myogenic differentiation, and can be a potential target to treat the diseases related to muscle dysfunction. creator: Liying Dong creator: Meng Wang creator: Xiaolei Gao creator: Xuan Zheng creator: Yixin Zhang creator: Liangjie Sun creator: Na Zhao creator: Chong Ding creator: Zeyun Ma creator: Yixiang Wang uri: https://doi.org/10.7717/peerj.13360 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Dong et al. title: HIF1α is dispensable for oocyte development and female fertility in mice link: https://peerj.com/articles/13370 last-modified: 2022-05-03 description: BackgroundIt has been thought that oocyte may develop in a low oxygen environment, as changes in follicle structure and formation of a fluid-filled antrum. The survival of hypoxic tissues is controlled by hypoxia-inducible factors (HIFs) that are activated in a low oxygen state. HIF1α is expressed in mature mouse oocytes and continues to be expressed after fertilization, from the 2-cell to blastocyst stage. However, the physiological roles of HIF pathway during oogenesis and embryogenesis have still not been elucidated in detail.MethodsMutant mice with oocyte-specific HIF1α deletion were generated by crossing Hif1αfl/fl mice with transgenic mice expressing Gdf9-promoter-mediated Cre recombinase. Breeding assay was carried out to detect female fertility. In vitro fertilization and embryo culture were used to assess early embryo development. Oocyte meiotic progression was also examined. Quantitative RT-PCR was used for analyzing of candidate genes expression.ResultsWe successfully generated mutant mice with oocyte-specific deletion of HIF1α. Oocytes loss of HIF1α did not affect female fertility, ovulation and early embryo development. Moreover, oocytes can mature in vitro, and form well-organized spindle in the absence of HIF1α. In addition, pronounced differences in Hif2α and Hif3α mRNA expression were not observed in HIF1α-deleted oocytes. These results revealed that HIF pathway in oocytes is not essential for female fertility. creator: Yujia Chen creator: Siyu Du creator: Zhenyue Huang creator: Longsen Han creator: Qiang Wang uri: https://doi.org/10.7717/peerj.13370 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Chen et al.