title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=656 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma via the PI3K/AKT signaling pathway link: https://peerj.com/articles/13844 last-modified: 2022-08-19 description: BackgroundCC chemokine receptor 9 (CCR9), an organ-specific chemokine receptor, interacts with its exclusive ligand CCL25 to promote tumor proliferation and metastasis. However, the effect of CCR9 on salivary adenoid cystic carcinoma (SACC) malignant behavior remains unknown. This study aimed to investigate the specific molecular mechanism by which CCR9/CCL25 modulates malignant progression in SACC.MethodsImmunohistochemistry staining and RT–qPCR analyses were performed to detect the correlation of CCR9 expression and tumor progression-associated markers in SACC. In vitro, SACC cell proliferation and apoptosis were evaluated using Cell Counting Kit-8 and colon formation, and cell migration and invasion were detected by wound healing and transwell assays. Vercirnon was used as an inhibitor of CCR9, and LY294002 was used as an inhibitor of the PI3K/AKT pathway in this study. Western blot and RT–qPCR assays were carried out to measure the downstream factors of the interaction of CCL25 and CCR9. The effect of CCL25 on the development of SACC in vivo was examined by a xenograft tumor model in nude mice following CCL25, Vercirnon and LY294002 treatment.ResultsCCR9 was highly expressed in SACC compared with adjacent salivary gland tissues, and its level was associated with tumor proliferation and metastases. CCL25 enhanced cell proliferation, migration, and invasion through its interaction with CCR9 and exerted an antiapoptotic effect on SACC cells. Targeting CCR9 via Vercirnon significantly reduced the phosphorylation level of AKT induced by CCL25. CCL25/CCR9 could activate its downstream factors through the PI3K/AKT signaling pathway, such as cyclin D1, BCL2 and SLUG, thus promoting SACC cell proliferation, antiapoptosis, invasion and metastasis. The in vivo data from the xenograft mouse models further proved that CCL25 administration promoted malignant tumor progression by activating the PI3K/AKT pathway.ConclusionThe interaction of CCL25 and CCR9 promotes tumor growth and metastasis in SACC by activating the PI3K/AKT signaling pathway, offering a promising strategy for SACC treatment. creator: Songling Chai creator: Zhihao Wen creator: Rongxin Zhang creator: Yuwen Bai creator: Jing Liu creator: Juanjuan Li creator: Wenyao Kongling creator: Weixian Chen creator: Fu Wang creator: Lu Gao uri: https://doi.org/10.7717/peerj.13844 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Chai et al. title: Regional impact of large-scale climate oscillations on ice out variability in New Brunswick and Maine link: https://peerj.com/articles/13741 last-modified: 2022-08-18 description: The available ice out (the date of disappearance of ice from a water body) records were analyzed from four relatively closely spaced lakes in southwestern New Brunswick (Harvey, Oromocto, Skiff) and eastern Maine (West Grand Lake), with the longest set of available observations being for Oromocto Lake starting in 1876. Results of a coherence analysis carried out on the ice out data from the four lakes indicates that there is regional coherence and correspondingly, that regional drivers influence ice out. These results also indicate that ice out dates for lakes from the region where records have not been kept can also be interpolated from these results. As the ice out record was coherent, further analysis was done for only Oromocto Lake on the basis of it having the longest ice out record. Cross-wavelet analysis was carried out between the ice out record and a variety of cyclic climate teleconnections and the sunspot record to identify which phenomena best explain the observed ice out trends. The most important observed contributors to ice out were the North Atlantic Oscillation (NAO) and the El Niño Southern Oscillation (ENSO), with observed periodicities at the interannual scale. At the decadal scale the Pacific Decadal Oscillation (PDO) and the 11-year solar cycle were the only patterns observed to significantly contribute to ice out. creator: Carling R. Walsh creator: R. Timothy Patterson uri: https://doi.org/10.7717/peerj.13741 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Walsh and Patterson title: Identifying important ecosystem service areas based on distributions of ecosystem services in the Beijing–Tianjin–Hebei region, China link: https://peerj.com/articles/13881 last-modified: 2022-08-18 description: Water conservation, soil conservation, biodiversity importance, and sandstorm prevention are important ecosystem services (ES) and the core challenges to sustainable economic and societal development in the Beijing–Tianjin–Hebei (BTH) region. Using the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model and observation data, we identified high-value ES areas in the BTH region. The high-value ES areas were mainly found in the northern and southwestern parts of the region, like the Yanshan Mountain Range and the Taihang Mountain Range. The ecosystem in the northern mountains is dominated by forest and grassland, and generally provides more valuable ES than does the eastern agricultural plain. Greater species richness was mainly found in the northern mountains with low human activity intensity. Due to its proximity, the Yanshan Mountain Range is critical to the health of the local ecosystem of Beijing. High biodiversity was present in the vicinity of the national nature reserves. Compared with other regions of China, changes in the BTH region are highly intense. Reinforcement of biodiversity conservation and ecosystem restoration in areas with a high degree of ES in the BTH region are capable of effectively improving habitat quality and regional ES. creator: Cuiyun Cheng creator: Shuping Zhang creator: Meichun Zhou creator: Yanchun Du creator: Chazhong Ge uri: https://doi.org/10.7717/peerj.13881 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Cheng et al. title: A simple hierarchical model for heterogeneity in the evolutionary correlation on a phylogenetic tree link: https://peerj.com/articles/13910 last-modified: 2022-08-18 description: Numerous questions in phylogenetic comparative biology revolve around the correlated evolution of two or more phenotypic traits on a phylogeny. In many cases, it may be sufficient to assume a constant value for the evolutionary correlation between characters across all the clades and branches of the tree. Under other circumstances, however, it is desirable or necessary to account for the possibility that the evolutionary correlation differs through time or in different sections of the phylogeny. Here, we present a method designed to fit a hierarchical series of models for heterogeneity in the evolutionary rates and correlation of two quantitative traits on a phylogenetic tree. We apply the method to two datasets: one for different attributes of the buccal morphology in sunfishes (Centrarchidae); and a second for overall body length and relative body depth in rock- and non-rock-dwelling South American iguanian lizards. We also examine the performance of the method for parameter estimation and model selection using a small set of numerical simulations. creator: Liam J. Revell creator: Ken S. Toyama creator: D. Luke Mahler uri: https://doi.org/10.7717/peerj.13910 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Revell et al. title: Incorporating nonlinearity with generalized functional responses to simulate multiple predator effects link: https://peerj.com/articles/13920 last-modified: 2022-08-18 description: Predicting the combined effects of predators on shared prey has long been a focus of community ecology, yet quantitative predictions often fail. Failure to account for nonlinearity is one reason for this. Moreover, prey depletion in multiple predator effects (MPE) studies generates biased predictions in applications of common experimental and quantitative frameworks. Here, we explore additional sources of bias stemming from nonlinearities in prey predation risk. We show that in order to avoid bias, predictions about the combined effects of independent predators must account for nonlinear size-dependent risk for prey as well as changes in prey risk driven by nonlinear predator functional responses and depletion. Historical failure to account for biases introduced by well-known nonlinear processes that affect predation risk suggest that we may need to reevaluate the general conclusions that have been drawn about the ubiquity of emergent MPEs over the past three decades. creator: Michael W. McCoy creator: Elizabeth Hamman creator: Molly Albecker creator: Jeremy Wojdak creator: James R. Vonesh creator: Benjamin M. Bolker uri: https://doi.org/10.7717/peerj.13920 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 McCoy et al. title: Enhancing georeferenced biodiversity inventories: automated information extraction from literature records reveal the gaps link: https://peerj.com/articles/13921 last-modified: 2022-08-18 description: We use natural language processing (NLP) to retrieve location data for cheilostome bryozoan species (text-mined occurrences (TMO)) in an automated procedure. We compare these results with data combined from two major public databases (DB): the Ocean Biodiversity Information System (OBIS), and the Global Biodiversity Information Facility (GBIF). Using DB and TMO data separately and in combination, we present latitudinal species richness curves using standard estimators (Chao2 and the Jackknife) and range-through approaches. Our combined DB and TMO species richness curves quantitatively document a bimodal global latitudinal diversity gradient for extant cheilostomes for the first time, with peaks in the temperate zones. A total of 79% of the georeferenced species we retrieved from TMO (N = 1,408) and DB (N = 4,549) are non-overlapping. Despite clear indications that global location data compiled for cheilostomes should be improved with concerted effort, our study supports the view that many marine latitudinal species richness patterns deviate from the canonical latitudinal diversity gradient (LDG). Moreover, combining online biodiversity databases with automated information retrieval from the published literature is a promising avenue for expanding taxon-location datasets. creator: Bjørn Tore Kopperud creator: Scott Lidgard creator: Lee Hsiang Liow uri: https://doi.org/10.7717/peerj.13921 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Kopperud et al. title: A cholesterogenic gene signature for predicting the prognosis of young breast cancer patients link: https://peerj.com/articles/13922 last-modified: 2022-08-18 description: PurposeWe aimed to establish a cholesterogenic gene signature to predict the prognosis of young breast cancer (BC) patients and then verified it using cell line experiments.MethodsIn the bioinformatic section, transcriptional data and corresponding clinical data of young BC patients (age ≤ 45 years) were downloaded from The Cancer Genome Atlas (TCGA) database for training set. Differentially expressed genes (DEGs) were compared between tumour tissue (n = 183) and normal tissue (n = 30). By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis. Subgroup analysis and external validations of GSE131769 from the Gene Expression Omnibus (GEO) were performed to verify the signature. Subsequently, in experiment part, cell experiments were performed to further verify the biological roles of the five cholesterogenic genes in BC.ResultsIn the bioinformatic section, a total of 97 upregulated genes and 124 downregulated cholesterogenic genes were screened as DEGs in the TCGA for training the model. A risk scoring signature contained five cholesterogenic genes (risk score = −1.169 × GRAMD1C −0.992 × NFKBIA + 0.432 × INHBA + 0.261 × CD24 −0.839 × ACSS2) was established, which could differentiate the prognosis of young BC patients between high-risk and low-risk group (<0.001). The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset. Then the prediction value of the signature was verified in GSE131769 with P = 0.033. In experiment part, although the downregulation of CD24, GRAMD1C and ACSS2 did not significantly affect cell viability, NFKBIA downregulation promoted the viability, colony forming ability and invasion capability of BC cells, while INHBA downregulation had the opposite effects.ConclusionThe five-cholesterogenic-gene signature had independent prognostic value and robust reliability in predicting the prognosis of young BC patients. The cell experiment results suggested that NFKBIA played a protective role, while INHBA played the pro-cancer role in breast cancer. creator: Xiaoping Li creator: Chaorong Zhou creator: Chaoran Qiu creator: Weiwen Li creator: Qihe Yu creator: Hui Huang creator: Yiwen Zhang creator: Xin Zhang creator: Liangliang Ren creator: Xin Huang creator: Qinghua Zhou uri: https://doi.org/10.7717/peerj.13922 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Li et al. title: Levels and correlates of knowledge of teething among Saudi Arabian families link: https://peerj.com/articles/13948 last-modified: 2022-08-18 description: BackgroundParental knowledge of teething has been repeatedly investigated; however, little emphasis has been made on the associated sociodemographic factors with good knowledge of the parents and whether or not good knowledge is translated into adopting proper pain-relieving practices. The present study aims to firstly assess the knowledge level and practices of Saudi parents regarding teething and then explore associated sociodemographic variables with good knowledge of teething to determine the relation between parents’ knowledge of teething and their adoption of pain-relieving practices.MethodsThis cross-sectional study recruited parents from the social networking sites Facebook, Twitter, Instagram, and WhatsApp, and they were asked to answer a pretested three-part internationally accepted questionnaire. Data were examined using descriptive statistics, chi-square analysis, multivariate logistic regression analysis, and Spearman rank-order correlation coefficient analysis.ResultsOne thousand four hundred ninety-nine parents responded and returned completed questionnaires. Of those, only 11.2% had good knowledge of teething. The majority of parents did not have basic knowledge of the teething period as well as believed that teething was associated with a runny nose (87.5%), diarrhea (77.9%), and sleep disturbance (72%). The results of multivariate logistic regression analysis indicated that parents with no primary school education (Odds Ratio: 0.29), or those who had an intermediate or secondary education level (OR: 0.55 and 0.78) were less likely to have good knowledge compared with parents who had a university degree. However, parents who earned intermediate monthly income (OR: 6.63) were more likely to have good knowledge of teething. With regards to practices used to relieve teething pain, inappropriate practices were observed regarding bottle feeding at night to soothe the child’s pain (72%) and applying topical analgesics to rub the gum (72.4%). A significant positive correlation was found between the knowledge score and the practice score of both fathers and mothers (r = 0.22 and 0.13, p < 0.0001).ConclusionA very low percentage of Saudi parents, mainly those with the highest education level and intermediate monthly income, had good knowledge of teething, which translated into appropriate practices to soothe the child’s pain regardless of the parent’s gender. Saudi parents should receive anticipatory guidance related to teething from all health professionals to ensure an uneventful teething period for their children. creator: Dina A. Alkhozaim creator: Sanaa N. Al-Haj Ali creator: Ra’fat I. Farah uri: https://doi.org/10.7717/peerj.13948 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Alkhozaim et al. title: Exploring the anticancer and antioxidant properties of Vicia faba L. pods extracts, a promising source of nutraceuticals link: https://peerj.com/articles/13683 last-modified: 2022-08-17 description: BackgroundPulse crops are considered the major sources of proteins, dietary fiber, micronutrients, and bioactive phytochemicals. Among the numerous pulse crops, broad beans (Vicia faba L.) have received particular attention due to their nutraceutical, functional and economic importance. Our attention was mainly focused on the broad bean pods (VFs), which are the primary by-product of the domestic and industrial processing of broad beans and an attractive source of valuable ingredients.MethodsIn order to investigate the VFs properties, the flours from broad beans of three different harvest periods were extracted with acetone, methanol and 70% aqueous ethanol and the dried extracts were analyzed, qualitatively and quantitatively, and tested for their antioxidant through DPPH and ABTS assay and anticancer activities using the MTT assay and immunofluorescence analysis.ResultsThe VF extracts demonstrated a good in vitro radical scavenging activity from the first stage of collection of all the V. faba L. extracts. Additionally, the extracts were tested for their cytotoxicity against a panel of cancer and normal cells and the outcomes indicated the ethanol extract as the most active against the melanoma cell line Sk-Mel-28, without affecting the viability of the normal cells. Finally, we found out that the ethanol extract interfered with the microtubules organization, leading to the cancer cells death by apoptosis. creator: Jessica Ceramella creator: Chiara La Torre creator: Michele De Luca creator: Domenico Iacopetta creator: Alessia Fazio creator: Alessia Catalano creator: Gaetano Ragno creator: Pasquale Longo creator: Maria Stefania Sinicropi creator: Camillo Rosano uri: https://doi.org/10.7717/peerj.13683 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Ceramella et al. title: Growth promotion and mycorrhizal colonization of Argan (Argania spinosa (L.) Skeels) inoculated with the edible desert truffle Tirmania nivea (Desf.) Trappe link: https://peerj.com/articles/13769 last-modified: 2022-08-17 description: This study presents the first evidence of the mycorrhizal compatibility between the edible desert truffle Tirmania nivea and the valuable fruit tree Argania spinosa. Seed germination trials demonstrated that soaking pre-treatment of argan seeds in hydrogen peroxide (9%) for five days combined with the application of a fungicide treatment on an inert sowing material maximized the seed germination of this tree species. The mycorrhizal synthesis was conducted under greenhouse conditions by inoculating, in vivo, the host plant seedlings with spores of T. nivea. The growth and mycorrhizal status of A. spinosa was assessed 15.5 months after inoculation. The desert truffle mycorrhization significantly promoted all the investigated morphological parameters of growth and improved the physiological performances of the host plant through enhancing plant water status and chlorophyll concentration. The mycorrhizal symbiosis led to the formation of typical desert truffle endomycorrhizae with intracellular coils. The resistance of A. spinosa to the harsh environmental conditions of desert habitats makes it a potential candidate for cultivation of desert truffles. creator: Ahlem Khrizi creator: Fatima El-Houaria Zitouni-Haouar creator: Zohra Fortas uri: https://doi.org/10.7717/peerj.13769 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Khrizi et al.