title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=593 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Association between the CASC16 rs4784227 polymorphism and breast cancer risk and prognosis in a northeast Chinese Han population link: https://peerj.com/articles/14462 last-modified: 2022-12-15 description: BackgroundBreast cancer (BC) poses a serious threat to women worldwide. This research was designed to explore the association between the rs4784227 polymorphism of cancer susceptibility candidate gene 16 (CASC16) and BC susceptibility and prognosis, aiming to provide further information for the early detection of BC and to accelerate comprehensive cancer management.MethodsA total of 1,733 subjects were recruited for this case-control study, of which 828 are BC patients and 905 are healthy individuals. The relevance between SNP rs4784227 and BC risk in diverse genetic models was analyzed by using the SNPStats analysis program and was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) using the binary logistic regression model. Pearson’s χ2 test was used to determine the correlation between the polymorphism and clinical characteristics of BC patients. Additionally, univariate survival analysis was performed by the Kaplan-Meier method and log-rank test, and multivariate survival analysis was performed by Cox regression.ResultsSNP rs4784227 was significantly associated with susceptibility to BC in the dominant model (CT/TT versus CC, OR = 1.237, 95% CI = 1.012–1.513, P = 0.038). The minor allele of SNP rs4784227 was significantly linked to an increased risk of BC (OR = 1.197, 95% CI = 1.022–1.401, P = 0.026). In addition, the rs4784227 polymorphism of CASC16 was associated with perineural invasion (P = 0.030), menstrual status (P = 0.016) and histological grade (P = 0.001, P = 0.003, P = 0.025; respectively) of BC patients. There was no significant association between the genotypes of rs4784227 and disease-free survival (DFS) or overall survival (OS) of breast cancer patients (P > 0.05).ConclusionsThe rs4784227 polymorphism of CASC16 may affect susceptibility to breast cancer and is associated with perineural invasion, menstrual status and histological grade in BC patients. Additionally, our results could not confirm that this polymorphism was related to breast cancer prognosis. creator: Yue Zhang creator: Changgui Kou creator: Lin Jia creator: Yangyang Gao creator: Xin Li creator: Hao Wu creator: Naifei Chen creator: Zheng Lv uri: https://doi.org/10.7717/peerj.14462 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Zhang et al. title: Comparison of rule- and ordinary differential equation-based dynamic model of DARPP-32 signalling network link: https://peerj.com/articles/14516 last-modified: 2022-12-15 description: Dynamic modelling has considerably improved our understanding of complex molecular mechanisms. Ordinary differential equations (ODEs) are the most detailed and popular approach to modelling the dynamics of molecular systems. However, their application in signalling networks, characterised by multi-state molecular complexes, can be prohibitive. Contemporary modelling methods, such as rule- based (RB) modelling, have addressed these issues. The advantages of RB modelling over ODEs have been presented and discussed in numerous reviews. In this study, we conduct a direct comparison of the time courses of a molecular system founded on the same reaction network but encoded in the two frameworks. To make such a comparison, a set of reactions that underlie an ODE model was manually encoded in the Kappa language, one of the RB implementations. A comparison of the models was performed at the level of model specification and dynamics, acquired through model simulations. In line with previous reports, we confirm that the Kappa model recapitulates the general dynamics of its ODE counterpart with minor differences. These occur when molecules have multiple sites binding the same interactor. Furthermore, activation of these molecules in the RB model is slower than in the ODE one. As reported for other molecular systems, we find that, also for the DARPP-32 reaction network, the RB representation offers a more expressive and flexible syntax that facilitates access to fine details of the model, easing model reuse. In parallel with these analyses, we report a refactored model of the DARPP-32 interaction network that can serve as a canvas for the development of more complex dynamic models to study this important molecular system. creator: Emilia M. Wysocka creator: Matthew Page creator: James Snowden creator: T. Ian Simpson uri: https://doi.org/10.7717/peerj.14516 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Wysocka et al. title: Ethanolic extract of Ya-nang (Tiliacora triandra) leaf powder induces apoptosis in cholangiocarcinoma cell lines via induction of hyperacetylation and inhibition of growth signaling link: https://peerj.com/articles/14518 last-modified: 2022-12-15 description: ObjectiveTo develop alternative medicine for reducing undesired side effects of chemotherapy in CCA patients, the anticancer activity of Tiliacora triandra leaf powder ethanolic (TLPE) extract against cholangiocarcinoma cell lines was investigated.MethodsAntiproliferation was studied using the MTT assay while apoptosis induction and cell cycle arrest were analyzed by flow cytometry. The levels of key proteins and phenolic acid content were analyzed by western blotting and reversed-phase HPLC, respectively.ResultsTLPE extract inhibited CCA cell growth in a dose- and time-dependent manner, with IC50 values of 7.86 ± 0.05 µg/ml for KKU-M213B cells and 8.59 ± 0.36 µg/ml for KKU-100 cells at an exposure time of 72 h. TLPE extract inhibited the growth of CCA cell lines by inducing apoptosis of both cell lines and causing an increased population of KKU-100 cells at G0/G1 phase. TLPE extract up-regulated Ac-H3 but down-regulated p-ERK, p53, Bax, CDK4 and Bcl2 expressions in KKU-M213B cells. TLPE extract up-regulated Ac-H3, p21 and Bax but down-regulated p-ERK, p53, CDK4 and Bcl2 expressions in KKU-100 cells. Additionally, phenolic acids including p-hydroxybenzoic, vanillic, syringic, p-coumaric, ferulic and sinapinic acids were identified.ConclusionThese results suggest the possibility of developing T. triandra leaf powder ethanolic extract as a chemotherapeutic or chemoprevention agent for cholangiocarcinoma. creator: Arunta Samankul creator: Gulsiri Senawong creator: Prasan Swatsitang creator: Banchob Sripa creator: Chanokbhorn Phaosiri creator: Somdej Kanokmedhakul creator: Thanaset Senawong uri: https://doi.org/10.7717/peerj.14518 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Samankul et al. title: Embryonic exposure to fentanyl induces behavioral changes and neurotoxicity in zebrafish larvae link: https://peerj.com/articles/14524 last-modified: 2022-12-15 description: The use of fentanyl during pregnancy, whether by prescription or illicit use, may result in high blood levels that pose an early risk to fetal development. However, little is known regarding the neurotoxicity that might arise from excessive fentanyl exposure in growing organisms, particularly drug-related withdrawal symptoms. In this study, zebrafish embryos were exposed to fentanyl solutions (0.1, 1, and 5 mg/L) for 5 days post fertilization (dpf), followed by a 5-day recovery period, and then the larvae were evaluated for photomotor response, anxiety behavior, shoaling behavior, aggression, social preference, and sensitization behavior. Fentanyl solutions at 1 and 5 mg/L induced elevated anxiety, decreased social preference and aggressiveness, and behavioral sensitization in zebrafish larvae. The expression of genes revealed that embryonic exposure to fentanyl caused substantial alterations in neural activity (bdnf, c-fos) and neuronal development and plasticity (npas4a, egr1, btg2, ier2a, vgf). These results suggest that fentanyl exposure during embryonic development is neurotoxic, highlighting the importance of zebrafish as an aquatic species in research on the neurobehavioral effects of opioids in vertebrates. creator: Binjie Wang creator: Jiale Chen creator: Zhong Sheng creator: Wanting Lian creator: Yuanzhao Wu creator: Meng Liu uri: https://doi.org/10.7717/peerj.14524 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Wang et al. title: Non-random host tree infestation by the Neotropical liana Marcgravia longifolia link: https://peerj.com/articles/14535 last-modified: 2022-12-15 description: The question whether or not tropical lianas infest host trees randomly or they exert host selection has implications for the structure and dynamics of tropical rainforests, particularly if colonization by lianas impacts host fitness. In this study, we present evidence that the Neotropical liana Marcgravia longifolia (Marcgraviaceae) infests host trees non-randomly. We identified host trees to species or genus level for 87 of the 100 M. longifolia individuals found in the study area of the Estación Biológica Quebrada Blanco (EBQB) in north-eastern Peruvian Amazonia. Data on host availability were taken from two 1-ha plots sampled at EBQB as part of a large-scale tree inventory in western Amazonia. Of the total of 88 tree genera with two or more individuals present in the inventory, 18 were represented amongst hosts. Host genera with a probability of colonization higher than expected by chance were Eschweilera (Lecythidaceae), Pouteria (Sapotaceae), Brosimum (Moraceae), and Hymenaea (Fabaceae). These findings suggest that M. longifolia exerts some level of host selectivity, but the mechanisms for this are completely unknown. Given the large number of animal species (41 bird species, three primate species) that are dispersing the seeds of M. longifolia and that have diverse ecological strategies, directed seed dispersal is unlikely to account for the observed patterns of host infestation. creator: Eckhard W. Heymann creator: Sarina Thiel creator: Filipa Paciência creator: Milagros N. Rimachi Taricuarima creator: Ricardo Zárate Gómez creator: Ney Shahuano Tello creator: Katrin Heer creator: Holger Sennhenn-Reulen creator: Roger Mundry uri: https://doi.org/10.7717/peerj.14535 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Heymann et al. title: The long-term dynamics of serum antibodies against SARS-CoV-2 link: https://peerj.com/articles/14547 last-modified: 2022-12-15 description: ObjectiveTo analyze the long-term dynamics of antibodies against SARS-CoV-2 and understand the impact of age, gender, and viral load on patients’ immunological response.MethodsSerum samples were obtained from 231 COVID-19 positive patients from Macaé, in Rio de Janeiro state, in Brazil, from June 2020 until January 2021. The production of IgA, IgM, IgG, and IgE against S glycoprotein was analyzed using the S-UFRJ assay, taking into account the age, gender, and viral load.ResultsAnalysis of antibody production over 7 months revealed that IgA positivity gradually decreased after the first month. Additionally, the highest percentage of IgM positivity occurred in the first month (97% of patients), and declined after this period, while IgG positivity remained homogeneous for all 7 months. The same analysis for IgE revealed that almost all samples were negative. The comparison of antibody production between genders showed no significant difference. Regarding the age factor and antibody production, patients aged ≥60 years produced almost twice more IgA than younger ones (17–39 years old). Finally, a relationship between viral load and antibody production was observed only for older patients.ConclusionsOur work provides an overview of long-term production of antibodies against SARS-CoV-2, suggesting prolonged production of IgA and IgM antibodies for 3 months and continued IgG production for over 7 months. In addition, it identified a correlation between viral load and IgM titers in the older group and, finally, different IgA production between the age groups. creator: Graziele Fonseca de Sousa creator: Thuany da Silva Nogueira creator: Lana Soares de Sales creator: Fernanda Ferreira Maissner creator: Odara Araújo de Oliveira creator: Hellade Lopes Rangel creator: Daniele das Graças dos Santos creator: Rodrigo Nunes-da-Fonseca creator: Jackson de Souza-Menezes creator: Jose Luciano Nepomuceno-Silva creator: Flávia Borges Mury creator: Raquel de Souza Gestinari creator: Amilcar Tanuri creator: Orlando da Costa Ferreira Jr creator: Cintia Monteiro-de-Barros uri: https://doi.org/10.7717/peerj.14547 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 de Sousa et al. title: Identification of prognostic factors and nomogram model for patients with advanced lung cancer receiving immune checkpoint inhibitors link: https://peerj.com/articles/14566 last-modified: 2022-12-15 description: Background and aimSome patients with lung cancer can benefit from immunotherapy, but the biomarkers that predict immunotherapy response were not well defined. Baseline characteristic of patients may be the most convenient and effective markers. Therefore, our study was designed to explore the association between baseline characteristics of patients with lung cancer and the efficacy of immunotherapy.MethodsA total of 216 lung cancer patients from Tianjin Medical University Cancer Institute & Hospital who received immunotherapy between 2017 and 2021 were included in the retrospective analysis. All baseline characteristic data were collected and then univariate log-rank analysis and multivariate COX regression analysis were performed. Kaplan–Meier analysis was used to evaluate patients’ progression-free survival (PFS). A nomogram based on significant biomarkers was constructed to predict PFS rate of patients receiving immunotherapy. We evaluated the prediction accuracy of nomogram using C-indices and calibration curves.ResultsUnivariate analysis of all collected baseline factors showed that age, clinical stage, white blood cell (WBC), lymphocyte (LYM), monocyte (MON), eosinophils (AEC), hemoglobin (HB), lactate dehydrogenase (LDH), albumin (ALB) and treatment line were significantly associated with PFS after immunotherapy. Then these 10 risk factors were included in a multivariate regression analysis, which indicated that age (HR: 1.95, 95% CI [1.01–3.78], P = 0.048), MON (HR: 1.74, 95% CI [1.07–2.81], P = 0.025), LDH (HR: 0.59, 95% CI [0.36–0.95], P = 0.030), and line (HR: 0.57, 95% CI [0.35–0.94], P = 0.026) were significantly associated with PFS in patients with lung cancer receiving immunotherapy. Patients with higher ALB showed a greater trend of benefit compared with patients with lower ALB (HR: 1.58, 95% CI [0.94–2.66], P = 0.084). Patients aged ≥51 years, with high ALB, low LDH, first-line immunotherapy, and high MON had better response rates and clinical benefits. The nomogram based on age, ALB, MON, LDH, line was established to predict the prognosis of patients treated with immune checkpoint inhibitor (ICI). The C-index of training cohort and validation cohort were close, 0.71 and 0.75, respectively. The fitting degree of calibration curve was high, which confirmed the high prediction value of our nomogram.ConclusionAge, ALB, MON, LDH, line can be used as reliable predictive biomarkers for PFS, response rate and cancer control in patients with lung cancer receiving immunotherapy. The nomogram based on age, ALB, MON, LDH, line was of great significance for predicting 1-year-PFS, 2-year-PFS and 3-year-PFS in patients with advanced lung cancer treated with immunotherapy. creator: Xiuqiong Chen creator: Zhaona Li creator: Jing Zhou creator: Qianhui Wei creator: Xinyue Wang creator: Richeng Jiang uri: https://doi.org/10.7717/peerj.14566 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Chen et al. title: Seroprevalence of Toxoplasma gondii infection in women with a gynecological tumor living in eastern China link: https://peerj.com/articles/14569 last-modified: 2022-12-15 description: The association between Toxoplasma gondii (T. gondii) infection and malignancy has attracted increased attention in recent years, but little is known of T. gondii infection among women diagnosed with a gynecological tumor (GT) in China. We conducted a case-control study involving 460 women diagnosed with a GT and 460 age-matched healthy controls (HCs) to estimate the infection process of T. gondii and understand the risk factors of T. gondii infection in patients with a GT. Levels of anti-T. gondii IgG and IgM were measured by enzyme-linked immunoassays every 12 months. After a median follow-up time of 4.3 years (range 4 to 5 years), 55/460 (11.96%) patients with a GT and 15/460 (3.26%) HCs were seroprevalence for T. gondii antibodies, respectively (P = 0.001). IgG antibodies against T. gondii were found in 54 GT patients (11.74%) and 15 HCs (3.26%), respectively (P = 0.001). The seroprevalence of T. gondii IgM antibodies was similar in patients with a GT and with HCs (2.83% vs 1.3%, P = 0.105). Multivariate stepwise logistic regression analysis revealed contact with cats (OR, 6.67; 95% CI [2.89–10.75]; P = 0.001), exposure to soil (OR, 2.16; 95% CI [1.14–4.10]; P = 0.019), being a farm-worker (OR, 4.17; 95% CI [1.20–11.49]; P = 0.006) and history of chemotherapy (OR, 3.16; 95% CI [1.56–6.45]; P = 0.001) to be independent risk factors for T. gondii infection. Women with an ovarian cancer or endometrial cancer had higher T. gondii seroprevalence than that of HCs. Moreover, T. gondii infection in patients with a GT mostly acquired within two years of diagnosis, but the infection in healthy controls had no obvious time characteristics. Here, we demonstrated that T. gondii infection is significantly higher in patients with a GT (especially in women with an ovarian tumor) compared to HCs. Thus, infection with this parasite should be avoided in patients with a GT, and the causal relationship between T. gondii and GTs should be studied in detail. creator: Zhongjun Wang creator: Tingting Qu creator: Huiyang Qi creator: Shuchao Zhao creator: Hailei Shi creator: Wenye Bai creator: Yang Yu creator: Xiao Wu creator: Peng Zhao uri: https://doi.org/10.7717/peerj.14569 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Wang et al. title: Patch and matrix characteristics determine the outcome of ecosystem engineering by mole rats in dry grasslands link: https://peerj.com/articles/14582 last-modified: 2022-12-15 description: BackgroundBurrowing mammals are important ecosystem engineers, especially in open ecosystems where they create patches that differ from the surrounding matrix in their structure or ecosystem functions.MethodsWe evaluated the fine-scale effects of a subterranean ecosystem engineer, the Lesser blind mole rat on the vegetation composition of sandy dry grasslands in Hungary. In this model system we tested whether the characteristics of the patch (mound size) and the matrix (total vegetation cover in the undisturbed grassland) influence the structural and functional contrasts between the mounds and the undisturbed grasslands. We sampled the vegetation of 80 mounds and 80 undisturbed grassland plots in four sites, where we recorded the total vegetation cover, and the occurrence and cover of each vascular plant species. We used two proxies to characterise the patches (mounds) and the matrix (undisturbed grassland): we measured the perimeter of the mounds and estimated the total vegetation cover of the undisturbed grasslands. First, we compared the vegetation characteristics of the mounds and the surrounding grasslands with general linear models. Second, we characterised the contrasts between the mounds and the undisturbed grassland by relative response indices (RRIs) of the vegetation characteristics studied in the first step.ResultsSpecies composition of the vegetation of the mounds and undisturbed grasslands was well separated in three out of the four study sites. Mounds were characterised by lower vegetation cover, lower cover of perennial graminoids, and higher diversity, and evenness compared to undisturbed grasslands. The contrast in vegetation cover between mounds and undisturbed grasslands increased with decreasing patch size. Increasing vegetation cover in the matrix grasslands increased the contrasts between the mounds and undisturbed grasslands in terms of total cover, perennial graminoid cover, diversity, and evenness. Our results suggest that mole rat mounds provide improved establishment conditions for subordinate species, because they are larger than other types of natural gaps and are characterised by less intense belowground competition. The ecosystem engineering effect, i.e., the contrast between the patches and the matrix was the largest in the more closed grasslands. creator: Orsolya Valkó creator: András Kelemen creator: Orsolya Kiss creator: Balázs Deák uri: https://doi.org/10.7717/peerj.14582 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Valkó et al. title: Genome-wide investigation and expression pattern of PHR family genes in cotton under low phosphorus stress link: https://peerj.com/articles/14584 last-modified: 2022-12-15 description: Phosphorus starvation response (PHR) protein is an important transcription factor in phosphorus regulatory network, which plays a vital role in regulating the effective utilization of phosphorus. So far, the PHR genes have not been systematically investigated in cotton. In the present study, we have identified 22, 23, 41 and 42 PHR genes in G. arboreum, G. raimondii, G. hirsutum and G. barbadense, respectively. Phylogenetic analysis showed that cotton PHR genes were classified into five distinct subfamilies. The gene structure, protein motifs and gene expression were further investigated. The PHR genes of G. hirsutum from the same subfamily had similar gene structures, all containing Myb_DNA-binding and Myb_CC_LHEQLE conserved domain. The structures of paralogous genes were considerably conserved in exons number and introns length. The cis-element prediction in their promoters showed that genes were not only regulated by light induction, but also were related to auxin, MeJA, abscisic acid-responsive elements, of which might be regulated by miRNA. The expression analysis showed that the GhPHR genes were differentially expressed in different tissues under various stresses. Furthermore, GhPHR6, GhPHR11, GhPHR18 and GhPHR38 were significantly changed under low phosphorus stress. The results of this study provide a basis for further cloning and functional verification of genes related to regulatory network of low phosphorus tolerance in cotton. creator: Yan Zhao creator: Peiyu Li creator: Huarui Wang creator: Jiping Feng creator: Yuxin Li creator: Shanshan Wang creator: Yuanjie Li creator: Yanyan Guo creator: Lin Li creator: Yao Su creator: Zhengwen Sun uri: https://doi.org/10.7717/peerj.14584 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Zhao et al.