title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=1088 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: The brain-derived neurotrophic factor Val66Met polymorphism increases segregation of structural correlation networks in healthy adult brains link: https://peerj.com/articles/9632 last-modified: 2020-08-05 description: BackgroundAlthough structural correlation network (SCN) analysis is an approach to evaluate brain networks, the neurobiological interpretation of SCNs is still problematic. Brain-derived neurotrophic factor (BDNF) is well-established as a representative protein related to neuronal differentiation, maturation, and survival. Since a valine-to-methionine substitution at codon 66 of the BDNF gene (BDNF Val66Met single nucleotide polymorphism (SNP)) is well-known to have effects on brain structure and function, we hypothesized that SCNs are affected by the BDNF Val66Met SNP. To gain insight into SCN analysis, we investigated potential differences between BDNF valine (Val) homozygotes and methionine (Met) carriers in the organization of their SCNs derived from inter-regional cortical thickness correlations.MethodsForty-nine healthy adult subjects (mean age = 41.1 years old) were divided into two groups according to their genotype (n: Val homozygotes = 16, Met carriers = 33). We obtained regional cortical thickness from their brain T1 weighted images. Based on the inter-regional cortical thickness correlations, we generated SCNs and used graph theoretical measures to assess differences between the two groups in terms of network integration, segregation, and modularity.ResultsThe average local efficiency, a measure of network segregation, of BDNF Met carriers’ network was significantly higher than that of the Val homozygotes’ (permutation p-value = 0.002). Average shortest path lengths (a measure of integration), average local clustering coefficient (another measure of network segregation), small-worldness (a balance between integration and segregation), and modularity (a representative measure for modular architecture) were not significantly different between group (permutation p-values ≧ 0.01).Discussion and ConclusionOur results suggest that the BDNF Val66Met polymorphism may potentially influence the pattern of brain regional morphometric (cortical thickness) correlations. Comparing networks derived from inter-regional cortical thickness correlations, Met carrier SCNs have denser connections with neighbors and are more distant from random networks than Val homozygote networks. Thus, it may be necessary to consider potential effects of BDNF gene mutations in SCN analyses. This is the first study to demonstrate a difference between Val homozygotes and Met carriers in brain SCNs. creator: Issei Ueda creator: Kazuhiro Takemoto creator: Keita Watanabe creator: Koichiro Sugimoto creator: Atsuko Ikenouchi creator: Shingo Kakeda creator: Asuka Katsuki creator: Reiji Yoshimura creator: Yukunori Korogi uri: https://doi.org/10.7717/peerj.9632 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Ueda et al. title: DNA barcoding of commercially important reef fishes in Weh Island, Aceh, Indonesia link: https://peerj.com/articles/9641 last-modified: 2020-08-05 description: Knowledge on the precise identification of fish resources is critical for sustainable fisheries management. This study employs the DNA barcoding approach to generate a molecular taxonomic catalogue of commercially important reef fishes in the waters of Weh Island (Aceh Province), the most northerly inhabited island in the biodiverse Indonesian Archipelago. The waters not only support artisanal fisheries but also a feeder for the industry in the greater island of Aceh. In total, 230 specimens from 72 species belonging to 32 genera and 17 families were DNA barcoded, representing a major segment of the captured reef fish taxa and a quarter of fish species diversity that had previously been recorded. The sequence read lengths were 639 bp revealing 359 conserved sites, 280 variable sites, 269 parsimony informative and 11 singletons. Our molecular findings paralleled the morphological identification with no evidence of cryptic species or new species discovery. This study is a significant contribution to the fisheries statistics of this area, which would facilitate assessment of species catch composition and hence for strategizing management plans. It is an important input to the DNA barcode library of Indonesian marine fishes and to the global DNA barcode entries in general. creator: Nur Fadli creator: Siti Azizah Mohd Nor creator: Ahmad Sofiman Othman creator: Hizir Sofyan creator: Zainal A. Muchlisin uri: https://doi.org/10.7717/peerj.9641 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Fadli et al. title: A prognostic gene model of immune cell infiltration in diffuse large B-cell lymphoma link: https://peerj.com/articles/9658 last-modified: 2020-08-05 description: BackgroundImmune cells in the tumor microenvironment are an important prognostic indicator in diffuse large B-cell lymphoma (DLBCL). However, information on the heterogeneity and risk stratification of these cells is limited. We sought to develop a novel immune model to evaluate the prognostic intra-tumoral immune landscape of patients with DLBCL.MethodsThe ESTIMATE and CIBERSORT algorithms were used to estimate the numbers of 22 infiltrating immune cells based on the gene expression profiles of 229 patients with DLBCL who were recruited from a public database. The least absolute shrinkage and selection operator (Lasso) penalized regression analyses and nomogram model were used to construct and evaluate the prognostic immunoscore (PIS) model for overall survival prediction. An immune gene prognostic score (IGPS) was generated by Gene Set Enrichment Analysis (GSEA) and Cox regression analysis was and validated in an independent NCBI GEO dataset (GSE10846).ResultsA higher proportion of activated natural killer cells was associated with a poor outcome. A total of five immune cells were selected in the Lasso model and DLBCL patients with high PIS showed a poor prognosis (hazard ratio (HR) 2.16; 95% CI [1.33–3.50]; P = 0.002). Differences in immunoscores and their related outcomes were attributed to eight specific immune genes involved in the cytokine–cytokine receptor interaction and chemokine signaling pathways. The IGPS based on a weighted formula of eight genes is an independent prognostic factor (HR: 2.14, 95% CI [1.40–3.28]), with high specificity and sensitivity in the validation dataset.ConclusionsOur findings showed that a PIS model based on immune cells is associated with the prognosis of DLBCL. We developed a novel immune-related gene-signature model associated with the PIS model and enhanced the prognostic functionality for the prediction of overall survival in patients with DLBCL. creator: Hao Zhou creator: Chang Zheng creator: De-Sheng Huang uri: https://doi.org/10.7717/peerj.9658 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Zhou et al. title: Medial knee cartilage is unlikely to withstand a lifetime of running without positive adaptation: a theoretical biomechanical model of failure phenomena link: https://peerj.com/articles/9676 last-modified: 2020-08-05 description: Runners on average do not have a high risk of developing knee osteoarthritis, even though running places very high loads on the knee joint. Here we used gait analysis, musculoskeletal modeling, and a discrete-element model of knee contact mechanics to estimate strains of the medial knee cartilage in walking and running in 22 young adults (age 23 ± 3 years). A phenomenological model of cartilage damage, repair, and adaptation in response to these strains then estimated the failure probability of the medial knee cartilage over an adult lifespan (age 23–83 years) for 6 km/day of walking vs. walking and running 3 km/day each. With no running, by age 55 the cumulative probability of medial knee cartilage failure averaged 36% without repair and 13% with repair, similar to reports on incidence of knee osteoarthritis in non-obese adults with no knee injuries, but the probability for running was very high without repair or adaptation (98%) and remained high after including repair (95%). Adaptation of the cartilage compressive modulus, cartilage thickness, and the tibiofemoral bone congruence in response to running (+1.15 standard deviations of their baseline values) was necessary for the failure probability of walking and running 3 km/day each to equal the failure probability of walking 6 km/day. The model results suggest two conclusions for further testing: (i) unlike previous findings on the load per unit distance, damage per unit distance on the medial knee cartilage is greater in running vs. walking, refuting the “cumulative load” hypothesis for long-term joint health; (ii) medial knee cartilage is unlikely to withstand a lifetime of mechanical loading from running without a natural adaptation process, supporting the “cartilage conditioning” hypothesis for long-term joint health. creator: Ross H. Miller creator: Rebecca L. Krupenevich uri: https://doi.org/10.7717/peerj.9676 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Miller and Krupenevich title: Expression of Aspergillus niger glucose oxidase in Pichia pastoris and its antimicrobial activity against Agrobacterium and Escherichia coli link: https://peerj.com/articles/9010 last-modified: 2020-08-04 description: The gene encoding glucose oxidase from Aspergillus niger ZM-8 was cloned and transferred to Pichia pastoris GS115, a transgenic strain P. pastoris GS115-His-GOD constructed. The growth curve of P. pastoris GS115-His-GOD was consistent with that of Pichia pastoris GS115-pPIC9K under non-induced culture conditions. Under methanol induction conditions, the growth of the GOD-transgenic strain was significantly lowered than P. pastoris GS115-pPIC9K with the induced-culture time increase, and the optical densities of GOD-transgenic strain reached one-third of that of the P. pastoris GS115-pPIC9K at 51 h. The activity of glucose oxidase in the cell-free supernatant, the supernatant of cell lysate, and the precipitation of cell lysate was 14.3 U/mL, 18.2 U/mL and 0.48 U/mL, respectively. The specific activity of glucose oxidase was 8.3 U/mg, 6.52 U/mg and 0.73 U/mg, respectively. The concentration of hydrogen peroxide formed by glucose oxidase from supernatant of the fermentation medium, the supernatant of the cell lysate, and the precipitation of cell lysate catalyzing 0.2 M glucose was 14.3 μg/mL, 18.2 μg/mL, 0.48 μg/mL, respectively. The combination of different concentrations of glucose oxidase and glucose could significantly inhibit the growth of Agrobacterium and Escherichia coli in logarithmic phase. The filter article containing supernatant of the fermentation medium, supernatant of the cell lysate, and precipitation of cell lysate had no inhibitory effect on Agrobacterium and E. coli. The minimum inhibitory concentration of hydrogen peroxide on the plate culture of Agrobacterium and E. coli was 5.6 × 103 μg/mL and 6.0 × 103 μg/mL, respectively. creator: Yonggang Wang creator: Jiangqin Wang creator: Feifan Leng creator: Jianzhong Ma creator: Alnoor Bagadi uri: https://doi.org/10.7717/peerj.9010 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Wang et al. title: OBAMA: OBAMA for Bayesian amino-acid model averaging link: https://peerj.com/articles/9460 last-modified: 2020-08-04 description: BackgroundBayesian analyses offer many benefits for phylogenetic, and have been popular for analysis of amino acid alignments. It is necessary to specify a substitution and site model for such analyses, and often an ad hoc, or likelihood based method is employed for choosing these models that are typically of no interest to the analysis overall.MethodsWe present a method called OBAMA that averages over substitution models and site models, thus letting the data inform model choices and taking model uncertainty into account. It uses trans-dimensional Markov Chain Monte Carlo (MCMC) proposals to switch between various empirical substitution models for amino acids such as Dayhoff, WAG, and JTT. Furthermore, it switches base frequencies from these substitution models or use base frequencies estimated based on the alignment. Finally, it switches between using gamma rate heterogeneity or not, and between using a proportion of invariable sites or not.ResultsWe show that the model performs well in a simulation study. By using appropriate priors, we demonstrate both proportion of invariable sites and the shape parameter for gamma rate heterogeneity can be estimated. The OBAMA method allows taking in account model uncertainty, thus reducing bias in phylogenetic estimates. The method is implemented in the OBAMA package in BEAST 2, which is open source licensed under LGPL and allows joint tree inference under a wide range of models. creator: Remco R. Bouckaert uri: https://doi.org/10.7717/peerj.9460 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Bouckaert title: Survival, growth and carbon content in a forest plantation established after a clear-cutting in Durango, Mexico link: https://peerj.com/articles/9506 last-modified: 2020-08-04 description: BackgroundForest plantations play an important role in carbon sequestration, helping to mitigate climate change. In this study, survival, biomass, growth rings and annual carbon content storage were evaluated in a mixed Pinus durangensis and P. cooperi plantation that was established after a clear-cutting. The plantation is eight years old and covers an area of 21.40 ha.MethodsSixteen sites of 100 m2 were distributed randomly. At each site, two trees distributed proportionally to the diametric categories were destructively sampled (one per tree species). Two cross-sections were cut from each tree: The first at the base of the stump and the second at 1.30 m. The width of tree rings of the first cross-section was measured using a stereoscopic microscope with precision in microns (µm). The year-by-year basal diameter of each tree was recorded and biomass and carbon content was estimated using allometric equations.ResultsThe estimated survival was 75.2%. The results of the ANOVA showed significant differences between the year-by-year width records of tree rings, the highest value corresponding to the fifth year. The average carbon sequestration per year is 0.30 kg for both studied tree species.ConclusionsP. durangensis and P. cooperi plantations adapt and develop well in Durango forests when they are established in areas that are subjected to clear-cutting. creator: Jesús Alejandro Soto-Cervantes creator: Artemio Carrillo-Parra creator: Rodrigo Rodríguez-Laguna creator: José Javier Corral-Rivas creator: Marín Pompa-García creator: Pedro Antonio Dominguez-Calleros uri: https://doi.org/10.7717/peerj.9506 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Soto-Cervantes et al. title: Identifying agricultural pesticides that may pose a risk for birds link: https://peerj.com/articles/9526 last-modified: 2020-08-04 description: In this study, we analyze changing patterns of pesticide use in agriculture in Great Britain over the 1990–2016 period, with respect to the risk they pose to birds. The weight of pesticides applied decreased by 51% between 1990 and 2016, but the area treated increased by 63% over the same period. Over this period, there has been considerable turnover in the pesticides used. The European Union (including Great Britain until 2020) has restricted or banned many pesticides for agricultural use, including organophosphates and carbamates. However, new generations of active substances have been introduced, such as the neonicotinoids, some of which have since been banned. In this analysis, we estimate the annual ‘toxic load’ of agricultural pesticide use in Great Britain for birds, measured as the total number of LD50 doses for corn buntings, Emberiza calandra. We have previously performed similar analyses for bees, for which the total toxic load increased six-fold during this period. In contrast, for birds the total toxic load fell by 80.5%, although still correspond to 8.3e+11 corn bunting LD50 doses in 2016. The decrease in toxicity is largely due to declining use of highly toxic organophosphates in recent years. We identify the pesticides in current use that may pose the highest risk to birds, which include a mix of insecticides, herbicides, fungicides, molluscicides, acaricides and plant growth regulators. The insecticide ethoprop was ranked highest in 2016, with a toxic load of 71 billion potential corn bunting kills. Some of the other chemicals presenting a high toxic load, such as the herbicide chlormequat, are not highly toxic to birds (in terms of LD50) but are used in very large quantities. However, it is important to stress that, in reality, only a tiny proportion of pesticides applied will be ingested by birds, and this will vary according to timing and method of application, persistence of the active substance and many other factors. We further note that impacts of pesticides on birds might often be indirect, for example via depleting their food supply, and that sublethal impacts may occur at much lower doses than the LD50, neither of which do we investigate here. Nonetheless, we suggest that this is a useful approach to highlight pesticides that might be worth closer study with regard to possible impacts. creator: Cannelle Tassin de Montaigu creator: Dave Goulson uri: https://doi.org/10.7717/peerj.9526 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Tassin de Montaigu and Goulson title: Regional distribution of Christensenellaceae and its associations with metabolic syndrome based on a population-level analysis link: https://peerj.com/articles/9591 last-modified: 2020-08-04 description: The link between the gut microbiota and metabolic syndrome (MetS) has attracted widespread attention. Christensenellaceae was recently described as an important player in human health, while its distribution and relationship with MetS in Chinese population is still unknown. This study sought to observe the association between Christensenellaceae and metabolic indexes in a large sample of residents in South China. A total of 4,781 people from the GGMP project were included, and the fecal microbiota composition of these individuals was characterized by 16S rRNA sequencing and analyzed the relation between Christensenellaceae and metabolism using QIIME (Quantitative Insight Into Microbial Ecology, Version 1.9.1). The results demonstrated that microbial richness and diversity were increased in the group with a high abundance of Christensenellaceae, who showed a greater complexity of the co-occurrence network with other bacteria than residents who lacked Christensenellaceae. The enriched bacterial taxa were predominantly represented by Oscillospira, Ruminococcaceae, RF39, Rikenellaceae and Akkermansia as the Christensenellaceae abundance increased, while the abundances of Veillonella, Fusobacterium and Klebsiella were significantly reduced. Furthermore, Christensenellaceae was negatively correlated with the pathological features of MetS, such as obesity, hypertriglyceridemia and body mass index (BMI). We found reduced levels of lipid biosynthesis and energy metabolism pathways in people with a high abundance of Christensenellaceae, which may explain the negative relationship between body weight and Christensenellaceae. In conclusion, we found a negative correlation between Christensenellaceae and MetS in a large Chinese population and reported the geographical distribution of Christensenellaceae in the GGMP study. The association data from this population-level research support the investigation of strains within Christensenellaceae as potentially beneficial gut microbes. creator: Xiang Li creator: Zewen Li creator: Yan He creator: Pan Li creator: Hongwei Zhou creator: Nianyi Zeng uri: https://doi.org/10.7717/peerj.9591 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Li et al. title: Proteins from Lignosus tigris with selective apoptotic cytotoxicity towards MCF7 cell line and suppresses MCF7-xenograft tumor growth link: https://peerj.com/articles/9650 last-modified: 2020-08-04 description: BackgroundLignosus tigris, a recently discovered species of the unique Lignosus family, has been traditionally used by the indigenous communities in Peninsular Malaysia to treat various ailments and as an alternative medicine for cancer treatment. The L. tigris cultivar sclerotia (Ligno TG-K) was found to contain numerous bioactive compounds with beneficial biomedicinal properties and the sclerotial extract exhibited potent antioxidant activity. However, the anticancer property of the Ligno TG-K including in vitro and in vivo antitumor effects as well as its anticancer active compounds and the mechanisms has yet to be investigated.MethodsThe cytotoxicity of the Ligno TG-K against human breast (MCF7), prostate (PC3) and lung (A549) adenocarcinoma cell lines was evaluated using MTT cytotoxicity assay. The cytotoxic mechanisms of the active high molecular weight proteins (HMWp) fraction were investigated through detection of caspases activity and apoptotic-related proteins expression by Western blotting. The in vivo antitumor activity of the isolated HMWp was examined using MCF7 mouse xenograft model. Shotgun LC-MS/MS analysis was performed to identify the proteins in the HMWp.Results and DiscussionCold water extract of the sclerotia inhibited proliferation of MCF7, A549 and PC3 cells with IC50 ranged from 28.9 to 95.0 µg/mL. Bioassay guided fractionation of the extract revealed that HMWp exhibited selective cytotoxicity against MCF7 cells via induction of cellular apoptosis by the activation of extrinsic and intrinsic signaling pathways. HMWp activated expression of caspase-8 and -9 enzymes, and pro-apoptotic Bax protein whilst inhibiting expression of tumor survivor protein, Bcl-2. HMWp induced tumor-cell apoptosis and suppressed growth of tumor in MCF-7 xenograft mice. Lectins, serine proteases, RNase Gf29 and a 230NA deoxyribonuclease are the major cytotoxic proteins that accounted for 55.93% of the HMWp.ConclusionThe findings from this study provided scientific evidences to support the traditional use of the L. tigris sclerotia for treatment of breast cancer. Several cytotoxic proteins with high abundance have been identified in the HMWp of the sclerotial extract and these proteins have potential to be developed into new anticancer agents or as adjunct cancer therapy. creator: Boon Hong Kong creator: Kean Hooi Teoh creator: Nget Hong Tan creator: Chon Seng Tan creator: Szu Ting Ng creator: Shin Yee Fung uri: https://doi.org/10.7717/peerj.9650 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Kong et al.