title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=1562 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Unilateral application of an external pneumatic compression therapy improves skin blood flow and vascular reactivity bilaterally link: https://peerj.com/articles/4878 last-modified: 2018-05-29 description: BackgroundWe sought to determine the effects of unilateral lower-limb external pneumatic compression (EPC) on bilateral lower-limb vascular reactivity and skin blood flow.MethodsThirty-two participants completed this two-aim study. In AIM1 (n = 18, age: 25.5 ± 4.7 years; BMI: 25.6 ± 3.5 kg/m2), bilateral femoral artery blood flow and reactivity (flow mediated dilation [FMD]) measurements were performed via ultrasonography at baseline (PRE) and immediately following 30-min of unilateral EPC treatment (POST). AIM2 (n = 14, age: 25.9 ± 4.5; BMI: 27.2 ± 2.7 kg/m2) involved 30-min unilateral EPC (n = 7) or sham (n = 7) treatment with thermographic bilateral lower-limb mean skin temperature (MST) measurements at baseline, 15-min of treatment (T15) and 0, 30 and 60-min (R0, R30, R60) following treatment.ResultsComparative data herein are presented as mean ± 95% confidence interval. AIM1: No significant effects on total reactive hyperemia blood flow were observed for the treated (i.e., compressed) or untreated (i.e., non-compressed) leg. A significant effect of time, but no time*leg interaction, was observed for relative FMD indicating higher reactivity bilaterally with unilateral EPC treatment (FMD: +0.41 ± 0.09% across both legs; p < 0.05). AIM2: Unilateral EPC treatment was associated with significant increases in whole-leg MST from baseline during (T15: +0.63 ± 0.56 °C in the visible untreated/contralateral leg, p < 0.025) and immediately following treatment (i.e., R0) in both treated (+1.53 ± 0.59 °C) and untreated (+0.60 ± 0.45 °C) legs (p < 0.0125). Across both legs, MST remained elevated with EPC at 30-min post-treatment (+0.60 ± 0.45 °C; p < 0.0167) but not at 60-min post (+0.27 ± 0.46 °C; p = 0.165). Sham treatment was associated with a significant increase in the treated leg immediately post-treatment (+1.12 ± 0.31 °C; p < 0.0167), but not in the untreated leg (−0.27 ± 0.12 °C). MST in neither the treated or untreated leg were increased relative to baseline at R30 or R60 (p > 0.05). Finally, during treatment and at all post-treatment time points (i.e., R0, R30 and R60), independent of treatment group (EPC vs. sham), there was a significant effect of region. The maximum increase in MST was observed at the R0 time point and was significantly (p < 0.05) larger in the thigh region (+1.02 ± 0.31 °C) than the lower-leg (+0.47 ± 0.29 °C) region. However, similar rates of MST decline from R0 in the thigh and lower leg regions were observed at the R30 and R60 time points.DiscussionUnilateral EPC may be an effective intervention for increasing skin blood flow and/or peripheral conduit vascular reactivity in the contralateral limb. While EPC was effective in increasing whole-leg MST bilaterally, there appeared to be a more robust response in the thigh compared to the lower-leg. Thus, proximity along the leg may be an important consideration in prospective treatment strategies. creator: Jeffrey S. Martin creator: Allison M. Martin creator: Petey W. Mumford creator: Lorena P. Salom creator: Angelique N. Moore creator: David D. Pascoe uri: https://doi.org/10.7717/peerj.4878 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Martin et al. title: MIPhy: identify and quantify rapidly evolving members of large gene families link: https://peerj.com/articles/4873 last-modified: 2018-05-29 description: After transitioning to a new environment, species often exhibit rapid phenotypic innovation. One of the fastest mechanisms for this is duplication followed by specialization of existing genes. When this happens to a member of a gene family, it tends to leave a detectable phylogenetic signature of lineage-specific expansions and contractions. These can be identified by analyzing the gene family across several species and identifying patterns of gene duplication and loss that do not correlate with the known relationships between those species. This signature, termed phylogenetic instability, has been previously linked to adaptations that change the way an organism samples and responds to its environment; conversely, low phylogenetic instability has been previously linked to proteins with endogenous functions. With the increase in genome-level data, there is a need to identify and quantify phylogenetic instability. Here, we present Minimizing Instability in Phylogenetics (MIPhy), a tool that solves this problem by quantifying the incongruence of a gene’s evolutionary history. The motivation behind MIPhy was to produce a tool to aid in interpreting phylogenetic trees. It can predict which members of a gene family are under adaptive evolution, working only from a gene tree and the relationship between the species under consideration. While it does not conduct any estimation of positive selection—which is the typical indication of adaptive evolution—the results tend to agree. We demonstrate the usefulness of MIPhy by accurately predicting which members of the mammalian cytochrome P450 gene superfamily metabolize xenobiotics and which metabolize endogenous compounds. Our predictions correlate very well with known substrate specificities of the human enzymes. We also analyze the Caenorhabditis collagen gene family and use MIPhy to predict genes that produce an observable phenotype when knocked down in C. elegans, and show that our predictions correlate well with existing knowledge. The software can be downloaded and installed from https://github.com/dave-the-scientist/miphy and is also available as an online web tool at http://www.miphy.wasmuthlab.org. creator: David M. Curran creator: John S. Gilleard creator: James D. Wasmuth uri: https://doi.org/10.7717/peerj.4873 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2018 Curran et al. title: Associations between psychometrically assessed life history strategy and daily behavior: data from the Electronically Activated Recorder (EAR) link: https://peerj.com/articles/4866 last-modified: 2018-05-29 description: Life history theory has generated cogent, well-supported hypotheses about individual differences in human biodemographic traits (e.g., age at sexual maturity) and psychometric traits (e.g., conscientiousness), but little is known about how variation in life history strategy (LHS) is manifest in quotidian human behavior. Here I test predicted associations between the self-report Arizona Life History Battery and frequencies of 12 behaviors observed over 72 h in 91 US college students using the Electronically Activated Recorder (EAR), a method of gathering periodic brief audio recordings as participants go about their daily lives. Bayesian multi-level aggregated binomial regression analysis found no strong associations between ALHB scores and behavior frequencies. One behavior, presence at amusement venues (bars, concerts, sports events) was weakly positively associated with ALHB-assessed slow LHS, contrary to prediction. These results may represent a challenge to the ALHB’s validity. However, it remains possible that situational influences on behavior, which were not measured in the present study, moderate the relationships between psychometrically-assessed LHS and quotidian behavior. creator: Joseph H. Manson uri: https://doi.org/10.7717/peerj.4866 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Manson title: Socio-economic factors and management regimes as drivers of tree cover change in Nepal link: https://peerj.com/articles/4855 last-modified: 2018-05-29 description: Despite the local and global importance of forests, deforestation is driven by various socio-economic and biophysical factors continues in many countries. In Nepal, in response to massive deforestation, the community forestry program has been implemented to reduce deforestation and support livelihoods. After four decades of its inception, the effectiveness of this program on forest cover change remains mostly unknown. This study analyses the spatial and temporal patterns of tree cover change along with a few socio-economic drivers of tree cover change to examine the effectiveness of the community forestry program for conserving forests or in reducing deforestation. We also investigate the socio-economic factors and policy responses as manifested through the community forestry program responsible for the tree cover change at the district level. The total tree cover area in the year 2000 in Nepal was ∼4,746,000 hectares, and our analysis reveals that between 2001 and 2016, Nepal has lost ∼46,000 ha and gained ∼12,200 ha of areas covered by trees with a substantial spatial and temporal variations. After accounting socio-economic drivers of forest cover change, our analysis showed that districts with the larger number of community forests had a minimum loss in tree cover, while districts with the higher proportion of vegetation covered by community forests had a maximum gain in tree cover. This indicates a positive contribution of the community forestry program to reducing deforestation and increasing tree cover. creator: Sujata Shrestha creator: Uttam B. Shrestha creator: Kamal Bawa uri: https://doi.org/10.7717/peerj.4855 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Shrestha et al. title: Genomic analysis of red-tide water bloomed with Heterosigma akashiwo in Geoje link: https://peerj.com/articles/4854 last-modified: 2018-05-29 description: Microbial community structures of harmful algal bloom (HAB) caused by Heterosigma akashiwo in Geoje were analyzed using the MiSeq platform. To analyze phytoplankton communities without cross-reactivity with predominant bacteria, a new phytoplankton-specific 23S universal primer set was designed by modifying two previously used ones. The new universal primer set turned out to be a useful tool for the analysis of the phytoplankton community; it showed a high specificity for phytoplankton without cross-reactivity to bacterial sequences as well as the wide taxon coverage presenting from prokaryotic cyanobacteria to eukaryotic algae. Next Generation Sequencing (NGS) data generated by two universal primer sets (16S and 23S) provided useful information about the H. akashiwo bloom. According to the 23S universal primer set, proportions of H. akashiwo increased by more than 200-fold as the bloom occurred and its numbers were high enough to detect in control sites. Its operational taxonomic units (OTUs) were detected in the bloom sites at low proportions suggesting that the 16S universal primer set may not be as effective for monitoring harmful algal blooming (HAB) as the 23S universal primer set. In addition, several abundant OTUs in Chlorophyta were not presented by the 16S universal primer set in this study. However, the 16S primer set was useful for detecting decreases in Foraminifera as HAB occurred suggesting that genomic analyses using two universal primer sets would provide more reliable data for understanding microbial community changes by various environmental or ecological events, including HAB. Genomic analyses using two universal primer sets was also useful for determining a correlation between microbial components as HAB occurred. Heterosigma akashiwo was positively correlated with other bloom species, including Karenia mikimotoi, Teleaulax amphioxeia, and bacteria in Verrucomicrobia. creator: Hye-Eun Kang creator: Tae-Ho Yoon creator: Sunyoung Yoon creator: Hak Jun Kim creator: Hyun Park creator: Chang-Keun Kang creator: Hyun-Woo Kim uri: https://doi.org/10.7717/peerj.4854 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Kang et al. title: Modeling transcriptional activation changes to Gal4 variants via structure-based computational mutagenesis link: https://peerj.com/articles/4844 last-modified: 2018-05-29 description: As a DNA binding transcriptional activator, Gal4 promotes the expression of genes responsible for galactose metabolism. The Gal4 protein from Saccharomyces cerevisiae (baker’s yeast) has become a model for studying eukaryotic transcriptional activation in general because its regulatory properties mirror those of several eukaryotic organisms, including mammals. Given the availability of a crystallographic structure for Gal4, here we implement an in silico mutagenesis technique that makes use of a four-body knowledge-based energy function, in order to empirically quantify the structural impacts associated with single residue substitutions on the Gal4 protein. These results were used to examine the structure-function relationship in Gal4 based on a recently published experimental mutagenesis study, whereby functional changes to a uniformly distributed set of 1,068 single residue Gal4 variants were obtained by measuring their transcriptional activation levels relative to wild-type. A significant correlation was observed between computed (scalar) structural effect data and measured activity values for this collection of single residue Gal4 variants. Additionally, attribute vectors quantifying position-specific environmental impacts were generated for each of the Gal4 variants via computational mutagenesis, and we implemented supervised classification and regression statistical machine learning algorithms to train predictive models of variant Gal4 activity based on these structural changes. All models performed well under cross-validation testing, with balanced accuracy reaching 91% among the classification models, and with the actual and predicted activity values displaying a correlation as high as r = 0.80 for the regression models. Reliable predictions of transcriptional activation levels for Gal4 variants that have yet to be studied can be instantly generated by submitting their respective structure-based feature vectors to the trained models for testing. Such a computational pre-screening of Gal4 variants may potentially reduce costs associated with running large-scale mutagenesis experiments. creator: Majid Masso creator: Nitin Rao creator: Purnima Pyarasani uri: https://doi.org/10.7717/peerj.4844 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Masso et al. title: Changes in species abundance after seven years of elevated atmospheric CO2 and warming in a Subarctic birch forest understorey, as modified by rodent and moth outbreaks link: https://peerj.com/articles/4843 last-modified: 2018-05-29 description: A seven-year long, two-factorial experiment using elevated temperatures (5 °C) and CO2 (concentration doubled compared to ambient conditions) designed to test the effects of global climate change on plant community composition was set up in a Subarctic ecosystem in northernmost Sweden. Using point-frequency analyses in permanent plots, an increased abundance of the deciduous Vaccinium myrtillus, the evergreens V. vitis-idaea and Empetrum nigrum ssp. hermaphroditum and the grass Avenella flexuosa was found in plots with elevated temperatures. We also observed a possibly transient community shift in the warmed plots, from the vegetation being dominated by the deciduous V. myrtillus to the evergreen V. vitis-idaea. This happened as a combined effect of V. myrtillus being heavily grazed during two events of herbivore attack—one vole outbreak (Clethrionomys rufocanus) followed by a more severe moth (Epirrita autumnata) outbreak that lasted for two growing seasons—producing a window of opportunity for V. vitis-idaea to utilize the extra light available as the abundance of V. myrtillus decreased, while at the same time benefitting from the increased growth in the warmed plots. Even though the effect of the herbivore attacks did not differ between treatments they may have obscured any additional treatment effects. This long-term study highlights that also the effects of stochastic herbivory events need to be accounted for when predicting future plant community changes. creator: Brita M. Svensson creator: Bengt Å. Carlsson creator: Jerry M. Melillo uri: https://doi.org/10.7717/peerj.4843 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Svensson et al. title: Sorting nexin-1 is a candidate tumor suppressor and potential prognostic marker in gastric cancer link: https://peerj.com/articles/4829 last-modified: 2018-05-29 description: Sorting nexin-1 (SNX1) is an important functional protein in cell endocytosis, efflux, protein sorting, cell signal transduction, etc; however, the expression, the role and clinical relevance of SNX1 have not been investigated in gastric cancer (GC). In this study, we first performed a bioinformatics investigation using the data obtained from The Cancer Genome Atlas (TCGA) database. The result showed that SNX1 mRNA levels were significantly lower in GC tissues than in paracancerous tissues. In a study of 150 cases of GC, including 60 cases with paired paracancerous and cancer tissues and 90 cases with detailed follow-up information, SNX1 expression was analyzed by immunohistochemistry. Our study on paired paracancerous and cancer tissues showed that SNX1 protein expression remarkably decreased in GC tissues (50/60, 83.33%). A study on 90 patients with detailed follow-up information showed that tumors with higher SNX1 protein level were correlated with better clinicopathologic stages (p = 0.0285), nodal status (p = 0.0286), smaller tumor sizes (p = 0.0294) and a better survival rate in patients with GC (p = 0.0245). Univariate analysis of the 90 patients with GC showed that low-level SNX1 was significantly correlated with decreased overall survival of GC patients (p = 0.008), and associated with a relatively higher cumulative hazard of death. Exogenous expression of SNX1 inhibited the growth, migration, invasion and promoted the apoptosis and enhanced the sensitivity of GC cells to the chemotherapeutic drug 5-Fluorouracil (5-Fu) in vitro, while knockdown of SNX1 by short hairpin RNA (shRNA) significantly promoted the growth, migration, invasion and reduced the apoptosis and the sensitivity of GC cells to 5-Fu. SNX1 also showed to influence the levels of epithelial-mesenchymal transition markers including Vimentin, Snail, and E-cadherin in GC cells in vitro. Taken together, we propose here that SNX1 serves as a tumor suppressor and prognostic marker that reduces tumor cell malignancy for GC. creator: Xiao-Yong Zhan creator: Yaqiong Zhang creator: Ertao Zhai creator: Qing-Yi Zhu creator: Yulong He uri: https://doi.org/10.7717/peerj.4829 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Zhan et al. title: Genome-wide characterization and expression analysis of GRAS gene family in pepper (Capsicum annuum L.) link: https://peerj.com/articles/4796 last-modified: 2018-05-29 description: Plant-specific GRAS transcription factors regulate various biological processes in plant growth, development and stress responses. However, this important gene family was not fully characterized in pepper (Capsicum annuum L.), an economically important vegetable crop. Here, a total of 50 CaGRAS members were identified in pepper genome and renamed by their respective chromosomal distribution. Genomic organization revealed that most CaGRAS genes (84%) have no intron. Phylogenetic analysis divided pepper CaGRAS members into 10 subfamilies, with each having distinct conserved domains and functions. For the expansion of the GRAS genes in pepper, segmental duplication contributed more than tandem duplication did. Gene expression analysis in various tissues demonstrated that most of CaGRAS genes exhibited a tissue- and development stage-specific expression pattern, uncovering their potential functions in pepper growth and development. Moreover, 21 CaGRAS genes were differentially expressed under cold, drought, salt and gibberellin acid (GA) treatments, indicating that they may implicated in plant response to abiotic stress. Notably, GA responsive cis-elements were detected in the promoter regions of the majority of CaGRAS genes, suggesting that CaGRAS may involve in signal cross-talking. The first comprehensive analysis of GRAS gene family in pepper genome by this study provide insights into understanding the GRAS-mediated regulation network, benefiting the genetic improvements in pepper and some other relative plants. creator: Baoling Liu creator: Yan Sun creator: Jinai Xue creator: Xiaoyun Jia creator: Runzhi Li uri: https://doi.org/10.7717/peerj.4796 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2018 Liu et al. title: Exosomes in cancer: small vesicular transporters for cancer progression and metastasis, biomarkers in cancer therapeutics link: https://peerj.com/articles/4763 last-modified: 2018-05-29 description: Cancer progression is a polygenic procedure in which the exosomes can function as substantial roles. Exosomes are tiny, phospholipid bilayer membrane nanovesicles of endocytic derivation with a diameter of 40–100 nm. These nanovesicles can transport bioactive molecules containing mRNAs, proteins, DNA fragments, and non-coding RNAs from a donor cell to recipient cells, and cause the alteration in genetic and epigenetic factors and reprogramming of the target cells. Many diverse cell types such as mesenchymal cells, immune cells, and cancer cells can induce the release of exosomes. Increasing evidence illustrated that the exosomes derived from tumor cells might trigger the tumor initiation, tumor cell growth and progression, metastasis, and drug resistance. The secreted nanovesicles of exosomes can play significant roles in cells communicate via shuttling the nucleic acid molecules and proteins to target cells and tissues. In this review, we discussed multiple mechanisms related to biogenesis, load, and shuttle of the exosomes. Also, we illustrated the diverse roles of exosomes in several types of human cancer development, tumor immunology, angiogenesis, and metastasis. The exosomes may act as the promising biomarkers for the prognosis of various types of cancers which suggested a new pathway for anti-tumor therapeutic of these nanovesicles and promoted exosome-based cancer for clinical diagnostic and remedial procedures. creator: Atefe Abak creator: Alireza Abhari creator: Sevda Rahimzadeh uri: https://doi.org/10.7717/peerj.4763 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2018 Abak et al.