title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=1739 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Survey of owner motivations and veterinary input of owners feeding diets containing raw animal products link: https://peerj.com/articles/3031 last-modified: 2017-03-02 description: BackgroundThe practice of feeding of diets containing raw animal products (RAP) to pets (dogs and cats) is discouraged by veterinary organizations and governmental public health organizations. Nevertheless, the practice of feeding RAP to pets is increasing in popularity. Pet owner motivations for feeding RAP diets to pets have not been explored and the benefits of RAP diets remain largely anecdotal. We hypothesized that pet owners feeding RAP diets would not rely on veterinary advice in choosing their pet’s diet. We also hypothesized that these owners would have lower levels of trust in veterinary advice with respect to nutrition relative to pet owners not feeding RAP.MethodsAn anonymous web-based survey was developed to identify pet owner motivations for feeding RAP diets, and to characterize the veterinarian-client relationships of individuals feeding RAP diets.ResultsThere were 2,337 respondents and 2,171 completed surveys. Of survey respondents, 804 reported feeding RAP at the time of the survey. While 20% of pet owners feeding RAP relied on online resources to determine what or how much RAP to feed, only 9% reported consulting with a veterinarian in making decisions about feeding RAP. Pet owners feeding RAP reported lower levels of trust in veterinary advice both ‘in general’ and ‘with respect to nutrition’ than pet owners not feeding RAP. Most pet owners reported that a discussion regarding their pet’s nutrition does not occur at every veterinary appointment.DiscussionPet owners feeding a RAP diet have lower trust in veterinary advice than pet owners not feeding a RAP diet. Owners feeding RAP are more reliant on online resources than their own veterinarian in deciding what and how much RAP to feed. Pet owners perceive that nutrition is not discussed at most veterinary appointments. Therefore, there is room for improvement in the veterinarian-client communication with regards to nutrition. creator: Stewart K. Morgan creator: Susan Willis creator: Megan L. Shepherd uri: https://doi.org/10.7717/peerj.3031 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2017 Morgan et al. title: New in vitro system to predict chemotherapeutic efficacy of drug combinations in fresh tumor samples link: https://peerj.com/articles/3030 last-modified: 2017-03-02 description: BackgroundTo find the best individual chemotherapy for cancer patients, the efficacy of different chemotherapeutic drugs can be predicted by pretesting tumor samples in vitro via the chemotherapy-resistance (CTR)-Test®. Although drug combinations are widely used among cancer therapy, so far only single drugs are tested by this and other tests. However, several first line chemotherapies are combining two or more chemotherapeutics, leading to the necessity of drug combination testing methods.MethodsWe established a system to measure and predict the efficacy of chemotherapeutic drug combinations with the help of the Loewe additivity concept in combination with the CTR-test. A combination is measured by using half of the monotherapy’s concentration of both drugs simultaneously. With this method, the efficacy of a combination can also be calculated based on single drug measurements.ResultsThe established system was tested on a data set of ovarian carcinoma samples using the combination carboplatin and paclitaxel and confirmed by using other tumor species and chemotherapeutics. Comparing the measured and the calculated values of the combination testings revealed a high correlation. Additionally, in 70% of the cases the measured and the calculated values lead to the same chemotherapeutic resistance category of the tumor.ConclusionOur data suggest that the best drug combination consists of the most efficient single drugs and the worst drug combination of the least efficient single drugs. Our results showed that single measurements are sufficient to predict combinations in specific cases but there are exceptions in which it is necessary to measure combinations, which is possible with the presented system. creator: Frank Christian Kischkel creator: Julia Eich creator: Carina I. Meyer creator: Paula Weidemüller creator: Jens Krapfl creator: Rauaa Yassin-Kelepir creator: Laura Job creator: Marius Fraefel creator: Ioana Braicu creator: Annette Kopp-Schneider creator: Jalid Sehouli creator: Rudy Leon De Wilde uri: https://doi.org/10.7717/peerj.3030 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2017 Kischkel et al. title: The effects of elevated pain inhibition on endurance exercise performance link: https://peerj.com/articles/3028 last-modified: 2017-03-02 description: BackgroundThe ergogenic effects of analgesic substances suggest that pain perception is an important regulator of work-rate during fatiguing exercise. Recent research has shown that endogenous inhibitory responses, which act to attenuate nociceptive input and reduce perceived pain, can be increased following transcranial direct current stimulation of the hand motor cortex. Using high-definition transcranial direct current stimulation (HD-tDCS; 2 mA, 20 min), the current study aimed to examine the effects of elevated pain inhibitory capacity on endurance exercise performance. It was hypothesised that HD-tDCS would enhance the efficiency of the endogenous pain inhibitory response and improve endurance exercise performance.MethodsTwelve healthy males between 18 and 40 years of age (M = 24.42 ± 3.85) were recruited for participation. Endogenous pain inhibitory capacity and exercise performance were assessed before and after both active and sham (placebo) stimulation. The conditioned pain modulation protocol was used for the measurement of pain inhibition. Exercise performance assessment consisted of both maximal voluntary contraction (MVC) and submaximal muscular endurance performance trials using isometric contractions of the non-dominant leg extensors.ResultsActive HD-tDCS (pre-tDCS, −.32 ± 1.33 kg; post-tDCS, −1.23 ± 1.21 kg) significantly increased pain inhibitory responses relative to the effects of sham HD-tDCS (pre-tDCS, −.91 ± .92 kg; post-tDCS, −.26 ± .92 kg; p = .046). Irrespective of condition, peak MVC force and muscular endurance was reduced from pre- to post-stimulation. HD-tDCS did not significantly influence this reduction in maximal force (active: pre-tDCS, 264.89 ± 66.87 Nm; post-tDCS, 236.33 ± 66.51 Nm; sham: pre-tDCS, 249.25 ± 88.56 Nm; post-tDCS, 239.63 ± 67.53 Nm) or muscular endurance (active: pre-tDCS, 104.65 ± 42.36 s; post-tDCS, 93.07 ± 33.73 s; sham: pre-tDCS, 123.42 ± 72.48 s; post-tDCS, 100.27 ± 44.25 s).DiscussionDespite increasing pain inhibitory capacity relative to sham stimulation, active HD-tDCS did not significantly elevate maximal force production or muscular endurance. These findings question the role of endogenous pain inhibitory networks in the regulation of exercise performance. creator: Andrew Flood creator: Gordon Waddington creator: Richard J. Keegan creator: Kevin G. Thompson creator: Stuart Cathcart uri: https://doi.org/10.7717/peerj.3028 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2017 Flood et al. title: Key bacterial families (Clostridiaceae, Erysipelotrichaceae and Bacteroidaceae) are related to the digestion of protein and energy in dogs link: https://peerj.com/articles/3019 last-modified: 2017-03-02 description: BackgroundMuch of the recent research in companion animal nutrition has focussed on understanding the role of diet on faecal microbiota composition. To date, diet-induced changes in faecal microbiota observed in humans and rodents have been extrapolated to pets in spite of their very different dietary and metabolic requirements. This lack of direct evidence means that the mechanisms by which microbiota influences health in dogs are poorly understood. We hypothesised that changes in faecal microbiota correlate with physiological parameters including apparent macronutrient digestibility.MethodsFifteen adult dogs were assigned to two diet groups, exclusively fed either a premium kibbled diet (kibble; K; n = 8) or a raw red meat diet (meat; M; n = 7) for nine weeks. Apparent digestibility of macronutrients (protein, fat, gross energy and dry matter), faecal weight, faecal health scores, faecal VFA concentrations and faecal microbial composition were determined. Datasets were integrated using mixOmics in R.ResultsFaecal weight and VFA levels were lower and the apparent digestibility of protein and energy were higher in dogs on the meat diet. Diet significantly affected 27 microbial families and 53 genera in the faeces. In particular, the abundances of Bacteriodes, Prevotella, Peptostreptococcus and Faecalibacterium were lower in dogs fed the meat diet, whereas Fusobacterium, Lactobacillus and Clostridium were all more abundant.DiscussionOur results show clear associations of specific microbial taxa with diet composition. For example, Clostridiaceae, Erysipelotrichaceae and Bacteroidaceae were highly correlated to parameters such as protein and fat digestibility in the dog. By understanding the relationship between faecal microbiota and physiological parameters we will gain better insights into the effects of diet on the nutrition of our pets. creator: Emma N. Bermingham creator: Paul Maclean creator: David G. Thomas creator: Nicholas J. Cave creator: Wayne Young uri: https://doi.org/10.7717/peerj.3019 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2017 Bermingham et al. title: Coat of many colours—DNA reveals polymorphism of mantle patterns and colouration in Caribbean Cyphoma Röding, 1798 (Gastropoda, Ovulidae) link: https://peerj.com/articles/3018 last-modified: 2017-03-02 description: The iconic gastropod genus Cyphoma is commonly observed in the Caribbean, where it lives in association with various octocorallian hosts. Each species in the genus Cyphoma has a unique, characteristic mantle pattern and colouration, which separates the valid taxa. Because of its abundance and recognisability Cyphoma gibbosum has been used as a model organism in several studies concerning allelochemicals, reef degradation, and physical defence mechanisms. Molecular analyses based on four molecular markers (COI, 16S, H3 and 28S) for three Cyphoma species (C. gibbosum, C. mcgintyi, C. signatum) and an unidentified black morph, collected from three localities in the Caribbean, show that they represent morphological varieties of a single, genetically homogeneous species. This outcome is in agreement with previous anatomical studies. As a result C. mcgintyi and C. signatum are synonymised with C. gibbosum, which is a key result for future work using C. gibbosum as a model organism. The striking morphological differences in mantle pattern and colouration are hypothesised to be the result of one of three possible scenarios: rapid divergence, supergenes (including balanced polymorphism), or incipient speciation. creator: Bastian T. Reijnen creator: Sancia E.T. van der Meij uri: https://doi.org/10.7717/peerj.3018 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2017 Reijnen and Van der Meij title: Asymmetry of mandibular dentition is associated with dietary specialization in snail-eating snakes link: https://peerj.com/articles/3011 last-modified: 2017-03-02 description: BackgroundIn vertebrates, the left-and-right pairs of homologous organs are generally present in equal numbers. A remarkable exception is known in the snail-eating snakes of the family Pareidae: almost all the pareid snakes have much more teeth on the right mandible than on the left for functional specialization in feeding on the dextral majority of land snails. Because the only exceptional species with symmetric dentition has been regarded as a slug-eater, the extent of dietary specialization on slugs could shape the degree of the lateral asymmetry of mandibular dentition (dentition asymmetry) even among snail eaters.MethodsTo test this, I compared the morphology and behavior of two sympatric species of Taiwanese snail-eating snakes, Pareas atayal and P. formosensis.ResultsSpecimens collected in the same locality showed that the dentition asymmetry of P. formosensis was significantly smaller than that of P. atayal. Congruent to its weak asymmetry, P. formosensis showed a strong preference of slugs to snails in the feeding experiment.DiscussionThe dietary specialization of P. formosensis on slugs would contribute to niche partitioning from the sympatric congener P. atayal. This study suggests that the diverse variation in the dentition asymmetry of pareid snakes is the result of their dietary specialization and divergence. creator: Masaki Hoso uri: https://doi.org/10.7717/peerj.3011 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2017 Hoso title: Exploring biomedical ontology mappings with graph theory methods link: https://peerj.com/articles/2990 last-modified: 2017-03-02 description: BackgroundIn the era of semantic web, life science ontologies play an important role in tasks such as annotating biological objects, linking relevant data pieces, and verifying data consistency. Understanding ontology structures and overlapping ontologies is essential for tasks such as ontology reuse and development. We present an exploratory study where we examine structure and look for patterns in BioPortal, a comprehensive publicly available repository of live science ontologies.MethodsWe report an analysis of biomedical ontology mapping data over time. We apply graph theory methods such as Modularity Analysis and Betweenness Centrality to analyse data gathered at five different time points. We identify communities, i.e., sets of overlapping ontologies, and define similar and closest communities. We demonstrate evolution of identified communities over time and identify core ontologies of the closest communities. We use BioPortal project and category data to measure community coherence. We also validate identified communities with their mutual mentions in scientific literature.ResultsWith comparing mapping data gathered at five different time points, we identified similar and closest communities of overlapping ontologies, and demonstrated evolution of communities over time. Results showed that anatomy and health ontologies tend to form more isolated communities compared to other categories. We also showed that communities contain all or the majority of ontologies being used in narrower projects. In addition, we identified major changes in mapping data after migration to BioPortal Version 4. creator: Simon Kocbek creator: Jin-Dong Kim uri: https://doi.org/10.7717/peerj.2990 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2017 Kocbek and Kim title: Obesity-induced diet leads to weight gain, systemic metabolic alterations, adipose tissue inflammation, hepatic steatosis, and oxidative stress in gerbils (Meriones unguiculatus) link: https://peerj.com/articles/2967 last-modified: 2017-03-02 description: BackgroundNowadays, the number of obese people in the world has reached alarming proportions. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. This leads the body to a pro-inflammatory pattern, which may affect the proper functioning of many tissues. Thus, studying the mechanisms by which obesity induces physiological disorders is necessary, and may be facilitated by the use of animal models, in particular rodents. We sought to characterize the metabolic and adipose tissue changes resulting from a diet rich in fats and simple sugars in gerbils.MethodsWe divided 14 gerbils into two experimental groups that received a diet rich in simple carbohydrates and fats with 5,86 kcal/g (OB, n = 7) or a standard diet with 4.15 kcal/g (CT; n = 7) for 11 weeks. The animals had free access to water and food. The animal weight and food consumption were measured weekly. Blood, adipose tissue and liver of each animal were collected at the end of experiment. The following parameters were determined: cholesterol (COL), triglycerides (TGL) and glycemia (GLI) in the plasma; cytokines (IL-6, IL-10 and TNF-α) and hormones (adiponectin and leptin) in adipose tissue; activity of superoxide dismutase (SOD) and catalase (CAT), extraction and differentiation of fat and histology in liver.ResultsThe consumption of a diet rich in simple carbohydrates and fats led to increased total body weight and increased relative weights of liver and adipose tissue. In addition, we observed increased fasting glucose levels and circulating triglycerides, along with high TNF-α production in adipose tissue and increased total fat, cholesterol and triglyceride contents in the liver, contributing to higher intensity of hepatic steatosis. On the other hand, the animals of this group showed depletion in the enzyme activity of SOD and CAT in the liver, as well as reduction of IL-10 and adiponectin levels in adipose tissue.DiscussionHigh intake of saturated fat and simple carbohydrates establish the gerbil as an experimental model for the study of metabolic and hepatic abnormalities resulting from obesity. creator: Luciana L.A. Ventura creator: Nathália C.L. Fortes creator: Helton C. Santiago creator: Marcelo V. Caliari creator: Maria A. Gomes creator: Dirce R. Oliveira uri: https://doi.org/10.7717/peerj.2967 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2017 Ventura et al. title: P2X7 antagonism using Brilliant Blue G reduces body weight loss and prolongs survival in female SOD1G93A amyotrophic lateral sclerosis mice link: https://peerj.com/articles/3064 last-modified: 2017-03-01 description: BackgroundAmyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterised by the accumulation of aggregated proteins, microglia activation and motor neuron loss. The mechanisms underlying neurodegeneration and disease progression in ALS are unknown, but the ATP-gated P2X7 receptor channel is implicated in this disease. Therefore, the current study aimed to examine P2X7 in the context of neurodegeneration, and investigate whether the P2X7 antagonist, Brilliant Blue G (BBG), could alter disease progression in a murine model of ALS.MethodsHuman SOD1G93A transgenic mice, which normally develop ALS, were injected with BBG or saline, three times per week, from pre-onset of clinical disease (62–64 days of age) until end-stage. During the course of treatment mice were assessed for weight, clinical score and survival, and motor coordination, which was assessed by rotarod performance. Various parameters from end-stage mice were assessed as follows. Motor neuron loss and microgliosis were assessed by immunohistochemistry. Relative amounts of lumbar spinal cord SOD1 and P2X7 were quantified by immunoblotting. Serum monocyte chemoattractant protein-1 was measured by ELISA. Splenic leukocyte populations were assessed by flow cytometry. Relative expression of splenic and hepatic P2X7 mRNA was measured by quantitative real-time PCR. Lumbar spinal cord SOD1 and P2X7 were also quantified by immunoblotting in untreated female SOD1G93A mice during the course of disease.ResultsBBG treatment reduced body weight loss in SOD1G93A mice of combined sex, but had no effect on clinical score, survival or motor coordination. BBG treatment reduced body weight loss in female, but not male, SOD1G93A mice. BBG treatment also prolonged survival in female, but not male, SOD1G93A mice, extending the mean survival time by 4.3% in female mice compared to female mice treated with saline. BBG treatment had no effect on clinical score or motor coordination in either sex. BBG treatment had no major effect on any end-stage parameters. Total amounts of lumbar spinal cord SOD1 and P2X7 in untreated female SOD1G93A mice did not change over time.DiscussionCollectively, this data suggests P2X7 may have a partial role in ALS progression in mice, but additional research is required to fully elucidate the contribution of this receptor in this disease. creator: Rachael Bartlett creator: Vanessa Sluyter creator: Debbie Watson creator: Ronald Sluyter creator: Justin J. Yerbury uri: https://doi.org/10.7717/peerj.3064 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2017 Bartlett et al. title: Genetic and structural study of DNA-directed RNA polymerase II of Trypanosoma brucei, towards the designing of novel antiparasitic agents link: https://peerj.com/articles/3061 last-modified: 2017-03-01 description: Trypanosoma brucei brucei (TBB) belongs to the unicellular parasitic protozoa organisms, specifically to the Trypanosoma genus of the Trypanosomatidae class. A variety of different vertebrate species can be infected by TBB, including humans and animals. Under particular conditions, the TBB can be hosted by wild and domestic animals; therefore, an important reservoir of infection always remains available to transmit through tsetse flies. Although the TBB parasite is one of the leading causes of death in the most underdeveloped countries, to date there is neither vaccination available nor any drug against TBB infection. The subunit RPB1 of the TBB DNA-directed RNA polymerase II (DdRpII) constitutes an ideal target for the design of novel inhibitors, since it is instrumental role is vital for the parasite’s survival, proliferation, and transmission. A major goal of the described study is to provide insights for novel anti-TBB agents via a state-of-the-art drug discovery approach of the TBB DdRpII RPB1. In an attempt to understand the function and action mechanisms of this parasite enzyme related to its molecular structure, an in-depth evolutionary study has been conducted in parallel to the in silico molecular designing of the 3D enzyme model, based on state-of-the-art comparative modelling and molecular dynamics techniques. Based on the evolutionary studies results nine new invariant, first-time reported, highly conserved regions have been identified within the DdRpII family enzymes. Consequently, those patches have been examined both at the sequence and structural level and have been evaluated in regard to their pharmacological targeting appropriateness. Finally, the pharmacophore elucidation study enabled us to virtually in silico screen hundreds of compounds and evaluate their interaction capabilities with the enzyme. It was found that a series of chlorine-rich set of compounds were the optimal inhibitors for the TBB DdRpII RPB1 enzyme. All-in-all, herein we present a series of new sites on the TBB DdRpII RPB1 of high pharmacological interest, alongside the construction of the 3D model of the enzyme and the suggestion of a new in silico pharmacophore model for fast screening of potential inhibiting agents. creator: Louis Papageorgiou creator: Vasileios Megalooikonomou creator: Dimitrios Vlachakis uri: https://doi.org/10.7717/peerj.3061 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2017 Papageorgiou et al.