Model-based in silico analysis of the PI3K/Akt pathway: the elucidation of cross-talk between diabetes and breast cancer
Background A positive association between diabetes and breast cancer has been identified by various epidemiological and clinical studies. However, the possible molecular interactions between the two heterogeneous diseases have not been fully determined yet. There are several underlying mechanisms which may increase the risk of breast cancer in diabetic patients. Introduction In this study, we focused on the role of O-GlcNAc transferase (OGT) enzyme in the regulation of phosphatidylinositol-3 kinase (PI3K) pathway through activation/deactivation of Akt protein. The efficiency of insulin signaling in adipocytes is reduced as a result of OGT overexpression which further attenuates Akt signaling; as a result, the efficiency of insulin signaling is reduced by downregulation of insulin-responsive genes. On the other hand, increased expression of OGT results in Akt activation in breast cancer cells, leading to enhanced cell proliferation and inhibition of the apoptosis. However, the interplay amongst these signaling pathways is still under investigation. Methods In this study, we used Petri nets (PNs) to model and investigate the role of PI3K and OGT pathways, acting as key players in crosstalk between diabetes and breast cancer, resulting in progression of these chronic diseases. Moreover, in silico perturbation experiments were applied on the model to analyze the effects of anti-cancer agents (shRNA and BZX) and anti-diabetic drug (Metformin) on the system. Results Our PN model reflects the alterations in protein expression and behavior and the correlation between breast cancer and diabetes. The analysis proposed two combination therapies to combat breast cancer progression in diabetic patients including combination of OGTmRNA silencing and OGT inhibitor (BZX) as first combination and BZX and Metformin as the second. Conclusion The PN model verified that alterations in O-GlcNAc signaling affect both insulin resistance and breast cancer. Moreover, the combination therapy for breast cancer patients consisting of anti-diabetic drugs such as Metformin along with OGT inhibitors, for example BZX, can produce better treatment regimens.
Rehman et al. (2018) Model-based in silico analysis of the PI3K/Akt pathway: the elucidation of cross-talk between diabetes and breast cancer. PeerJ 6:e5917 https://doi.org/10.7717/peerj.5917
A real-time PCR assay for quantification of parasite burden in murine models of leishmaniasis
Eukaryotic parasites in the genus Leishmania place approximately 350 million people per year at risk of disease. In addition to their global health significance, Leishmania spp. have served as an important model for delineating basic concepts in immunology such as T-helper cell polarization. There have been many qPCR-based assays reported for measuring parasite burden in humans and animals. However, these are largely optimized for use in clinical diagnosis and not specifically for animal models. This has led several of these assays to have suboptimal characteristics for use in animal models. For example, multi-copy number genes have been frequently used to increase sensitivity but are subject to greater plasticity within the genome and thus may confound effects of experimental manipulations in animal models. In this study, we developed a sybr-green based quantitative touchdown PCR assay for a highly conserved and single-copy putative RNA-binding protein, DRBD3. With primers that share greater than 90% sequence identity across all sequenced Leishmania spp., we demonstrate that this assay has a lower limit of detection of 100 fg of parasite DNA for Leishmania major, L. donovani, L. venezuelensis, and L. panamensis. Using C57BL6/J mice, we used this assay to monitor parasite burden over 1 month of infection with two strains of L. major (Seidman and Friedlin), and L. venezeuelensis. These characteristics rival the sensitivity of previously reported qPCR based methods of parasite quantitation while amplifying a stable, single copy gene. Use of this protocol in the future will lead to improved accuracy in animal based models and help to tease apart differences in biology of host-parasite interactions.
Antonia et al. (2018) A real-time PCR assay for quantification of parasite burden in murine models of leishmaniasis. PeerJ 6:e5905 https://doi.org/10.7717/peerj.5905
Comparison of incisional complications between skin closures using a simple continuous or intradermal pattern: a pilot study in horses undergoing ventral median celiotomy
Background Development of incisional complications following ventral median celiotomy might depend on suture pattern for skin closure. Methods In this prospective study, 21 healthy male horses underwent celiotomy. Skin closure was either performed via a continuous percutaneous pattern (CO group; 5 warmbloods/5 ponies) or an intradermal pattern (ID group; 5 warmbloods/6 ponies). Follow-up examination of the incisional site included daily monitoring for edema, dehiscence, and drainage. Transcutaneous ultrasound was performed at Days 3, 6, and 10 as well as on Week 8 and 12 to evaluate size of edema and presence or absence of sinus formation, and hernia formation. Prevalence of incisional infection on base of positive microbiological analysis at any time up to Day 10 was evaluated and compared between ID and CO group. Furthermore, edema size was analysed by a linear mixed-effect model for group and time dependency. Results Observed incisional complications included edema (9/10 in CO, 10/11 in ID), suture sinus formation (2/10 in CO, 1/11 in ID), surgical site infection (2/10 in CO, 0/11 in ID), and incisional hernia (1/10 in CO, 0/11 in ID). The overall prevalence of incisional infection was 9.5% without significant differences between both groups (20% in CO, 0% in ID; p = 0.214). Edema size was not dependent on time or group (p = 0.545 and p = 0.627, respectively). Discussion CO and ID suture pattern are appropriate for skin closure following ventral median celiotomy in horses. None of the animals in the continuous ID group developed surgical site infections, even without the use of antibiotics.
Scharner et al. (2018) Comparison of incisional complications between skin closures using a simple continuous or intradermal pattern: a pilot study in horses undergoing ventral median celiotomy. PeerJ 6:e5772 https://doi.org/10.7717/peerj.5772
Risk and protective factors for drug dependence in two Moroccan high-risk male populations
Background Substance use is linked to biological, environmental, and social factors. This study provides insights on protective and risk factors for drug dependence in two Moroccan, high-risk, male samples. Methods Data from the “Mental and Somatic Health without borders” (MeSHe) survey were utilized in the present study. The MeSHe survey assesses somatic and mental health parameters by self-report from prison inmates (n = 177) and outpatients from an addiction institution (n = 54). The “Drug dependence” and the “No drug dependence” groups were identified based on the Arabic version of the Drug Use Disorder Identification Test’s (DUDIT) validated cutoff for identifying individuals with drug dependence, specifically in Morocco. Results The majority of participants who had at least high school competence (67.6%), were living in a partnership (53.7%), were a parent (43.1%), and/or had a job (86.8%) belonged to the “No drug dependence” group, while the presence of mental health problems was typical among the “Drug dependence” group (47.4%). A multivariable regression model (χ2 (df = 5, N = 156) = 63.90, p < 0.001) revealed that the presence of depression diagnosis remains a significant risk factor, while a higher level of education, having a child, and being employed are protective factors from drug dependence. Discussion Findings support the importance of increasing academic competence and treating depression as prevention from the persistence of drug addiction in male high-risk populations.
Sfendla et al. (2018) Risk and protective factors for drug dependence in two Moroccan high-risk male populations. PeerJ 6:e5930 https://doi.org/10.7717/peerj.5930
Histological analysis of post-eruption tooth wear adaptations, and ontogenetic changes in tooth implantation in the acrodontan squamate Pogona vitticeps
Teeth have been a focus of research in both extinct and extant taxa alike; a significant portion of dental literature is concerned with dental patterning and replacement. Most non-mammalian vertebrates continuously replace their dentition but an anomalous group of squamates has forgone this process in only having one tooth generation; these squamates all have apically implanted teeth, a condition known as acrodonty. Acrodont dentition and various characteristics attributed to it, including a lack of replacement, have often been defined ambiguously. This study explores this type of implantation through histology in the ontogeny of the acrodont agamid Pogona vitticeps. The non-replacing teeth of this squamate provides an opportunity to study wear adaptations, maintenance of occlusion in a non-mammalian system, and most importantly post-eruption changes in the tooth bone interface. In this study the post-eruption changes combined with dental wear likely gives the appearance of acrodont implantation.
Haridy (2018) Histological analysis of post-eruption tooth wear adaptations, and ontogenetic changes in tooth implantation in the acrodontan squamate Pogona vitticeps. PeerJ 6:e5923 https://doi.org/10.7717/peerj.5923
Porewater salinity in a southeastern United States salt marsh: controls and interannual variation
In coastal marsh ecosystems, porewater salinity strongly affects vegetation distribution and productivity. To simulate marsh porewater salinity, an integrated, spatially explicit model was developed, accounting for tidal inundation, evaporation, and precipitation, as well as lateral and vertical exchanges in both surface waters and the subsurface. It was applied to the Duplin River marsh, Sapelo Island, USA, over a 3-year period, which covered both drought and wet conditions. Simulated porewater salinity in the low and high marsh correlated with Duplin River salinity, with evapotranspiration and precipitation leading to substantial variations in porewater salinities across seasons, in particular in the high marsh. The model revealed substantial interannual variability in marsh soil conditions, and—due to its process-based approach linked to external forcings—can be used to explore effects of sea level rise and changes in hydrological forcings on marsh soil conditions.
Miklesh et al. (2018) Porewater salinity in a southeastern United States salt marsh: controls and interannual variation. PeerJ 6:e5911 https://doi.org/10.7717/peerj.5911
Modelling the dynamics of a large rock landslide in the Dolomites (eastern Italian Alps) using multi-temporal DEMs
Latest advances in topographic data acquisition techniques have greatly enhanced the possibility to analyse landscapes in order to understand the processes that shaped them. High-resolution Digital Elevation Models (DEMs), such as LiDAR-derived ones, provide detailed topographic information. In particular, if multi-temporal DEMs are available, it is possible to carry out a detailed geomorphic change detection analysis. This analysis may provide information about the dynamics of large landslides and may thus, be useful for landslide risk assessments. However, LiDAR-derived DEMs are mostly available only as post-event surveys. The technique is relatively recent, and local or national authorities only started widespread surveys in the last decade. Therefore, it is of a certain interest to analyse the effectiveness of DEMs derived from technical cartography to produce reliable volumetric estimates related to large landslides. This study evaluates the use of a multi-source DEM of Difference (DoD) analysis for the investigation of a large landslide –Le Laste–, which occurred on November 12, 2014 on Mount Antelao (eastern Italian Alps). The landslide initiated as a 365,000 m3 rockslide close to the summit of the mountain and transformed into a debris avalanche during its runout. The comparison of pre- and post-event DEMs allowed for the identification and quantification of erosion and deposition areas, and for the estimation of landslide volume. A sound back-analysis of the landslide with the 3D numerical model DAN3D was based on this comparison and on seismic records of the event. These seismic records proved to be remarkably useful, as they allowed for the calibration of the simulated landslide velocity. This ensured the reliability of the model notwithstanding the topographic datasets, intrinsic uncertainties. We found that using a pre-event DEM derived from technical cartography tends to slightly overestimate the volume with respect to the use of the more accurate LiDAR-derived DEM. In recent years, the landslide risk around Mt. Antelao has been increasing alongside the ever-growing population and human activities in the area. Sediment accumulations produced by the Le Laste landslide significantly amplified the debris flow hazard by providing new sediment sources. Therefore, it is crucial to delineate the distribution of this material to enable an adequate debris flow hazard assessment. The material properties derived from the back-analysis of the Le Laste landslide can be used to simulate the runout of possible future events, and to generate reliable hazard zone maps, which are necessary for effective risk mitigation.
Spatial and Geographic Information Science
Gatter et al. (2018) Modelling the dynamics of a large rock landslide in the Dolomites (eastern Italian Alps) using multi-temporal DEMs. PeerJ 6:e5903 https://doi.org/10.7717/peerj.5903
Amphibian life history in a temperate environment of the Mexican Plateau: dimorphism, phenology and trophic ecology of a hylid frog, Hyla eximia (=Dryophytes eximius)
The study of demographic and life history aspects of an organism provides valuable information for its conservation. Here, we analyze the phenology of the Mountain Treefrog Hyla eximia (= Dryophytes eximius) in a temperate environment of the Mexican Plateau. Females were larger in snout-vent length and body mass than males. The peak period of activity occurred in the rainy season (May–September), with amplexus and egg deposition occurring between June and July, and larval development from July to August. A logistic model best explained observed male growth patterns, while the Von Bertalanffy model better described female growth. Notably, males grew faster than females, although females reached a larger overall body size. The diet of this species is made up of 10 prey categories. The index of diet importance indicated that males feed mainly on Coleoptera and Diptera, while females feed on Coleoptera, Diptera, Hemiptera, and Aranea. Both females and males showed a significant abundance of plant material in their stomachs, suggesting that H. eximia might exhibit highly specialized feeding behavior. Reproduction was seasonal, and both female and male reproductive cycles are synchronized with the rainy season. These natural history characteristics provide information to better understand their responses to environmental conditions.
Hernández-Salinas et al. (2018) Amphibian life history in a temperate environment of the Mexican Plateau: dimorphism, phenology and trophic ecology of a hylid frog, Hyla eximia (=Dryophytes eximius). PeerJ 6:e5897 https://doi.org/10.7717/peerj.5897
Changes in stigma and help-seeking in relation to postpartum depression: non-clinical parenting intervention sample
Postpartum depression (PPD) is a prevalent mental illness affecting women, and less commonly, men in the weeks and months after giving birth. Despite the high incidence of PPD in Australia, rates for help-seeking remain low, with stigma and discrimination frequently cited as the most common deterrents to seeking help from a professional source. The present study sought to investigate PPD stigma in a sample of parents and to examine the effects of an intervention on stigma and help-seeking behaviour. A total of 212 parents aged 18–71 years (M = 36.88, 194 females) completed measures of personal and perceived PPD stigma and attitudes towards seeking mental health services and were randomly assigned to one of four groups: an intervention group (video documentary or factsheet related to PPD) or a control group (video documentary or factsheet not related to PPD). Results showed that there were no effects for type of intervention on either personal or perceived PPD stigma scores. No effect was found for help-seeking propensity. Males had higher personal PPD stigma than females and older age was associated with lower personal PPD stigma. Familiarity with PPD was associated with perceived PPD stigma in others but not personal PPD stigma. More work needs to be conducted to develop interventions to reduce PPD stigma in the community.
Thorsteinsson et al. (2018) Changes in stigma and help-seeking in relation to postpartum depression: non-clinical parenting intervention sample. PeerJ 6:e5893 https://doi.org/10.7717/peerj.5893
Cancer and mTOR inhibitors in kidney transplantation recipients
Background Previous studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known. Methods In the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014. Results Patients were divided into two groups: mTOR inhibitors users (study group, n = 828) and mTOR inhibitors non-users (control group, n = 3,735). The median follow-up duration was 7.8 years. The risk of de novo cancer (hazards ratio (HR) 0.80, 95% CI [0.60–1.09], p = 0.16) and risk of death (HR 1.14, 95% CI [0.82–1.60], p = 0.43) was not different between mTOR inhibitor user and non-user groups. Neither high- nor low-dose exposure to mTOR inhibitors was associated with increased risk of cancer or mortality. Analysis of cancer subtypes showed no influence by mTOR inhibitors. In addition, the cause of mortality was not significantly different between the two groups. Discussion We could not find the association of mTOR inhibitors use and risk of de novo cancer development or mortality in patients with kidney transplantation in Chinese patients. Cumulative exposure to mTOR inhibitors did not change the results.
Kao et al. (2018) Cancer and mTOR inhibitors in kidney transplantation recipients. PeerJ 6:e5864 https://doi.org/10.7717/peerj.5864