The Human Plasma Membrane Peripherome: Visualization and Analysis of Interactions

A major part of membrane function is conducted by proteins, both integral and peripheral. Peripheral membrane proteins temporarily adhere to biological membranes, either to the lipid bilayer or to integral membrane proteins with non-covalent interactions. The aim of this study was to construct and analyze the interactions of the human plasma membrane peripheral proteins (peripherome hereinafter). For this purpose, we collected a dataset of peripheral proteins of the human plasma membrane. We also collected a dataset of experimentally verified interactions for these proteins. The interaction network created from this dataset has been visualized using Cytoscape. We grouped the proteins based on their subcellular location and clustered them using the MCL algorithm in order to detect functional modules. Moreover, functional and graph theory based analyses have been performed to assess biological features of the network. Interaction data with drug molecules show that ~10% of peripheral membrane proteins are targets for approved drugs, suggesting their potential implications in disease. In conclusion, we reveal novel features and properties regarding the protein-protein interaction network created by peripheral proteins of the human plasma membrane.Comment: 39 pages, 5 figures, 3 supplement figures, under review in BMR

Bacteriology and Antimicrobial Susceptibility Patterns of Childhood Acute Bacterial Conjunctivitis in Western Greece

Acute bacterial conjunctivitis is a common, highly contagious infection in children and is usually treated empirically with broad spectrum topical antibiotics. In the current study we investigated bacteriology and antibiotic susceptibility patterns in childhood acute bacterial conjunctivitis in Western Greece. We conducted a retrospective analysis of presumed acute bacterial conjunctivitis cases in ''Karamandaneio'' Pediatric General Hospital of Patras, Western Greece, between February 1, 2013 and January 31, 2018. Specimens from the lower conjunctiva fornix were isolated from 191 cases and outcomes were analyzed to identify the pathogenic bacteria of acute bacterial conjunctivitis and their corresponding antibiotic susceptibility patterns. Patients were divided into 3 groups; Group A included neonates under 28 days of life, Group B children from 1 month to 2 years and Group C from 2 years to 14 years. Results revealed that Staphylococcus spp., Haemophilus spp. and Streptococcus spp. were the most prevalent pathogens. No significant differences in isolated pathogens were found between the age groups. Antibiotic resistance rates were higher against ampicillin, ceftriaxone, ceftazidime and sulfamethoxazole. Resistance rates to Ciprofloxacin were low while none of the evaluated isolates were resistant to vancomycin. We concluded that predominant pathogens of childhood acute bacterial conjunctivitis in Western Greece were Staphylococcus spp., Haemophilus spp. and Streptococcus spp. Continuous surveillance, focused in distinct geographic areas, is encouraged to prepare more precise protocols of empirical treatment. Epub: October 1, 2019

Financial correlations at ultra-high frequency: theoretical models and empirical estimation

A detailed analysis of correlation between stock returns at high frequency is compared with simple models of random walks. We focus in particular on the dependence of correlations on time scales - the so-called Epps effect. This provides a characterization of stochastic models of stock price returns which is appropriate at very high frequency.Comment: 22 pages, 8 figures, 1 table, version to appear in EPJ

Red supergiant stars in the Large Magellanic Cloud. II. Infrared properties and mid-infrared variability

The characteristics of IR properties and MIR variability of RSGs in the LMC are analyzed based on 12 bands of NIR to MIR co-added data from 2MASS, Spitzer and WISE, and $\sim$6.6 years of MIR time-series data collected by the ALLWISE and NEOWISE-R projects. 773 RSGs candidates were compiled from the literature and verified by using the CMD, SED and MIR variability. About 15\% of valid targets in the $IRAC1-IRAC2$/$IRAC2-IRAC3$ diagram may show PAH emission. We show that arbitrary dereddening Q parameters related to the IRAC4, S9W, WISE3, WISE4, and MIPS24 bands could be constructed based on a precise measurement of MIR interstellar extinction law. Several peculiar outliers in our sample are discussed, in which one outlier might be a RSG right before the explosion or an x-AGB star in the very late evolutionary stage based on the MIR spectrum and photometry. There are 744 identified RSGs in the final sample having both the WISE1- and WISE2-band time-series data. The results show that the MIR variability is increasing along with the increasing of brightness. There is a relatively tight correlation between the MIR variability, MLR, and the warm dust or continuum, where the MIR variability is evident for the targets with $K_S-WISE3>1.0~mag$ and $WISE4<6.5~mag$, while the rest of the targets show much smaller MIR variability. The MIR variability is also correlated with the MLR for which targets with larger variability also show larger MLR with an approximate upper limit of $-6.1~M_\odot/yr^{-1}$. Both the variability and the luminosity may be important for the MLR since the WISE4-band flux is increasing exponentially along with the degeneracy of luminosity and variability. The identified RSG sample has been compared with the theoretical evolutionary models and shown that the discrepancy between observation and evolutionary models can be mitigated by considering both variability and extinction.Comment: 24 pages, 22 figures, A&A accepte

Validation of the English version of the 14-Item Mediterranean diet adherence screener of the PREDIMED study, in people at high cardiovascular risk in the UK

The aim of this study was to examine the validity of the English version of the PREvencion con DIetaMEDiterranea (PREDIMED) 14-item Mediterranean Diet Adherence Screener (MEDAS), a brief questionnaire assessing adherence to the Mediterranean diet (MedDiet), which was used in the PREDIMED trial for assessment and immediate feedback. This instrument (MEDAS) was administered to 96 adults with a high cardiovascular risk (66% women, mean age 68.3 ± 6.0 years), recruited from general practices in Bristol, UK. Participants then completed a 3-day estimated food record, and the MEDAS was administered again one month later. A MedDiet score (range = 0-14) was calculated from the MEDAS' administrations and food record to assess concurrent validity and test-retest reliability. Predictive validity was assessed by examining the association of the MEDAS-derived score with cardiometabolic risk factors and dietary intakes derived from the food records. The MEDAS-derived MedDiet score was higher by 1.47 points compared to food records (5.47 vs.4.00, p < 0.001), correlated moderately with the record-derived score (r = 0.50, p < 0.001; ICC = 0.53, p < 0.001) and there was borderline fair agreement between the two methods (¿ = 0.19, 95% CI 0.07-0.31, p = 0.002; 95% limits of agreement -2.2, 5.1). Exact agreement within score categories and gross misclassificationwere 45.8% and 21.9%, respectively. The distribution of dietary intakes, reported on the food records by the MEDAS-derived total MedDiet score, was in the expected direction, but no association was observed with cardiometabolic risk factors. The two administrations of the MEDAS produced similar mean total MedDiet scores (5.5 vs. 5.4, p = 0.706), which were correlated (r and ICC = 0.69, p < 0.001) and agreed fairly (¿ = 0.38, 95% CI 0.24-0.52, p < 0.001; 95% limits of agreement -3.1, 3.2). The English version of the MEDAS has acceptable accuracy and reliability for assessing MedDiet adherence among individuals with a high cardiovascular risk, in the UK, and can be used to rank individuals according to MedDiet adherence in research and practice

Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GR βgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin- aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet

Nature’s contribution to people provided by pastoral systems across European, African, and Middle East Mediterranean countries: trends, approaches and gaps

Mediterranean pastoral systems are providers of a wide array of Nature’s Contribution to People (NCP). They are ‘complex systems’ characterized by limited resources and socio-economic dynamics currently threatened by climate and social changes. Despite a growing number of scientifc articles dealing with NCP, there is a high risk that the existing literature has left out the complexity of such systems. In the light of ongoing social, economic, and climatic changes in the Mediterranean basin, neglecting the complexity of pastoral systems can lead to signifcant research biases, missing the priorities afecting the stability and continuity of such systems. A combination of frameworks of analysis provided by the Millennium Ecosystem Assessment and by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services was applied to understand if and to what extent the complexity of Mediterranean pastoral systems has been considered in the available literature. Most of the 126 papers report studies conducted in the European Union zone (102 papers), with the majority in Spain (50). Fewer studies have been conducted in the Middle East (15 papers) and Africa zones (9 papers). Despite results confrming the importance of pastoral systems as providers of NCP, most of the eligible papers focused on regulating NCP. A lack of a multisectoral approach and integration of knowledge suggests that the complexity of Mediterranean pastoral systems has been overlooked by researchers. The creation of ‘hybrid knowledge’ bridging the expertise of diferent stakeholders could be the key ingredient to properly address the complexity of Mediterranean pastoral systems.This study was carried out with the support of project PACTORES (PAstoral ACTORs, ES, and Society as key elements of agro-pastoral systems in the Mediterranean), ERANETMED ‘EURO-MEDITERRANEAN Cooperation through ERANET joint activities and beyond’- Joint Transnational Call 2016 - Environmental challenges and solutions for vulnerable communities (ERANETMED2-72-303). We would like to thank the late Marco Toderi for his considerable help and inspiration and without whom this research would never have been possible. Open access funding provided by Università Politecnica delle Marche within the CRUI-CARE Agreement.info:eu-repo/semantics/publishedVersio