Differential Signaling Profiles of MC4R Mutations with Three Different Ligands

The melanocortin 4 receptor (MC4R) is a key player in hypothalamic weight regulation and energy expenditure as part of the leptin-melanocortin pathway. Mutations in this G protein coupled receptor (GPCR) are the most common cause for monogenetic obesity, which appears to be mediated by changes in the anorectic action of MC4R via GS-dependent cyclic adenosine-monophosphate (cAMP) signaling as well as other signaling pathways. To study potential bias in the effects of MC4R mutations between the different signaling pathways, we investigated three major MC4R mutations: a GS loss-of-function (S127L) and a GS gain-of-function mutant (H158R), as well as the most common European single nucleotide polymorphism (V103I). We tested signaling of all four major G protein families plus extracellular regulated kinase (ERK) phosphorylation and β-arrestin2 recruitment, using the two endogenous agonists, α- and β-melanocyte stimulating hormone (MSH), along with a synthetic peptide agonist (NDP-α-MSH). The S127L mutation led to a full loss-of-function in all investigated pathways, whereas V103I and H158R were clearly biased towards the Gq/11 pathway when challenged with the endogenous ligands. These results show that MC4R mutations can cause vastly different changes in the various MC4R signaling pathways and highlight the importance of a comprehensive characterization of receptor mutations

Improving the use of Information and Communication Technology (ICT) in the University of Nicosia in Cyprus through the identification and implementation of appropriate international best practice

"The pace of modern life and the rising of technological advancements and resources result in numerous revolutions in our daily routines, transforming them into a digitised world (Oliver, 2002). In fact, the phenomenon of Information and Communication Technologies (ICT) as the computer infrastructures and telecommunication services that empower users to process and store data and enable access to numerous networks, have completely influenced and renovated all the diverse fields in the industrial ecosphere, including the Higher Educational System (American Library Association,1983). The advent of ICT and the massive effects emerging through it have been investigated by a large number of researchers. More precisely, according to Toro and Joshi (2012), the sphere of ICT is classified as a remarkable tool that enriches the access to global information and communication. While ICT enhances the entry to worldwide collaboration, it also provides an enhanced educational quality, such as in learning and evaluation procedures through the use of technological tools. Nevertheless, the application of ICT has not only assisted the academic practices of Higher Educational Institutions, but it has simultaneously automated and enriched administrative procedures as well, such as the administration of student and staff records, the procurement management and payroll (Ben- Zion Barta et.al.,1995; Zainally,2008; Fu,2013). On the other hand, while the phenomenon of ICT has provided extensive benefits to Higher Education, a number of barriers and challenges have been examined as well in the established literature, including policy strategies, environmental and cultural challenges and educational issues. In fact, the great awareness that scientists have raised in the area of ICT and more precisely in its implementation in Higher Education, as well as the great need of examining the new technological advancements have triggered my interest to study this topic. This study aims to investigate and analyse the application of ICT at the University of Nicosia (UNic) in Cyprus, both for academic and administrative practices. Through the review of four chosen global Universities, an assessment and contrast between each of them and UNic will aid in classifying the weak and strong points of ICT employment at UNic. Subsequently, this will guide the researcher to propose specific recommendations to various problems, for a more effective and enhanced use of ICT at this University. 2 To examine the phenomenon of ICT application at UNic, a mixed methods research was employed, denoting that both qualitative and quantitative data were gathered. As regards the qualitative data, interviews were the data collection tool; more precisely, a total of 11 academic and administrative staff members were interviewed regarding their views towards the ICT at UNic. Among the main findings of the qualitative research was the composition of the framework of UNic’s ICT, showing the available Information Systems and services. Additionally, the enthusiasm of the interviewed administrative staff towards potential updates and modifications of their current Information Systems, despite their limited computer education, was also a major finding of this study. The online questionnaire, as the quantitative data collection method, was responded by 30 current students of UNic expressing their insights regarding the available Student Information Systems. The fundamental results emerging through the experiment were the following: the ‘Student Intranet’ was entitled with a 73.3% as the system that requires the most updates to become more efficient, as well as with a 2.33% mean as the one with the highest number of errors. It is acknowledged that the study was conducted under certain limitations; importantly, time limitations considerably constrained the process of conducting interviews to current staff at UNic, whereas space limitations restricted further elaboration.

Graph Edits for Counterfactual Explanations: A comparative study

Counterfactuals have been established as a popular explainability technique which leverages a set of minimal edits to alter the prediction of a classifier. When considering conceptual counterfactuals on images, the edits requested should correspond to salient concepts present in the input data. At the same time, conceptual distances are defined by knowledge graphs, ensuring the optimality of conceptual edits. In this work, we extend previous endeavors on graph edits as counterfactual explanations by conducting a comparative study which encompasses both supervised and unsupervised Graph Neural Network (GNN) approaches. To this end, we pose the following significant research question: should we represent input data as graphs, which is the optimal GNN approach in terms of performance and time efficiency to generate minimal and meaningful counterfactual explanations for black-box image classifiers

Μηχανισμοί αντοχής στον αναστολέα καρβαπενεμασών avibactam

H Avibactam είναι ένας νέος αναστολέας β-λακταμάσης που χρησιμοποιείται συχνά σε συνδυασμό με την Ceftazidime για τη θεραπεία λοιμώξεων που προκαλούνται από πολυανθεκτικά βακτήρια. Παρά το γεγονός ότι ο συγκεκριμένος αναστολέας είναι αποτελεσματικός έναντι πολλών βακτηριακών στελεχών, ορισμένα έχουν ήδη αναπτύξει μηχανισμούς αντοχής. Υπάρχουν διάφοροι γνωστοί μηχανισμοί αντοχής στην Avibactam. Οι μηχανισμοί αυτοί μπορούν να ταξινομηθούν ευρέως σε δύο κατηγορίες. Στους ενζυματικούς και στους μη ενζυματικούς. Ενζυματικοί μηχανισμοί: 1. Παραγωγή ενζύμων υδρόλυσης της Avibactam: Τα βακτήρια μπορούν να παράγουν ένζυμα β-λακταμάσης που στοχεύουν ειδικά και αποδομούν τον αναστολέα καθιστώντας τον αναποτελεσματικό. Ένα τέτοιο ένζυμο είναι για παράδειγμα η καρβαπενεμάση KPC-2 που παράγεται από ορισμένα στελέχη K. pneumoniae. Το ένζυμο υδρολύει την Avibactam όπως και τις καρβαπενέμες, καθιστώντας αυτά τα αντιβιοτικά αναποτελεσματικά. 2. Επαγωγή της λειτουργίας άλλων β-λακταμασών: Τα βακτήρια μπορεί να αυξήσουν την παραγωγή άλλων ενζύμων όπως των εκτεταμένου φάσματος β-λακταμασών, τα οποία δεν επηρεάζονται από τη δράση της Avibactam. Αυτό επιτρέπει στα στελέχη να συνεχίζουν να υδρολύουν τα αντιβιοτικά προκαλώντας αντοχή. Για παράδειγμα κάποια στελέχη Enterobacter cloacae επάγουν την παραγωγή ESBL, καθιστώντας την Avibactam λιγότερο αποτελεσματική. Μη ενζυματικοί μηχανισμοί: 1. Αλλαγή στη βακτηριακή κυτταρική μεμβράνη: Τα βακτήρια μπορούν να τροποποιήσουν τις κυτταρικές τους μεμβράνες για να αποτρέψουν την είσοδο της Avibactam στο κύτταρο, γεγονός που μειώνει την αποτελεσματικότητά της. Αυτό μπορεί να επιτευχθεί αλλάζοντας την έκφραση της εξωτερικής μεμβράνης και εισχωρώντας στον περιπλασμικό χώρο όπου βρίσκονται τα ένζυμα της β-λακταμάσης. Αυτός ο μηχανισμός έχει περιγραφεί σε στελέχη Pseudomonas aeruginosa. 2. Αντλίες εκροής: Τα βακτήρια μπορεί να χρησιμοποιήσουν αντλίες εκροής για να αντλήσουν την Avibactam από το εσωτερικό του κυττάρου, εμποδίζοντάς τη να φτάσει στο στόχο της. Ο μηχανισμός έχει περιγραφεί σε στελέχη Εnterobacter cloacae, όπου η Avibactam εκρέει ενεργά έξω από το κύτταρο μέσω ενός συγκεκριμένου συστήματος αντλίας εκροής. Συνοπτικά η αντοχή στην Avibactam μπορεί να επιτευχθεί μέσω πολλαπλών μοριακών μηχανισμών. Η κατανόηση αυτών είναι σημαντική προκειμένου να αποφευχθεί η εξάπλωσή τους και να διασωθεί όσο το δυνατόν περισσότερο αυτός ο νέος αντιμικροβιακός παράγοντας.Avibactam is a beta-lactamase inhibitor that is often used in combination with Ceftazidime to treat infections caused by multidrug-resistant bacteria. While avibactam is effective against many strains of bacteria, some have already developed resistance mechanisms to this drug. There are several known molecular resistance mechanisms of resistance to avibactam. The molecular mechanisms of resistance to avibactam can be broadly classified into two categories: enzymatic and non-enzymatic mechanisms. Enzymatic mechanisms: 1. Production of avibactam-hydrolyzing enzymes: Bacteria can produce β-lactamase enzymes that specifically target and degrade avibactam, rendering it ineffective. One such enzyme is for example the KPC-2 carbapenemase produced by some K. pneumoniae strains. KPC-2 hydrolyzes avibactam and carbapenems, making these antibiotics innefective. 2. Upregulation of other β-lactamase enzymes: Bacteria may increase the production of other β-lactamase enzymes, such as extended-spectrum β-lactamases (ESBLs), which are not affected by avibactam. This allows the bacteria to continue to break down antibiotics and cause infection. For example some Enterobacter cloacae strains can upregulate ESBLs, making avibactam less effective. Non-enzymatic mechanisms: 1. Changes in bacterial cell membranes: Bacteria may modify their cell membranes to prevent avibactam from entering the cell, which reduces its effectiveness. This can be achieved by altering the expression of outer membrane and entering the periplasmic space where the β-lactamase enzymes are located. This mechanism has been reported in some strains of Pseudomonas aeruginosa. 2. Efflux pumps: Bacteria may use efflux pumps to pump out avibactam from within the cell, preventing it from reaching its target. This mechanism has been reported for example in some strains of Enterobacter cloacae, where avibactam is actively effluxed out of the cell by a specific efflux pump system. In summary, resistance to avibactam can occur through multiple molecular mechanisms. Understanding these mechanisms is important in order to avoid their spread and to save as much as possible this new antimicrobial agent

Effect of river inputs on environmental status and potentially harmful phytoplankton in a coastal area of eastern Mediterranean (Maliakos Gulf, Greece)

In this work we study the response of phytoplankton and potentially harmful species to river inflows in a coastal area of eastern Mediterranean, within the context of environmental status assessment suggested by the European Commission’s Water Framework Directive (WFD, 2000/60/EC) and Marine Strategy Framework Directive (MSFD, 2008/56/EC). The spatio-temporal distribution of phytoplankton communities and biomass (as chlorophyll a), potentially harmful species, nutrient levels, dissolved oxygen, salinity and temperature were studied. A marginal good to moderate physicochemical status was assigned in the delta of Spercheios river that outflows in Maliakos Gulf. Silicates and nitrates were indicated as proxies of freshwater influence in Maliakos Gulf, whereas ammonium, nitrites and phosphates as proxies of pollutants from non-point sources. Phytoplankton biomass and abundances reached high levels throughout Maliakos Gulf inter-seasonally. High silicates favored the dominance of Diatoms. The potentially harmful species were blooming frequently, with higher levels in the estuary, and they were associated with low salinity, showing the riverine influence on them. Pseudo-nitzschia was the most frequent potentially harmful genus with an interesting strong linkage with low silicates and nitrates. Maliakos Gulf demonstrated an overall mesotrophic condition and failed to achieve good ecological status

Cardiovascular disease risk factors among children of different socioeconomic status in Istanbul, Turkey: Directions for public health and nutrition policy

OBJECTIVES: The aim of the current study was to examine the influence of socioeconomic status (SES) on physiological (lipid profile, obesity indices) and behavioral (dietary habits, physical activity) cardiovascular disease (CVD) risk factors among primary schoolchildren in Istanbul. DESIGN: Cross sectional study. SETTING: One private school and two public schools from different SES districts in Istanbul. PARTICIPANTS: 510 randomly selected children aged 12 and 13 years old (257 boys, 253 girls). RESULTS: The prevalence of overweight (15.2%) and the energy intake (p < 0.001 and p < 0.05 for boys and girls respectively) were found to be higher for the middle/ high SES group for both genders. Regarding biochemical indices, middle/ high SES children had higher values of High Density Lipoprotein-cholesterol (HDL-C) (p < 0.001 and p < 0.05 for boys and girls respectively) and lower values of TC/HDL-C ratio and LDL-C/HDL-C ratio (p < 0.05 and p < 0.001 for boys and girls respectively). This could be attributed to the higher physical activity levels observed for middle/ high SES children (p < 0.001). CONCLUSION: The findings of the current study revealed a coexistence of both overweight and higher energy intake in middle/ high SES children, as well as a coexistence of underweight and lower physical activity levels in low SES children. These observations should guide the public health policy in developing appropriate intervention strategies to efficiently tackle these health and social issues early in life

Levels of soluble ICAM-1 in premature and full-term neonates with infection.

BACKGROUND: Infection in the neonatal period is an extremely serious condition and diagnosis is difficult. C-reactive protein (CRP) is widely used as a marker of infection; however, its usefulness is limited in the early phase. The role of soluble intracellular adhesion molecule-1 (sICAM-1), an adhesion molecule, has been examined in recent studies as an early marker of neonatal infection with controversial results. AIM: Assessment of sICAM-1 concentrations and correlation with CRP, which is the currently used marker of infection, in order to use sICAM as an early diagnostic tool in neonates suspected for infection METHODS: Blood samples and blood cultures were obtained from two groups of pre-term and full-term neonates with clinical suspicion of infection prior to the initiation of antibiotics. The sICAM-1 and CRP values were compared with the corresponding noninfected ones (n = 10 each). RESULTS: The sICAM-1 levels were found increased in the group of both premature and term neonates with infection compared with the corresponding healthy ones (P < 0.0001). Prematurity combined with infection resulted in excessive increase of the levels of sICAM-1 in comparison with full-term infected newborns (p < 0.001). CRP values were normal in all samples except one in both full-term and premature infected neonates on day 1 of clinically suspected infection. Serial detection of CRP values on days 2 and 4 of infection revealed a pattern according to which CRP values in premature neonates continued rising, while in the group of full terms these values, after rising on the second day, lowered on day 4. CONCLUSIONS: Increased sICAM-1 levels can be detected early in both full-term and premature neonates with sepsis while CRP levels are within normal range at the same time. Assessment of sICAM-1 concentrations may be used as a diagnostic tool in neonates suspected for infection, resulting in earlier initiation of antibiotic therapy and therefore improving their outcome