Glucocorticoid receptor and its cross-talk with other cellular signaling factors in bipolar affective disorder

Η διπολική (μανιο-καταθλιπτική) διαταραχή συνίσταται σε εναλλαγή φάσεων κατάθλιψης με φάσεις μανίας. Η διπολική νόσος χαρακτηρίζεται από υπερλειτουργία του υποθάλαμο- υπoφυσιο-επινεφριδιακού άξονα και αντίσταση στα γλυκοκορτικοειδή. Ο υποδοχέας των γλυκοκορτικοειδών (GR), η φωσφορυλιωμένη του μορφή και η συνομιλία του με άλλες πρωτεΐνες, όπως για παράδειγμα τις πρωτεΐνες του θερμικού σοκ (HSP90, HSP70), παίζουν ρόλο «κλειδί» στην υποθάλαμο-υποφυσιακή λειτουργία στην κατάθλιψη. Στην παρούσα διατριβή μελετήθηκαν, η πρωτείνη GR, η ισομορφή β του GR, ο φωσφορυλιωμένος GR (ολική μορφή και τοπο-εδική μορφή στη θέση Ser211), οι πρωτείνες και οι παράγοντες του θερμικού (HSP90, HSP70, HSF1, HSF4), καθώς και τα σύμπλοκα του GR (HSP90/HSP70-GR) σε λεμφοκύτταρα από ασθενείς σε φάση κατάθλιψης, νορμοθυμίας, μανίας, και από φυσιολογικούς μάρτυρες, που αποτέλεσαν την ομάδα ελέγχου. Επίσης, αντικείμενο της παρούσας εργασίας αποτέλεσε ο ρόλος της απόπτωσης στην κατάθλιψη, νορμοθυμία και μανία, μέσω μελέτης των προαποπτωτικών πρωτεϊνών, του κυτοχρώματος c, και του Bax. Χρησιμοποιώντας τεχνικές Μοριακής Βιολογίας (υποκυτταρική κλασμάτωση, ανοσοκατακρήμνιση, Western Blot, Gel Shift) αποδεικνύεται για πρώτη φορά ότι η νόσος χαρακτηρίζεται από: α) μειωμένη ποσότητα του ολικού φωσφορυλιωμένου GR (pGR) και ανυψωμένα επίπεδα του φωσφορυλιωμένου GR στη θέση Ser211 (pGR-S211), β) μη-ανιχνεύσιμη GRβ πρωτείνη, γ) μειωμένα ολικά πρωτεϊνικά επίπεδα των HSP90 και HSP70 και μειωμένη πυρηνική πρωτείνη HSP70, δ) μειωμένα επίπεδα του HSF1, που συνοδεύονται από ανυψωμένα επίπεδα του HSF4, ενός μεταγραφικού παράγοντα που ανιχνεύθηκε για πρώτη φορά σε λεμφοκύτταρα, στ) μειωμένη σύνδεση του HSF στο DNA, ζ) αυξημένα επίπεδα των ετεροδιμερών HSP90-GR και HSP70-GR, και η) αυξημένα επίπεδα του κυτοχρώματος c και μειωμένα κυτοσολικά επίπεδα του Bax. Συμπερασματικά, η μελέτη έδειξε ότι η διπολική διαταραχή (κατάθλιψη ή μανία) χαρακτηρίζεται από σημαντικές μεταβολές στην GR-μεσολαβούμενη μετάδοση μηνύματος και της συνομιλίας του με παράγοντες του θερμικού σοκ καθώς και από ενδείξεις απόπτωσης. Τα αποτελέσματα που προέκυψαν από την παρούσα μελέτη, οδηγούν στην ενοχοποίηση των μορίων που μελετήθηκαν στην αιτιοπαθογένεια της διπολικής νόσου και προσδίδουν ένα ρόλο για την απόπτωση στη νόσο

Incipient Salinization: A Case Study of the Spring of Asclepieion in Lentas (Ancient Lebena), Crete

Sanctuaries devoted to Asclepius were established and operated for almost a thousand years in various Greek and Roman cities throughout the Mediterranean region. The Asclepieion sanctuary in Lentas (formerly known as Ancient Lebena) in Crete was famous for receiving water from a sacred spring. In Ancient Lebena, Levinaion was a famous centre for hydrotherapy, physiotherapy, and a psychiatric hospital. In the present paper, we aim to assess the hydrochemical status of this sacred spring that holds a prominent position in archaeological and historical studies. The main objectives of this study are: Initially, to present supervisory evidence (archaeological, geological, hydrochemical) of an area that was a water resource management model for many centuries, carrying out therapeutic work. The second objective is to present and compare hydrochemical data in the last century, i.e., from 1915 to 2021. The third objective is to highlight and warn of an incipient saltwater intrusion in the area along the Lentas coast. The fourth objective is to propose an alternative and sustainable form of water resources management in the region that requires the study and rational utilization of the sporadic small water springs in the region. Our study focuses on a basic hydrochemical analysis of spring and borehole water in the remains of Levinaion in the Lentas region, and their comparison with sparse historical data of the sacred spring water, aiming to interpret the impact of the changes in the spring water resources that occurred in recent decades due to urban modernization. Our results highlight (i) visible fluctuations in chemical composition of borehole water samples; (ii) a neutral to alkaline pH in borehole waters and an alkaline pH in spring waters; (iii) undetectable arsenic in Lentas borehole water, unlike historical data of Lentas spring water; (iv) low values of dissolved radon in Lentas borehole water and the spring water of Kefalovrysa; and (v) a timeless constant and hypothermic nature of the water of both the sacred spring and borehole of Lentas, and also of the Kefalovrysa spring. The recorded historical data, i.e., from 1915 to 1957, due to the absence of substantial anthropogenic activity in the area, can be used as reference values (natural background levels, NBLs) for the Lentas area. Our findings emerge with the need to bring again the flowing spring water of the sacred spring of Lentas in its original form through sustainable management and re-discover its beneficial therapeutical effects

Synergies of Radiomics and Transcriptomics in Lung Cancer Diagnosis: A Pilot Study

Radiotranscriptomics is an emerging field that aims to investigate the relationships between the radiomic features extracted from medical images and gene expression profiles that contribute in the diagnosis, treatment planning, and prognosis of cancer. This study proposes a methodological framework for the investigation of these associations with application on non-small-cell lung cancer (NSCLC). Six publicly available NSCLC datasets with transcriptomics data were used to derive and validate a transcriptomic signature for its ability to differentiate between cancer and non-malignant lung tissue. A publicly available dataset of 24 NSCLC-diagnosed patients, with both transcriptomic and imaging data, was used for the joint radiotranscriptomic analysis. For each patient, 749 Computed Tomography (CT) radiomic features were extracted and the corresponding transcriptomics data were provided through DNA microarrays. The radiomic features were clustered using the iterative K-means algorithm resulting in 77 homogeneous clusters, represented by meta-radiomic features. The most significant differentially expressed genes (DEGs) were selected by performing Significance Analysis of Microarrays (SAM) and 2-fold change. The interactions among the CT imaging features and the selected DEGs were investigated using SAM and a Spearman rank correlation test with a False Discovery Rate (FDR) of 5%, leading to the extraction of 73 DEGs significantly correlated with radiomic features. These genes were used to produce predictive models of the meta-radiomics features, defined as p-metaomics features, by performing Lasso regression. Of the 77 meta-radiomic features, 51 can be modeled in terms of the transcriptomic signature. These significant radiotranscriptomics relationships form a reliable basis to biologically justify the radiomics features extracted from anatomic imaging modalities. Thus, the biological value of these radiomic features was justified via enrichment analysis on their transcriptomics-based regression models, revealing closely associated biological processes and pathways. Overall, the proposed methodological framework provides joint radiotranscriptomics markers and models to support the connection and complementarities between the transcriptome and the phenotype in cancer, as demonstrated in the case of NSCLC

Content and Other Resources Recommendations for Individuals with Intellectual Disability: A Review

In this review paper, we look into how a recommendation system can be adapted to and support people with intellectual disability (ID). We start by reviewing and comparing the main classes of techniques for general-purpose content recommendation. Then, centering on individuals with ID, we collect information on their special needs that may be relevant to or affected by content recommendation tasks. We review the few existing recommendation systems specifically designed or adapted to the needs of this population and finally, based on the reviewed literature sources, we catalog the traits that a future content recommendation system should have in order to respond well to the identified special needs. We hope this listing of desirable traits and future directions in our concluding sections will stimulate research towards opening the doors to the digital world for individuals with ID

Content and Other Resources Recommendations for Individuals with Intellectual Disability: A Review

In this review paper, we look into how a recommendation system can be adapted to and support people with intellectual disability (ID). We start by reviewing and comparing the main classes of techniques for general-purpose content recommendation. Then, centering on individuals with ID, we collect information on their special needs that may be relevant to or affected by content recommendation tasks. We review the few existing recommendation systems specifically designed or adapted to the needs of this population and finally, based on the reviewed literature sources, we catalog the traits that a future content recommendation system should have in order to respond well to the identified special needs. We hope this listing of desirable traits and future directions in our concluding sections will stimulate research towards opening the doors to the digital world for individuals with ID

Shape-influenced clustering of dynamic patterns of gene profiles

Summarization: Statistical evaluation of temporal gene expression profiles plays an important role in particular biological processes and conditions. We introduce a clustering method for this purpose, which is based on the expression patterns but is also influenced by temporal changes. We compare the results of our platform with methods based on expression or the rank of temporal changes. The proposed platform is illustrated with a temporal gene expression dataset comprised of primary human chondrocytes and mesenchymal stem cells (MSCs). We derived three clusters in each cell type and compared the content of these classes in terms of temporal changes, which can support biological performance. For statistical evaluation we introduce a validity measure that takes under consideration these temporal changes and we also perform an enrichment analysis of three central genes in each cluster. Even though we can detect certain statistical similarities, these might be due to different biological processes. Our proposed platform contributes to both the statistical and biological validation of temporal profiles.Παρουσιάστηκε στο: Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC

Experimental model construction and validation of the ErbB signaling pathway

Summarization: The importance of ErbB receptor signaling in breast cancer is consistent with its functional role in normal development of mammary gland. The study of the ErbB signaling network and its bidirectional cross-talk with hormonal receptors, such as estrogen receptor (ER) encloses information about the molecular mechanisms on breast cancer evolution, progression and endocrine resistance. With this analysis we attempt to examine the differences in activation/inhibition of intracellular signaling molecules within ErbB signaling cascade on ER+ and ER-breast cancer patients. With the proposed framework we model the genetic interactions in the ErbB signaling pathway directly from expression data as Gaussian approximations and compare them with the KEGG canonical ErbB pathway in order to identify significant molecular deformations characterizing the studied population. The results indicate a distinct profile of activation/inhibition between the two ER populations and highlight the primary role of PI3K/Akt pathway in breast cancer progression and targeted treatment strategies.Παρουσιάστηκε στο: 13th International Conference on Bioinformatics and Bioengineering (BIBE

A generic framework for the elicitation of stable and reliable gene expression signatures

Summarization: In the recent years microarray technologies have gained a lot of popularity for their ability to quickly measure the expression of thousands of genes and provide valuable information for linking complex diseases such as cancer to their genetic underpinnings. Nevertheless the large number of parameters to be estimated in relation to the small number of available samples gives rise to an “ill posed” problem where the possible solution is not stable under slight changes either in the dataset or the initial conditions and starting points. In this work we present a generic classification framework that works in an iterative manner and converges to a stable solution that combines good accuracy with biologically meaningful feature selection. The methodology is orthogonal to the specific classification algorithm used. We compare some of the most widely used classifiers based on their average discrimination power and the size of the derived gene signature. According to our proposed model named Stable Bootstrap Validation (SBV), a unified `77 common-gene signature' was selected, which is closely associated with several aspects of breast tumorigenesis and progression, as well as patient-specific molecular and clinical characteristics.Presented on

Supplemenatry Material_Chlis et al_MBEC2014

<p>Supplementary material for "Searching for Significant Genes in Cancer Metastasis by Tissue Comparisons"</p