Εκτίμηση Εδαφικής Υγρασίας από Πολυφασματικά και Ραντάρ Δορυφορικά Δεδομένα με χρήση του Google Earth Engine και Τεχνικών Μηχανικής Μάθησης

Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) “Γεωπληροφορική

Ο ενδοκυττάριος σηματοδοτικός άξονας PC1/mTOR ως παθογενετικός μηχανισμός στην ψωρίαση

Οι πολυκυστίνες PC1 (πολυκυστίνη-1) και PC2 (πολυκυστίνη-2) λειτουργούν ως μηχανοευαίσθητα εργαλεία των ευκαρυωτικών ανθρώπινων κυττάρων. Αντιλαμβάνονται τα εξωτερικά ερεθίσματα του περιβάλλοντος του κυττάρου και τα μετατρέπουν σε βιοχημικά μηνύματα ,ενεργοποιώντας ,τελικά ,πληθώρα σηματοδοτικών μονοπατιών. Επίσης, χάρη στην υψηλή ομολογία που μοιράζονται με συγκεκριμένες πρωτεΐνες της οικογένειας των TRP καναλιών, κατηγοριοποιούνται ως υποδοχείς ιόντων και συγκεκριμένα ιόντων ασβεστίου. Στα κερατινοκύτταρα ,η μηχανοδιέγερση ρυθμίζει τον πολλαπλασιασμό, τη διαφοροποίηση, τη μορφολογία και τη μεταναστευτικότητα του συγκεκριμένου κυτταρικού τύπου. Το ασβέστιο λειτουργεί ως κύριος ρυθμιστής της διαφοροποίησης των κερατινοκυττάρων και του σχηματισμού του επιθηλιακού φραγμού, ρυθμίζοντας διάφορα σηματοδοτικά μονοπάτια. Γνωρίζοντας τις ιδιότητες των πολυκυστινών ως μηχανοσένσορες και υποδοχείς ιόντων ασβεστίου,υποθέσαμε ότι σχετίζονται με παθογενετικούς μηχανισμούς που δημιουργούν ψωριασικούς ιστούς. Συγκεκριμένα επιλέξαμε το σηματοδοτικό μονοπάτι PC1/mTOR.Ο mTOR αποτελεί βασικό μόριο ,που εμπλέκεται σε πολλές κυτταρικές λειτουργίες ,όπως ο κυτταρικός κύκλος και η αγγειογένεση και έχει σχετιστεί με την ανάπτυξη ψωριασικών πλακών. H PC1 ρυθμίζει τη φωσφορυλίωση του mTOR , καταστέλλοντας την ενεργοποίηση του. Σε ψωριασικούς ιστούς έχει δειχθεί αυξημένη ενεργοποίηση του mTOR μέσω του μονοπατιού PI3K/Akt/mTOR του ,ρυθμίζοντας κατ’επέκταση και τον κυτταρικό πολλαπλασιασμό, διαφοροποίηση και μετανάστευση. Μέσω ανοσοϊστοχημείας, Western Blot και PCR σε ψωριασικούς ιστούς ,εντοπίσαμε μειωμένη έκφραση PC1 σε σχέση με τους φυσιολογικούς ιστούς .Στην in vitro μελέτη ,χρησιμοποιώντας την κυτταρική σειρά HaCaT (αθανατοποιημένα ανθρώπινα κερατινοκύτταρα) μέσω τεχνικών Western Blot και ανοσοϊστοχημείας ,διερευνούμε τα επίπεδα του mTOR και της ενεργοποιημένης φωσφορυλιωμένης μορφής του (p-mTOR) σε φυσιολογική κατάσταση και σε κατάσταση αποσιώπησης του γονιδίου της PC1.Polycystin-1 and polycystin-2 are useful as mechanotransductive tools, by receiving external mechanical stimuli and convert them to biochemical message, which in turn will activate other signaling pathways in eukaryote human cells. Both PC1 and PC2, thanks to the high homology that they share with certain protein-receptors, they are categorized in TRPP (Transient Receptor Potential Polycystic) ,a family of transient receptor potential ion channel and in particular as calcium ion receptors. Mechanotransduction regulates proliferation, differentiation, morphology and migration of keratinocytes. Calcium acts as a master regulator of differentiation of keratinocytes and formation of the epithelial barrier , by regulating various signaling pathways. Knowing the properties of polycystins as mechanosensors and calcium ion receptors, we assumed to be associated with pathogenetic mechanisms that create psoriatic tissues. Specifically, we choose to study PC1/mTOR signaling pathway. mTOR is a key molecule involved in many cellular functions ,such as cell cycle and angiogenesis and has been implicated with development of psoriatic plaques. PC1 modulates the phosphorylation of mTOR, by suppressing its activation. In psoriatic tissues have shown increased activation of mTOR via the PI3K / Akt / mTOR pathway, which results in increased cell proliferation, differentiation and migration. Using immunohistochemistry, Western Blot and PCR in psoriatic tissues , we detected decreased expression of PC1 in contrast to normal tissues. For in vitro experiments we choose HaCaT (immortalized human keratinocytes) cell line and we investigate the levels of mTOR and the activated phosphorylated form of (p-mTOR) in a normal state and silence state of PC1 gene, by using Western Blot and immunohistochemistry

«Συσχέτιση των μηχανοευαίσθητων πολυκυστινών και φλεγμονωδών παραγόντων στην παθογένεια του ορθοκολικού καρκίνου»

Οι πολυκυστίνες 1 και 2 (PC1, PC2) είναι πρωτεΐνες που εκφράζονται σε πολλά είδη επιθηλιακών κυττάρων, συμμετέχοντας αιτιολογικά στην παθογένεια της αυτοσωμικής επικρατούσας πολυκυστικής νόσου των νεφρών. Λειτουργούν ως μηχανο‐αισθητήρια μόρια που ρυθμίζουν την κυτταρική απόκριση και διαθέτουν ομοιοστατικό ρόλο σε βασικές λειτουργίες του κυττάρου που διαταράσσονται κατά την ογκογένεση, πιθανολογώντας τη βιολογική συμμετοχή τους κυρίως στις διαδικασίες επέκτασης και μετάστασης του όγκου. Επιπλέον οι πολυκυστίνες παρουσιάζουν σημαντικό ρόλο στην αυτοάνοση επικρατή πολυκυστική νόσο των νεφρών, στον καρκίνο του παχέος εντέρου και στην ψωρίαση. Το κοινό χαρακτηριστικό αυτών των 3 ασθενειών είναι η στενή παθογενετική σύνδεση με μηχανισμούς φλεγμονής. Ο ορθοκολικός καρκίνος αποτελεί έναν από τους βασικότερους πολυπαραγοντικούς καρκίνους, ενώ καίριο ρόλο διαδραματίζει στην εξέλιξη του η ανάπτυξη φλεγμονής στο περιβάλλον του παχέος εντέρου. Στόχος της μεταπτυχιακής διπλωματικής ήταν η διερεύνηση για πρώτη φορά του ρόλου των πολυκυστινών στην φλεγμονή κατά την καρκινογένεση χρησιμοποιώντας ως μοντέλο, καρκινικές σειρές ορθοκολικού καρκίνου (ΟΚΚ), που είναι μια συχνή κακοήθεια και στα δύο φύλα αρκετά καλά μελετημένη και ιεραρχικά δομημένη. Η υποέκφραση της Πολυκυστίνης-1 προάγει την ενεργοποίηση μορίων όπως ο mTOR, με επακόλουθη έκφραση του VEGF, που αποτελεί βασικό παράγοντα κατά την φλεγμονή. Επίσης, η μεταγραφική αποσιώπηση της Πολυκυστίνης 1, οδηγεί σε συσσώρευση του ΙΚΚβ στο κυτταρόπλασμα και αυξημένη ενεργοποίηση του NF-κΒ, ο οποίος στη συνέχεια ρυθμίζει την έκφραση γονιδίων που σχετίζονται με φλεγμονή. Επίσης ο μεταγραφικός παράγοντας STAT3, ο οποίος ενεργοποιεί αρκετά γονίδια κυτταροκινών επηρεάζεται από την υποέκφραση της Πολυκυστίνης-1 και εμφανίζει αυξημένα επίπεδα ενεργοποίησης στα καρκινικά κύτταρα παχέος εντέρου. Τέλος, το φλεγμονώδες περιβάλλον στον καρκίνο του παχέος εντέρου επηρεάζει την έκφραση της Πολυκυστίνης-1, με τις προφλεγμονώδεις κυτταροκίνες να προκαλούν μείωση στην έκφραση της. Συμπερασματικά, η Πολυκυστίνη-1 μπορεί να αποτελέσει έναν νέο τελεστή της φλεγμονής, που εμπλέκονται σε παθολογικούς μηχανισμούς ανάπτυξης επιθετικού φαινοτύπου στον ορθοκολικό καρκίνο, και να αποτελέσει ένα νέο μόριο θεραπευτικής στόχευσης.Polycystins 1 and 2 (PC1, PC2) are proteins that are expressed in many types of epithelial cells, contributing to the pathogenesis of autosomal dominant polycystic kidney disease. They function as motor ‐ sensing molecules that regulate cellular response and play a homeostatic role in key cellular functions that are disturbed during oncogenesis, potentially assuming their biological involvement mainly in the processes of tumor expansion and metastasis. They also appear to play a key role in colon cancer, autoimmune dominant polycystic kidney disease and psoriasis. The common feature of these 3 diseases is the close pathogenetic association with inflammatory mechanisms. Colorectal cancer is one of the most important multifactorial cancers. The development of inflammation in the colon environment plays a key role in its development. The aim of the master's thesis was to investigate for the first time the role of polycystins in inflammation during carcinogenesis using a model of colorectal cancer (CRC) as a model, which is a common malignancy in both sexes that is well thought out and hierarchically structured. Hypoexpression of Polycystin-1 promotes activation of molecules such as mTOR, with subsequent expression of VEGF, which is a key factor in inflammation. Also, transcriptional silencing of Polycystin 1, leads to accumulation of IKKβ in the cytoplasm and increased activation of NF-Kb, which then regulates the expression of inflammatory-related genes. STAT3, which also activates several cytokine genes, is affected by Polycystin-1 hypoexpression and exhibits elevated levels of activation. Finally, inflammatory environment in colorectal cancer affects the expression of Polycystin-1, with pro-inflammatory cytokines causing a decrease in its expression. In conclusion, Polycystin-1 may be a novel effector of inflammation, involved in pathological mechanisms of development of an aggressive phenotype in colorectal cancer, and may be a new therapeutic targeting molecule

The Combined Effect of Promoting the Mediterranean Diet and Physical Activity on Metabolic Risk Factors in Adults:A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Adhering to the Mediterranean diet (MD) and physical activity (PA) public health guidelines have independently been linked to health benefits in adults. These behaviours form essential components of the traditional Mediterranean lifestyle. However, their combined effect on metabolic risk has not been systematically assessed. This systematic review with meta-analysis (PROSPERO; CRD42017073958) aimed to examine, for the first time, the combined effect of promoting the MD and PA compared with no treatment, treatment with MD or PA alone, or a different dietary and/or PA treatment, and estimate its magnitude on metabolic risk factors. Medline, Embase, CINAHL and Web of Science were systematically searched until March 2018 for English language controlled interventions reporting the combined effects of the MD and PA on one or multiple metabolic risk factors in adults. Two researchers independently conducted data extraction and risk of bias assessment using a rigorous methodology. Reporting followed PRISMA guidelines. Quality of reporting and risk of bias were assessed using the CONSORT guidelines and the Cochrane Collaboration's tool, respectively. Data from 12 articles reporting 11 randomised controlled trials (n = 1684) were included in the qualitative synthesis; across them, risk of bias was considered low, unclear and high for 42%, 25% and 33% of domains, respectively. Between-study heterogeneity ranged from 44% (triglycerides) to 98% (insulin and high density lipoprotein cholesterol (HDL)-cholesterol). Compared to a control condition, there was strong evidence (p < 0.001) of a beneficial effect of promoting the MD and PA on body weight (-3.68 kg, 95% CI (confidence intervals) -5.48, -1.89), body mass index (-0.64 kg/m², 95% CI -1.10, -0.18), waist circumference (-1.62 cm, 95% CI -2.58, -0.66), systolic (-0.83 mmHg, 95% CI -1.57, -0.09) and diastolic blood pressure (-1.96 mmHg, 95% CI -2.57, -1.35), HOMA-IR index (-0.90, 95% CI -1.22, -0.58), blood glucose (-7.32 mg/dL, 95% CI -9.82, -4.82), triglycerides (-18.47 mg/dL, 95% CI -20.13, -16.80), total cholesterol (-6.30 mg/dL, 95% CI -9.59, -3.02) and HDL-cholesterol (+3.99 mg/dL, 95% CI 1.22, 6.77). There was no evidence of an effect on insulin concentrations. The data presented here provide systematically identified evidence that concurrently promoting the MD and PA is likely to provide an opportunity for metabolic risk reduction. However, due to the high degree of heterogeneity, most likely due to the variation in control group treatment, and the small number of included studies, findings from the pooled analysis should be interpreted with caution. These findings also highlight the need for high quality randomised controlled trials examining the combined effect of the MD and PA on metabolic risk

Resilience explanations from adolescents challenged by unemployment

My study is a sub-study of the Resilient Youth in Stressed Environments (RYSE) Project (ethics clearance, UP17/05/01). The RYSE project focuses on gaining a more thorough understanding of the resilience of youth living in communities that are dependent on the petrochemical industry, as well as the associated risks. The purpose of my qualitative sub-study was to explore how older adolescents from the eMbalenhle community explain resilience in the face of unemployment. The current literature tends to be reliant on academic understandings of resilience. In order to gain a more comprehensive understanding of resilience, it is important to recognise the perspectives of resilience of adolescents who live in a highly stressed environment that is confronted by multiple risks. In order to achieve the purpose of my study, I assumed an interpretivist approach. This approach is appropriate for developing an understanding of adolescents’ individual experiences and perceptions of resilience in a petrochemical community and in the face of unemployment. To guarantee that my question was answered, I utilised a phenomenological research design. The RYSE Project has established a Community Advisory Panel (CAP), and the CAP purposively sampled the participants involved in my study. Seven adolescents (all male) between the ages of 18 and 24 were recruited from eMbalenhle in the Govan Mbeki municipality in Mpumalanga. An Arts-based activity (draw and talk) and an informal group discussion were used to generate data. An inductive, thematic analysis of the data was conducted in order to identify themes. Ungar’s (2011) Social Ecology of Resilience Theory (SERT) provided the theoretical framework for my study. The main themes that emerged from the data, regarding resilience enablers among adolescents in the face of unemployment, were: Having a vision, appropriating opportunities, and drawing on social support. The themes that arose from the adolescents’ explanations of resilience support the SERT. I think these themes are important for educational psychologists who work with adolescents challenged by unemployment in eMbalenhle because they highlight the importance of social support and community in interventions. In addition, these themes provide possible individual strategies, from the perspective of adolescents, that could allow for positive adaptation despite adversity.Dissertation (MEd)--University of Pretoria, 2019.Educational PsychologyMEdUnrestricte

A combination of hot water treatment and modified atmosphere packaging maintains quality of advanced maturity 'Caldesi 2000' nectarines and 'Royal Glory' peaches

Advanced maturity nectarines cv. Caldesi 2000 [Prunus persica var. nectarina (Ait.) Maxim.] and peaches cv. Royal Glory [Prunus persica (L.) Batch] were treated in 46°C hot water containing 200 mM NaCl for 25 min, sealed in low thickness PE bags and stored at 0°C for 1 and 2 weeks. Quality was evaluated initially and after each storage period plus 1 day shelf life. Hot water treatment (an acceptable treatment to reduce spoilage from fungi) did not cause any fruit damage based on external observations, specific conductivity and total phenol content evaluations, but reduced firmness loss (possibly in combination with MA packaging) especially in the white-flesh nectarines and kept the cellular membranes functioning better. PE bags were of low thickness and MA conditions inside the bags were found inadequate (O2 levels &gt;15%, CO2 levels &lt;5%) to significantly affect the ripening process during cold storage, but could be harmful after 10 h at room temperature (O 2 levels &lt;3%, CO2 levels &gt;13%). Mass losses were kept low in PE bags. Juice soluble solids concentration, pH and acidity were not affected by the hot water treatment before and after cold storage. Hot water combined with MA packaging during storage resulted in good quality fruit after 1 week duration for postharvest handling. © 2005 Elsevier B.V. All rights reserved

Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential

The serine/threonine kinase mechanistic target of rapamycin (mTOR) plays a pivotal role in the regulation of cell proliferation, survival, and motility in response to availability of energy and nutrients as well as mitogens. The mTOR signaling axis regulates important biological processes, including cellular growth, metabolism, and survival in many tissues. In the skin, dysregulation of PI3K/AKT/mTOR pathway may lead to severe pathological conditions characterized by uncon-trolled proliferation and inflammation, including skin hyperproliferative as well as malignant dis-eases. Herein, we provide an update on the current knowledge regarding the pathogenic implica-tion of the mTOR pathway in skin diseases with inflammatory features (such as psoriasis, atopic dermatitis, pemphigus, and acne) and malignant characteristics (such as cutaneous T cell lymphoma and melanoma) while we critically discuss current and future perspectives for therapeutic targeting of mTOR axis in clinical practice. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential

The serine/threonine kinase mechanistic target of rapamycin (mTOR) plays a pivotal role in the regulation of cell proliferation, survival, and motility in response to availability of energy and nutrients as well as mitogens. The mTOR signaling axis regulates important biological processes, including cellular growth, metabolism, and survival in many tissues. In the skin, dysregulation of PI3K/AKT/mTOR pathway may lead to severe pathological conditions characterized by uncontrolled proliferation and inflammation, including skin hyperproliferative as well as malignant diseases. Herein, we provide an update on the current knowledge regarding the pathogenic implication of the mTOR pathway in skin diseases with inflammatory features (such as psoriasis, atopic dermatitis, pemphigus, and acne) and malignant characteristics (such as cutaneous T cell lymphoma and melanoma) while we critically discuss current and future perspectives for therapeutic targeting of mTOR axis in clinical practice