Identification and characterization of DUSP27, a novel dual-specific protein phosphatase

AbstractA novel human dual-specific protein phosphatase (DSP), designated DUSP27, is here described. The DUSP27 gene contains three exons, rather than the predicted 4–14 exons, and encodes a 220 amino acid protein. DUSP27 is structurally similar to other small DSPs, like VHR and DUSP13. The location of DUSP27 on chromosome 10q22, 50kb upstream of DUSP13, suggests that these two genes arose by gene duplication. DUSP27 is an active enzyme, and its kinetic parameters and were determined. DUSP27 is a cytosolic enzyme, expressed in skeletal muscle, liver and adipose tissue, suggesting its possible role in energy metabolism

Integrated signaling and transcriptome analysis reveals Src family kinase individualities and novel pathways controlled by their constitutive activity

The Src family kinases (SFKs) Lck and Lyn are crucial for lymphocyte development and function. Albeit tissue-restricted expression patterns the two kinases share common functions; the most pronounced one being the phosphorylation of ITAM motifs in the cytoplasmic tails of antigenic receptors. Lck is predominantly expressed in T lymphocytes; however, it can be ectopically found in B-1 cell subsets and numerous pathologies including acute and chronic B-cell leukemias. The exact impact of Lck on the B-cell signaling apparatus remains enigmatic and is followed by the long-lasting question of mechanisms granting selectivity among SFK members. In this work we sought to investigate the mechanistic basis of ectopic Lck function in B-cells and compare it to events elicited by the predominant B-cell SFK, Lyn. Our results reveal substrate promiscuity displayed by the two SFKs, which however, is buffered by their differential susceptibility toward regulatory mechanisms, revealing a so far unappreciated aspect of SFK member-specific fine-tuning. Furthermore, we show that Lck- and Lyn-generated signals suffice to induce transcriptome alterations, reminiscent of B-cell activation, in the absence of receptor/co-receptor engagement. Finally, our analyses revealed a yet unrecognized role of SFKs in tipping the balance of cellular stress responses, by promoting the onset of ER-phagy, an as yet completely uncharacterized process in B lymphocytes

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Ο ηλεκτρονικός εκφοβισμός στην εποχή της πανδημίας λόγω του COVID- 19: Απόψεις των εκπαιδευτικών

Η παρούσα πτυχιακή εργασία πραγματεύεται το φαινόμενου του ηλεκτρονικού εκφοβισμού κατά την περίοδο της πανδημίας μέσα από τις απόψεις των εκπαιδευτικών της Πρωτοβάθμιας Εκπαίδευσης. Η δομή της εκτείνεται σε δύο βασικούς τομείς, τον θεωρητικό και τον ερευνητικό. Στο θεωρητικό άξονα, επιδιώκεται η προσέγγιση των όρων που συμπεριλαμβάνει η οικεία εργασία, μέσα από την βιβλιογραφική ανασκόπηση, με σκοπό την πλήρη κατανόησή τους. Το θεωρητικό μέρος περιλαμβάνει πέντε κεφάλαια. Στο πρώτο, διατυπώνεται η προβληματική της μελέτης. Στο δεύτερο κεφάλαιο αποσαφηνίζονται βιβλιογραφικά, οι όροι που πραγματεύονται στα επόμενα κεφάλαια. Στο τρίτο επιχειρείται ο προσδιορισμός των παραγόντων που συντελούν στην έξαρση του ηλεκτρονικού εκφοβισμού, ενώ στο τέταρτο αναφέρονται οι επιπτώσεις του φαινομένου. Τέλος, στο πέμπτο κεφάλαιο, παρουσιάζονται τα μέτρα που μπορούν να ληφθούν έτσι ώστε να αντιμετωπιστεί το ζήτημα του ηλεκτρονικού εκφοβισμού. Ο ερευνητικός τομέας σχετίζεται με την εμπειρική μελέτη. Στο τμήμα αυτό αναπτύσσεται η μεθοδολογία της έρευνας, το δείγμα που λήφθηκε, η αξιοπιστία – εγκυρότητα καθώς και οι περιορισμοί της. Παράλληλα, παρατίθενται οι σκοποί, η διαδικασία συλλογής δεδομένων, όπως και τα μέσα που χρησιμοποιήθηκαν. Η οικεία μελέτη πραγματοποιήθηκε με τη χρήση ενός δείγματος 13 εκπαιδευτικών, οι οποίοι εργάζονται στο ιδιωτικό σχολείο της Λεοντείου Σχολής του νομού Αττικής. Οι εκπαιδευτικοί κλήθηκαν να απαντήσουν σε ερωτήσεις που αφορούσαν στην άποψή τους αναφορικά με τον ηλεκτρονικό εκφοβισμό, τα αίτια του, τους προτεινόμενους τρόπους αντιμετώπισής του, καθώς και άλλα σημαντικά ερωτήματα.The present dissertation deals with the phenomenon of cyberbullying during the pandemic through the views of Primary school teachers. Its structure extends to two main areas, the theoretical and the research area. In the theoretical axis, the approach of the terms included in the relevant work is sought, through the bibliographic review, in order to fully understand them. The theoretical part consists of five chapters. In the first, the problem of the study is formulated. The second chapter clarifies bibliographically, the terms realized in the following chapters. Τhe third attempts to identify the factors that contribute to the escalation of cyberbullying, while the fourth reports the effects of the phenomenon. Finally, the fifth chapter presents the measures that can be taken to address the issue of cyberbullying. The research field is related to the empirical study. This section develops the research methodology, the sample taken, its reliability - validity as well as its limitations. At the same time, the purposes, the data collection process, as well as the means used are listed. The relevant study was carried out using a sample of 13 teachers, who work in the private school of the Leontiou School of the prefecture of Attica. Teachers were asked to answer questions regarding their views on cyberbullying, its causes, suggested ways to deal with it, and other important questions

Use of indicators for the assessment of pressures of water in the Watery Departments of Hpeiros with accent in the agricultural sector

208 σ.Μεταπτυχιακή Εργασία -- Εθνικό Μετσόβιο Πολυτεχνείο. Διεπιστημονικό - Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών "Περιβάλλον και Ανάπτυξη"Στόχος της συγκεκριμένης διπλωματικής είναι η οπτικοποίηση και αποτίμηση της κατάστασης της χρήσης αγροτικού νερού και των παραμέτρων που την επηρεάζουν στην Περιφέρεια Ηπείρου από το 1980 έως σήμερα. Το μέσο για την υλοποίηση αυτής της διαδικασίας ήταν οι δείκτες με την πλατφόρμα προσέγγισης DPSIR και η χαρτογράφιση έγινε τη βοήθεια του σχεδιαστικού προγράμματος GIS.The aim of this dissertation is to visualize and value the situation of use of agricultural water and indicators that are influenced in the Region of Hepirus from 1980 till today. Is described the procedure of mapping and depiction of the situation of irrigatory water in the Region of Hpirus. Initially, is mentioned the methological approach of growth of indicators, what are the advantages and disadvantages of the above and it is described analytically the DPSIR framework.Κωνσταντίνα Δ. Νίκ

Haematopoietic protein tyrosine phosphatase (HePTP) phosphorylation by cAMP-dependent protein kinase in T-cells: dynamics and subcellular location.

The HePTP (haematopoietic protein tyrosine phosphatase) is a negative regulator of the ERK2 (extracellular signal-regulated protein kinase 2) and p38 MAP kinases (mitogen-activated protein kinases) in T-cells. This inhibitory function requires a physical association of HePTP through an N-terminal KIM (kinase-interaction motif) with ERK and p38. We previously reported that PKA (cAMP-dependent protein kinase) phosphorylates Ser-23 within the KIM of HePTP, resulting in dissociation of HePTP from ERK2. Here we follow the phosphorylation of this site in intact T-cells. We find that HePTP is phosphorylated at Ser-23 in resting T-cells and that this phosphorylation increases upon treatment of the cells with agents that elevate intracellular cAMP, such as prostaglandin E2. HePTP phosphorylation occurred at discrete regions at the cell surface. Phosphorylation was reduced by inhibitors of PKA and increased by inhibitors of protein phosphatases PP1 and PP2A, but not by inhibitors of calcineurin. In vitro, PP1 efficiently dephosphorylated HePTP at Ser-23, while PP2A was much less efficient. Activation of PP1 by treatment of the cells with ceramide suppressed Ser-23 phosphorylation, as did transfection of the catalytic subunit of PP1. Phosphorylation at Ser-23 is also increased in a transient manner upon T-cell antigen receptor ligation. In contrast, treatment of cells with phorbol ester had no effect on HePTP phosphorylation at Ser-23. We conclude from these results that HePTP is under continuous control by PKA and a serine-specific phosphatase, probably PP1, in T-cells and that this basal phosphorylation at Ser-23 can rapidly change in response to external stimuli. This, in turn, will affect the ability of HePTP to inhibit the ERK and p38 MAP kinases