Iron induces insulin resistance in cardiomyocytes via regulation of oxidative stress

York University Librarie

Inherited Disorders of Iron Overload

Dietary iron absorption and systemic iron traffic are tightly controlled by hepcidin, a liver-derived peptide hormone. Hepcidin inhibits iron entry into plasma by binding to and inactivating the iron exporter ferroportin in target cells, such as duodenal enterocytes and tissue macrophages. Hepcidin is induced in response to increased body iron stores to inhibit further iron absorption and prevent iron overload. The mechanism involves the BMP/SMAD signaling pathway, which triggers transcriptional hepcidin induction. Inactivating mutations in components of this pathway cause hepcidin deficiency, which allows inappropriately increased iron absorption and efflux into the bloodstream. This leads to hereditary hemochromatosis (HH), a genetically heterogenous autosomal recessive disorder of iron metabolism characterized by gradual buildup of unshielded non-transferrin bound iron (NTBI) in plasma and excessive iron deposition in tissue parenchymal cells. The predominant HH form is linked to mutations in the HFE gene and constitutes the most frequent genetic disorder in Caucasians. Other, more severe and rare variants are caused by inactivating mutations in HJV (hemojuvelin), HAMP (hepcidin) or TFR2 (transferrin receptor 2). Mutations in SLC40A1 (ferroportin) that cause hepcidin resistance recapitulate the biochemical phenotype of HH. However, ferroportin-related hemochromatosis is transmitted in an autosomal dominant manner. Loss-of-function ferroportin mutations lead to ferroportin disease, characterized by iron overload in macrophages and low transferrin saturation. Aceruloplasminemia and atransferrinemia are further inherited disorders of iron overload caused by deficiency in ceruloplasmin or transferrin, the plasma ferroxidase and iron carrier, respectively

Negative Feedback Regulation of the Yeast Cth1 and Cth2 mRNA Binding Proteins Is Required for Adaptation to Iron Deficiency and Iron Supplementation

Iron (Fe) is an essential element for all eukaryotic organisms because it functions as a cofactor in a wide range of biochemical processes. Cells have developed sophisticated mechanisms to tightly control Fe utilization in response to alterations in cellular demands and bioavailability. In response to Fe deficiency, the yeast Saccharomyces cerevisiae activates transcription of the CTH1 and CTH2 genes, which encode proteins that bind to AU-rich elements (AREs) within the 3′ untranslated regions (3′UTRs) of many mRNAs, leading to metabolic reprogramming of Fe-dependent pathways and decreased Fe storage. The precise mechanisms underlying Cth1 and Cth2 function and regulation are incompletely understood. We report here that the Cth1 and Cth2 proteins specifically bind in vivo to AREs located at the 3′UTRs of their own transcripts in an auto- and cross-regulated mechanism that limits their expression. By mutagenesis of the AREs within the CTH2 transcript, we demonstrate that a Cth2 negative-feedback loop is required for the efficient decline in Cth2 protein levels observed upon a rapid rise in Fe availability. Importantly, Cth2 autoregulation is critical for the appropriate recovery of Fe-dependent processes and resumption of growth in response to a change from Fe deficiency to Fe supplementation

Oral iron supplementation: new formulations, old questions

Iron deficiency anemia and pre-anemic iron deficiency are the most frequent pathologies. The first line of treatment involves oral iron supplementation. The simplest, least expensive, and most frequently prescribed drug is ferrous sulfate, while other ferrous salts and ferric complexes with polysaccharides or succinylated milk proteins are also widely used. In recent years, novel iron formulations have been developed, such as the lipophilic iron donor ferric maltol, or nanoparticle encapsulated sucrosomial® iron. Oral iron supplementation is usually efficacious in correcting iron deficiency anemia and replenishing iron stores but causes gastrointestinal side effects that reduce compliance. When oral iron supplementation is contraindicated, intravenous iron therapy can rapidly achieve therapeutic targets without gastrointestinal complications. Herein, we critically review literature on relative efficacy and tolerability of currently available oral iron supplements, and summarize recent data on optimal dosage and frequency

The stylistic identity of the metapoet: a corpus-based comparative analysis using translations of modern Greek poetry

The aim of this study is to explore the stylistic identity of four translators of modern Greek poetry into English and to outline each translator’s distinct stylistic profile. In line with views on the subject expressed by Malmkjær (1996) and Baker (2000) a translator’s profile is seen as being composed by consistent patterns that can be identified throughout their work and which leave their personal mark on the text. A corpus-based methodology is used for the identification and exploration of these patterns, through a Specialized Corpus of English Translations of Modern Greek Poetry (SCETOMGP). This corpus contains translations by Rae Dalven, Kimon Friar, Edmund Keeley & Phillip Sherrard (working in collaboration) and David Connolly. The source-texts are taken from C.P. Cavafy, George Seferis, Yiannis Ritsos and Odysseus Elytis, who were extensively translated during the second half of the 20th century. The main purpose of the corpus is to facilitate direct comparison between the retranslations of the same poem. Such direct comparisons form the core of this study and have the advantage of making the issue of source-text influence on each translator directly observable, alongside their other stylistic traits. A detailed account of the theoretical views or reflections each translator has put forth is also presented. Following Holmes (1994) the translator of poetry is seen here as a meta-poet who requires skills similar to those of a critic and an original poet, and certain skills that are specific only to the translator. Consequently, the translators’ views on issues of language, literature, style and translation not only provide the backdrop for exploring any stylistic patterns found in the texts, but are seen as part of their stylistic profile. The distinguishing stylistic features for each translator are explored in both quantitative and qualitative terms. Overall word frequencies for each translator are examined, the stylistic features that are prominent in each case are identified, and their impact is considered. Special attention is also paid to the way those stylistic features that Boase-Beier (2005) calls ‘universal aspects of literature’ are treated by each translator. The next stage of the study involves the identification and sorting out of the patterns of stylistic features that consistently manifest in a translator’s work and examining how these patterns relate to their theoretical views and reflections. In the final stage, the stylistic profile of each translator is compiled by complementing the textual and contextual data together with each translator’s use of paratexts and extra-textual material

APPLICATION OF BED THICKNESS DISTRIBUTIONS IN LATE EOCENE-OLIGOCENE TURBIDITE DEPOSITS OF GREECE: SOME PRELIMINARY RESULTS

Μια απλή εφαρμογή των κατανομών πάχους στρωμάτων επιχειρήθηκε σε φυσικές τομές τουρβιδιτών Άνω Ηωκαινικής - Ολιγοκαινικής ηλικίας σε τρεις διαφορετικές περιοχές της Ελλάδας. Οι τρεις τομές που με^ήθηκαν βρίσκονται στο Ευηνοχώρι Αιτ/νίας (Δυτική Ελλάδα), το νησί της Καρπάθου (ΝΑ Ελλάδα) και το νησί της Λήμνου (ΒΑ Ελλάδα). Όλες οι τομές παρουσιάζουν παρόμοια ιζηματολογικά χαρακτηριστικά. Τρία είδη διαγραμμάτων χρησιμοποιήθηκαν: διάγραμμα λογαρίθμου- λογαρίθμου, λογαρίθμου-κλίμακας πιθανότητας και καμπύλης συχνότητας. Οι κατανομές του πάχους των στρωμάτων και στα τρία είδη διαγραμμάτων δείχνουν ομοιότητα ανάμεσα στους τουρβιδίτες Δυτικής και ΝΑ Ελλάδας και διαφορά τους από αυτούς της ΒΑ Ελλάδας. Το γεγονός αυτό πιθανά οφείλεται σε διαφορετική μορφολογία των λεκανών ιζηματογένεσης των τουρβιδιτών, λόγω διαφορετικών τεκτονικών διεργασιών.A simple application of bed thickness distributions was attempted in outcrops of Late Eocene-Oligocene turbidites in three dispersed localities of Greece. The three studied sections are located at Evinohori area (West Greece), Karpathos Island (SE Greece) and Limnos Island (NE Greece). All outcrops show similar sedimentological characteristics. Three types of plots were used: log-log, log-probability and frequency curves. Bed thickness data indicate similarity between West-SE Greece turbidites and discrimination from NE Greece turbidites which is attributed to different basin morphology due to different tectonic processes

THE USE OF STATISTICAL ANALYSIS IN THE LITHOSTRATIGRAPHY OF SUBMARINE FAN DEPOSITS. AN EXAMPLE FROM SOUTHEAST GREECE (KARPATHOS ISLAND)

Τα τελευταία χρόνια γίνεται προσπάθεια από πολλούς γεωλόγους στην κατεύθυνση της ποσοτικοποίησης και στατιστικής ανάλυσης των γεωλογικών δεδομένων. Ένα από τα πεδία αυτής της έρευνας είναι οι αποθέσεις υποθαλάσσιων ριπιδίων («φλύσχης»). Η στατιστική ανάλυση σε τέτοιου είδους αποθέσεις εστιάζεται κυρίως στο πάχος των στρωμάτων και έχει σαν στόχο τον προσδιορισμό παραμέτρων όπως το περιβάλλον απόθεσης, η πηγή τροφοδοσίας ιζήματος, οι υδροδυναμικές συνθήκες απόθεσης κτλ. Κύρια εργαλεία ανάλυσης είναι οι λογαριθμικές κατανομές του πάχους των στρωμάτων. Στην παρουσίαση δίνονται παραδείγματα διαφόρων ειδών λογαριθμικών κατανομών που έχουν προταθεί τα τελευταία χρόνια, καθώς και ένα παράδειγμα εφαρμογής τους σε αποθέσεις υποθαλάσσιων ριπιδίων στη ΝΑ Ελλάδα (Κάρπαθος).Examples of various types of statistical analysis of submarine fan bed thickness distributions that have been proposed in the past are reported, as well as an example of their application in Late Eocene-Oligocene submarine fan deposits of SE Greece (Karpathos Island). Generally, the sandstone bed thickness data measured in two outcrops of Karpathos submarine fans seems to follow power law (fractal) cumulative distributions. A deviation from the power law was observed as amalgamationprocedures become more frequent. These observations gave important information about Tertiary turbidite sedimentation in the area which probably was punctuated and had a single main sediment source. Information taken from statistical analysis of submarine fans bed thickness data has immediate applicability in hydrocarbon exploration because sandstones constitute ideal reservoirs

APPLICATION OF BED THICKNESS DISTRIBUTIONS IN TURBIDITE DEPOSITS OF LEMNOS ISLAND, NE GREECE

Οι αποθέσεις υποθαλάσσιων ριπιδίων στο νησί της Λήμνου, στην ΒΑ Ελλάδα, παρέχουν μια πρώτης τάξεως ευκαιρία για την διερεύνηση της επίδρασης διαδικασιών όπως, η διάβρωση και η συμπαγοποίηση στην α)„λαγή του σχήματος μιας κατανομής τύπου power-law. Η κατανομή των παχών σε δύο φυσικές τομές τουρβιδιτικών αποθέσεων ηλικίας Αν. Ηωκαίνου- Κ. Ολιγοκαίνου προσδιορίστηκαν στατιστικά. Τα ιζήματα της τομής Ι στα ΝΑ τμήματα του νησιού έχουν ερμηνευθεί σαν αποθέσεις εξωτερικού ριπιδίου ενώ τα ιζήματα της τομής 2 σαν αποθέσεις εσωτερικού ριπιδίου. Οι δύο τομές έχουν καλή συσχέτιση με την κατανομή power-law ενισχύοντας την υπόθεση ότι αποκλίσεις από την power-law κατανομή μπορούν να θεωρηθούν σαν ενδείξεις για διάβρωση και συμπαγοποίηση. Η βασική διαφορά των δύο μελετηθέντων φυσικών τομών είναι ότι ο εκθέτης της κατανομής power-law μειώνεται απότομα από την τομή 1 στην τομή 2 επιβεβαιώνοντας την άποψη ότι είναι ανάλογος με τον διαθέσιμο χώρο ιζηματογένεσης.The submarine fan deposits in Lemnos Island, of the NE Greece provide a perfect opportunity to investigate the influence of processes such as erosion and bed amalgamation in the alternation of the shape of a power-law cumulative frequency distribution. The bed thickness distribution in two outcrops of late Eocene to early Oligocene turbidite deposits that correspond to different sub-environment, has been assessed statistically. Sediments of the outcrop 1 at the SE parts of the Lemnos Island interpreted as outer fan deposits and sediments of the outcrop 2 located at the NE parts of the island as inner fan deposits show both a good fit to the power-law, amplifying the hypothesis that departures from power-law statistics might be used as evidence of erosion and bed amalgamation. The main difference between these two outcrops is that the power law exponent decreases abruptly from outcrop 1 to outcrop 2, confirming with the aspect that the power law exponent can be considered as a good indicator for the available sedimentary space

APPLICATION OF BED THICKNESS DISTRIBUTIONS IN LATE EOCENE-OLIGOCENE TURBIDITE DEPOSITS OF GREECE: SOME PRELIMINARY RESULTS

Μια απλή εφαρμογή των κατανομών πάχους στρωμάτων επιχειρήθηκε σε φυσικές τομές τουρβιδιτών Άνω Ηωκαινικής - Ολιγοκαινικής ηλικίας σε τρεις διαφορετικές περιοχές της Ελλάδας. Οι τρεις τομές που με^ήθηκαν βρίσκονται στο Ευηνοχώρι Αιτ/νίας (Δυτική Ελλάδα), το νησί της Καρπάθου (ΝΑ Ελλάδα) και το νησί της Λήμνου (ΒΑ Ελλάδα). Όλες οι τομές παρουσιάζουν παρόμοια ιζηματολογικά χαρακτηριστικά. Τρία είδη διαγραμμάτων χρησιμοποιήθηκαν: διάγραμμα λογαρίθμου- λογαρίθμου, λογαρίθμου-κλίμακας πιθανότητας και καμπύλης συχνότητας. Οι κατανομές του πάχους των στρωμάτων και στα τρία είδη διαγραμμάτων δείχνουν ομοιότητα ανάμεσα στους τουρβιδίτες Δυτικής και ΝΑ Ελλάδας και διαφορά τους από αυτούς της ΒΑ Ελλάδας. Το γεγονός αυτό πιθανά οφείλεται σε διαφορετική μορφολογία των λεκανών ιζηματογένεσης των τουρβιδιτών, λόγω διαφορετικών τεκτονικών διεργασιών.A simple application of bed thickness distributions was attempted in outcrops of Late Eocene-Oligocene turbidites in three dispersed localities of Greece. The three studied sections are located at Evinohori area (West Greece), Karpathos Island (SE Greece) and Limnos Island (NE Greece). All outcrops show similar sedimentological characteristics. Three types of plots were used: log-log, log-probability and frequency curves. Bed thickness data indicate similarity between West-SE Greece turbidites and discrimination from NE Greece turbidites which is attributed to different basin morphology due to different tectonic processes