GEOMORPHOLOGY, SEDIMENTOLOGY AND GEOCHEMISTRY IN THE MARINE AREA BETWEEN SIFNOS AND KIMOLOS ISLANDS, GREECE

Στην ελάχιστα μελετημένη θαλάσσια περιοχή μεταξύ των νησιών Σίφνου και Κιμώλου πραγματοποιήθηκε μια εκτεταμένη ωκεανογραφική μελέτη, με σκοπό την καταγραφή της υποθαλάσσιας μορφολογίας και των χαρακτηριστικών των επιφανειακών ιζημάτων, καθώς και της πηγής προέλευσης αυτών. Έγιναν καταγραφές με πολυδεσμικό βυθόμετρο και δειγματοληψίες επιφανειακών ιζημάτων με box corer με το Ω/Κ Αιγαίο και ακολούθησαν αναλύσεις μεγέθους κόκκων, ορυκτολογίας και γεωχημείας. Ένα μεγάλο βαθυμετρικό βύθισμα εντοπίστηκε βόρεια της Κιμώλου, με μέγιστο βάθος 743 μ., που συγκεντρώνει λεπτόκοκκα ιζήματα. Η κατανομή των ιζημάτων ως προς το μέγεθος κόκκων χαρακτηρίζεται από σταδιακή μείωση του μεγέθους από νότο προς βορρά. Η ορυκτολογική σύσταση περιλαμβάνει ασβεστίτη, Mg-ασβεστίτη, αραγωνίτη, δολομίτη, χαλαζία, Κ-άστριους, πλαγιόκλαστα, αμφίβολους και αργιλικά ορυκτά. Οι κύριες ιζηματολογικές επαρχίες που αναγνωρίστηκαν είναι 1) η ρηχή περιοχή πλησίον της Κιμώλου, με υψηλό περιεχόμενο σε Si, Al, K, Rb και Ba, 2) η βαθιά περιοχή δυτικά της Σίφνου, όπου εμφανίζεται και το μεγάλο βύθισμα, που χαρακτηρίζεται από υψηλό περιεχόμενο σε Fe, Ti, Na, Mg, S, Cr, Cu, Ni, V, Zn και 3) το στενό μεταξύ Σίφνου και Κιμώλου, με υψηλότερο περιεχόμενο σε Ca, S και Sr. Στο βύθισμα αυτό, παρατηρήθηκε σημαντικός εμπλουτισμός των ιζημάτων σε μαγγάνιο, ενώ τα οξείδια του Mn φαίνεται να προσροφούν διάφορα μέταλλα.An extensive oceanographic survey was conducted in the marine area between Kimolos and Sifnos Islands, a rather poorly-studied sector of the Aegean Sea, in order to gain better understanding of submarine geomorphological features and associated sediment provenance. Multi-beam bathymetry and surface sediment sampling with a box corer were carried out on board R/V Aegaeo, followed by grain-size analysis, XRD and XRF measurements. A large circular depression was identified north of Kimolos reaching a water depth of 743 m, filled with fine grained sediments. Surface sediment distribution is characterized by gradual decrease in grain-size from silty sand to silt in a S-N direction. The mineralogical composition comprises calcite, Mgcalcite, aragonite, dolomite, quartz, K feldspars, plagioclase, amphiboles and clay minerals. Major sediment provinces identified were: (i) the shallow sector proximal to Kimolos, characterized by higher contents in Si, Al, K, Rb and Ba; (ii) the deep area west of Sifnos, including the large depression, characterized by higher contents in Fe, Ti, Na, Mg, S, Cr, Cu, Ni, V, Zn; and (iii) the south passage between Kimolos and Sifnos, which exhibits higher Ca, S, and Sr contents. Manganese enrichment was observed in and around the bathymetric depression, where Mn oxides act efficiently as scavengers of a suite of metals

The Hsc/Hsp70 Co-Chaperone Network Controls Antigen Aggregation and Presentation during Maturation of Professional Antigen Presenting Cells

The maturation of mouse macrophages and dendritic cells involves the transient deposition of ubiquitylated proteins in the form of dendritic cell aggresome-like induced structures (DALIS). Transient DALIS formation was used here as a paradigm to study how mammalian cells influence the formation and disassembly of protein aggregates through alterations of their proteostasis machinery. Co-chaperones that modulate the interplay of Hsc70 and Hsp70 with the ubiquitin-proteasome system (UPS) and the autophagosome-lysosome pathway emerged as key regulators of this process. The chaperone-associated ubiquitin ligase CHIP and the ubiquitin-domain protein BAG-1 are essential for DALIS formation in mouse macrophages and bone-marrow derived dendritic cells (BMDCs). CHIP also cooperates with BAG-3 and the autophagic ubiquitin adaptor p62 in the clearance of DALIS through chaperone-assisted selective autophagy (CASA). On the other hand, the co-chaperone HspBP1 inhibits the activity of CHIP and thereby attenuates antigen sequestration. Through a modulation of DALIS formation CHIP, BAG-1 and HspBP1 alter MHC class I mediated antigen presentation in mouse BMDCs. Our data show that the Hsc/Hsp70 co-chaperone network controls transient protein aggregation during maturation of professional antigen presenting cells and in this way regulates the immune response. Similar mechanisms may modulate the formation of aggresomes and aggresome-like induced structures (ALIS) in other mammalian cell types

Inhibition of Proliferation and Induction of Apoptosis in Multiple Myeloma Cell Lines by CD137 Ligand Signaling

BACKGROUND: Multiple myeloma (MM) is a malignancy of terminally-differentiated plasma cells, and the second most prevalent blood cancer. At present there is no cure for MM, and the average prognosis is only three to five years. Current treatments such as chemotherapy are able to prolong a patient's life but rarely prevent relapse of the disease. Even hematopoietic stem cell transplants and novel drug combinations are often not curative, underscoring the need for a continued search for novel therapeutics. CD137 and its ligand are members of the Tumor Necrosis Factor (TNF) receptor and TNF superfamilies, respectively. Since CD137 ligand cross-linking enhances proliferation and survival of healthy B cells we hypothesized that it would also act as a growth stimulus for B cell cancers. METHODOLOGY/PRINCIPAL FINDINGS: Proliferation and survival of B cell lymphoma cell lines were not affected or slightly enhanced by CD137 ligand agonists in vitro. But surprisingly, they had the opposite effects on MM cells, where CD137 ligand signals inhibited proliferation and induced cell death by apoptosis. Furthermore, secretion of the pro-inflammatory cytokines, IL-6 and IL-8 were also enhanced in MM but not in non-MM cell lines in response to CD137 ligand agonists. The secretion of these cytokines in response to CD137 ligand signaling was consistent with the observed activation of the classical NF-kappaB pathway. We hypothesize that the induction of this pathway results in activation-induced cell death, and that this is the underlying mechanism of CD137-induced MM cell death and growth arrest. CONCLUSIONS/SIGNIFICANCE: These data point to a hitherto unrecognized role of CD137 and CD137 ligand in MM cell biology. The selective inhibition of proliferation and induction of cell death in MM cells by CD137 ligand agonists may also warrant a closer evaluation of their therapeutic potential