Acriflavine targets oncogenic STAT5 signaling in myeloid leukemia cells

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Significance of Frequencies, Compositions, and/or Antileukemic Activity of (DC-stimulated) Invariant NKT, NK and CIK Cells on the Outcome of Patients With AML, ALL and CLL

Invariant natural killer T (iNKT)/natural killer (NK)/cytokine-induced killer (CIK) cells are important for immune surveillance. (I) Novel combinations of antibody 6B11 (targeting the V alpha 24-J alpha 18-invariant T-cell receptor) with CD4/CD8/CD1d/V alpha 24 for iNKT subset detection and "T/NK cell-like"-iNKT subsets were defined. Compared with healthy peripheral blood mononuclear cells (MNC) (significantly) lower proportions of iNKT cells (6B11 (+)/6B11 (+)CD3 (+)/6B11 (+)CD161(+)), NK cells (CD3(-)CD56(+)/CD3(-)CD161(+)), and CIK cells (CD3(+)CD56(+)/CD3(+)CD161(+)) were found in peripheral blood MNC from acute myeloid (AML)/acute myeloid, lymphoid (ALL)/chronic lymphoid leukemia (CLL) patients in acute disease stages. Subtyping of iNKT cells revealed (significantly) higher proportions of CD3(+) T cells and CD161(+) NK cells in AML/ALL/CLL expressing 6B11 compared with healthy MNC. Prognostic evaluations showed higher proportions of iNKT/NK/CIK cells in favorable AML subgroups (younger age, primary, no extramedullary disease, achievement/maintenance of complete remission) or adult ALL and CLL patients. (II) iNKT/NK/CIK cell frequencies increased after (vs. before) mixed lymphocyte cultures of T-cell-enriched immune reactive cells stimulated with MNC/whole blood with or without pretreatment with "cocktails" (dendritic cells generating methods/kits inducing blasts' conversion to leukemia-derived dendritic cells from AML patients). Individual "cocktails" leading to "highest" iNKT cell frequencies could be defined. Antileukemic blast lytic activity correlated significantly with frequencies of iNKT/NK/CIK cells. In summary healthy MNC show significantly more iNKT/NK/CIK cells compared with AML/ALL/CLL MNC, a shift in the iNKT cell composition is seen in healthy versus leukemic samples and iNKT/NK/CIK cell-proportions in AML/ALL/CLL MNC samples correlate with prognosis. "Cocktail"-treated AML blasts lead to higher iNKT/NK/CIK cell frequencies and samples with antileukemic activity show significantly higher frequencies of iNKT/NK/CIK cells. Proportions of iNKT/NK/CIK cells should regularly be evaluated in AML/ALL/CLL diagnosis panels for quantitative/prognostic estimation of individual patients' anti leukemic potential and their role in dendritic cells/leukemia-derived dendritic cells triggered immune surveillance

Continent elevation, mountains, and erosion : freeboard implications

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): B05410, doi:10.1029/2008JB006176.To the simplest approximation, Earth's continental crust is a floating aggregate on the planet's surface that is first attracted to subduction zones and, upon arrival, thickened by mountain building (then producing some extension). Thickened regions are thinned again by erosion. A comparison between 65 Ma and the present shows that the modern state is significantly more mountainous. An estimated average continental elevation increase relative to average ocean floor depth of about 54 m and sea level decrease relative to the ocean floor of about 102 m add up to a 156-m increase of continent elevation over sea level since 65 Ma. Both are affected most strongly by the roughly 1.7% continent surface area decrease caused by Cenozoic mountain building. This includes contributions from erosion. Volumes of sediments in deltas and submarine fans indicate an average thickness of 371 m deposited globally in the ocean basins since 65 Ma. This relatively large change of continent area over a short span of Earth history has significant consequences. Extrapolating, if continent area change exceeded 5% in the past, either severe erosion or flooded continents occurred. If continent elevation (freeboard) remains at the present value of a few hundred meters, the past continent-ocean area ratio might have been quite different, depending on earlier volumes of continental crust and water. We conclude that, along with the ages of ocean basins, continental crustal thickening exerts a first-order control on the global sea level over hundreds of million years

Sedimentary cycles in a Mesoproterozoic aeolian erg-margin succession: Mangabeira Formation, Espinhaço Supergroup, Brazil

Aeolian systems were abundant and widespread in the early Proterozoic, post-2.2 Ga. However, the majority of aeolian successions of such great age are intensely deformed and are preserved only in a fragmentary state meaning that, hitherto, few attempts have been made to apply a sequence stratigraphic approach to determine mechanisms of aeolian construction, accumulation and preservation in such systems. The Mangabeira Formation is a well preserved Mesoproterozoic erg successions covering part of the São Francisco Craton, northeastern Brazil. The lower unit of the Mangabeira Formation (~ 500 m thick) comprises aeolian deposits of dune, interdune, and sand-sheet origin, as well as some of waterlain origin. These deposits are organized into vertically stacked depositional cycles, each 6 to 20 m thick, and characterized by aeolian sandsheet and waterlain deposits succeeded by aeolian dune and interdune deposits indicative of a drying-upward trend. Aeolian cross-strata exhibit a mean dip direction to the north. Each of these cycles likely arose in response to climatic oscillation from relatively humid to arid conditions, possibly related to orbital forcing. The lower unit of the Mangabeira Formation comprises up to 14 erg sequences. The accumulation and preservation of each was determined by the relative rate of water-table rise and the availability of sand for aeolian transport, both of which changed through time, resulting in the preservation of a succession of repeated drying-upward cycles

Microfossils from the late Mesoproterozoic – early Neoproterozoic Atar/El Mreïti Group, Taoudeni Basin, Mauritania, northwestern Africa

The well-preserved Meso-Neoproterozoic shallow marine succession of the Atar/El Mreïti Group, in the Taoudeni Basin, Mauritania, offers a unique opportunity to investigate the mid-Proterozoic eukaryotic record in Western Africa. Previous investigations focused on stromatolites, biomarkers, chemostratigraphy and palaeoredox conditions. However, only a very modest diversity of organic-walled microfossils (acritarchs) has been documented. Here, we present a new, exquisitely well-preserved and morphologically diverse assemblage of organic-walled microfossils from three cores drilled through the Atar/El Mreïti Group. A total of 48 distinct entities including 11 unambiguous eukaryotes (ornamented and process-bearing acritarchs), and 37 taxonomically unresolved taxa (including 9 possible eukaryotes, 6 probable prokaryotes, and 22 other prokaryotic or eukaryotic taxa) were observed. Black shales preserve locally abundant fragments of benthic microbial mats. We also document one of the oldest records of Leiosphaeridia kulgunica, a species showing a pylome interpreted as a sophisticated circular excystment structure, and one of the oldest records of Trachyhystrichosphaera aimika and T. botula, two distinctive process-bearing acritarchs present in well-dated 1.1 Ga formations at the base of the succession. The general assemblage composition and the presence of three possible index fossils (A. tetragonala, S. segmentata and T. aimika) support a late Mesoproterozoic to early Neoproterozoic (Tonian) age for the Atar/El Mreïti Group, consistent with published lithostratigraphy, chemostratigraphy and geochronology. This study provides the first evidence for a moderately diverse eukaryotic life, at least 1.1 billion years ago in Western Africa. Comparison with coeval worldwide assemblages indicate that a broadly similar microbial biosphere inhabited (generally redox-stratified) oceans, placing better time constraints on early eukaryote palaeogeography and biostratigraphy

Quaternary uplift rates of the Central Anatolian Plateau, Turkey: insights from cosmogenic isochron-burial nuclide dating of the Kızılırmak River terraces

The Central Anatolian Plateau (CAP) in Turkey is a relatively small plateau (300 × 400 km) with moderate average elevations of ∼1 km situated between the Pontide and Tauride orogenic mountain belts. Kızılırmak, which is the longest river (1355 km) within the borders of Turkey, flows within the CAP and slowly incises into lacustrine and volcaniclastic units before finally reaching the Black Sea. We dated the Cappadocia section of the Kızılırmak terraces in the CAP by using cosmogenic burial and isochron-burial dating methods with 10Be and 26Al as their absolute dating can provide insight into long-term incision rates, uplift and climatic changes. Terraces at 13, 20, 75 and 100 m above the current river indicate an average incision rate of 0.051 ± 0.01 mm/yr (51 ± 1 m/Ma) since ∼1.9 Ma. Using the base of a basalt fill above the modern course of the Kızılırmak, we also calculated 0.05–0.06 mm/yr mean incision and hence rock uplift rate for the last 2 Ma. Although this rate might be underestimated due to normal faulting along the valley sides, it perfectly matches our results obtained from the Kızılırmak terraces. Although up to 5–10 times slower, the Quaternary uplift of the CAP is closely related to the uplift of the northern and southern plateau margins respectively