Selective cleavage of 28S rRNA variable regions V3 and V13 in myeloid leukemia cell apoptosis

AbstractVigorous apoptosis is induced 3–4 hours after activation of cAMP-dependent protein kinase I in the rat myeloid leukemia cell line IPC-81 [J. Cell. Physiol. 146 (1991) 73-80]. We will report a novel feature of apoptosis in these cells: a selective and temporarily ordered cleavage within the two largest 28S ribosomal RNA variable regions (V3 and V13). The cleavage of 28S rRNA coincided with internucleosomal DNA fragmentation and cessation of cellular protein synthesis. The implication of 28S variable regions as targets in apoptosis is a clue to the function of these so far apparently superfluous parts of eukaryotic ribosomes

In Vivo Activation of cAMP Signaling Induces Growth Arrest and Differentiation in Acute Promyelocytic Leukemia

Differentiation therapy for acute myeloid leukemia uses transcriptional modulators to reprogram cancer cells. The most relevant clinical example is acute promyelocytic leukemia (APL), which responds dramatically to either retinoic acid (RA) or arsenic trioxide (As2O3). In many myeloid leukemia cell lines, cyclic adenosine monophosphate (cAMP) triggers growth arrest, cell death, or differentiation, often in synergy with RA. Nevertheless, the toxicity of cAMP derivatives and lack of suitable models has hampered trials designed to assess the in vivo relevance of theses observations. We show that, in an APL cell line, cAMP analogs blocked cell growth and unraveled As2O3-triggered differentiation. Similarly, in RA-sensitive or RA-resistant mouse models of APL, continuous infusions of 8-chloro-cyclic adenosine monophosphate (8-Cl-cAMP) triggered major growth arrest, greatly enhanced both spontaneous and RA- or As2O3-induced differentiation and accelerated the restoration of normal hematopoiesis. Theophylline, a well-tolerated phosphodiesterase inhibitor which stabilizes endogenous cAMP, also impaired APL growth and enhanced spontaneous or As2O3-triggered cell differentiation in vivo. Accordingly, in an APL patient resistant to combined RA–As2O3 therapy, theophylline induced blast clearance and restored normal hematopoiesis. Taken together, these results demonstrate that in vivo activation of cAMP signaling contributes to APL clearance, independently of its RA-sensitivity, thus raising hopes that other myeloid leukemias may benefit from this therapeutic approach

A giant comet-like cloud of hydrogen escaping the warm Neptune-mass exoplanet GJ 436b

Exoplanets orbiting close to their parent stars could lose some fraction of their atmospheres because of the extreme irradiation. Atmospheric mass loss primarily affects low-mass exoplanets, leading to suggest that hot rocky planets might have begun as Neptune-like, but subsequently lost all of their atmospheres; however, no confident measurements have hitherto been available. The signature of this loss could be observed in the ultraviolet spectrum, when the planet and its escaping atmosphere transit the star, giving rise to deeper and longer transit signatures than in the optical spectrum. Here we report that in the ultraviolet the Neptune-mass exoplanet GJ 436b (also known as Gliese 436b) has transit depths of 56.3 +/- 3.5% (1 sigma), far beyond the 0.69% optical transit depth. The ultraviolet transits repeatedly start ~2 h before, and end >3 h after the ~1 h optical transit, which is substantially different from one previous claim (based on an inaccurate ephemeris). We infer from this that the planet is surrounded and trailed by a large exospheric cloud composed mainly of hydrogen atoms. We estimate a mass-loss rate in the range of ~10^8-10^9 g/s, which today is far too small to deplete the atmosphere of a Neptune-like planet in the lifetime of the parent star, but would have been much greater in the past.Comment: Published in Nature on 25 June 2015. Preprint is 28 pages, 12 figures, 2 table

LA PROTEINE ANTI-APOPTOTIQUE BCL-2 ET LA PROTEINE PRION CELLULAIRE SONT DES PARTENAIRES DE LA LECTINE ENDOGENE CBP70 DANS DES LIGNEES DE CELLULES LEUCEMIQUES HUMAINES

PARIS5-BU Saints-Pères (751062109) / SudocSudocFranceF

Technologie des anneaux en schiste dans le groupe de Blicquy/Villeneuve-Saint-Germain à Vaux-et-Borset (Hesbaye, Belgique) : interférences de sous-systèmes techniques

The Blicquy/Villeneuve-Saint-Germain settlement of Vaux-et-Borset (Liege province, Belgium) has produced a remarkable corpus of material relating to the manufacture of schist rings. The data are of considerable importance in terms of both quantity and quality. Through a typo-technological study it is possible to distinguish the various manufacturing sequences employed. Using these results, the authors have undertaken a programme of experimental study and microscopic analysis on both archaeological and experimental artefacts, with a view to reconstructing the know-how and the tools (flint, sandstone and schist) involved in the different stages of working this soft stone. These studies lead to the formulation of major hypotheses on the importance of the schist technical subsystem in the definition of the Blicquy /Villeneuve-Saint-Germain group at Vaux-et- Borset.Le village du groupe de Blicquy/Villeneuve-Saint-Germain de Vaux-et-Borset (province de Liège, Belgique) a livré un corpus remarquable de vestiges issus de la fabrication ď anneaux en schiste. Cet ensemble documentaire s'est révélé très pertinent numériquement et qualitativement. L'étude typotechnologique a permis de différencier les schémas opératoires des fabrications mises en oeuvre. A partir de ces résultats, les auteurs ont mené un programme d'analyses expérimentales et microscopiques combinées sur les pièces archéologiques et expérimentales portant sur la reconstitution des savoir-faire et des dispositifs instrumentaux (outils en silex, en grès et en schiste) impliqués dans cet artisanat de la pierre tendre, aux différentes étapes de sa réalisation. Ces travaux aboutissent à la formulation d'hypothèses conséquentes concernant la spécificité du sous-système technique du travail du schiste dans la définition de l'industrie du groupe de Blicquy /Villeneuve Saint -Germain à Vaux-et-Borset.Burnez-Lanotte Laurence, Caspar Jean-Paul, Vanguestaine Michel. Technologie des anneaux en schiste dans le groupe de Blicquy/Villeneuve-Saint-Germain à Vaux-et-Borset (Hesbaye, Belgique) : interférences de sous-systèmes techniques. In: Bulletin de la Société préhistorique française, tome 102, n°3, 2005. pp. 551-596

The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus

International audienceRetinoic acid is a vitamin A derivative with striking effects on development and cell differentiation. Several nuclear retinoic acid receptors (RARs), acting as ligand-inducible transcription factors, have been characterized and indirect evidence suggests that they have distinct roles. One of the most intriguing properties of retinoic acid is its ability to induce in vivo differentiation of acute promyelocytic leukaemia (APL) cells into mature granulocytes, leading to morphological complete remissions. Because the RAR alpha gene maps to chromosome 17q21 (ref. 14), close to the t(15;17) (q21-q11-22) translocation specifically associated with APL, we analysed RAR alpha gene structure and expression in APL cells. We report here that, in one APL-derived cell line, the RAR alpha gene has been translocated to a locus, myl, on chromosome 15, resulting in the synthesis of a myl/RAR alpha fusion messenger RNA. Using two probes located on either side of the cloned breakpoint, we have found genomic rearrangements of one or other locus in six patients out of eight, demonstrating that the RAR alpha and/or myl genes are frequently rearranged in APL and the breakpoints are clustered. These findings strongly implicate retinoic acid receptor alpha in leukaemogenesis