The Ks-band Tully-Fisher Relation - A Determination of the Hubble Parameter from 218 ScI Galaxies and 16 Galaxy Clusters

The value of the Hubble Parameter (H0) is determined using the morphologically type dependent Ks-band Tully-Fisher Relation (K-TFR). The slope and zero point are determined using 36 calibrator galaxies with ScI morphology. Calibration distances are adopted from direct Cepheid distances, and group or companion distances derived with the Surface Brightness Fluctuation Method or Type Ia Supernova. Distances are determined to 16 galaxy clusters and 218 ScI galaxies with minimum distances of 40.0 Mpc. From the 16 galaxy clusters a weighted mean Hubble Parameter of H0=84.2 +/-6 km s-1 Mpc-1 is found. From the 218 ScI galaxies a Hubble Parameter of H0=83.4 +/-8 km s-1 Mpc-1 is found. When the zero point of the K-TFR is corrected to account for recent results that find a Large Magellanic Cloud distance modulus of 18.39 +/-0.05 a Hubble Parameter of 88.0 +/-6 km s-1 Mpc-1 is found. A comparison with the results of the Hubble Key Project (Freedman et al 2001) is made and discrepancies between the K-TFR distances and the HKP I-TFR distances are discussed. Implications for Lamda-CDM cosmology are considered with H0=84 km s-1 Mpc-1. (Abridged)Comment: 37 pages including 12 tables and 7 figures. Final version accepted for publication in the Journal of Astrophysics & Astronom

Evidence for a mitochondrial localization of the retinoblastoma protein

<p>Abstract</p> <p>Background</p> <p>The retinoblastoma protein (Rb) plays a central role in the regulation of cell cycle, differentiation and apoptosis. In cancer cells, ablation of Rb function or its pathway is a consequence of genetic inactivation, viral oncoprotein binding or deregulated hyperphosphorylation. Some recent data suggest that Rb relocation could also account for the regulation of its tumor suppressor activity, as is the case for other tumor suppressor proteins, such as p53.</p> <p>Results</p> <p>In this reported study, we present evidence that a fraction of the total amount of Rb protein can localize to the mitochondria in proliferative cells taken from both rodent and human cells. This result is also supported by the use of Rb siRNAs, which substantially reduced the amount of mitochondrial Rb, and by acellular assays, in which [³⁵S]-Methionine-labeled Rb proteins bind strongly to mitochondria isolated from rat liver. Moreover, endogenous Rb is found in an internal compartment of the mitochondria, within the inner-membrane. This is consistent with the protection of Rb from alkaline treatment, which destroys any interaction of proteins that are weakly bound to mitochondria.</p> <p>Conclusion</p> <p>Although a few data regarding an unspecific cytosolic localization of Rb protein have been reported for some tumor cells, our results are the first evidence of a mitochondrial localization of Rb. The mitochondrial localization of Rb is observed in parallel with its classic nuclear location and paves the way for the study of potential as-yet-unknown roles of Rb at this site.</p

Cooperation between Engulfment Receptors: The Case of ABCA1 and MEGF10

The engulfment of dying cells is a specialized form of phagocytosis that is extremely conserved across evolution. In the worm, it is genetically controlled by two parallel pathways, which are only partially reconstituted in mammals. We focused on the recapitulation of the CED-1 defined pathway in mammalian systems. We first explored and validated MEGF10, a novel receptor bearing striking structural similarities to CED-1, as a bona fide functional ortholog in mammals and hence progressed toward the analysis of molecular interactions along the corresponding pathway. We ascertained that, in a system of forced expression by transfection, MEGF10 function can be modulated by the ATP binding cassette transporter ABCA1, ortholog to CED-7. Indeed, the coexpression of either a functional or a mutant ABCA1 exerted a transdominant positive or negative modulation on the MEGF10-dependent engulfment. The combined use of biochemical and biophysical approaches indicated that this functional cooperation relies on the alternate association of these receptors with a common partner, endogenously expressed in our cell system. We provide the first working model structuring in mammals the CED-1 dependent pathway

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Contribution a l'etude des genes actives pendant la differenciation erythrocytaire terminale : regulation du gene humain codant la porphobilinogene desaminase

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

ETUDE DE LA PROTEINE RB DANS L'APOPTOSE INDUITE PAR INACTIVATION DE L'ANTIGENE T DU VIRUS SV40

L'APOPTOSE ET LA SENESCENCE REPLICATIVE SONT DEUX FORMES D'ARRET IRREVERSIBLE DE LA PROLIFERATION CELLULAIRE. L'APOPTOSE EST UNE MORT CELLULAIRE PHYSIOLOGIQUE TANDIS QUE LA SENESCENCE REFLETE LA CAPACITE PROLIFERATIVE LIMITEE DES CELLULES. AFIN D'ETUDIER LE DETERMINISME MOLECULAIRE DE L'ENGAGEMENT DES CELLULES DANS L'APOPTOSE OU LA SENESCENCE, J'AI UTILISE DES FIBROBLASTES DE RAT IMMORTALISES PAR UN MUTANT THERMOSENSIBLE DE L'ANTIGENE T DU VIRUS SV40. A TEMPERATURE RESTRICTIVE, L'ANTIGENE T EST INACTIVE ET LIBERE LA PROTEINE P53 QUI PEUT INDUIRE L'ARRET DE PROLIFERATION ET L'APOPTOSE. LE PHENOTYPE ASSOCIE A LA PERTE DE L'ETAT IMMORTALISE VARIE EN FONCTION DE LA LIGNEE ETUDIEE : LES CELLULES DE LA LIGNEE RETSAF MEURENT PAR APOPTOSE ALORS QUE LES CELLULES DE LA LIGNEE RETSA15 DEVIENNENT SENESCENTES. OUTRE LA PROTEINE P53, L'ANTIGENE T INHIBE LA PROTEINE ONCOSUPPRESSIVE RB. CETTE PROTEINE EST UN REGULATEUR NEGATIF DU FACTEUR DE TRANSCRIPTION E2F-1 QUI FAVORISE L'ENTREE DES CELLULES EN PHASE S DU CYCLE CELLULAIRE AINSI QUE L'EFFET PRO-APOPTOTIQUE DE P53. L'ETUDE COMPARATIVE DES CELLULES RETSAF ET RETSA15 M'A PERMIS D'OBSERVER QUE LA PROTEINE RB EST REGULEE DE FACON DIFFERENTE DANS CES DEUX LIGNEES, A LA FOIS PAR DES PROCESSUS DE PHOSPHORYLATION ET DE CLIVAGE PROTEOLYTIQUE. A TEMPERATURE RESTRICTIVE, L'INACTIVATION DE LA PROTEINE RB PAR PHOSPHORYLATION DANS LES CELLULES RETSAF FAVORISERAIT L'ACTIVITE DU FACTEUR E2F-1, LA PROGRESSION DES CELLULES DANS LE CYCLE CELLULAIRE ET PEUT ETRE L'APOPTOSE. DE FACON SURPRENANTE, LE CLIVAGE DE LA PROTEINE RB PAR DES PROTEASES A CYSTEINE (CASPASES), TELLES QUE LES CASPASES-6 ET -7, FAVORISERAIT LA SURVIE DES CELLULES RETSA15 ET LEUR ARRET DANS LE CYCLE CELLULAIRE. EN ACCORD AVEC CETTE OBSERVATION, J'AI MIS EN EVIDENCE QUE LA PROTEINE BCL-2, UN INHIBITEUR UNIVERSEL DE L'APOPTOSE, FAVORISE LE CLIVAGE DE RB. CETTE PROPRIETE DE BCL-2 POURRAIT PARTICIPER A UNE VOIE D'INHIBITION DE L'APOPTOSE ENCORE JAMAIS DECRITE.PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Production et élimination des radicaux libres : les tests cellulaires

International audienc

Tickets for p53 journey among organelles

International audienc

Cloning and functional characterization of the rat α2B-adrenergic receptor gene promoter region: Evidence for binding sites for erythropoiesis-related transcription factors GATA1 and NF-E2

International audienceIn the rat, the alpha2B-adrenergic receptor (alpha2B-AR) is encoded by the rat non-glycosylated (RNG) gene and is primarily expressed in the kidney, brain and liver of adult animals. High levels of alpha2B-AR are also found during fetal life in the placenta, liver and blood, where it is borne by cells of the erythropoietic lineage. As a first step to define the mechanisms responsible for the spatio-temporal pattern of alpha2B-AR expression, a genomic fragment containing 2.8 kb of the 5'-flanking region, the ORF and approximately 20 kb of the 3'-flanking region of the RNG gene was isolated. RNase protection assays performed on RNA from placenta or kidney using a series of riboprobes permitted to locate the transcription start site 372 bases upstream from the start codon. Transient transfection of various cells, including rat proximal tubule in primary culture, with constructs containing luciferase as a reporter gene demonstrated that: (i) the 5'-flanking region exhibited a strong and sense-dependent transcriptional activity and (ii) the 332 bp fragment (-732/-401 relative to the start codon), which lacks a TATA box but contains Sp1 sites, is sufficient to drive expression. Analysis of chromatin susceptibility to DNaseI digestion identified two hypersensitive sites (HS1 and HS2) located 1.7 and 1.0 kb, respectively, upstream from ATG and containing recognition sequences for erythroid transcription factors. EMSA showed specific binding of GATA1 and NF-E2 to these elements. Taken together, the results suggest that the chromatin environment in the vicinity of these boxes plays a critical role for alpha2B-AR expression during fetal life

reaper and bax initiate two different apoptotic pathways affecting mitochondria and antagonized by bcl-2 in Drosophila

International audiencebcl-2 was the first regulator of apoptosis shown to be involved in oncogenesis. Subsequent studies in mammals, in the nematode and in Drosophila revealed wide evolutionary conservation of the regulation of apoptosis. Although dbok/debcl, a member of the bcl-2 gene family described in Drosophila, shows pro-apoptotic activities, no anti-apoptotic bcl-2 family gene has been studied in Drosophila. We have previously reported that the human anti-apoptotic gene bcl-2 is functional in Drosophila, suggesting that the fruit fly shares regulatory mechanisms with vertebrates and the nematode, involving anti-apoptotic members of the bcl-2 family. We now report that bcl-2 suppresses rpr-induced apoptosis in Drosophila. Additionally, we have compared features of bax-and rpr-induced apoptosis. Flow cytometry analysis of wing disc cells demonstrate that both killers trigger mitochondrial defects. Interestingly, bcl-2 suppresses both bax-and rpr-induced mitochondrial defects while the caspase-inhibitor p35 is specific to the rpr pathway. Finally, we show that the inhibition of apoptosis by bcl-2 is associated with the down-regulation of rpr expression