20 research outputs found
HOXA1 binds RBCK1/HOIL-1 and TRAF2 and modulates the TNF/NF-ÎșB pathway in a transcription-independent manner
HOX proteins define a family of key transcription factors regulating animal embryogenesis. HOX genes have also been linked to oncogenesis and HOXA1 has been described to be active in several cancers, including breast cancer. Through a proteome-wide interaction screening, we previously identified the TNFR-associated proteins RBCK1/HOIL-1 and TRAF2 as HOXA1 interactors suggesting that HOXA1 is functionally linked to the TNF/NF-ÎșB signaling pathway. Here, we reveal a strong positive correlation between expression of HOXA1 and of members of the TNF/NF-ÎșB pathway in breast tumor datasets. Functionally, we demonstrate that HOXA1 can activate NF-ÎșB and operates upstream of the NF-ÎșB inhibitor IÎșB. Consistently, we next demonstrate that the HOXA1-mediated activation of NF-ÎșB is non-transcriptional and that RBCK1 and TRAF2 influences on NF-ÎșB are epistatic to HOXA1. We also identify an 11 Histidine repeat and the homeodomain of HOXA1 to be required both for RBCK1 and TRAF2 interaction and NF-ÎșB stimulation. Finally, we highlight that activation of NF-ÎșB is crucial for HOXA1 oncogenic activity
MPV17 does not control cancer cell proliferation
MPV17 is described as a mitochondrial inner membrane channel. Although its function remains elusive, mutations in the MPV17 gene result in hepato-cerebral mitochondrial DNA depletion syndrome in humans. In this study, we show that MPV17 silencing does not induce depletion in mitochondrial DNA content in cancer cells. We also show that MPV17 does not control cancer cell proliferation despite the fact that we initially observed a reduced proliferation rate in five MPV17-silenced cancer cell lines with two different shRNAs. However, shRNA-mediated MPV17 knockdown performed in this work provided misguiding results regarding the resulting proliferation phenotype and only a rescue experiment was able to shed definitive light on the implication of MPV17 in cancer cell proliferation. Our results therefore emphasize the caution that is required when scientific conclusions are drawn from a work based on lentiviral vector-based gene silencing and clearly demonstrate the need to systematically perform a rescue experiment in order to ascertain the specific nature of the experimental results
Enhancement of Antiferromagnetic Correlations Induced by Nonmagnetic Impurities: Origin and Predictions for NMR Experiments
Spin models that have been proposed to describe dimerized chains, ladders,
two dimensional antiferromagnets, and other compounds are here studied when
some spins are replaced by spinless vacancies, such as it occurs by
doping. A small percentage of vacancies rapidly destroys the spin gap, and
their presence induces enhanced antiferromagnetic correlations near those
vacancies. The study is performed with computational techniques which includes
Lanczos, world-line Monte Carlo, and the Density Matrix Renormalization Group
methods. Since the phenomenon of enhanced antiferromagnetism is found to occur
in several models and cluster geometries, a common simple explanation for its
presence may exist. It is argued that the resonating-valence-bond character of
the spin correlations at short distances of a large variety of models is
responsible for the presence of robust staggered spin correlations near
vacancies and lattice edges. The phenomenon takes place regardless of the long
distance properties of the ground state, and it is caused by a ``pruning'' of
the available spin singlets in the vicinity of the vacancies. The effect
produces a broadening of the low temperature NMR signal for the compounds
analyzed here. This broadening should be experimentally observable in the
structurally dimerized chain systems
, , , and
, in ladder materials such as , in the
spin-Peierls systems and , and in several others since it
is a universal effect common to a wide variety of models and compounds.Comment: 18 pages revtex with 26 figures include
The genome of the obligate intracellular parasite Trachipleistophora hominis : new insights into microsporidian genome dynamics and reductive evolution
The dynamics of reductive genome evolution for eukaryotes living inside other eukaryotic cells are poorly understood compared to well-studied model systems involving obligate intracellular bacteria. Here we present 8.5 Mb of sequence from the genome of the microsporidian Trachipleistophora hominis, isolated from an HIV/AIDS patient, which is an outgroup to the smaller compacted-genome species that primarily inform ideas of evolutionary mode for these enormously successful obligate intracellular parasites. Our data provide detailed information on the gene content, genome architecture and intergenic regions of a larger microsporidian genome, while comparative analyses allowed us to infer genomic features and metabolism of the common ancestor of the species investigated. Gene length reduction and massive loss of metabolic capacity in the common ancestor was accompanied by the evolution of novel microsporidian-specific protein families, whose conservation among microsporidians, against a background of reductive evolution, suggests they may have important functions in their parasitic lifestyle. The ancestor had already lost many metabolic pathways but retained glycolysis and the pentose phosphate pathway to provide cytosolic ATP and reduced coenzymes, and it had a minimal mitochondrion (mitosome) making Fe-S clusters but not ATP. It possessed bacterial-like nucleotide transport proteins as a key innovation for stealing host-generated ATP, the machinery for RNAi, key elements of the early secretory pathway, canonical eukaryotic as well as microsporidian-specific regulatory elements, a diversity of repetitive and transposable elements, and relatively low average gene density. Microsporidian genome evolution thus appears to have proceeded in at least two major steps: an ancestral remodelling of the proteome upon transition to intracellular parasitism that involved reduction but also selective expansion, followed by a secondary compaction of genome architecture in some, but not all, lineages.Publisher PDFPeer reviewe
Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development
 X-chromosome inactivation (XCI) in female mammals allows dosage compensation for X-linked gene products between the sexes1. The developmental regulation of this process has been extensively investigated in mice, where the X chromosome of paternal origin (Xp) is silenced during early embryogenesis owing to imprinted expression of the regulatory RNA, Xist (X-inactive specific transcript). Paternal XCI is reversed in the inner cell mass of the blastocyst and random XCI subsequently occurs in epiblast cells. Here we show that other eutherian mammals have very different strategies for initiating XCI. In rabbits and humans, the Xist homologue is not subject to imprinting and XCI begins later than in mice. Furthermore,Xist is upregulated on both X chromosomes in a high proportion of rabbit andhuman embryo cells, even in the inner cell mass. In rabbits, this triggers XCI on both X chromosomes in some cells. In humans, chromosome-wide XCI has not initiated even by the blastocyst stage, despite the upregulation of XIST. The choice of which X chromosome will finally become inactive thus occurs downstream of Xist upregulation in both rabbits and humans, unlike in mice. Our study demonstrates the remarkable diversity in XCI regulation and highlights differences between mammals in their requirement for dosage compensation during early embryogenesis
AVuPUR: Evaluation de la vulnérabilité des riviÚres péri-urbaines
[Departement_IRSTEA]RE [TR1_IRSTEA]RIE / TRANSFEAU [TR2_IRSTEA]METHODO / SYNERGIENational audienceLe dĂ©veloppement de l'urbanisation et les pollutions associĂ©es augmentent la pression sur les riviĂšres pĂ©ri-urbaines ainsi que le risque d'inondation. Il est important de bien identifier les facteurs sur lesquels les gestionnaires peuvent agir pour limiter ces risques et dĂ©finir des scĂ©narios d'amĂ©nagement adaptĂ©s. La directive cadre sur l'eau impose notamment aux gestionnaires de limiter l'impact des rejets dans les cours d'eau et de mettre en Âœuvre des amĂ©nagements permettant de restaurer leur qualitĂ© Ă©cologique. Pour mener Ă bien cette tĂąche, il est donc important de disposer, sur ces bassins versants pĂ©ri-urbains, d'outils de modĂ©lisation intĂ©grĂ©e du cycle de l'eau, couplĂ©s Ă une stratĂ©gie de mesure et de suivi adaptĂ©e afin d'Ă©tablir un diagnostic de l'Ă©tat actuel et d'Ă©valuer l'impact de diffĂ©rents scĂ©narios d'amĂ©nagement. L'objectif gĂ©nĂ©ral du projet est donc de progresser sur la simulation de long terme du cycle hydrologique des bassins pĂ©ri-urbains en prenant mieux en compte la variabilitĂ© spatiale et temporelle des facteurs naturels (topographie, sols, gĂ©ologie) et anthropiques (occupation des sols, routes, zones urbanisĂ©es, dĂ©versoirs d'orage, rĂ©seaux d'eau pluviale) qui peuvent l'influencer. Le projet se propose de dĂ©velopper/amĂ©liorer des outils de modĂ©lisation de ces bassins versants en s'appuyant sur une instrumentation renforcĂ©e et une description fine de l'espace. Ces modĂšles seront ensuite utilisĂ©s pour quantifier l'impact des modifications d'occupation des sols sur le rĂ©gime hydrologique (notamment la frĂ©quence des crues) et la gĂ©omorphologie des cours d'eau. Les sites d'Ă©tude choisis sont deux bassins versants soumis Ă une urbanisation rapide en pĂ©riphĂ©rie de Lyon (Yzeron, 150 km2, voir Figure 1) et de Nantes (ChĂ©zine, 34 km2, Figure 7). Le premier est situĂ© en zone de relief assez marquĂ© avec un climat de type MĂ©diterranĂ©en. Le second est en zone de plaine avec un climat de type ocĂ©anique. Les gestionnaires de ces bassins versant sont partie prenante du projet
AVuPUR: Evaluation de la vulnérabilité des riviÚres péri-urbaines
National audienceLe dĂ©veloppement de l'urbanisation et les pollutions associĂ©es augmentent la pression sur les riviĂšres pĂ©ri-urbaines ainsi que le risque d'inondation. Il est important de bien identifier les facteurs sur lesquels les gestionnaires peuvent agir pour limiter ces risques et dĂ©finir des scĂ©narios d'amĂ©nagement adaptĂ©s. La directive cadre sur l'eau impose notamment aux gestionnaires de limiter l'impact des rejets dans les cours d'eau et de mettre en Âœuvre des amĂ©nagements permettant de restaurer leur qualitĂ© Ă©cologique. Pour mener Ă bien cette tĂąche, il est donc important de disposer, sur ces bassins versants pĂ©ri-urbains, d'outils de modĂ©lisation intĂ©grĂ©e du cycle de l'eau, couplĂ©s Ă une stratĂ©gie de mesure et de suivi adaptĂ©e afin d'Ă©tablir un diagnostic de l'Ă©tat actuel et d'Ă©valuer l'impact de diffĂ©rents scĂ©narios d'amĂ©nagement. L'objectif gĂ©nĂ©ral du projet est donc de progresser sur la simulation de long terme du cycle hydrologique des bassins pĂ©ri-urbains en prenant mieux en compte la variabilitĂ© spatiale et temporelle des facteurs naturels (topographie, sols, gĂ©ologie) et anthropiques (occupation des sols, routes, zones urbanisĂ©es, dĂ©versoirs d'orage, rĂ©seaux d'eau pluviale) qui peuvent l'influencer. Le projet se propose de dĂ©velopper/amĂ©liorer des outils de modĂ©lisation de ces bassins versants en s'appuyant sur une instrumentation renforcĂ©e et une description fine de l'espace. Ces modĂšles seront ensuite utilisĂ©s pour quantifier l'impact des modifications d'occupation des sols sur le rĂ©gime hydrologique (notamment la frĂ©quence des crues) et la gĂ©omorphologie des cours d'eau. Les sites d'Ă©tude choisis sont deux bassins versants soumis Ă une urbanisation rapide en pĂ©riphĂ©rie de Lyon (Yzeron, 150 km2, voir Figure 1) et de Nantes (ChĂ©zine, 34 km2, Figure 7). Le premier est situĂ© en zone de relief assez marquĂ© avec un climat de type MĂ©diterranĂ©en. Le second est en zone de plaine avec un climat de type ocĂ©anique. Les gestionnaires de ces bassins versant sont partie prenante du projet
AVuPUR: Evaluation de la vulnérabilité des riviÚres péri-urbaines
[Departement_IRSTEA]RE [TR1_IRSTEA]RIE / TRANSFEAU [TR2_IRSTEA]METHODO / SYNERGIENational audienceLe dĂ©veloppement de l'urbanisation et les pollutions associĂ©es augmentent la pression sur les riviĂšres pĂ©ri-urbaines ainsi que le risque d'inondation. Il est important de bien identifier les facteurs sur lesquels les gestionnaires peuvent agir pour limiter ces risques et dĂ©finir des scĂ©narios d'amĂ©nagement adaptĂ©s. La directive cadre sur l'eau impose notamment aux gestionnaires de limiter l'impact des rejets dans les cours d'eau et de mettre en Âœuvre des amĂ©nagements permettant de restaurer leur qualitĂ© Ă©cologique. Pour mener Ă bien cette tĂąche, il est donc important de disposer, sur ces bassins versants pĂ©ri-urbains, d'outils de modĂ©lisation intĂ©grĂ©e du cycle de l'eau, couplĂ©s Ă une stratĂ©gie de mesure et de suivi adaptĂ©e afin d'Ă©tablir un diagnostic de l'Ă©tat actuel et d'Ă©valuer l'impact de diffĂ©rents scĂ©narios d'amĂ©nagement. L'objectif gĂ©nĂ©ral du projet est donc de progresser sur la simulation de long terme du cycle hydrologique des bassins pĂ©ri-urbains en prenant mieux en compte la variabilitĂ© spatiale et temporelle des facteurs naturels (topographie, sols, gĂ©ologie) et anthropiques (occupation des sols, routes, zones urbanisĂ©es, dĂ©versoirs d'orage, rĂ©seaux d'eau pluviale) qui peuvent l'influencer. Le projet se propose de dĂ©velopper/amĂ©liorer des outils de modĂ©lisation de ces bassins versants en s'appuyant sur une instrumentation renforcĂ©e et une description fine de l'espace. Ces modĂšles seront ensuite utilisĂ©s pour quantifier l'impact des modifications d'occupation des sols sur le rĂ©gime hydrologique (notamment la frĂ©quence des crues) et la gĂ©omorphologie des cours d'eau. Les sites d'Ă©tude choisis sont deux bassins versants soumis Ă une urbanisation rapide en pĂ©riphĂ©rie de Lyon (Yzeron, 150 km2, voir Figure 1) et de Nantes (ChĂ©zine, 34 km2, Figure 7). Le premier est situĂ© en zone de relief assez marquĂ© avec un climat de type MĂ©diterranĂ©en. Le second est en zone de plaine avec un climat de type ocĂ©anique. Les gestionnaires de ces bassins versant sont partie prenante du projet