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Articles importants dans Nature, Science ou Cell



  1. #91
    diazométhane

    Re : Articles importants dans Nature, Science ou Cell


    ------

    Intéressant pour approfondir les mécanismes d'action de l'immunodéfience acquise :

    http://download.cell.com/pdfs/0092-8...7407012846.pdf

    -----

  2. Publicité
  3. #92
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Pour le début de l'année, voilà deux petits articles fort intriguants :


    tRNA–mRNA mimicry drives translation initiation from a viral IRES
    Nature Structural & Molecular Biology 15, 57 - 64 (2007)

    David A Costantino, Jennifer S Pfingsten, Robert P Rambo & Jeffrey S Kieft

    Internal ribosome entry site (IRES) RNAs initiate protein synthesis in eukaryotic cells by a noncanonical cap-independent mechanism. IRESes are critical for many pathogenic viruses, but efforts to understand their function are complicated by the diversity of IRES sequences as well as by limited high-resolution structural information. The intergenic region (IGR) IRESes of the Dicistroviridae viruses are powerful model systems to begin to understand IRES function. Here we present the crystal structure of a Dicistroviridae IGR IRES domain that interacts with the ribosome's decoding groove. We find that this RNA domain precisely mimics the transfer RNA anticodon–messenger RNA codon interaction, and its modeled orientation on the ribosome helps explain translocation without peptide bond formation. When combined with a previous structure, this work completes the first high-resolution description of an IRES RNA and provides insight into how RNAs can manipulate complex biological machines.


    TER1, the RNA subunit of fission yeast telomerase
    Nature Structural & Molecular Biology 15, 26 - 33 (2007)

    Jessica Leonardi, Jessica A Box, Jeremy T Bunch & Peter Baumann

    Telomerase is the ribonucleoprotein complex that adds telomeric repeats to the ends of chromosomes. Its protein subunit TERT is highly conserved among eukaryotes, whereas the RNA subunit varies greatly in size and sequence, hindering the identification of telomerase RNAs in some important model organisms. Here we report the identification and functional characterization of TER1, the telomerase RNA component from fission yeast Schizosaccharomyces pombe. Deletion of ter1+ caused progressive shortening of telomeres and cellular senescence followed by chromosome circularization. Interactions between Est1 and Trt1, the two known protein components of fission yeast telomerase, were dependent on TER1, supporting its role as a scaffold for the assembly of protein subunits. Using a series of template mutations, we show that translocation or dissociation site variability and template-primer slippage account for the sequence heterogeneity of fission yeast telomeres.


    Sinon, pour résoudre le problème d'accessibilité aux textes complets, si vous ne pouvez pas les trouver en fac ou dans le labo d'accueil, vous pouvez toujours envoyer un mail au chercheur correspondant. C'est ce que je fais et ils sont généralement contents que de petits étudiants s'intéressent à leur boulot Et vous avez votre publi tranquille

    Cordialement,
    An expert is one who knows more and more about less and less.

  4. #93
    Vinc

    Re : Articles importants dans Nature, Science ou Cell

    Oui ou demander à certains gentils modérateurs (ou autres d'ailleurs!)

    V.
    Primum non nocere.

  5. #94
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Citation Envoyé par Vinc Voir le message
    Oui ou demander à certains gentils modérateurs (ou autres d'ailleurs!)

    V.
    Très certainement, Vinc.
    Taper la discute avec les chercheurs par mail te permet d'avoir des infos sur leurs prochains articles

    Sinon, en voilà un autre (le gars a passé un super Jour de l'An )

    Nucleosome destabilization in the epigenetic regulation of gene expression Henikoff S, Nature Reviews Genetics Jan 1, 2008.

    Assembly, mobilization and disassembly of nucleosomes can influence the regulation of gene expression and other processes that act on eukaryotic DNA. Distinct nucleosome-assembly pathways deposit dimeric subunits behind the replication fork or at sites of active processes that mobilize pre-existing nucleosomes. Replication-coupled nucleosome assembly appears to be the default process that maintains silent chromatin, counteracted by active processes that destabilize nucleosomes. Nucleosome stability is regulated by the combined effects of nucleosome-positioning sequences, histone chaperones, ATP-dependent nucleosome remodellers, post-translational modifications and histone variants. Recent studies suggest that histone turnover helps to maintain continuous access to sequence-specific DNA-binding proteins that regulate epigenetic inheritance, providing a dynamic alternative to histone-marking models for the propagation of active chromatin.

    Bonne lecture!

    Cordialement,
    An expert is one who knows more and more about less and less.

  6. #95
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Salut, tout le monde,
    l'année commence quand même pas mal! Voilà un article vraiment intéressant :

    DNA polymerase zeta (pol zeta) in higher eukaryotes

    Gregory N Gan1, John P Wittschieben1, Birgitte Ø Wittschieben1,* and Richard D Wood1

    1Department of Pharmacology, University of Pittsburgh Medical School, Pittsburgh, PA 15213, USA, Cell Research (2008) 18:174–183. doi: 10.1038/cr.2007.117; published online 24 December 2007

    Most current knowledge about DNA polymerase zeta (pol zeta) comes from studies of the enzyme in the budding yeast Saccharomyces cerevisiae, where pol zeta consists of a complex of the catalytic subunit Rev3 with Rev7, which associates with Rev1. Most spontaneous and induced mutagenesis in yeast is dependent on these gene products, and yeast pol zeta can mediate translesion DNA synthesis past some adducts in DNA templates. Study of the homologous gene products in higher eukaryotes is in a relatively early stage, but additional functions for the eukaryotic proteins are already apparent. Suppression of vertebrate REV3L function not only reduces induced point mutagenesis but also causes larger-scale genome instability by raising the frequency of spontaneous chromosome translocations. Disruption of Rev3L function is tolerated in Drosophila, Arabidopsis, and in vertebrate cell lines under some conditions, but is incompatible with mouse embryonic development. Functions for REV3L and REV7(MAD2B) in higher eukaryotes have been suggested not only in translesion DNA synthesis but also in some forms of homologous recombination, repair of interstrand DNA crosslinks, somatic hypermutation of immunoglobulin genes and cell-cycle control. This review discusses recent developments in these areas.

    Ce numéro de Cell Research est entièrement consacré à la réparation et ce qui est encore meilleur est que la plupart (si ce n'est pas tous, je n'ai pas encore tout vu ) des articles sont en accès libre

    Bonne lecture!

    Cordialement,
    An expert is one who knows more and more about less and less.

  7. #96
    Vinc

    Re : Articles importants dans Nature, Science ou Cell

    Bonjour!
    Un article assez surprenant dans The British Journal of Cancer!


    High birth weight as an important risk factor for infant leukemia

    S Koifman1, M S Pombo-de-Oliveira2

    In this paper, we compared the birth weight distribution among 201 infant leukaemia (IL) cases with that of 440 noncancer controls enrolled in Brazil in 1999-2005. Compared with the general population and the stratum 2500-2999 g as reference, IL cases weighing 3000-3999 g presented an odds ratio (OR) of 1.68 (95% CI: 1.03-2.76), and those of 4000 g or more, an OR of 2.28 (95% CI: 1.08-4.75), Ptrend<0.01. Using hospital-based controls, the OR for 4000 g or more, compared to 2500-2999 g, was 1.30 (95% CI: 1.02-1.43) after adjusting for confounders (gender, income, maternal age, pesticide and hormonal exposure during pregnancy). The results suggest that high birth weight is associated with increased risk of IL.

    http://www.nature.com/bjc/journal/v9...C0B023B930AF23

    British Journal of Cancer (2008) 98, 664-667.
    doi:10.1038/sj.bjc.6604202 www.bjcancer.com Published online 29 January 2008



    V.
    Primum non nocere.

  8. Publicité
  9. #97
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Bonjour,

    Et un autre article assez surprenant qui parle d'un virus d'Archaea capable de se développer en-dehors de la cellule!

    Structural and genomic properties of the hyperthermophilic archaeal virus ATV with an extracellular stage of the reproductive cycle

    Prangishvili D, Vestergaard G, Häring M, Aramayo R, Basta T, Rachel R, Garrett RA, J Mol Biol. 2006 Jun 23;359(5):1203-16. Epub 2006 Apr 27.

    A novel virus, ATV, of the hyperthermophilic archaeal genus Acidianus has the unique property of undergoing a major morphological development outside of, and independently of, the host cell. Virions are extruded from host cells as lemon-shaped tail-less particles, after which they develop long tails at each pointed end, at temperatures close to that of the natural habitat, 85 degrees C. The extracellularly developed tails constitute tubes, which terminate in an anchor-like structure that is not observed in the tail-less particles. A thin filament is located within the tube, which exhibits a periodic structure. Tail development produces a one half reduction in the volume of the virion, concurrent with a slight expansion of the virion surface. The circular, double-stranded DNA genome contains 62,730 bp and is exceptional for a crenarchaeal virus in that it carries four putative transposable elements as well as genes, which previously have been associated only with archaeal self-transmissable plasmids. In total, it encodes 72 predicted proteins, including 11 structural proteins with molecular masses in the range of 12 to 90 kDa. Several of the larger proteins are rich in coiled coil and/or low complexity sequence domains, which are unusual for archaea. One protein, in particular P800, resembles an intermediate filament protein in its structural properties. It is modified in the two-tailed, but not in the tail-less, virion particles and it may contribute to viral tail development. Exceptionally for a crenarchaeal virus, infection with ATV results either in viral replication and subsequent cell lysis or in conversion of the infected cell to a lysogen. The lysogenic cycle involves integration of the viral genome into the host chromosome, probably facilitated by the virus-encoded integrase and this process can be interrupted by different stress factors.

    Cordialement,
    An expert is one who knows more and more about less and less.

  10. #98
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Bonjour,

    Voici quelques une petite chose intéressante du dernier Journal Of Virology

    Journal of Virology, March 2008, p. 2376-2384, Vol. 82, No. 5
    0022-538X/08/$08.00+0 doi:10.1128/JVI.02100-07

    Pseudodiploid Genome Organization Aids Full-Length Human Immunodeficiency Virus Type 1 DNA Synthesis

    Steven R. King, Nisha K. Duggal, Clement B. Ndongmo, Crystal Pacut, and Alice Telesnitsky

    Template switching between copackaged human immunodeficiency virus type 1 (HIV-1) genomic RNAs is genetically silent when identical RNAs are copackaged but yields recombinants when virions contain two distinct RNAs. Sequencing has revealed that errors at retroviral recombination junctions are infrequent, suggesting that template switching is not intrinsically mutagenic. Here, we tested the hypothesis that template switching may instead contribute to replication fidelity. This hypothesis predicts that reverse transcription of a single-copy gene will be more error prone than replication in the presence of a second copy. To test this, HIV-1-based vectors containing both lacZ and the puromycin resistance marker were expressed either alone or with an excess of an "empty" vector lacking lacZ and puro. This resulted in virions with either RNA homodimers or haploid genomes with only a single lacZ-puro RNA. In untreated cells, lacZ inactivation rates suggested that haploid vector reverse transcription was slightly more error prone than that of homodimerized pseudodiploid vectors. Haploid reverse transcription was at least threefold more error prone than pseudodiploid-templated synthesis when slowed by hydroxyurea treatment or stopped prematurely with zidovudine. Individual products of one- and two-copy genes revealed both nucleotide substitutions and deletions, with deletions more frequent than point mutations among haploid genome products. Similar spectra of defective products were observed at early reverse transcription time points and among products of haploid virions. These results indicate that faithful, full-length reverse transcription products were underrepresented in the absence of a reserve of genetic information and suggest that template switching contributes to HIV-1 genomic integrity.

    http://jvi.asm.org/cgi/content/abstract/82/5/2376?etoc

    Bonne lecture

    Cordialement,
    An expert is one who knows more and more about less and less.

  11. #99
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Depuis le temps que l'un de mes profs en parle et qu'il nous conjure de nous taire
    Maintenant, c'est officiel :

    Mesophilic crenarchaeota: proposal for a third archaeal phylum, the Thaumarchaeota

    Céline Brochier-Armanet, Bastien Boussau, Simonetta Gribaldo & Patrick Forterre, Nature Reviews Microbiology 6, 245-252 (March 2008) | doi:10.1038/nrmicro1852

    The archaeal domain is currently divided into two major phyla, the Euryarchaeota and Crenarchaeota. During the past few years, diverse groups of uncultivated mesophilic archaea have been discovered and affiliated with the Crenarchaeota. It was recently recognized that these archaea have a major role in geochemical cycles. Based on the first genome sequence of a crenarchaeote, Cenarchaeum symbiosum, we show that these mesophilic archaea are different from hyperthermophilic Crenarchaeota and branch deeper than was previously assumed. Our results indicate that C. symbiosum and its relatives are not Crenarchaeota, but should be considered as a third archaeal phylum, which we propose to name Thaumarchaeota (from the Greek 'thaumas', meaning wonder).

    http://www.nature.com/nrmicro/journa...micro1852.html

    Bonne lecture

    Cordialement,
    An expert is one who knows more and more about less and less.

  12. #100
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Bonjour,

    Voici un autre article "évolution"

    Natural selection has driven population differentiation in modern humans
    Luis B Barreiro, Guillaume Laval, Hélène Quach, Etienne Patin & Lluís Quintana-Murci, Nature Genetics Published online: 3 February 2008 | doi:10.1038/ng.78

    The considerable range of observed phenotypic variation in human populations may reflect, in part, distinctive processes of natural selection and adaptation to variable environmental conditions. Although recent genome-wide studies have identified candidate regions under selection1, 2, 3, 4, 5, it is not yet clear how natural selection has shaped population differentiation. Here, we have analyzed the degree of population differentiation at 2.8 million Phase II HapMap single-nucleotide polymorphisms6. We find that negative selection has globally reduced population differentiation at amino acid–altering mutations, particularly in disease-related genes. Conversely, positive selection has ensured the regional adaptation of human populations by increasing population differentiation in gene regions, primarily at nonsynonymous and 5'-UTR variants. Our analyses identify a fraction of loci that have contributed, and probably still contribute, to the morphological and disease-related phenotypic diversity of current human populations.

    http://www.nature.com/ng/journal/vao...abs/ng.78.html

    Et son communiqué de presse en français sur le site de Pasteur.

    Bonne lecture

    Cordialement,
    An expert is one who knows more and more about less and less.

  13. #101
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Hello,

    Voici un article intéressant pas tout à fait tout chaud-tout récent

    Mutant huntingtin can paradoxically protect neurons from death


    T Zuchner and P Brundin, Cell Death and Differentiation (2008) 15, 435–442; doi:10.1038/sj.cdd.4402261; published online 2 November 2007


    Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a mutation in the gene huntingtin and characterized by motor, cognitive and psychiatric symptoms. Huntingtin contains a CAG repeat in exon 1. An expansion of this CAG repeat above 35 results in misfolding of Huntingtin, giving rise to protein aggregates and neuronal cell death. There are several transgenic HD mouse models that reproduce most of the features of the human disorder, for example protein inclusions, some neurodegeneration as well as motor and cognitive symptoms. At the same time, a subgroup of the HD transgenic mouse models exhibit dramatically reduced susceptibility to excitotoxicity. The mechanism behind this is unknown. Here, we review the literature regarding this phenomenon, attempt to explain what protein domains are crucial for this phenomenon and point toward a putative mechanism. We suggest, that the C-terminal domain of exon 1 Huntingtin, namely the proline rich domain, is responsible for mediating a neuroprotective effect against excitotoxicity. Furthermore, we point out the possible importance of this mechanism for future therapies in neurological disorders that have been suggested to be associated with excitotoxicity, for example Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.

    http://www.nature.com/cdd/journal/v1.../4402261a.html

    Et le mieux c'est qu'il est en accès libre

    Cordialement,
    An expert is one who knows more and more about less and less.

  14. #102
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Bonjour,

    J'aime bien EMBO Voici qui est bel et bon :


    Role of 16S ribosomal RNA methylations in translation initiation in Escherichia coli
    Gautam Das, Dinesh Kumar Thotala, Suman Kapoor, Sheelarani Karunanithi, Suman S Thakur1, N Sadananda Singh and Umesh Varshney
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka, India


    Translation initiation from the ribosomal P-site is the specialty of the initiator tRNAs (tRNAfMet). Presence of the three consecutive G-C base pairs (G29-C41, G30-C40 and G31-C39) in their anticodon stems, a highly conserved feature of the initiator tRNAs across the three kingdoms of life, has been implicated in their preferential binding to the P-site. How this feature is exploited by ribosomes has remained unclear. Using a genetic screen, we have isolated an Escherichia coli strain, carrying a G122D mutation in folD, which allows initiation with the tRNAfMet containing mutations in one, two or all the three G-C base pairs. The strain shows a severe deficiency of methionine and S-adenosylmethionine, and lacks nucleoside methylations in rRNA. Targeted mutations in the methyltransferase genes have revealed a connection between the rRNA modifications and the fundamental process of the initiator tRNA selection by the ribosome.

    Et le reste est ici. Bonne lecture

    Cordialement,
    An expert is one who knows more and more about less and less.

  15. Publicité
  16. #103
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Et puis, lorsque l'on reste tard dans le labo et qu'il pleut dehors, on va voir à gauche, à droite et voilà ce que l'on trouve :


    Imputing missing genotypic data of single-nucleotide polymorphisms using neural networks

    Yan V Sun and Sharon L R Kardia, European Journal of Human Genetics (2008) 16, 487–495; doi:10.1038/sj.ejhg.5201988; published online 16 January 2008

    With advances in high-throughput single-nucleotide polymorphism (SNP) genotyping, the amount of genotype data available for genetic studies is steadily increasing, and with it comes new abilities to study multigene interactions as well as to develop higher dimensional genetic models that more closely represent the polygenic nature of common disease risk. The combined impact of even small amounts of missing data on a multi-SNP analysis may be considerable. In this study, we present a neural network method for imputing missing SNP genotype data. We compared its imputation accuracy with fastPHASE and an expectation–maximization algorithm implemented in HelixTree. In a simulation data set of 1000 SNPs and 1000 subjects, 1, 5 and 10% of genotypes were randomly masked. Four levels of linkage disequilibrium (LD), LD R2<0.2, R2<0.5, R2<0.8 and no LD threshold, were examined to evaluate the impact of LD on imputation accuracy. All three methods are capable of imputing most missing genotypes accurately (accuracy >86%). The neural network method accurately predicted 92.0–95.9% of the missing genotypes. In a real data set comparison with 419 subjects and 126 SNPs from chromosome 2, the neural network method achieves the highest imputation accuracies >83.1% with missing rate from 1 to 5%. Using 90 HapMap subjects with 1962 SNPs, fastPHASE had the highest accuracy (approx97%) while the other two methods had >95% accuracy. These results indicate that the neural network model is an accurate and convenient tool, requiring minimal parameter tuning for SNP data recovery, and provides a valuable alternative to usual complete-case analysis.

    La suite est ici

    Perso, il y a plein de trucs que je ne comprends pas, mais ce sera sujet à discussion dans un autre topic

    Bonne lecture

    Cordialement,
    An expert is one who knows more and more about less and less.

  17. #104
    tortuga

    Re : Articles importants dans Nature, Science ou Cell

    MaliciaR = pubcrawler!

  18. #105
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Mais euh C'est que je suis abonnée à un tas d'alertes, alors...

    Cordialement,
    An expert is one who knows more and more about less and less.

  19. #106
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Bonjour,

    En voilà un de marrant


    Increased Transmission of Mutations by Low-Condition Females: Evidence for Condition-Dependent DNA Repair

    Aneil F. Agrawal*, Alethea D. Wang; PLoS Biol 6(2): e30 doi:10.1371/journal.pbio.0060030

    Evidence is mounting that mutation rates are sufficiently high for deleterious alleles to be a major evolutionary force affecting the evolution of sex, the maintenance of genetic variation, and many other evolutionary phenomena. Though point estimates of mutation rates are improving, we remain largely ignorant of the biological factors affecting these rates at the individual level. Of special importance is the possibility that mutation rates are condition-dependent with low-condition individuals experiencing more mutation. Theory predicts that such condition dependence would dramatically increase the rate at which populations adapt to new environments and the extent to which populations suffer from mutation load. Despite its importance, there has been little study of this phenomenon in multicellular organisms. Here, we examine whether DNA repair processes are condition-dependent in Drosophila melanogaster. In this species, damaged DNA in sperm can be repaired by maternal repair processes after fertilization. We exposed high- and low-condition females to sperm containing damaged DNA and then assessed the frequency of lethal mutations on paternally derived X chromosomes transmitted by these females. The rate of lethal mutations transmitted by low-condition females was 30% greater than that of high-condition females, indicating reduced repair capacity of low-condition females. A separate experiment provided no support for an alternative hypothesis based on sperm selection.

    Et c'est un open access, ici : http://biology.plosjournals.org/perl...o.0060030&ct=1

    Bonne lecture

    Cordialement,
    An expert is one who knows more and more about less and less.

  20. #107
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Il y en a qui s'amusent


    Activation of protein splicing with light in yeast

    Amy B Tyszkiewicz & Tom W Muir, Nature Methods - 5, 303 - 305 (2008), doi:10.1038/nmeth.1189


    Spatiotemporal regulation of protein function is a key feature of living systems; experimental tools that provide such control are of great utility. Here we report a genetically encoded system for controlling a post-translational process, protein splicing, with light. Studies in Saccharomyces cerevisiae demonstrate that fusion of a photodimerization system from Arabidopsis thaliana to an artificially split intein permits rapid activation of protein splicing to yield a new protein product.

    http://www.nature.com/nmeth/journal/...meth.1189.html


    Bonne lecture
    An expert is one who knows more and more about less and less.

  21. #108
    Vinc

    Re : Articles importants dans Nature, Science ou Cell

    Aller Malicia je prends le relais


    Elevated tRNAiMet synthesis can drive cell proliferation and oncogenic transformation

    Lynne Marshall,1,2 Niall S. Kenneth,1 and Robert J. White1,2,

    1 Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
    2 Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK


    Characteristics of transformed and tumor cells include increased levels of protein synthesis and elevated expression of RNA polymerase (pol) III products, such as tRNAs and 5S rRNA. However, whether deregulated pol III transcription contributes to transformation has been unclear. Generating cell lines expressing an inducible pol III-specific transcription factor, Brf1, allowed us to raise tRNA and 5S rRNA levels specifically. Brf1 induction caused an increase in cell proliferation and oncogenic transformation, whereas depletion of Brf1 impeded transformation. Among the gene products induced by Brf1 is the tRNAiMet that initiates polypeptide synthesis. Overexpression of tRNAiMet is sufficient to stimulate cell proliferation and allow immortalized fibroblasts to form foci in culture and tumors in mice. The data indicate that elevated tRNA synthesis can promote cellular transformation.


    Cell, Vol 133, 78-89, 04 April 2008

  22. Publicité
  23. #109
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Sympa ton article, Vinc

    Ce que voilà n'est pas vraiment un article, plutôt un résumé, les articles auxquels il se réfère sont cités à la fin. Vraiment intéressant, même un microbiologiste comme moi apprécie

    Tumorigenesis: Turning the hands of time
    SOURCE: Nature Reviews Cancer

    The discovery of a link between DNA damage response (DDR) signaling and the scheduling of circadian rhythms may help us discover why there is an increase in tumorigenesis when circadian rhythms are altered.

    Mammals exhibit oscillations in metabolism, physiology and behaviour with a near 24 h periodicity, a phenomenon known as the circadian rhythm. Changes to circadian oscillations, or phases, are associated with an increased risk of cancer and accelerated tumour progression, although why this might be remains unclear. The van der Horst laboratory now provide evidence for a link between DNA damage response (DDR) signalling and the scheduling of circadian rhythms.

    The circadian rhythm is driven by the central pacemaker — or clock — in the brain, which synchronizes oscillations in peripheral tissues by modulating the activity of numerous pathways, including cell cycle and DDR signalling. As this process commonly involves feedback regulation from the periphery to the clock, Oklejewicz and colleagues asked whether DNA damage could affect the timing of circadian phases. Using a luciferase reporter gene under the control of the clock-regulated Per2 promoter in Rat-1 fibroblasts they found that exposure to ionizing radiation (IR) advanced circadian phases in a dose-dependent manner, essentially resetting the clock. The mechanism underlying this change was unique to DNA damage and did not mimic the changes induced by other agents, such as forskolin or dexamethasone. Next, they showed that C57BL/6J mice exposed to a non-lethal dose of IR also exhibited phase advancement of circadian behaviour, indicating that exposure to IR affects the central pacemaker and not just peripheral oscillations.

    So, how is the central pacemaker altered by DNA damage? The authors showed that abrogation of ataxia-telangiectasia mutated (ATM, which primarily regulates the DDR to IR) kinase activity, reduced the phase advancement in Rat-1 fibroblasts, indicating that ATM-dependent signalling can mediate clock resetting. Consistently, they also found that primary human fibroblasts derived from patients with the cancer-predisposed ataxia-telangiectasia (ATM-deficient) or Nijmegen breakage syndrome (defective for NBS (also known as nibrin), an important player in the DDR) did not exhibit phase advancement after exposure to IR. They also showed that ultraviolet irradiation (to which the kinase ataxia-telangiectasia and rad3-related (ATR) primarily responds) and oxidative DNA damage resulted in phase advancement, indicating that DDR signalling might be a regulatory input to which the central pacemaker responds. Interestingly, DNA damage-mediated phase advancement of the clock did not appear to involve the modulation of known clock genes, leaving open the question of how the DDR feeds back to the clock. However, the clock proteins PER1 and TIM1 (also known as TIMELESS) were previously shown to be targets of ATM and ATR and are promising candidates.

    Defective DDR signalling is associated with increased cancer predisposition, as is reflected by the plethora of cancer-prone syndromes that are caused by mutations in DDR genes. This study now provides an interesting link that could improve our understanding of the underlying mechanisms that lead to increased tumorigenesis when circadian rhythms are altered.

    Gemma K. Alderton

    References :


    1. Oklejewicz, M. et al. Phase resetting of the mammalian circadian clock by DNA damage. Curr. Biol. 18, 286–291 (2008)
    2. Fu, L. & Lee, C. C. The circadian clock: pacemaker and tumour suppressor. Nature Rev. Cancer 3, 350–361 (2003)


    Cordialement,
    An expert is one who knows more and more about less and less.

  24. #110
    drosoman

    Re : Articles importants dans Nature, Science ou Cell

    Salut
    Cet article me semble en effet fort interessant. Sauf que je reste sur ma faim. Et c'est peut etre bien parceque je passe a cote du take home message !!! Alors si quelqu'un peut m'eclairer... Ce que j'en comprends, c'est finalement l'impact de la reponse aux lesions de l'ADN, sur le cycle circadien. C'est extremement interessant, mais ca fait aussi beaucoup de sens, une cellule etant rythmee, et ce rythme etant crucial pour notamment sa division, son cycle cellulaire, de tels dommages qui impactent la division et disons les microcycles, peuvent aussi impacter des cycles plus importants comme le cycle circadien. Maintenant, est ce que ca a un rapport avec l'influence inverse, comment le cycle ciracdien influence la tumorigenese ? Je ne suis pas persuadé et de fait reste un peu dubitatif sur la facon de vendre le papier... Votre avis ?

    Cordialement
    Nico

  25. #111
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Ca faisait un moment que je n'avais pas fait de pub-crawling


    The Arabidopsis MutS homolog AtMSH5 is required for normal meiosis

    Xiaoduo Lu1,2,*, Xiaolin Liu2,3,*, Lizhe An1, Wei Zhang4, Jian Sun2,3, Huijuan Pei1, Hongyan Meng2,3, Yunliu Fan2,3 and Chunyi Zhang2, Cell Research (2008) 18:589–599. doi: 10.1038/cr.2008.44


    MSH5, a member of the MutS homolog DNA mismatch repair protein family, has been shown to be required for proper homologous chromosome recombination in diverse organisms such as mouse, budding yeast and Caenorhabditis elegans. In this paper, we show that a mutant Arabidopsis plant carrying the putative disrupted AtMSH5 gene exhibits defects during meiotic division, producing a proportion of nonviable pollen grains and abnormal embryo sacs, and thereby leading to a decrease in fertility. AtMSH5 expression is confined to meiotic floral buds, which is consistent with a possible role during meiosis. Cytological analysis of male meiosis revealed the presence of numerous univalents from diplotene to metaphase I, which were associated with a great reduction in chiasma frequencies. The average number of residual chiasmata in the mutant is reduced to 2.54 per meiocyte, which accounts for approx25% of the amount in the wild type. Here, quantitative cytogenetical analysis reveals that the residual chiasmata in Atmsh5 mutants are randomly distributed among meiocytes, suggesting that AtMSH5 has an essential role during interference-sensitive chiasma formation. Taken together, the evidence indicates that AtMSH5 promotes homologous recombination through facilitating chiasma formation during prophase I in Arabidopsis.

    Le reste est ici : http://www.nature.com/cr/journal/v18...cr200844a.html

    Bonne lecture


    Cordialement,
    An expert is one who knows more and more about less and less.

  26. #112
    piwi

    Re : Articles importants dans Nature, Science ou Cell

    Rien de bien surprenant là dedans non?
    Enfin là comme ça, je ne reste pas bouché bée devant la nouvelle.
    Je sers la science et c'est ma joie.... Il parait.

  27. #113
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Citation Envoyé par piwi Voir le message
    Rien de bien surprenant là dedans non?
    Enfin là comme ça, je ne reste pas bouché bée devant la nouvelle.
    Non, en effet Mais personnellement, je connaissais les homologues chez les Eucaryotes côté "animaux" Et comme on ne parle pas trop de la réparation, encore moins chez les Plantes (du tout, en fait) en cours, j'ai pensé que c'est intéressant de populariser la chose


    Cordialement,
    An expert is one who knows more and more about less and less.

  28. #114
    piwi

    Re : Articles importants dans Nature, Science ou Cell

    Bon en même temps j'ai la tête dans la meiose et les remaniements à longueur de journée, c'est sûr que je ne m'emerveille pas facilement devant ces papiers. Pas blasé mais critique
    Je sers la science et c'est ma joie.... Il parait.

  29. Publicité
  30. #115
    LXR

    Re : Articles importants dans Nature, Science ou Cell

    Je reviens 1 mois en arrière avec le papier de Vinc . Je trouve ceci très intéressant dans les premières étapes de la tumorigenèse, et pour les zones tumorales qui ne sont pas en hypoxie. Pourquoi je parle d'hypoxie? On sait que l'hypoxie est accompagnée d'une baisse des nutriments disponibles. D'ailleurs cette limite métabolique arrive avant la limite en oxygène étant donné que la limite de diffusion de molécules énergétiques comme le glucose et plus restreinte que celle d'un gaz comme l'oxygène. Enfin bref c'était pour faire un rappel pour expliquer que ces cellules pour survivre diminuent toutes les dépenses énergétiques "inutiles", dont la synthèse protéique qui est extrêmement coûteuse de ce point de vue. Certaines régions 5'-UTR d'ARNm comme celle du facteur hypoxique HIF-1a ont une force suffisante pour continuer à être traduit malgré ce "serrage de ceinture". Il me semble donc intéressant que l'équipe en question extrapole son étude aux régions hypoxiques des tumeurs afin de voir si le tRNAiMet est réprimé, car on a ici deux profils traductionnels qui sont presque opposés. Une extension de l'étude pourrrait permettre de mieux comprendre le comportement de la traduction selon les régions tumorales.

    Pour Drosoman, regarde du côté des récepteurs nucléaires ROR (retinoid-related orphan nuclear receptor) qui relient le système immunitaire aux rythmes circadiens. Cette liaison est encore floue mais leur forte implication dans les deux mécanismes est claire. Je ne pense pas que ces récepteurs aient encore été étudiés dans le cancer, donc peut-être pas de réponse de ce côté là. En tout cas il y a beaucoup de choses derrière les rythmes biologiques...bon courage!

    Greg
    Never give up.

  31. #116
    LXR

    Re : Articles importants dans Nature, Science ou Cell

    Si vous aimez les maths appliqués à la biologie, et ici à la cancérologie, allez voir cette magnifique revue (ça n'engage que moi hein ). Le mécanisme de cancérisation étant de plus en plus vaste, la modélisation mathématique apporte une vision nouvelle de plusieurs mécanismes et de l'oncogenèse en général. Super intéressant et rare!!

    Integrative mathematical oncology

    Integrative mathematical oncology.
    Anderson AR, Quaranta V.

    Division of Mathematics, University of Dundee, Dundee, DD1 4HN, Scotland, UK. anderson@maths.dundee.ac.uk

    Cancer research attracts broad resources and scientists from many disciplines, and has produced some impressive advances in the treatment and understanding of this disease. However, a comprehensive mechanistic view of the cancer process remains elusive. To achieve this it seems clear that one must assemble a physically integrated team of interdisciplinary scientists that includes mathematicians, to develop mathematical models of tumorigenesis as a complex process. Examining these models and validating their findings by experimental and clinical observations seems to be one way to reconcile molecular reductionist with quantitative holistic approaches and produce an integrative mathematical oncology view of cancer progression.

    Greg
    Never give up.

  32. #117
    John78

    Re : Articles importants dans Nature, Science ou Cell

    Vu que notre pubmed-crawleuse préférée est sur la touche , j'en profite pour mettre cette histoire rigolote qui montre le bricolage évolutif du vivant pour contourner la perte d'un gène clé. En plus je trouve la démonstration et les manips assez élegantes :
    --------------------------------------------------------------------------

    Nature. 2008 May 1;453(7191):120-3.

    Life without RNase P.

    Randau L, Schröder I, Söll D.

    The universality of ribonuclease P (RNase P), the ribonucleoprotein essential for transfer RNA (tRNA) 5' maturation, is challenged in the archaeon Nanoarchaeum equitans. Neither extensive computational analysis of the genome nor biochemical tests in cell extracts revealed the existence of this enzyme. Here we show that the conserved placement of its tRNA gene promoters allows the synthesis of leaderless tRNAs, whose presence was verified by the observation of 5' triphosphorylated mature tRNA species. Initiation of tRNA gene transcription requires a purine, which coincides with the finding that tRNAs with a cytosine in position 1 display unusually extended 5' termini with an extra purine residue. These tRNAs were shown to be substrates for their cognate aminoacyl-tRNA synthetases. These findings demonstrate how nature can cope with the loss of the universal and supposedly ancient RNase P through genomic rearrangement at tRNA genes under the pressure of genome condensation.

    --------------------------------------------------------------------------

    A+
    J

  33. #118
    MaliciaR

    Re : Articles importants dans Nature, Science ou Cell

    Bonjour,

    Voilà un truc vraiment curieux : jusqu'à 200 000 copies de génomes dans une bactérie C'est deux-cents-milles-ploïde, ça?

    Extreme polyploidy in a large bacterium

    Jennifer E. Mendell*, Kendall D. Clements, J. Howard Choat, and Esther R. Angert*, PNAS


    Cells rely on diffusion to move metabolites and biomolecules. Diffusion is highly efficient but only over short distances. Although eukaryotic cells have broken free of diffusion-dictated constraints on cell size, most bacteria and archaea are forced to remain small. Exceptions to this rule are found among the bacterial symbionts of surgeonfish; Epulopiscium spp. are cigar-shaped cells that reach lengths in excess of 600 µm. A large Epulopiscium contains thousands of times more DNA than a bacterium such as Escherichia coli, but the composition of this DNA is not well understood. Here, we present evidence that Epulopiscium contains tens of thousands of copies of its genome. Using quantitative, single-cell PCR assays targeting single-copy genes, we have determined that copy number is positively correlated with Epulopiscium cell size. Although other bacteria are known to possess multiple genomes, polyploidy of the magnitude observed in Epulopiscium is unprecedented. The arrangement of genomes around the cell periphery may permit regional responses to local stimuli, thus allowing Epulopiscium to maintain its unusually large size. Surveys of the sequences of single-copy genes (dnaA, recA, and ftsZ) revealed genetic homogeneity within a cell consistent with only a small amount (1%) of the parental DNA being transferred to the next generation. The results also suggest that the abundance of genome copies in Epulopiscium may allow for an unstable genetic feature, a long mononucleotide tract, in an essential gene. With the evolution of extreme polyploidy and large cell size, Epulopiscium has acquired some of the advantages of eukaryotic cells.

    La suite peut être trouvée là :
    http://www.pnas.org/cgi/content/abstract/105/18/6730


    Bonne lecture


    Cordialement,
    An expert is one who knows more and more about less and less.

  34. #119
    Vinc

    Re : Articles importants dans Nature, Science ou Cell

    Bonjour à tous!

    Encore un énorme papier de Robert Weinberg, dans Cell...


    The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells


    Sendurai A. Mani, Wenjun Guo, Mai-Jing Liao, Elinor Ng. Eaton, Ayyakkannu Ayyanan, Alicia Y. Zhou, Mary Brooks, Ferenc Reinhard, Cheng Cheng Zhang, Michail Shipitsin, Lauren L. Campbell, Kornelia Polyak, Cathrin Brisken, Jing Yang, Robert A. Weinberg

    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.


    The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties.


    Cell 133, 704–715, May 16, 2008 Elsevier Inc.


    http://http://www.ncbi.nlm.nih.gov/p...ubmed_RVDocSum


    V.
    Dernière modification par Vinc ; 28/05/2008 à 14h20.
    Primum non nocere.

  35. #120
    LXR

    Re : Articles importants dans Nature, Science ou Cell

    Ce papier m'étonne qu'à moitié. En effet l'EMT implique un remodelage des marques épigénétiques définissant un phénotype épithélial pour les "reconfigurer" en phénotype mésenchymateux. On a donc affaire à un processus de différenciation nécessitant sans doute une étape intermédiaire de dédifférenciation qui enlève les marques épigénétiques épithéliales. Donc l'émergence de cellules avec un phénotype stem-like pouvait être prévisible. Mais comment que ce soit, chapeau à la Weinberg's Team.

    Greg
    Never give up.

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