204 research outputs found
Analyse de la régulation de l'homéostasie des télomères et de la chromatine dans le maintien de l'intégrité génomique chez la levure Saccharomyces cerevisiae
Toute l'information génétique octroyant l'existence à une cellule est encodée par les milliards de paires de bases d'ADN retrouvées principalement à l'intérieur du noyau. Toutefois, pour des raisons d'espace et d'accessibilité, tout cet ADN est soumis à de nombreuses étapes de compaction en plus d'être fractionné dans le but de former ultimement les chromosomes. Malgré que l'extrême compaction de l'ADN permette la protection des acides nucléiques contre la dégradation, certaines structures demeurent vulnérables et nécessitent une protection toute particulière. C'est le cas de séquences se retrouvant à l'extrémité des chromosomes, les télomères. Les télomères sont constitués de répétitions en tandem d'ADN non codant associées avec de nombreuses protéines spécialisées permettant une protection efficace contre la perte d'informations génétiques dû à la dégradation enzymatique ou à l'érosion naturelle. Ces structures télomériques sont normalement maintenues par une machinerie spécialisée, la télomérase, qui composée d'une sous unité ARN et de partenaires protéiques permet l'ajout de séquences télomériques spécifiquement aux extrémités. Cette enzyme essentielle est régulée par de nombreuses protéines et parmi celles-ci, de nombreuses observations font état du rôle essentiel joué par deux protéines kinases, les protéines Tel1p et Mec1p. Ces kinases occupent une double fonction; elles sont importantes pour la régulation de la taille des télomères, mais sont également au coeur de la réponse cellulaire face aux dommages à l'ADN. Étant donné la nature des télomères, soit des extrémités d'ADN libres, ceux-ci sont identiques en de nombreux points aux cassures double brins d'ADN expliquant probablement la double implication de ces protéines. Durant mes études, je me suis particulièrement intéressé à la double fonction jouée par les kinases Tel1p et Mec1p au niveau des télomères et du processus de réponse aux dommages à l'ADN. Dans un premier temps, avec l'aide d'un collègue j'ai pu démontrer l'étendue des fonctions télomériques et de réponses aux dommages à l'ADN jouées par Tel1p via l'isolation et la caractérisation d'un allèle de séparation de fonctions. Dans un deuxième temps, en poursuivant mes analyses génétiques sur la kinase Tel1p, j'ai pu déterminer que cette protéine possédait des fonctions indépendantes à celles octroyées par son domaine kinase, observation allant à l'encontre de l'idée générale que Tel1p sans fonction kinase opérationnelle simulait un allèle nul. Dans la même ligne de pensée, mes études ont permis d'identifier un nouveau mécanisme de régulation de la télomérase essentiel joué par les kinases Mec1p et Tel1p. En parallèle, je me suis intéressé aux mécanismes cellulaires permettant une régulation de l'enroulement global de l'ADN permettant son accessibilité à toutes les machineries cellulaires de transcription, de réparation et de réplication de l'ADN. Mes travaux ont permis d'identifier qu'une modification des histones, protéines critiques dans le processus de compaction de l'ADN, était extrêmement importante dans le processus de réponse aux dommages à l'ADN. En effet la triméthylation de l'histone H3 sur sa lysine 4 permet à la cellule de pouvoir efficacement réparer les dommages via la réparation de bout non-homologue et permettait de stabiliser les fourches de réplications soumises à un stress cellulaire. Globalement mes résultats m'ont permis de mieux comprendre deux moyens distincts utilisés par les cellules pour maintenir l'intégrité de leur génome : les rôles joués par les kinases Tel1p et Mec1p aux télomères et dans la réparation des dommages à l'ADN, ainsi que l'implication de la modification d'histone H3K4me3 dans le processus de réponse aux dommages à l'ADN
Statistics of gamma-ray point sources below the Fermi detection limit
An analytic relation between the statistics of photons in pixels and the
number counts of multi-photon point sources is used to constrain the
distribution of gamma-ray point sources below the Fermi detection limit at
energies above 1 GeV and at latitudes below and above 30 degrees. The derived
source-count distribution is consistent with the distribution found by the
Fermi collaboration based on the first Fermi point source catalogue. In
particular, we find that the contribution of resolved and unresolved active
galactic nuclei (AGN) to the total gamma-ray flux is below 20% - 25%. In the
best fit model, the AGN-like point source fraction is 17% +- 2%. Using the fact
that the Galactic emission varies across the sky while the extra-galactic
diffuse emission is isotropic, we put a lower limit of 51% on Galactic diffuse
emission and an upper limit of 32% on the contribution from extra-galactic weak
sources, such as star-forming galaxies. Possible systematic uncertainties are
discussed.Comment: 26 pages, 10 figures, 1 table; v2: clarifications and references
added, v3: more detailed presentation of the metho
Age-Related Decline in Reproductive Sensitivity to Inhibition by Short Photoperiod in Peromyscus Leucopus
Seasonal environments favor the timing, of reproduction to match seasons when Successful reproduction is most likely. Most species of temperate zone mammals suppress reproduction in winter using changes in day length as a cue. In many species, individuals vary genetically in how strongly they respond to these seasonal cues. Individuals also may modify their response to day length depending upon other factors, including their age. Age-specific changes might occur because young, peripubertal rodents are more strongly affected by harsh conditions than adults, and therefore might be more sensitive to inhibitory photoperiods. We tested the hypothesis that genetic variation in responses to photoperiod persists as individuals age. Young males from a captive population of white-footed mice (Peromyscus leucopus) that is genetically variable for reproductive inhibition by short day length (SD) were tested for photoperiod responses. Mice were placed in SD within 3 days after birth, tested at age 70 days, allowed to mature for at least 18 weeks at long day length, and then tested again as adults aged \u3e= 34 weeks. Young males were more likely to be strongly reproductively Suppressed by SD than adults, indicating that age-specific changes in reproductive strategy occur in this Population. However, males that were reproductively photoresponsive when young also were more likely to be reproductively photoresponsive as adults. Thus, genetic tendency for reproductive sensitivity to photoperiod is a trait retained from puberty to adulthood, but attenuates with age
Mean-flux Regulated PCA Continuum Fitting of SDSS Lyman-alpha Forest Spectra
Continuum fitting is an important aspect of Lyman-alpha forest science, since
errors in the estimated optical depths scale with the fractional continuum
error. However, traditional methods of estimating continua in noisy and
moderate-resolution spectra (S/N < 10 pixel^-1 and R ~ 2000, respectively, such
as SDSS) using power-law extrapolation or the mean spectrum, achieve no better
than ~ 10-15% RMS accuracy. To improve on this, we introduce mean-flux
regulated/principal component analysis (MF-PCA) continuum fitting. In this
technique, PCA fitting is carried out redwards of the quasar Lyman-alpha line
in order to provide a prediction for the shape of the Lyman-alpha forest
continuum. The slope and amplitude of this continuum prediction is then
corrected using external constraints for the Lyman-alpha forest mean-flux. From
tests on mock spectra, we find that MF-PCA reduces the errors to 8% RMS in S/N
~ 2 spectra, and 5. The residual Fourier power
in the continuum is decreased by a factor of a few in comparison with dividing
by the mean continuum, enabling Lyman-alpha flux power spectrum measurements to
be extended to ~2x larger scales. Using this new technique, we make available
continuum fits for 12,069 z>2.3 Lyman-alpha forest spectra from SDSS DR7 for
use by the community. This technique is also applicable to future releases of
the ongoing BOSS survey, which is obtaining spectra for ~ 150,000 Lyman-alpha
forest spectra at low signal-to-noise (S/N ~ 2).Comment: 14 pages; 11 figures; submitted to AJ. Continua publicly available
via anonymous FTP or Data Conservancy repositor
Extended Lyman-Alpha Emission around Star-forming Galaxies
Lyman-alpha (Lya) photons that escape the interstellar medium of star-forming
galaxies may be resonantly scattered by neutral hydrogen atoms in the
circumgalactic and intergalactic media, thereby increasing the angular extent
of the galaxy's Lya emission. We present predictions of this extended, low
surface brightness Lya emission based on radiative transfer modeling in a
cosmological reionization simulation. The extended emission can be detected
from stacked narrowband images of Lya emitters (LAEs) or of Lyman break
galaxies (LBGs). Its average surface brightness profile has a central cusp,
then flattens to an approximate plateau beginning at an inner characteristic
scale below ~0.2 Mpc (comoving), then steepens again beyond an outer
characteristic scale of ~1 Mpc. The inner scale marks the transition from
scattered light of the central source to emission from clustered sources, while
the outer scale marks the spatial extent of scattered emission from these
clustered sources. Both scales tend to increase with halo mass, UV luminosity,
and observed Lya luminosity. The extended emission predicted by our simulation
is already within reach of deep narrowband photometry using large ground-based
telescopes. Such observations would test radiative transfer models of emission
from LAEs and LBGs, and they would open a new window on the circumgalactic
environment of high-redshift star-forming galaxies.Comment: 14 pages, 10 figures, accepted for publication in ApJ, revised
according to the referee's comments, more discussions and test
Insights to Molecular and Bulk Mechanical Properties of Glassy Carbon Through Molecular Dynamics Simulation and Mechanical Tensile Testing
With increasing interest in the use of glassy carbon (GC) for a wide variety
of application areas, the need for developing fundamental understanding of its
mechanical properties has come to the forefront. Further, recent theoretical
and modeling works that shed some light on the synthesis of GC through the
process of pyrolysis of polymer precursors have highlighted the possibilities
of a revisit to investigation of its mechanical properties at a fundamental
level. While there are isolated reports on the experimental determination of
its elastic modulus, insights into stress-strain behavior of GC material under
tension and compression obtained through simulation, either at molecular level
or for the bulk material is missing. This current study fills the gap at the
molecular level and investigates the mechanical properties of GC using
molecular dynamics (MD) simulations which model the atomistic level formation
and breaking of bonds using bond-order based reactive force field formulations.
The molecular model considered for this simulation has a characteristics 3D
cagey structure of 5-, 6-, and 7-membered carbon rings and graphitic domain of
a flat graphene-like structure. The GC molecular model was subjected to loading
under varying strain rates (0.4/ns, 0.6/ns, 1.25/ns, and 2.5/ns) and varying
temperatures (300 - 800 K) in each of the three axes x, y, and z. The
simulation showed that GC molecule has distinct stress-strain curves under
tension and compression. In tension, MD modeling predicted mean elastic modulus
of 5.71 GPa for a single GC molecule with some dependency on strain rates and
temperature, while in compression, the elastic modulus was also found to depend
on the strain rates as well as temperature and was predicted to have a mean
value of 35 GP
He II Ly{\beta} Gunn-Peterson Absorption: New HST Observations, and Theoretical Expectations
Observations of He II Ly{\alpha} Gunn-Peterson troughs have proved to be a
valuable probe of the epoch of helium reionization at z~3. Since this optical
depth can become unmeasurably large even for modest He II fractions, various
alternate techniques have been proposed to push to higher redshift, and among
the more promising is looking at higher order Lyman-series troughs. We here
report four new observations of the He II Ly{\beta} trough, including new data
on the only sightline with a prior Ly{\beta} observation. However, the
effective optical depth ratio {\tau}_eff,{\beta}/{\tau}_eff,{\alpha} is not
simply predicted by (f_{\beta} {\lambda}_{\beta})/(f_{\alpha}
{\lambda}_{\alpha})=0.16, and we analyze cosmological simulations to find that
the correct ratio for helium at z~3 is ~0.35. In one case we infer
{\tau}_eff,{\alpha} > 8.8, strong evidence that helium was not fully reionized
at z=3.2--3.5, in agreement with previous measurements suggesting a later
completion of reionization.Comment: ApJ accepted. 25 pages, 3 figures, 4 table
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