Effet du stress prolifératif sur la fonction des cellules souches hématopoïétiques : rôles des gènes Scl, E2A et Heb

Le système hématopoïétique est un tissu en constant renouvellement et les cellules souches hématopoïétiques (CSHs) sont indispensables pour soutenir la production des cellules matures du sang. Deux fonctions définissent les CSHs; la propriété d’auto-renouvellement, soit la capacité de préserver l’identité cellulaire suivant une division, et la multipotence, le potentiel de différenciation permettant de générer toutes les lignées hématopoïétiques. Chez l’adulte, la majorité des CSHs sont quiescentes et l’altération de cet état corrèle avec une diminution du potentiel de reconstitution des CSHs, suggérant que la quiescence protège les fonctions des CSHs. La quiescence est un état réversible et dynamique et les réseaux génétiques le contrôlant restent peu connus. Un nombre croissant d’évidences suggère que si à l’état d’homéostasie il y a une certaine redondance entre les gènes impliqués dans ces réseaux de contrôle, leurs rôles spécifiques sont révélés en situation de stress. La famille des bHLHs (basic helix-loop-helix) inclue différentes classes des protéines dont ceux qui sont tissu-spécifiques comme SCL, et les protéines E, comme E12/E47 et HEB. Certains bHLHs sont proposés êtres important pour la fonction des cellules souches, mais cela ne fait pas l’unanimité, car selon le contexte cellulaire, il y a redondance entre ces facteurs. La question reste donc entière, y a-t-il un rôle redondant entre les bHLHs d’une même classe pour la fonction à long-terme des CSHs? Les travaux présentés dans cette thèse visaient dans un premier temps à explorer le lien encore mal compris entre la quiescence et la fonction des CSHs en mesurant leurs facultés suite à un stress prolifératif intense et dans un deuxième temps, investiguer l’importance et la spécificité de trois gènes pour la fonction des CSHs adultes, soit Scl/Tal1, E2a/Tcf3 et Heb/Tcf12. Pour répondre à ces questions, une approche cellulaire (stress prolifératif) a été combinée avec une approche génétique (invalidation génique). Plus précisément, la résistance des CSHs au stress prolifératif a été étudiée en utilisant deux tests fonctionnels quantitatifs optimisés, soit un traitement basé sur le 5-fluorouracil, une drogue de chimiothérapie, et la transplantation sérielle en nombre limite. Dans la mesure où la fonction d’un réseau génique ne peut être révélée que par une perturbation intrinsèque, trois modèles de souris, i.e. Scl+/-, E2a+/- et Heb+/- ont été utilisés. Ceci a permis de révéler que l’adaptation des CSHs au stress prolifératif et le retour à l’équilibre est strictement contrôlé par les niveaux de Scl, lesquels règlent le métabolisme cellulaire des CSHs en maintenant l’expression de gènes ribosomaux à un niveau basal. D’autre part, bien que les composantes du réseau puissent paraître redondants à l’équilibre, mes travaux montrent qu’en situation de stress prolifératif, les niveaux de Heb restreignent la prolifération excessive des CSHs en induisant la sénescence et que cette fonction ne peut pas être compensée par E2a. En conclusion, les résultats présentés dans cette thèse montrent que les CSHs peuvent tolérer un stress prolifératif intense ainsi que des dommages à l’ADN non-réparés, tout en maintenant leur capacité de reconstituer l’hématopoïèse à long-terme. Cela implique cependant que leur métabolisme revienne au niveau de base, soit celui trouvé à l’état d’homéostasie. Par contre, avec l’augmentation du nombre de division cellulaire les CSHs atteignent éventuellement une limite d’expansion et entrent en sénescence.

Use of Natural Vegetative Barriers to Limit Expansion of Blacktailed Prairie Dog Towns

Prairie dog (Cynomys ludovicianus) control has historically consisted of lethal methods to maintain, reduce, or eliminate populations in South Dakota and throughout the species range. Non-lethal methods of control are desired to meet changing management objectives for the black-tailed prairie dog. The use of naturally occurring buffer strips as vegetative barriers may be effective in limiting prairie dog town expansion. The objectives of this study were: 1) to evaluate effective width of vegetative barriers in limiting prairie dog towns expansion in western South Dakota; and 2) to document effect native vegetation height on expansion of prairie dog towns in western South Dakota. Five study sites were established in western South Dakota on rangelands containing prairie dog towns of adequate size. Electric fences were constructed for the purpose of excluding cattle and creating buffer strips of native grasses and shrubs. Prairie dogs were poisoned to create a prairie dog free buffer zone adjacent to active prairie dog towns. Grazing was allowed on both sides of the buffer strip. When grazing pressure was not sufficient, mowing was used to simulate grazing. Buffer strips were 100 meters long and 10, 25, and 40 meters in width. A zero meter control was included on all study sites. Quadrats (25) were randomly distributed throughout the buffer strips. Evaluation of study sites included visual obstruction, vegetation cover, vegetation frequency, vegetation height, and vegetation identification. Barrier penetration was evaluated by the presence of new active burrows behind vegetative barriers. Significant relationships were documented for both VOR and vegetation height. No significant difference was found between frequency of breakthroughs and buffer widths.

Russian wheat aphids (Diuraphis noxia) in China : native range expansion or recent introduction?

In this study, we explore the population genetics of the Russian wheat aphid (RWA) (Diuraphis noxia), one of the world’s most invasive agricultural pests, in north-western China. We have analysed the data of 10 microsatellite loci and mitochondrial sequences from 27 populations sampled over 2 years in China. The results confirm that the RWAs are holocyclic in China with high genetic diversity indicating widespread sexual reproduction. Distinct differences in microsatellite genetic diversity and distribution revealed clear geographic isolation between RWA populations in northern and southern Xinjiang, China, with gene flow interrupted across extensive desert regions. Despite frequent grain transportation from north to south in this region, little evidence for RWA translocation as a result of human agricultural activities was found. Consequently, frequent gene flow among northern populations most likely resulted from natural dispersal, potentially facilitated by wind currents. We also found evidence for the longterm existence and expansion of RWAs in China, despite local opinion that it is an exotic species only present in China since 1975. Our estimated date of RWA expansion throughout China coincides with the debut of wheat domestication and cultivation practices in western Asia in the Holocene. We conclude that western China represents the limit of the far eastern native range of this species. This study is the most comprehensive molecular genetic investigation of the RWA in its native range undertaken to date and provides valuable insights into the history of the association of this aphid with domesticated cereals and wild grasses.

The virial expansion of a classical interacting system

We consider N particles interacting pairwise by an inverse square potential in one dimension (Calogero-Sutherland-Moser model). For a system placed in a harmonic trap, its classical partition function for the repulsive regime is recognised in the literature. We start by presenting a concise re-derivation of this result. The equation of state is then calculated both for the trapped and the homogeneous gas. Finally, the classical limit of Wu's distribution function for fractional exclusion statistics is obtained and we re-derive the classical virial expansion of the homogeneous gas using this distribution function.

New Mass Limit for White Dwarfs: Super-Chandrasekhar Type Ia Supernova as a New Standard Candle

Type Ia supernovae, sparked off by exploding white dwarfs of mass close to the Chandrasekhar limit, play the key role in understanding the expansion rate of the Universe. However, recent observations of several peculiar type Ia supernovae argue for its progenitor mass to be significantly super-Chandrasekhar. We show that strongly magnetized white dwarfs not only can violate the Chandrasekhar mass limit significantly, but exhibit a different mass limit. We establish from a foundational level that the generic mass limit of white dwarfs is 2.58 solar mass. This explains the origin of overluminous peculiar type Ia supernovae. Our finding further argues for a possible second standard candle, which has many far reaching implications, including a possible reconsideration of the expansion history of the Universe. DOI: 10.1103/PhysRevLett.110.071102

Quantum Flows as Markovian Limit of Emission, Absorption and Scattering Interactions

Gough, John, (2004) 'Quantum Flows as Markovian Limit of Emission, Absorption and Scattering Interactions', Communications in Mathematical Physics 254 pp.498-512 RAE2008

Cryptic lineages and Pleistocene population expansion in a Brazilian Cerrado frog

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

LIMIT CYCLES of DISCONTINUOUS PIECEWISE LINEAR DIFFERENTIAL SYSTEMS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bifurcation of limit cycles from an n-dimensional linear center inside a class of piecewise linear differential systems

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

HEAT-KERNEL EXPANSION AT FINITE TEMPERATURE

We show how the zero-temperature result for the heat-kernel asymptotic expansion can be generalized to the finite-temperature one. We observe that this general result depends on the interesting ratio square-root tau/beta, where tau is the regularization parameter and beta = 1/T, so that the zero-temperature limit beta --> infinity corresponds to the cutoff limit tau --> 0. As an example, we discuss some aspects of the axial model at finite temperature.

On the limit cycles of a class of piecewise linear differential systems in R-4 with two zones

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Layered superconductivity models at the London limit and their continuum properties

We write the London limit of the Lawrence Doniach free energy in terms of the local magnetic field and of the average supercurrent over the interplane distance. Starting from this formulation we study a model where the supercurrent at the buffer layers is obtained from the superconducting sheets by a Taylor expansion. The continuum limit of this model gives corrections to the anisotropic London theory due to the layered structure.

Post-sphaleron baryogenesis and an upper limit on the neutron-antineutron oscillation time

A recently proposed scenario for baryogenesis, called post-sphaleron baryogenesis (PSB), is discussed within a class of quark-lepton unified framework based on the gauge symmetry SU(2)L×SU(2) R×SU(4)c realized in the multi-TeV scale. The baryon asymmetry of the Universe in this model is produced below the electroweak phase transition temperature after the sphalerons have decoupled from the Hubble expansion. These models embed naturally the seesaw mechanism for neutrino masses and predict color-sextet scalar particles in the TeV range which may be accessible to the LHC experiments. A necessary consequence of this scenario is the baryon-number-violating ΔB=2 process of neutron-antineutron (n-n̄) oscillations. In this paper we show that the constraints of PSB, when combined with the neutrino oscillation data and restrictions from flavor changing neutral currents mediated by the colored scalars, imply an upper limit on the n-n̄ oscillation time of 5×1010 sec regardless of the quark-lepton unification scale. If this scale is relatively low, in the (200-250) TeV range, τn-n̄ is predicted to be less than 1010 sec, which is accessible to the next generation of proposed experiments. © 2013 American Physical Society.

The Ground State Energy per Site of the Quantum and Classical Edwards-Anderson Spin Glass in the Thermodynamic Limit

We derive general rigorous lower bounds for the average ground state energy per site e ((d)) of the quantum and classical Edwards-Anderson spin-glass model in dimensions d=2 and d=3 in the thermodynamic limit. For the classical model they imply that e ((2))a parts per thousand yena'3/2 and e ((3))a parts per thousand yena'2.204a <-.