9 research outputs found

    The splicing-factor related protein SFPQ/PSF interacts with RAD51D and is necessary for homology-directed repair and sister chromatid cohesion

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    DNA double-stranded breaks (DSBs) are among the most severe forms of DNA damage and responsible for chromosomal translocations that may lead to gene fusions. The RAD51 family plays an integral role in preserving genome stability by homology directed repair of DSBs. From a proteomics screen, we recently identified SFPQ/PSF as an interacting partner with the RAD51 paralogs, RAD51D, RAD51C and XRCC2. Initially discovered as a potential RNA splicing factor, SFPQ was later shown to have homologous recombination and non-homologous end joining related activities and also to bind and modulate the function of RAD51. Here, we demonstrate that SFPQ interacts directly with RAD51D and that deficiency of both proteins confers a severe loss of cell viability, indicating a synthetic lethal relationship. Surprisingly, deficiency of SFPQ alone also leads to sister chromatid cohesion defects and chromosome instability. In addition, SFPQ was demonstrated to mediate homology directed DNA repair and DNA damage response resulting from DNA crosslinking agents, alkylating agents and camptothecin. Taken together, these data indicate that SFPQ association with the RAD51 protein complex is essential for homologous recombination repair of DNA damage and maintaining genome integrity

    Comparison of Community Climate System Model Simulations and Paleoclimate Data for the Western Pacific Warm Pool Climate during the Last Glacial Maximum

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    A highly debated research topic has been understanding the magnitude of tropical cooling in the western Pacic warm pool (WPWP) from the Last Glacial Maximum (LGM) to present-day. Paleoclimate data indicates a range of LGM cooling from 1-5°C. Using a radiative-convective model with an entraining plume calculation, the present-day and LGM snowlines can be explained with a 3.5°C surface cooling in the WPWP during the LGM. NCAR's CCSM 3 and 4 simulate LGM cooling of 2°C. By comparing the results of CCSM3 and CCSM4, the higher resolution CCSM4 replicated LGM boundary conditions more accurately, increased LGM precipitation rates 0.4 mm/day, and reduced the transport of drier subtropical air from the Northern Hemisphere into the WPWP. One of the major issues in the CCSM identied in this thesis is the propagation of a temperature signal associated with the boundary layer over mountains to the upper-levels of the troposphere

    Modern and glacial tropical snowlines controlled by sea surface temperature and atmospheric mixing

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    International audienceDuring the Last Glacial Maximum, tropical sea surface temperatures were 1 to 3 degrees C cooler than present(1-4), but the altitude of the snowlines of tropical glaciers(5,6) was lower than would be expected in light of these sea surface temperatures. Indeed, both glacial and twentieth-century snowlines seem to require lapse rates that are steeper than a moist adiabat(7,8). Here we use estimates of Last Glacial Maximum sea surface temperature in the Indo-Pacific warm pool based on the clumped isotope palaeotemperature proxy in planktonic foraminifera and coccoliths, along with radiative-convective calculations of vertical atmospheric thermal structure, to assess the controls on tropical glacier snowlines. Using extensive new data sets for the region, we demonstrate that mean environmental lapse rates are steeper than moist adiabatic during the recent and glacial. We reconstruct glacial sea surface temperatures 4 to 5 degrees C cooler than modern. We include modern and glacial sea surface temperatures in calculations of atmospheric convection that account for mixing between rising air and ambient air, and derive tropical glacier snowlines with altitudes consistent with twentieth-century and Last Glacial Maximum reconstructions. Sea surface temperature changes <= 3 degrees C are excluded unless glacial relative humidity values were outside the range associated with deep convection in the modern. We conclude that the entrainment of ambient air into rising air masses significantly alters the vertical temperature structure of the troposphere in modern and ancient regions of deep convection. Furthermore, if all glacial tropical temperatures were cooler than previously estimated, it would imply a higher equilibrium climate sensitivity than included in present models(9,10)

    The Microcirculation in Inflammation

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    The Microcirculation in Inflammation

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    Fe Iron

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