20 research outputs found
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ExoFiT: ExoMars-Like Field Trials – a Mission Simulation.
International audienceHere, we focus on the ExoMars-Like Field Trial (ExoFiT), a series of realistic mission simulations based on the ESA ExoMars rover mission slated to be launched in 2020. The mission will carry a suite of instruments to carry out its mission objectives focused on geological and exobiological researc
Salt-bridge modulates differential calcium-mediated ligand binding to integrin α1- and α2-I domains
Structure of PITPβ in Complex with Phosphatidylcholine: Comparison of Structure and Lipid Transfer to Other PITP Isoforms ,
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Recovery and curation of the Winchcombe (CM2) meteorite
The Winchcombe meteorite fell on February 28, 2021 and was the first recovered meteorite fall in the UK for 30 years, and the first UK carbonaceous chondrite. The meteorite was widely observed by meteor camera networks, doorbell cameras, and eyewitnesses, and 213.5 g (around 35% of the final recovered mass) was collected quickly—within 12 h—of its fall. It, therefore, represents an opportunity to study very pristine extra‐terrestrial material and requires appropriate careful curation. The meteorite fell in a narrow (600 m across) strewn field ~8.5 km long and oriented approximately east–west, with the largest single fragment at the farthest (east) end in the town of Winchcombe, Gloucestershire. Of the total known mass of 602 g, around 525 g is curated at the Natural History Museum, London. A sample analysis plan was devised within a month of the fall to enable scientists in the UK and beyond to quickly access and analyze fresh material. The sample is stored long term in a nitrogen atmosphere glove box. Preliminary macroscopic and electron microscopic examinations show it to be a CM2 chondrite, and despite an early search, no fragile minerals, such as halite, sulfur, etc., were observed
Genetic Ablation of Phosphatidylinositol Transfer Protein Function in Murine Embryonic Stem Cells
Phosphatidylinositol transfer proteins (PITPs) regulate the interface between signal transduction, membrane-trafficking, and lipid metabolic pathways in eukaryotic cells. The best characterized mammalian PITPs are PITPα and PITPβ, two highly homologous proteins that are encoded by distinct genes. Insights into PITPα and PITPβ function in mammalian systems have been gleaned exclusively from cell-free or permeabilized cell reconstitution and resolution studies. Herein, we report for the first time the use of genetic approaches to directly address the physiological functions of PITPα and PITPβ in murine cells. Contrary to expectations, we find that ablation of PITPα function in murine cells fails to compromise growth and has no significant consequence for bulk phospholipid metabolism. Moreover, the data show that PITPα does not play an obvious role in any of the cellular activities where it has been reconstituted as an essential stimulatory factor. These activities include protein trafficking through the constitutive secretory pathway, endocytic pathway function, biogenesis of mast cell dense core secretory granules, and the agonist-induced fusion of dense core secretory granules to the mast cell plasma membrane. Finally, the data demonstrate that PITPα-deficient cells not only retain their responsiveness to bulk growth factor stimulation but also retain their pluripotency. In contrast, we were unable to evict both PITPβ alleles from murine cells and show that PITPβ deficiency results in catastrophic failure early in murine embryonic development. We suggest that PITPβ is an essential housekeeping PITP in murine cells, whereas PITPα plays a far more specialized function in mammals than that indicated by in vitro systems that show PITP dependence
Conformational Dynamics of the Major Yeast Phosphatidylinositol Transfer Protein Sec14p: Insight into the Mechanisms of Phospholipid Exchange and Diseases of Sec14p-Like Protein Deficiencies
Molecular dynamics simulations coupled with functional analyses of the major yeast phosphatidylinositol/phosphatidylcholine transfer protein Sec14p identify structural elements involved in regulating the ability of Sec14p to execute phospholipid exchange. The molecular dynamics simulations suggest large rigid body motions within the Sec14p molecule accompany closing and opening of an A(10)/T(4)/A(11) helical gate, and that “state-of-closure” of this helical gate determines access to the Sec14p phospholipid binding cavity. The data also project that conformational dynamics of the helical gate are controlled by a hinge unit (residues F(212), Y(213), K(239), I(240), and I(242)) that links to the N- and C-terminal ends of the helical gate, and by a novel gating module (composed of the B(1)LB(2) and A(12)LT(5) substructures) through which conformational information is transduced to the hinge. The (114)TDKDGR(119) motif of B(1)LB(2) plays an important role in that transduction process. These simulations offer new mechanistic possibilities for an important half-reaction of the Sec14p phospholipid exchange cycle that occurs on membrane surfaces after Sec14p has ejected bound ligand, and is reloading with another phospholipid molecule. These conformational transitions further suggest structural rationales for known disease missense mutations that functionally compromise mammalian members of the Sec14-protein superfamily