44 research outputs found

    The Cytosolic Protein G0S2 Maintains Quiescence in Hematopoietic Stem Cells

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    Bone marrow hematopoietic stem cells (HSCs) balance proliferation and differentiation by integrating complex transcriptional and post-translational mechanisms regulated by cell intrinsic and extrinsic factors. We found that transcripts of G0/G1 switch gene 2 (G0S2) are enriched in lineage− Sca-1+ c-kit+ (LSK) CD150+ CD48− CD41− cells, a population highly enriched for quiescent HSCs, whereas G0S2 expression is suppressed in dividing LSK CD150+ CD48− cells. Gain-of-function analyses using retroviral expression vectors in bone marrow cells showed that G0S2 localizes to the mitochondria, endoplasmic reticulum, and early endosomes in hematopoietic cells. Co-transplantation of bone marrow cells transduced with the control or G0S2 retrovirus led to increased chimerism of G0S2-overexpressing cells in femurs, although their contribution to the blood was reduced. This finding was correlated with increased quiescence in G0S2-overexpressing HSCs (LSK CD150+ CD48−) and progenitor cells (LS−K). Conversely, silencing of endogenous G0S2 expression in bone marrow cells increased blood chimerism upon transplantation and promoted HSC cell division, supporting an inhibitory role for G0S2 in HSC proliferation. A proteomic study revealed that the hydrophobic domain of G0S2 interacts with a domain of nucleolin that is rich in arginine-glycine-glycine repeats, which results in the retention of nucleolin in the cytosol. We showed that this cytosolic retention of nucleolin occurs in resting, but not proliferating, wild-type LSK CD150+ CD48− cells. Collectively, we propose a novel model of HSC quiescence in which elevated G0S2 expression can sequester nucleolin in the cytosol, precluding its pro-proliferation functions in the nucleolus

    Fundamental shift in vitamin B12 eco-physiology of a model alga demonstrated by experimental evolution

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    A widespread and complex distribution of vitamin requirements exists over the entire tree of life, with many species having evolved vitamin dependence, both within and between different lineages. Vitamin availability has been proposed to drive selection for vitamin dependence, in a process that links an organism's metabolism to the environment, but this has never been demonstrated directly. Moreover, understanding the physiological processes and evolutionary dynamics that influence metabolic demand for these important micronutrients has significant implications in terms of nutrient acquisition and, in microbial organisms, can affect community composition and metabolic exchange between coexisting species. Here we investigate the origins of vitamin dependence, using an experimental evolution approach with the vitamin B 12 -independent model green alga Chlamydomonas reinhardtii. In fewer than 500 generations of growth in the presence of vitamin B 12, we observe the evolution of a B 12 -dependent clone that rapidly displaces its ancestor. Genetic characterization of this line reveals a type-II Gulliver-related transposable element integrated into the B 12 -independent methionine synthase gene (METE), knocking out gene function and fundamentally altering the physiology of the alga

    Ex Vivo Expansion of Murine and Human Hematopoietic Stem Cells

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    Guest-Adaptable and Water-Stable Peptide-Based Porous Materials by Imidazolate Side Chain Control

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    The peptide‐based porous 3D framework, ZnCar, has been synthesized from Zn2+ and the natural dipeptide carnosine (β‐alanyl‐L ‐histidine). Unlike previous extended peptide networks, the imidazole side chain of the histidine residue is deprotonated to afford Zn–imidazolate chains, with bonding similar to the zeolitic imidazolate framework (ZIF) family of porous materials. ZnCar exhibits permanent microporosity with a surface area of 448 m2 g−1, and its pores are 1D channels with 5 Å openings and a characteristic chiral shape. This compound is chemically stable in organic solvents and water. Single‐crystal X‐ray diffraction (XRD) showed that the ZnCar framework adapts to MeOH and H2O guests because of the torsional flexibility of the main His‐β‐Ala chain, while retaining the rigidity conferred by the Zn–imidazolate chains. The conformation adopted by carnosine is driven by the H bonds formed both to other dipeptides and to the guests, permitting the observed structural transformations

    Implementation of Industry 4.0 in Germany, Brazil and Portugal: Barriers and Benefits

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    Part 5: Industry 4.0 ImplementationsInternational audienceIndustry 4.0 is a subject that has attracted the interests of researches worldwide for its ability to achieve productivity gains and to provide competitiveness to the companies. Although much research has been done on technical studies, little attention has been paid to the challenges that decision-makers, executives and managers face to implement the concepts of Industry 4.0 in their companies. This research was based on secondary data, involving a research made with 246 companies in Brazil, 287 in Germany and 72 in Portugal, which studied the internal and external obstacles and expectations of these 605 companies. The originality and practical implication of this research is to compare these three countries, studying common and different points to implement the concepts of Industry 4.0, so researchers can conduct their studies to try to provide answers to practical expectations, linking research to practice
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