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  • 1
    Publication Date: 2018-11-30
    Description: Myelodysplastic syndromes (MDSs) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis. Anemia is the defining cytopenia of MDS patients, yet the molecular mechanisms for dyserythropoiesis in MDSs remain to be fully defined. Recent studies have revealed that heterozygous loss-of-function mutation of DNA dioxygenase TET2 is 1 of the most common mutations in MDSs and that TET2 deficiency disturbs erythroid differentiation. However, mechanistic insights into the role of TET2 on disordered erythropoiesis are not fully defined. Here, we show that TET2 deficiency leads initially to stem cell factor (SCF)–dependent hyperproliferation and impaired differentiation of human colony-forming unit–erythroid (CFU-E) cells, which were reversed by a c-Kit inhibitor. We further show that this was due to increased phosphorylation of c-Kit accompanied by decreased expression of phosphatase SHP-1, a negative regulator of c-Kit. At later stages, TET2 deficiency led to an accumulation of a progenitor population, which expressed surface markers characteristic of normal CFU-E cells but were functionally different. In contrast to normal CFU-E cells that require only erythropoietin (EPO) for proliferation, these abnormal progenitors required SCF and EPO and exhibited impaired differentiation. We termed this population of progenitors "marker CFU-E" cells. We further show that AXL expression was increased in marker CFU-E cells and that the increased AXL expression led to increased activation of AKT and ERK. Moreover, the altered proliferation and differentiation of marker CFU-E cells were partially rescued by an AXL inhibitor. Our findings document an important role for TET2 in erythropoiesis and have uncovered previously unknown mechanisms by which deficiency of TET2 contributes to ineffective erythropoiesis.
    Keywords: Red Cells, Iron, and Erythropoiesis
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2018-09-05
    Description: Neutrophil extracellular trap (NET) formation can generate short-term, functional anucleate cytoplasts and trigger loss of cell viability. We demonstrated that the necroptotic cell death effector mixed lineage kinase domain–like (MLKL) translocated from the cytoplasm to the plasma membrane and stimulated downstream NADPH oxidase–independent ROS production, loss of cytoplasmic granules, breakdown of the nuclear membrane, chromatin decondensation, histone hypercitrullination, and extrusion of bacteriostatic NETs. This process was coordinated by receptor-interacting protein kinase-1 (RIPK1), which activated the caspase-8–dependent apoptotic or RIPK3/MLKL-dependent necroptotic death of mouse and human neutrophils. Genetic deficiency of RIPK3 and MLKL prevented NET formation but did not prevent cell death, which was because of residual caspase-8–dependent activity. Peptidylarginine deiminase 4 (PAD4) was activated downstream of RIPK1/RIPK3/MLKL and was required for maximal histone hypercitrullination and NET extrusion. This work defines a distinct signaling network that activates PAD4-dependent NET release for the control of methicillin-resistant Staphylococcus aureus (MRSA) infection.
    Print ISSN: 1945-0877
    Topics: Medicine
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  • 3
    Publication Date: 2018-05-31
    Description: A magnetically modified rice husk biochar (MBC) was successfully prepared by a hydrothermal method from original biochar (BC) and subsequently used to remove phenanthrene (PHE) from aqueous solutions. The porosity, specific surface area and hydrophobicity of BC were significantly improved (approx. two times) after magnetic modification. The adsorption data fitted well to pseudo-second-order kinetic and Langmuir models. Compared with BC, MBC had a faster adsorption rate and higher adsorption capacity of PHE. The adsorption equilibrium for PHE on MBC was achieved within 1.0 h. The maximum adsorption capacity of PHE on MBC was 97.6 mg g –1 based on the analysis of the Sips model, which was significantly higher than that of other sources of BCs. The adsorption mechanism of the two BCs was mainly attributed to the action of surface functional groups and –-conjugated reactions. The adsorption of PHE on MBC mainly occurred in the functional groups of C–O and Fe 3 O 4 , but that on BC was mainly in the functional groups of –OH, N–H, C=C and C–O.
    Keywords: environmental engineering
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 4
    Publication Date: 2018-01-26
    Description: Reemergence of high- T c superconductivity in the (Li 1-x Fe x )OHFe 1-y Se under high pressure Reemergence of high-〈i〉T〈/i〉〈sub〉c〈/sub〉 superconductivity in the (Li〈sub〉1-x〈/sub〉Fe〈sub〉 x 〈/sub〉)OHFe〈sub〉1-y〈/sub〉Se under high pressure, Published online: 25 January 2018; doi:10.1038/s41467-018-02843-7 The understanding of the reemergence of pressure induced superconductivity in alkali-metal intercalated FeSe is hampered by sample complexities. Here, Sun et al. report the electronic properties of (Li1–xFe x )OHFe1–ySe single crystal not only in the reemerged superconducting state but also in the normal state.
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2018-08-21
    Description: The influence of Arctic amplification on mid-latitude summer circulation The influence of Arctic amplification on mid-latitude summer circulation, Published online: 20 August 2018; doi:10.1038/s41467-018-05256-8 Accelerated global warming in the Arctic might have profound impacts on mid-latitude weather particularly in winter, although the evidence for an effect also in summer is also growing. Here Coumou et al. show that these interactions could lead to more persistent hot-dry extremes in mid-latitudes.
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2018-02-21
    Description: The immune balance of the respiratory tract is strictly regulated. Extracellular vesicles (EVs) have been reported to participate in maintaining the immune balance in the intestinal tract, but whether they are involved in regulation of the immune balance in the respiratory tract has yet to be revealed. In this study, we found that physiological EVs from lungs of WT mice (L-EVs) could be isolated, which contained the immunosuppressive cytokines TGF-β1 and IL-10. Among L-EV subsets, only the CD8α + CD11c + EV subset was positive for TGF-β1 and IL-10 and could inhibit CD4 + T cell proliferation via TGF-β1 in vitro and relieve murine asthmatic symptoms. Mechanistically, L-EVs were effective at inhibiting OVA peptide–specific CD4 + T cell proliferation in a TGF-β1– and IL-10–dependent manner. In addition, they could prevent CD4 + T cells from hilar lymph nodes from secreting IL-4, IL-9, and IL-17A via IL-10 ex vivo, suggesting inhibition of Th2, Th9, and Th17 cell responses. Altogether, our results indicate that EVs from the lungs are involved in control of the immune balance in the respiratory tract, which reveals a novel mechanism in the maintenance of respiratory tract immune homeostasis.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 7
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-05-04
    Description: In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that the combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning.
    Keywords: Development, Engineering
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2018-07-13
    Description: It is known that insulin-like growth factor-1 (IGF-1) also functions as a hematopoietic factor, although its direct effect on thrombopoiesis remains unclear. In this study, we show that IGF-1 is able to promote CD34 + cell differentiation toward megakaryocytes (MKs), as well as the facilitation of proplatelet formation (PPF) and platelet production from cultured MKs. The in vivo study demonstrates that IGF-1 administration accelerates platelet recovery in mice after 6.0 Gy of irradiation and in mice that received bone marrow transplantation following 10.0 Gy of lethal irradiation. Subsequent investigations reveal that extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt activation mediate the effect of IGF-1 on thrombopoiesis. Notably, Akt activation induced by IGF-1 is more apparent than that of ERK1/2, compared with that of thrombopoietin (TPO) treatment. Moreover, the effect of IGF-1 on thrombopoiesis is independent of TPO signaling because IGF-1 treatment can also lead to a significant increase of platelet counts in homozygous TPO receptor mutant mice. Further analysis indicates that the activation of Akt triggered by IGF-1 requires the assistance of steroid receptor coactivator-3 (SRC-3). Therefore, our data reveal a distinct role of IGF-1 in regulating thrombopoiesis, providing new insights into TPO-independent regulation of platelet generation.
    Keywords: Platelets and Thrombopoiesis
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 9
    Publication Date: 2018-11-01
    Description: Huge amount of aged oily sludge was generated during the drilling and transportation of crude oil. Sometimes, the sludge exhibited characters of combined pollution, such as saline-alkali oily sludge. Orthogonal experiments of L 16 (4 5 ) were conducted to evaluate the long-term effects of total petroleum hydrocarbons (TPH) concentration, microbial agents (Oil Gator and ZL) and bulking agents (peat and wheat bran) on the biodegradation of aged saline-alkali oily sludge. Compared with the control group, the significant improvement in the removal rate of TPH was exhibited with the addition of microbial agents and bulking agents after 231 days of the experimental period. Based on the values of mean range ( R ), it was revealed that the predominant influencing factor of the bioremediation was TPH concentration. After biostimulation and bioaugmentation, the quantity of petroleum hydrocarbon-degrading bacteria in the oily sludge increased by 2–4 orders of magnitude. Furthermore, the bioremediation improved the microbial diversity based on the analysis of PCR-DGGE. It was inferred that the addition of microbial agents and bulking agents reconstructed the microbial ecological niche. The principal component analysis indicated that the differentiation of the microbial community was generated by the biostimulation and bioaugmentation in comparison with the control samples.
    Keywords: environmental engineering, environmental science
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 10
    Publication Date: 2018-11-01
    Description: Pure WO 3 and Ag-WO 3 (mixed solid solutions Ag with WO 3 ) have been successfully synthesized by sol-gel method and the influences of calcination temperature on the particle size, morphology of the WO 3 and Ag-WO 3 nanoparticles were investigated. Powder X-ray diffraction results show that the hexagonal to monoclinic phase transition occurs at calcination temperature varying from 300°C to 500°C. SEM images show that calcination temperature plays an important role in controlling the particle size and morphology of the as-prepared WO 3 and Ag-WO 3 nanoparticles. The NO 2 gas sensing properties of the sensors based on WO 3 and Ag-WO 3 nanoparticles calcined at different temperatures were investigated and the experimental results exhibit that the gas sensing properties of the Ag-WO 3 sensors were superior to those of the pure WO 3 . Especially, the sensor based on Ag-WO 3 calcined at 500°C possessed larger response, better selectivity, faster response/recovery and better longer-term stability to NO 2 than the others at relatively low operating temperature (150°C).
    Keywords: materials science, nanotechnology, analytical chemistry
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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