2,262 research outputs found

    UBR2 of the N-end rule pathway is required for chromosome stability via histone ubiquitylation in spermatocytes and somatic cells

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    The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells. © 2012 Kwon et al

    Techno-economic assessment of fertiliser drawn forward osmosis process for greenwall plants from urban wastewater

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    © 2019 Institution of Chemical Engineers Pressure-assisted osmosis (PAO) has been suggested to integrate with fertiliser driven forward osmosis (FDFO) to improve the overall efficiency of simultaneous wastewater reuse and fertiliser osmotic dilution. This study aims to demonstrate the techno-economic feasibility of pressure-assisted fertiliser driven forward osmosis (PAFDO) hybrid system compared to the existing ultraviolet and reverse osmosis (UV–RO) process. The results showed that coupling FDFO with PAO (i.e. PAFDO) could help fulfill the water quality required for greenwall fertigation. An economic analysis on capital and operational costs for the PAFDO showed that the PAO mode application at a lower FDFO dilution stage could significantly reduce the costs. However, when considering the different applied pressures in PAO (i.e. 2, 4, and 6 bar), the increase in the total water cost was not significant. This indicates that the dilution stage for applying PAO is more sensitive to the total water cost of the PAFDO than the applied pressure. A coupling of higher average water flux (>10 L/m2h) and lower draw solution (DS) dilution factor (DF < 60) is recommended. Therefore, this could make the PAFDO system economically viable compared to the benchmark for the UV-RO disinfection system

    Oxygen-Vacancy-Induced Orbital Reconstruction of Ti Ions at the Interface of LaAlO3/SrTiO3 Heterostructures: A Resonant Soft-X-Ray Scattering Study

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    Resonant soft-x-ray scattering measurements have been performed to investigate interface electronic structures of (LaAlO3/SrTiO3) superlattices. Resonant scattering intensities at superlattice reflections show clear evidence of degeneracy lifting in t(2g) states of interface Ti ions. Polarization dependence of intensities indicates the energy of d(xy) states is lower by similar to 1 eV than two other t(2g) states. The energy splitting is insensitive to epitaxial strain. The orbital reconstruction is induced by oxygen vacancies and confined to the interface within two unit cells, indicating charge compensation at the polar interfaces. DOI: 10.1103/PhysRevLett.110.017401X112723Nsciescopu

    Quantum confinement effect in ZnO/Mg0.2Zn0.8O multishell nanorod heterostructures

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    We report on photoluminescence measurements of Mg0.2Zn0.8O/ZnO/Mg0.2Zn0.8O multishell layers on ZnO core nanorods. Dominant excitonic emissions in the photoluminescence spectra show a blueshift depending on the ZnO shell layer thickness attributed to the quantum confinement effect in the nanorod heterostructure radial direction. Furthermore, near-field scanning optical microscopy clearly shows sharp photoluminescence peaks from the individual nanorod quantum structures, corresponding to subband levels.open114747sciescopu

    Dynamic magnetoelectric coupling in "electronic ferroelectric" LuFe2O4

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    Magnetoelectric (ME) coupling characteristics of LuFe2O4 were examined by monitoring the electrical voltage induced by an oscillating magnetic field under a static bias field (H-0). Interestingly, the room-temperature dynamic ME output exhibited a constant plateau behavior up to a certain static-field strength but showed a sudden drop above this critical value. In addition, two evidences of the intrinsic ME coupling were obtained by monitoring the pyroelectric response near the ferrimagnetic ordering temperature (similar to 250 K) and by examining the temperature-dependent magnetization near the ferroelectric transition point (similar to 345 K) between the two-dimensional charge-density-wave (CDW) state and the three-dimensional CDW state. (C) 2007 American Institute of Physics.open114951sciescopu

    Ferroelectric polarization switching with a remarkably high activation energy in orthorhombic GaFeO3 thin films

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    Orthorhombic GaFeO3 (o-GFO) with the polar Pna2(1) space group is a prominent ferrite owing to its piezoelectricity and ferrimagnetism, coupled with magnetoelectric effects. Herein, we demonstrate large ferroelectric remanent polarization in undoped o-GFO thin films by adopting either a hexagonal strontium titanate (STO) or a cubic yttrium-stabilized zirconia (YSZ) substrate. The polarization-electric-field hysteresis curves of the polar c-axis-grown o-GFO film on a SrRuO3/STO substrate show the net switching polarization of similar to 35 mu C cm(-2) with an unusually high coercive field (E-c) of +/- 1400 kV cm(-1) at room temperature. The positive-up and negative-down measurement also demonstrates the switching polarization of similar to 26 mu C cm(-2). The activation energy for the polarization switching, as obtained by density-functional theory calculations, is remarkably high, 1.05 eV per formula unit. We have theoretically shown that this high value accounts for the extraordinary high E-c and the stability of the polar Pna2(1) phase over a wide range of temperatures up to 1368 K.111714Ysciescopu

    Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist

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    Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the Delta dblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+) T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1 beta. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra.open111815sciescopu

    The Cell Shape-determining Csd6 Protein from Helicobacter pylori Constitutes a New Family of L,D-Carboxypeptidase

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    Helicobacter pylori causes gastrointestinal diseases, including gastric cancer. Its high motility in the viscous gastric mucosa facilitates colonization of the human stomach and depends on the helical cell shape and the flagella. In H. pylori, Csd6 is one of the cell shape-determining proteins that play key roles in alteration of cross-linking or by trimming of peptidoglycan muropeptides. Csd6 is also involved in deglycosylation of the flagellar protein FlaA. To better understand its function, biochemical, biophysical, and structural characterizations were carried out. We show that Csd6 has a three-domain architecture and exists as a dimer in solution. The N-terminal domain plays a key role in dimerization. The middle catalytic domain resembles those of L,D-transpeptidases, but its pocket-shaped active site is uniquely defined by the four loops I to IV, among which loops I and III show the most distinct variations from the known L,D-transpeptidases. Mass analyses confirm that Csd6 functions only as an L,D-carboxypeptidase and not as an L,D-transpeptidase. The D-Ala-complexed structure suggests possible binding modes of both the substrate and product to the catalytic domain. The C-terminal nuclear transport factor 2-like domain possesses a deep pocket for possible binding of pseudaminic acid, and in silico docking supports its role in deglycosylation of flagellin. On the basis of these findings, it is proposed that H. pylori Csd6 and its homologs constitute a new family of L,D-carboxypeptidase. This work provides insights into the function of Csd6 in regulating the helical cell shape and motility of H. pylori.1165Ysciescopu

    Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using Tc-99m-HMPAO

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    Exosomes known as nano-sized extracellular vesicles attracted recent interests due to their potential usefulness in drug delivery. Amid remarkable advances in biomedical applications of exosomes, it is crucial to understand in vivo distribution and behavior of exosomes. Here, we developed a simple method for radiolabeling of macrophage-derived exosome-mimetic nanovesicles (ENVs) with Tc-99m-HMPAO under physiologic conditions and monitored in vivo distribution of Tc-99m-HMPAO-ENVs using SPECT/CT in living mice. ENVs were produced from the mouse RAW264.7 macrophage cell line and labeled with Tc-99m-HMPAO for 1 hr incubation, followed by removal of free Tc-99m-HMPAO. SPECT/CT images were serially acquired after intravenous injection to BALB/c mouse. When ENVs were labeled with Tc-99m-HMPAO, the radiochemical purity of Tc-99m-HMPAO-ENVs was higher than 90% and the expression of exosome specific protein (CD63) did not change in Tc-99m-HMPAO-ENVs. Tc-99m-HMPAOENVs showed high serum stability (90%) which was similar to that in phosphate buffered saline until 5 hr. SPECT/CT images of the mice injected with Tc-99m-HMPAO-ENVs exhibited higher uptake in liver and no uptake in brain, whereas mice injected with Tc-99m-HMPAO showed high brain uptake until 5 hr. Our noninvasive imaging of radiolabeled-ENVs promises better understanding of the in vivo behavior of exosomes for upcoming biomedical application.114327Ysciescopu

    Barley plasma membrane intrinsic proteins (PIP aquaporins) as water and CO2 transporters

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    We identified barley aquaporins and demonstrated that one, HvPIP2;1, transports water and CO2. Regarding water homeostasis in plants, regulations of aquaporin expression were observed in many plants under several environmental stresses. Under salt stress, a number of plasma membrane-type aquaporins were down-regulated, which can prevent continuous dehydration resulting in cell death. The leaves of transgenic rice plants that expressed the largest amount of HvPIP2;1 showed a 40% increase in internal CO2 conductance compared with leaves of wild-type rice plants. The rate of CO2 assimilation also increased in the transgenic plants. The goal of our plant aquaporin research is to determine the key aquaporin species responsible for water and CO2 transport, and to improve plant water relations, stress tolerance, CO2 uptake or assimilation, and plant productivity via molecular breeding of aquaporins.</p
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