2,605 research outputs found

    Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gαs/Gαq-mediated protein kinases A/C.

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    VLGR1 (very large G protein-coupled receptor 1), also known as MASS1 (monogenic audiogenic seizure susceptible 1), is an orphan G protein-coupled receptor that contains a large extracellular N terminus with 35 calcium-binding domains. A truncating mutation in the Mass1 gene causes autosomal recessive, sound-induced seizures in the Frings mouse. However, the function of MASS1 and the mechanism underlying Frings mouse epilepsy are not known. Here, we found that MASS1 protein is enriched in the myelinated regions of the superior and inferior colliculi, critical areas for the initiation and propagation of audiogenic seizures. Using a panel of myelin antibodies, we discovered that myelin-associated glycoprotein (MAG) expression is dramatically decreased in Frings mice. MASS1 inhibits the ubiquitylation of MAG, thus enhancing the stability of this protein, and the calcium-binding domains of MASS1 are essential for this regulation. Furthermore, MASS1 interacts with Gαs/Gαq and activates PKA and PKC in response to extracellular calcium. Suppression of signaling by MASS1 RNAi or a specific inhibitor abrogates MAG up-regulation. We postulate that MASS1 senses extracellular calcium and activates cytosolic PKA/PKC pathways to regulate myelination by means of MAG protein stability in myelin-forming cells of the auditory pathway. Further work is required to determine whether MAG dysregulation is a cause or consequence of audiogenic epilepsy and whether there are other pathways regulated by MASS1

    Effects of English Teaching with Interactive Whiteboards in the Elementary English Classrooms

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    The purpose of the study was to probe the effectiveness of English language teaching through Interactive Whiteboards (IWBs). Three specific factors were probed: (a) the results from immediate test and retention test; (b) students’ perceptions related to the utilization of IWBs; (c) the advantages and disadvantages of the technology-supported instruction. Forty-three students from Grade 3 students in Sahes Elementary School in Taiwan were engaged in either technology-supported group or none technology-supported group. The results revealed that the experimental group through technology-supported instruction significantly outperformed the control group on students’ immediate test and retention test. Moreover, students’ perceptions related to the IWBs indicated that most of them enjoying learning English in the technology-supported classrooms. Finally, the results also showed the advantages and disadvantages through the IWBs instructions. The study revealed that teaching through technology was an effective way to help students in English learning

    Ab initio study of the giant ferroelectric distortion and pressure induced spin-state transition in BiCoO3

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    Using configuration-state-constrained electronic structure calculations based on the generalized gradient approximation plus Hubbard U method, we sought the origin of the giant tetragonal ferroelectric distortion in the ambient phase of the potentially multiferroic material BiCoO3 and identified the nature of the pressure induced spin-state transition. Our results show that a strong Bi-O covalency drives the giant ferroelectric distortion, which is further stabilized by an xy-type orbital ordering of the high-spin (HS) Co3+ ions. For the orthorhombic phase under 5.8 GPa, we find that a mixed HS and low-spin (LS) state is more stable than both LS and intermediate-spin (IS) states, and that the former well accounts for the available experimental results. Thus, we identify that the pressure induced spin-state transition is via a mixed HS+LS state, and we predict that the HS-to-LS transition would be complete upon a large volume decrease of about 20%.Comment: 6 pages, 6 figures, 2 table

    MicroRNA-23a promotes myelination in the central nervous system.

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    Demyelinating disorders including leukodystrophies are devastating conditions that are still in need of better understanding, and both oligodendrocyte differentiation and myelin synthesis pathways are potential avenues for developing treatment. Overexpression of lamin B1 leads to leukodystrophy characterized by demyelination of the central nervous system, and microRNA-23 (miR-23) was found to suppress lamin B1 and enhance oligodendrocyte differentiation in vitro. Here, we demonstrated that miR-23a-overexpressing mice have increased myelin thickness, providing in vivo evidence that miR-23a enhances both oligodendrocyte differentiation and myelin synthesis. Using this mouse model, we explored possible miR-23a targets and revealed that the phosphatase and tensin homologue/phosphatidylinositol trisphosphate kinase/Akt/mammalian target of rapamycin pathway is modulated by miR-23a. Additionally, a long noncoding RNA, 2700046G09Rik, was identified as a miR-23a target and modulates phosphatase and tensin homologue itself in a miR-23a-dependent manner. The data presented here imply a unique role for miR-23a in the coordination of proteins and noncoding RNAs in generating and maintaining healthy myelin

    A generic theory for Majorana zero modes in 2D superconductors

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    It is well known that non-Abelian Majorana zero modes (MZM) harbor at vortex cores in a px+ipyp_{x}+\text{i}p_{y} topological superconductor, which can be realized in a 2D spin-orbit coupled system with a single Fermi surface and by proximity coupling to an ss-wave superconductor. Here we show that existence of non-Abelian MZMs is unrelated to the bulk topology of a 2D superconductor, and propose that such exotic modes can be resulted in much broader range of superconductors, being topological or trivial. For a generic 2D system with multiple Fermi surfaces and gapped out by superconducting pairings, we show that at least a single MZM survives if there are only odd number of Fermi surfaces of which the corresponding superconducting orders have vortices, and such MZM is protected by an emergent Chern-Simons invariant, irrespective of the bulk topology of the superconductor. This result may enrich new experimental schemes for realizing non-Aelian MZMs. In particular, we propose a minimal scheme to realize the MZMs in a 2D superconducting Dirac semimetal with trivial bulk topology, which can be well achieved based on the recent cold atom experiments.Comment: 5 pages, 3 figures, plus Supplementary Materia

    AMPK- mediated formation of stress granules is required for dietary restriction- induced longevity in Caenorhabditis elegans

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    Stress granules (SGs) are nonmembranous organelles that are dynamically assembled and disassembled in response to various stressors. Under stressed conditions, polyadenylated mRNAs and translation factors are sequestrated in SGs to promote global repression of protein synthesis. It has been previously demonstrated that SG formation enhances cell survival and stress resistance. However, the physiological role of SGs in organismal aging and longevity regulation remains unclear. In this study, we used TIAR- 1::GFP and GTBP- 1::GFP as markers to monitor the formation of SGs in Caenorhabditis elegans. We found that, in addition to acute heat stress, SG formation could also be triggered by dietary changes, such as starvation and dietary restriction (DR). We found that HSF- 1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK- eEF2K signaling is required for starvation and DR- induced SG formation but not heat shock. Moreover, our data suggest that this AMPK- eEF2K pathway- mediated SG formation is required for lifespan extension by DR, but dispensable for the longevity by reduced insulin/IGF- 1 signaling. Collectively, our findings unveil a novel role of SG formation in DR- induced longevity.In addition to heat stress, starvation and dietary restriction (DR) can activate stress granule (SG) formation in Caenorhabditis elegans. HSF- 1 and AMPK are two key regulators for the SG formations. HSF- 1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK- eEF2K pathway is required for starvation and DR- induced SG formation but not heat shock. Furthermore, AMPK- mediated SG formation contributes to DR- induced longevity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/1/acel13157-sup-0008-Figurelegends.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/2/acel13157-sup-0001-FigS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/3/acel13157-sup-0006-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/4/acel13157-sup-0007-TableS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/5/acel13157-sup-0005-FigS5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/6/acel13157-sup-0003-FigS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/7/acel13157.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/8/acel13157-sup-0002-FigS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/9/acel13157-sup-0004-FigS4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/10/acel13157_am.pd
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