224 research outputs found

    Tsuji functions with segments of Julia

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46297/1/209_2005_Article_BF01112579.pd

    SUMOylation of DEC1 Protein Regulates Its Transcriptional Activity and Enhances Its Stability

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    Differentiated embryo-chondrocyte expressed gene 1 (DEC1, also known as sharp2, stra13, or BHLHB2) is a mammalian basic helix-loop-helix protein that is involved in many aspects of gene regulation through acting as a transcription factor. Changes in DEC1 expression levels have been implicated in the development of cancers. Using COS-7 cell, we showed that DEC1 can be modified by the small ubiquitin-like modifiers, SUMO1, 2 and 3. Two major SUMOylation sites (K159 and K279) were identified in the C-terminal domain of DEC1. Substitution of either K159 or K279 with arginine reduced DEC1 SUMOylation, but substitution of both K159 and K279 abolished SUMOylation, and more protein appeared to be retained in the cytoplasm compared to wild-type DEC1. The expression of DEC1 was up-regulated after serum starvation as previously reported, but at the same time, serum starvation also led to more SUMOylation of DEC1. In MCF-7 cells SUMOylation also stabilized DEC1 through inhibiting its ubiquitination. Moreover, SUMOylation of DEC1 promoted its repression of CLOCK/BMAL1-mediated transcriptional activity through recruitment of histone deacetylase1. These findings suggested that posttranslational modification of DEC1 in the form of SUMOylation may serve as a key factor that regulates the function of DEC1 in vivo

    Consistent improvement with eculizumab across muscle groups in myasthenia gravis

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    Eculizumab improves fatigue in refractory generalized myasthenia gravis

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    Molecular Signatures Reveal Circadian Clocks May Orchestrate the Homeorhetic Response to Lactation

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    Genes associated with lactation evolved more slowly than other genes in the mammalian genome. Higher conservation of milk and mammary genes suggest that species variation in milk composition is due in part to the environment and that we must look deeper into the genome for regulation of lactation. At the onset of lactation, metabolic changes are coordinated among multiple tissues through the endocrine system to accommodate the increased demand for nutrients and energy while allowing the animal to remain in homeostasis. This process is known as homeorhesis. Homeorhetic adaptation to lactation has been extensively described; however how these adaptations are orchestrated among multiple tissues remains elusive. To develop a clearer picture of how gene expression is coordinated across multiple tissues during the pregnancy to lactation transition, total RNA was isolated from mammary, liver and adipose tissues collected from rat dams (n = 5) on day 20 of pregnancy and day 1 of lactation, and gene expression was measured using Affymetrix GeneChips. Two types of gene expression analysis were performed. Genes that were differentially expressed between days within a tissue were identified with linear regression, and univariate regression was used to identify genes commonly up-regulated and down-regulated across all tissues. Gene set enrichment analysis showed genes commonly up regulated among the three tissues enriched gene ontologies primary metabolic processes, macromolecular complex assembly and negative regulation of apoptosis ontologies. Genes enriched in transcription regulator activity showed the common up regulation of 2 core molecular clock genes, ARNTL and CLOCK. Commonly down regulated genes enriched Rhythmic process and included: NR1D1, DBP, BHLHB2, OPN4, and HTR7, which regulate intracellular circadian rhythms. Changes in mammary, liver and adipose transcriptomes at the onset of lactation illustrate the complexity of homeorhetic adaptations and suggest that these changes are coordinated through molecular clocks

    Status and future prospect of 48Ca double beta decay search in CANDLES

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    The observation of neutrino-less double beta decay (0νββ) would be the most practical way to prove the Majorana nature of the neutrino and lepton number violation. CANDLES studies 48Ca double beta decay using CaF2 scintillator. The main advantage of 48Ca is that it has the highest Q-value (4.27 MeV) among all the isotope candidates for 0νββ. The CANDLES III detector is currently operating with 300kg CaF2 crystals in the Kamioka underground observatory, Japan. In 2014, a detector cooling system and a magnetic cancellation coil was installed with the aim to increase light emission of CaF2 scintillator and photo-electron collection efficiency of the photo-multipliers. After this upgrade, light yield was increased to 1000 p.e./MeV which is 1.6 times larger than before. According to data analysis and simulation, main background source in CANDLES is turned out to be high energy external gamma-ray originating neutron capture on the surrounding materials, so called (n,γ). Upgrading the detector by installing neutron and gamma-ray shield can reduce the remaining main backgrounds by two order magnitude. In this report, we discuss the detail of (n,γ) and background reduction by additional shielding

    Status and future prospect of 48Ca double beta decay search in CANDLES

    Get PDF
    The observation of neutrino-less double beta decay (0νββ) would be the most practical way to prove the Majorana nature of the neutrino and lepton number violation. CANDLES studies 48Ca double beta decay using CaF2 scintillator. The main advantage of 48Ca is that it has the highest Q-value (4.27 MeV) among all the isotope candidates for 0νββ. The CANDLES III detector is currently operating with 300kg CaF2 crystals in the Kamioka underground observatory, Japan. In 2014, a detector cooling system and a magnetic cancellation coil was installed with the aim to increase light emission of CaF2 scintillator and photo-electron collection efficiency of the photo-multipliers. After this upgrade, light yield was increased to 1000 p.e./MeV which is 1.6 times larger than before. According to data analysis and simulation, main background source in CANDLES is turned out to be high energy external gamma-ray originating neutron capture on the surrounding materials, so called (n,γ). Upgrading the detector by installing neutron and gamma-ray shield can reduce the remaining main backgrounds by two order magnitude. In this report, we discuss the detail of (n,γ) and background reduction by additional shielding
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