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111.
Functional involvement of Tudor and dPRMT5 in the piRNA processing pathway in Drosophila germlines 下载免费PDF全文
Kazumichi M Nishida Tomoko N Okada Takeshi Kawamura Toutai Mituyama Yoshinori Kawamura Sachi Inagaki Haidong Huang Dahua Chen Tatsuhiko Kodama Haruhiko Siomi Mikiko C Siomi 《The EMBO journal》2009,28(24):3820-3831
In Drosophila, the PIWI proteins, Aubergine (Aub), AGO3, and Piwi are expressed in germlines and function in silencing transposons by associating with PIWI‐interacting RNAs (piRNAs). Recent studies show that PIWI proteins contain symmetric dimethyl‐arginines (sDMAs) and that dPRMT5/Capsuleen/DART5 is the modifying enzyme. Here, we show that Tudor (Tud), one of Tud domain‐containing proteins, associates with Aub and AGO3, specifically through their sDMA modifications and that these three proteins form heteromeric complexes. piRNA precursor‐like molecules are detected in these complexes. The expression levels of Aub and AGO3, along with their degree of sDMA modification, were not changed by tud mutations. However, the population of transposon‐derived piRNAs associated with Aub and AGO3 was altered by tud mutations, whereas the total amounts of small RNAs on Aub and AGO3 was increased. Loss of dprmt5 did not change the stability of Aub, but impaired its association with Tud and lowered piRNA association with Aub. Thus, in germline cells, piRNAs are quality‐controlled by dPRMT5 that modifies PIWI proteins, in tight association with Tud. 相似文献
112.
Ayumu Niida Yoko Kanematsu-Yamaki Tomoko Asakawa Yoshimasa Ishimura Hisashi Fujita Kouta Matsumiya Naoki Nishizawa Yusuke Adachi Taisuke Mochida Kazue Tsuchimori Mariko Yoneyama-Hirozane Junichi Sakamoto Hideki Hirabayashi Hideo Fukui Shiro Takekawa Taiji Asami 《Bioorganic & medicinal chemistry》2018,26(3):566-572
Neuropeptide Y2 receptor (Y2R) agonism is an important anorectic signal and a target of antiobesity drug discovery. Recently, we synthesized a short-length Y2R agonist, PYY-1119 (4-imidazolecarbonyl-[d-Hyp24,Iva25,Pya(4)26,Cha27,36,γMeLeu28,Lys30,Aib31]PYY(23–36), 1) as an antiobesity drug candidate. Compound 1 induced marked body weight loss in diet-induced obese (DIO) mice; however, 1 also induced severe vomiting in dogs at a lower dose than the minimum effective dose administered to DIO mice. The rapid absorption of 1 after subcutaneous administration caused the severe vomiting. Polyethylene glycol (PEG)- and alkyl-modified derivatives of 1 were synthesized to develop Y2R agonists with improved pharmacokinetic profiles, i.e., lower maximum plasma concentration (Cmax) and longer time at maximum concentration (Tmax). Compounds 5 and 10, modified with 20?kDa PEG at the N-terminus and eicosanedioic acid at the Lys30 side chain of 1, respectively, showed high Y2R binding affinity and induced significant body weight reduction upon once-daily administration to DIO mice. Compounds 5 and 10, with their relatively low Cmax and long Tmax, partially attenuated emesis in dogs compared with 1. These results indicate that optimization of pharmacokinetic properties of Y2R agonists is an effective strategy to alleviate emesis induced by Y2R agonism. 相似文献
113.
Sima Babayeva Brittany Rocque Lamine Aoudjit Yulia Zilber Jane Li Cindy Baldwin Hiroshi Kawachi Tomoko Takano Elena Torban 《The Journal of biological chemistry》2013,288(33):24035-24048
The noncanonical Wnt/planar cell polarity (PCP) pathway controls a variety of cell behaviors such as polarized protrusive cell activity, directional cell movement, and oriented cell division and is crucial for the normal development of many tissues. Mutations in the PCP genes cause malformation in multiple organs. Recently, the PCP pathway was shown to control endocytosis of PCP and non-PCP proteins necessary for cell shape remodeling and formation of specific junctional protein complexes. During formation of the renal glomerulus, the glomerular capillary becomes enveloped by highly specialized epithelial cells, podocytes, that display unique architecture and are connected via specialized cell-cell junctions (slit diaphragms) that restrict passage of protein into the urine; podocyte differentiation requires active remodeling of cytoskeleton and junctional protein complexes. We report here that in cultured human podocytes, activation of the PCP pathway significantly stimulates endocytosis of the core slit diaphragm protein, nephrin, via a clathrin/β-arrestin-dependent endocytic route. In contrast, depletion of the PCP protein Vangl2 leads to an increase of nephrin at the cell surface; loss of Vangl2 functions in Looptail mice results in disturbed glomerular maturation. We propose that the PCP pathway contributes to podocyte development by regulating nephrin turnover during junctional remodeling as the cells differentiate. 相似文献
114.
Toshikazu Ushijima Tomoko Nomoto Takashi Sugimura David E. Housman Minako Nagao 《Mammalian genome》1998,9(12):1008-1012
Mapping of genetic suppressors, modifiers, and quantitative trait loci (QTLs) requires genetic markers that can be efficiently
and inexpensively genotyped for a large number of individuals. To isolate rat genetic markers suitable for this purpose, representational
difference analysis (RDA) was performed with amplicons prepared by PCR with the B1 repetitive sequence used as the primer
(B1-amplicons). In total, 48 polymorphic DNA fragments were isolated by five series of RDA, subtracting the B1-amplicons prepared
from an ACI/N (ACI) rat from those prepared from BUF/Nac (BUF), and vice versa. All the polymorphic fragments detected ``presence-or-absence'
polymorphisms with B1-amplicons prepared from ACI, BUF, and their F2 progeny, and each fragment was linkage mapped. Dot-blotting amplicons onto filters at a high density and hybridization of
the filters with these B1-RDA markers made it possible to genotype a large number of rats simultaneously for multiple loci.
These B1-RDA markers were polymorphic between two given inbred strains of rat at frequencies between 30% and 70%. This is
the first report on the isolation of B1-RDA markers among inbred strains of rats.
Received: 15 July 1998 / Accepted: 18 August 1998 相似文献
115.
The quantity of organic acids ( lactic acid, acetic acid, propionic acid and butyric acid ) in the content of the gastrointestinal tract of germ-free and conventional rats and the effects of the organic acid on the motility of the gastrointestinal tract of rats were investigated.Organic acids were detected only in the gastrointestinal contents of conventional rats but not in those of germ-free rats.Lactic acid detected in the stomach of rats stimulated the motility of both small and large bowel while acetic acid, propionic acid and butyric acid found in the cecum stimulated the motility of the large bowel but not of small bowel. 相似文献
116.
Effects of struvite formation and nitratation promotion on nitrogenous emissions such as NH3, N2O and NO during swine manure composting 总被引:4,自引:0,他引:4
To reduce nitrogenous emissions from composting, two different countermeasures were applied simultaneously in swine manure composting. One was forming struvite by adding Mg and P at the start of composting, and the other was to promote nitratation (nitrite being oxidized nitrate) by adding nitrite-oxidizing bacteria after the thermophilic phase of composting. In the laboratory- and mid-scale composting experiments, 25-43% of NH3, 52-80% of N2O and 96-99% of NO emissions were reduced. From the nitrogen balance, it was revealed that the struvite formation reduced not only NH3, but also other nitrogenous emissions except N2O. The amount of total nitrogen losses was reduced by 60% by the two combined countermeasures, against 51% by the struvite formation alone. However, the nitratation promotion dissolved struvite crystals due to the pH decline, diminishing the effect of struvite as a slow-release fertilizer. 相似文献
117.
Matsumoto R Shibata TF Kohtsuka H Sekifuji M Sugii N Nakajima H Kojima N Fujii Y Kawsar SM Yasumitsu H Hamako J Matsui T Ozeki Y 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2011,158(4):266-273
A lectin - designated OXYL for the purposes of this study that strongly recognizes complex-type oligosaccharides of serum glycoproteins - was purified from a crinoid, the feather star Oxycomanthus japonicus, the most basal group among extant echinoderms. OXYL was purified through a combination of anion-exchange and affinity chromatography using Q-sepharose and fetuin-sepharose gel, respectively. Lectin was determined to be a 14-kDa polypeptide by sodium dodecyl sulphate-polyacrylamide gel electrophoresis under reducing conditions. However, 14-kDa and 28-kDa bands appeared in the same proportion under non-reducing conditions. Gel permeation chromatography showed a 54-kDa peak, suggesting that lectin consists of four 14-kDa subunits. Divalent cations were not indicated, and stable haemagglutination activity was demonstrated at pH 4-12 and temperatures below 60°C. Surface plasmon resonance analysis of OXYL against fetuin showed k(ass) and k(diss) values of 1.4×10(-6)M(-1)s(-1) and 3.1×10(-3)s(-1), respectively, indicating that it has a strong binding affinity to the glycoprotein as lectin. Frontal affinity chromatography using 25 types of prydylamine-conjugated glycans indicated that OXYL specifically recognizes multi-antennary complex-type oligosaccharides containing type-2 N-acetyllactosamines (Galβ1-4GlcNAc) if α2-3-linked sialic acid is linked at the non-reducing terminal. However, type-1 N-acetyllactosamine (Galβ1-3GlcNAc) chains and α2-6-linked sialic acids were never recognized by OXYL. This profiling study showed that OXYL essentially recognizes β1-4-linkage at C-1 position and free OH group at C-6 position of Gal in addition to the conservation of N-acetyl groups at C-2 position and free OH groups at C-3 position of GlcNAc in N-acetyllactosamine. This is the first report on glycomics on a lectin purified from an echinoderm belonging to the subphylum Pelmatozoa. 相似文献
118.
Yuka Tanaka Tomoko Inoue-Yokoo Kasem Kulkeaw Chiyo Yanagi-Mizuochi Senji Shirasawa Yoichi Nakanishi Daisuke Sugiyama 《PloS one》2015,10(9)
In mice, hematopoietic cells home to bone marrow from fetal liver prenatally. To elucidate mechanisms underlying homing, we performed immunohistochemistry with the hematopoietic cell marker c-Kit, and observed c-Kit(+) cells localized inside muscle surrounding bone after 14.5 days post coitum. Flow cytometric analysis showed that CD45(+) c-Kit(+) hematopoietic cells were more abundant in muscle than in bone marrow between 14.5 and 17.5 days post coitum, peaking at 16.5 days post coitum. CD45(+) c-Kit(+) cells in muscle at 16.5 days post coitum exhibited higher expression of Gata2, among several hematopoietic genes, than did fetal liver or bone marrow cells. Colony formation assays revealed that muscle hematopoietic cells possess hematopoietic progenitor activity. Furthermore, exo utero transplantation revealed that fetal liver hematopoietic progenitor cells home to muscle and then to BM. Our findings demonstrate that hematopoietic progenitor cell homing occurs earlier than previously reported and that hematopoietic progenitor cells reside in muscle tissue before bone marrow hematopoiesis occurs during mouse embryogenesis. 相似文献
119.
120.
Kohyama K Sawada H Nonaka M Kobori C Hayakawa F Sasaki T 《Bioscience, biotechnology, and biochemistry》2007,71(2):358-365
The difficulty in masticating and swallowing rice cake was quantified. Healthy subjects ate pieces of rice cake (9 g and 3 g) and a modified product (9 g). We used electromyography to measure the activity of the jaw-closing and -opening muscles during chewing, as well as the suprahyoid muscle activity, laryngeal movement, and sound during swallowing. The smaller the rice cake, the shorter the mastication time, the fewer the number of chews, and the less the jaw-closing muscle activity. A modified rice cake product (9 g) was consumed with less mastication effort than the standard rice cake (9 g) and with the same effort as the standard (3 g). Both the sample amount and texture influenced mastication, although neither factor caused a significant difference in swallowing characteristics. These observations suggest that swallowing was induced when the bolus properties became suitable for swallowing, as healthy subjects could adjust their mastication technique according to the food amount and texture. 相似文献