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61.
Different contributions of local‐ and distant‐regulatory changes to transcriptome divergence between stickleback ecotypes 下载免费PDF全文
62.
Ribonuclease P (RNase P) is a ribonucleoprotein complex involved in the processing of the 5′-leader sequence of precursor tRNA. Human RNase P protein subunits Rpp21 and Rpp29, which bind to each other, with catalytic RNA (H1 RNA) are sufficient for activating endonucleolytic cleavage of precursor tRNA. Here we have determined the crystal structure of the complex between the Pyrococcus horikoshii RNase P proteins PhoRpp21 and PhoRpp29, the archaeal homologs of Rpp21 and Rpp29, respectively. PhoRpp21 and PhoRpp29 form a heterodimeric structure where the two N-terminal helices (α1 and α2) in PhoRpp21 predominantly interact with the N-terminal extended structure, the β-strand (β2), and the C-terminal helix (α3) in PhoRpp29. The interface is dominated by hydrogen bonds and several salt bridges, rather than hydrophobic interactions. The electrostatic potential on the surface of the heterodimer shows a positively charged cluster on one face, suggesting a possible RNA-binding surface of the PhoRpp21-PhoRpp29 complex. The present structure, along with the result of a mutational analysis, suggests that heterodimerization between PhoRpp21 and PhoRpp29 plays an important role in the function of P. horikoshii RNase P. 相似文献
63.
Nagai S Okazaki M Segawa H Bergwitz C Dean T Potts JT Mahon MJ Gardella TJ Jüppner H 《The Journal of biological chemistry》2011,286(2):1618-1626
The parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTHR1) in cells of the renal proximal tubule mediates the reduction in membrane expression of the sodium-dependent P(i) co-transporters, NPT2a and NPT2c, and thus suppresses the re-uptake of P(i) from the filtrate. In most cell types, the liganded PTHR1 activates Gα(S)/adenylyl cyclase/cAMP/PKA (cAMP/PKA) and Gα(q/11)/phospholipase C/phosphatidylinositol 1,4,5-trisphosphate (IP(3))/Ca(2+)/PKC (IP(3)/PKC) signaling pathways, but the relative roles of each pathway in mediating renal regulation P(i) transport remain uncertain. We therefore explored the signaling mechanisms involved in PTH-dependent regulation of NPT2a function using potent, long-acting PTH analogs, M-PTH(1-28) (where M = Ala(1,12), Aib(3), Gln(10), Har(11), Trp(14), and Arg(19)) and its position 1-modified variant, Trp(1)-M-PTH(1-28), designed to be phospholipase C-deficient. In cell-based assays, both M-PTH(1-28) and Trp(1)-M-PTH(1-28) exhibited potent and prolonged cAMP responses, whereas only M-PTH(1-28) was effective in inducing IP(3) and intracellular calcium responses. In opossum kidney cells, a clonal cell line in which the PTHR1 and NPT2a are endogenously expressed, M-PTH(1-28) and Trp(1)-M-PTH(1-28) each induced reductions in (32)P uptake, and these responses persisted for more than 24 h after ligand wash-out, whereas that of PTH(1-34) was terminated by 4 h. When injected into wild-type mice, both M-modified PTH analogs induced prolonged reductions in blood P(i) levels and commensurate reductions in NPT2a expression in the renal brush border membrane. Our findings suggest that the acute down-regulation of NPT2a expression by PTH ligands involves mainly the cAMP/PKA signaling pathway and are thus consistent with the elevated blood P(i) levels seen in pseudohypoparathyroid patients, in whom Gα(s)-mediated signaling in renal proximal tubule cells is defective. 相似文献
64.
Ko Chiba Masahiro Tsuchiya Masashi Koide Yoshihiro Hagiwara Keiichi Sasaki Yoshinori Hattori Makoto Watanabe Shunji Sugawara Makoto Kanzaki Yasuo Endo 《PloS one》2015,10(11)
Physical exercise reportedly stimulates IL-1 production within working skeletal muscles, but its physiological significance remains unknown due to the existence of two distinct IL-1 isoforms, IL-1α and IL-1β. The regulatory complexities of these two isoforms, in terms of which cells in muscles produce them and their distinct/redundant biological actions, have yet to be elucidated. Taking advantage of our masticatory behavior (Restrained/Gnawing) model, we herein show that IL-1α/1β-double-knockout (IL-1-KO) mice exhibit compromised masseter muscle (MM) activity which is at least partially attributable to abnormalities of glucose handling (rapid glycogen depletion along with impaired glucose uptake) and dysfunction of IL-6 upregulation in working MMs. In wild-type mice, masticatory behavior clearly increased IL-1β mRNA expression but no incremental protein abundance was detectable in whole MM homogenates, whereas immunohistochemical staining analysis revealed that both IL-1α- and IL-1β-immunopositive cells were recruited around blood vessels in the perimysium of MMs after masticatory behavior. In addition to the aforementioned phenotype of IL-1-KO mice, we found the IL-6 mRNA and protein levels in MMs after masticatory behavior to be significantly lower in IL-1-KO than in WT. Thus, our findings confirm that the locally-increased IL-1 elicited by masticatory behavior, although present small in amounts, contributes to supporting MM activity by maintaining normal glucose homeostasis in these muscles. Our data also underscore the importance of IL-1-mediated local interplay between autocrine myokines including IL-6 and paracrine cytokines in active skeletal muscles. This interplay is directly involved in MM performance and fatigability, perhaps mediated through maintaining muscular glucose homeostasis. 相似文献
65.
Taichiro Takemura Masahiro Yamashita Makoto K. Shimada Sadayuki Ohkura Takayoshi Shotake Mikio Ikeda Tomoyuki Miura Masanori Hayami 《Journal of virology》2002,76(4):1642-1648
Simian T-cell leukemia viruses (STLVs) are the simian counterparts of human T-cell leukemia viruses (HTLVs). A novel, divergent type of STLV (STLV-L) from captive baboons was reported in 1994, but its natural prevalence remained unclear. We investigated the prevalence of STLV-L in 519 blood samples from wild-living nonhuman primates in Ethiopia. Seropositive monkeys having cross-reactive antibodies against HTLV were found among 22 out of 40 hamadryas baboons, 8 of 96 anubis baboons, 24 of 50 baboons that are hybrids between hamadryas and anubis baboons, and 41 of 177 grivet monkeys, but not in 156 gelada baboons. A Western blotting assay showed that sera obtained from seropositive hamadryas and hybrid baboons exhibited STLV-L-like reactivity. A PCR assay successfully amplified STLV sequences, which were subsequently sequenced and confirmed as being closely related to STLV-L. Surprisingly, further PCR showed that nearly half of the hamadryas (20 out of 40) and hybrid (19 out of 50) baboons had STLV-L DNA sequences. In contrast, most of the seropositive anubis baboons and grivet monkeys carried typical STLV-1 but not STLV-L. These observations demonstrate that STLV-L naturally prevails among hamadryas and hybrid baboons at significantly high rates. STLV-1 and -2, the close relative of STLV-L, are believed to have jumped across simian-human barriers, which resulted in widespread infection of HTLV-1 and -2. Further studies are required to know if STLV-L is spreading into human populations. 相似文献
66.
Shigematsu S Khan AH Kanzaki M Pessin JE 《Molecular endocrinology (Baltimore, Md.)》2002,16(5):1060-1068
To investigate the potential role of microtubules in the regulation of insulin-responsive glucose transporter (GLUT4) trafficking in adipocytes, we examined the effects of microtubule depolymerizing and stabilizing agents. In contrast to previous reports, disruption or stabilization of microtubule structures had no significant effect on insulin-stimulated GLUT4 translocation. However, consistent with a more recent study (Molero, J. C., J. P. Whitehead, T. Meerloo, and D. E. James, 2001, J Biol Chem 276:43829-43835) nocodazole did inhibit glucose uptake through a direct interaction with the transporter itself independent of the translocation process. In addition, the initial rate of GLUT4 endocytosis was not significantly affected by microtubule depolymerization. However, these internalized GLUT4 compartments are confined to regions just beneath the plasma membrane and were not exposed to the extracellular space. Furthermore, they were unable to undergo further sorting steps and trafficking to the perinuclear region. Nevertheless, these apparent early endocytic GLUT4 compartments fully responded to a second insulin stimulation with an identical extent of plasma membrane translocation. Together, these data demonstrate that although microtubular organization may play a role in the trafficking of GLUT4 early endocytic vesicles back to the perinuclear region, they do not have a significant role in insulin-stimulated GLUT4 exocytosis, initial endocytosis from the plasma membrane and/or recycling back to the plasma membrane. 相似文献
67.
We investigated the effects of estradiol-treated females on the behavior of male budgerigars. In comparison to control females,
females given implants of estradiol showed elevated nest behavior and darker cere color, which are characteristics of breeding
females. After we confirmed the efficacy of estradiol treatment on behavior and morphology, each female was paired with a
male mate. Males paired with estradiol-treated females showed more courtship behavior (auditory and visual display, and courtship
feeding) to their mates than males paired with control females. These data indicate that budgerigar females with a high estrogen
level enhance males' courtship behavior. Since males did not show response to estradiol-treated females soon after females
were introduced, effects of estradiol-treated female budgerigars may be mediated by the endocrine system, rather than wholly
by the nervous system, of males.
Electronic Publication 相似文献
68.
Aerobic exercise training reduces plasma endothelin-1 concentration in older women. 总被引:10,自引:0,他引:10
Seiji Maeda Takumi Tanabe Takashi Miyauchi Takeshi Otsuki Jun Sugawara Motoyuki Iemitsu Shinya Kuno Ryuichi Ajisaka Iwao Yamaguchi Mitsuo Matsuda 《Journal of applied physiology》2003,95(1):336-341
Endothelial function deteriorates with aging. On the other hand, exercise training improves the function of vascular endothelial cells. Endothelin-1 (ET-1), which is produced by vascular endothelial cells, has potent constrictor and proliferative activity in vascular smooth muscle cells and, therefore, has been implicated in regulation of vascular tonus and progression of atherosclerosis. We previously reported significantly higher plasma ET-1 concentration in middle-aged than in young humans, and recently we showed that plasma ET-1 concentration was significantly decreased by aerobic exercise training in healthy young humans. We hypothesized that plasma ET-1 concentration increases with age, even in healthy adults, and that lifestyle modification (i.e., exercise) can reduce plasma ET-1 concentration in previously sedentary older adults. We measured plasma ET-1 concentration in healthy young women (21-28 yr old), healthy middle-aged women (31-47 yr old), and healthy older women (61-69 yr old). The plasma level of ET-1 significantly increased with aging (1.02 +/- 0.08, 1.33 +/- 0.11, and 2.90 +/- 0.20 pg/ml in young, middle-aged, and older women, respectively). Thus plasma ET-1 concentration was markedly higher in healthy older women than in healthy young or middle-aged women (by approximately 3- and 2-fold, respectively). In healthy older women, we also measured plasma ET-1 concentration after 3 mo of aerobic exercise (cycling on a leg ergometer at 80% of ventilatory threshold for 30 min, 5 days/wk). Regular exercise significantly decreased plasma ET-1 concentration in the healthy older women (2.22 +/- 0.16 pg/ml, P < 0.01) and also significantly reduced their blood pressure. The present study suggests that regular aerobic-endurance exercise reduces plasma ET-1 concentration in older humans, and this reduction in plasma ET-1 concentration may have beneficial effects on the cardiovascular system (i.e., prevention of progression of hypertension and/or atherosclerosis by endogenous ET-1). 相似文献
69.
Momoi A Yoda H Steinbeisser H Fagotto F Kondoh H Kudo A Driever W Furutani-Seiki M 《Mechanisms of development》2003,120(4):477-489
The dorsal ectoderm of vertebrate gastrula is first specified into anterior fate by an activation signal and posteriorized by a graded transforming signal, leading to the formation of forebrain, midbrain, hindbrain and spinal cord along the anteroposterior (A-P) axis. Transplanted non-axial mesoderm rather than axial mesoderm has an ability to transform prospective anterior neural tissue into more posterior fates in zebrafish. Wnt8 is a secreted factor that is expressed in non-axial mesoderm. To investigate whether Wnt8 is the neural posteriorizing factor that acts upon neuroectoderm, we first assigned Frizzled 8c and Frizzled 9 to be functional receptors for Wnt8. We then, transplanted non-axial mesoderm into the embryos in which Wnt8 signaling is cell-autonomously blocked by the dominant-negative form of Wnt8 receptors. Non-axial mesodermal transplants in embryos in which Wnt8 signaling is cell-autonomously blocked induced the posterior neural markers as efficiently as in wild-type embryos, suggesting that Wnt8 signaling is not required in neuroectoderm for posteriorization by non-axial mesoderm. Furthermore, Wnt8 signaling, detected by nuclear localization of beta-catenin, was not activated in the posterior neuroectoderm but confined in marginal non-axial mesoderm. Finally, ubiquitous over-expression of Wnt8 does not expand neural ectoderm of posterior character in the absence of mesoderm or Nodal-dependent co-factors. We thus conclude that other factors from non-axial mesoderm may be required for patterning neuroectoderm along the A-P axis. 相似文献
70.
Shinji Takamatsu Toshiyuki Katsumata Noboru Inoue Toshinori Watanabe Yasuhisa Fujibayashi Makoto Takeuchi 《Glycoconjugate journal》2003,20(7-8):473-481
Over the past two decades, sugar chain structures of human chorionic gonadotropin (hCG) produced in healthy people, three types of trophoblastic disease, and some types of cell lines have been analyzed. The abnormal biantennary structure of hCG is a good marker for the diagnosis of malignant choriocarcinoma. In spite of much research, hCG with an abnormal biantennary structure is only detected in the urine of choriocarcinoma or pregnant diabetic patients. We hypothesized that the formation mechanism of the abnormal biantennary sugar chain structure is mainly caused by high GnT-IV activity. To confirm this, we measured the N-acetylglucosaminyltransferase (GnT)-IV activity and hCG productivity in three choriocarcinoma cell lines, and selected JEG-3 cells. hCG samples were purified from medium conditioned by JEG-3 cells, and their sugar chain structures were analyzed. We detected an abnormal biantennary structure, and the proportions were different from those previously reported in the urine samples of choriocarcinoma patients. These findings proved our hypothesis and suggest the usefulness of JEG-3 cells for further analyses of abnormal biantennary structure formation. Published in 2004. 相似文献