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61.
62.
Visualization and solubilization of rat brain opiate receptors with a “κ” ligand selectivity pattern 总被引:2,自引:0,他引:2
Remi Quirion Wayne D. Bowen Miles Herkenham Candace B. Pert 《Cellular and molecular neurobiology》1982,2(4):333-346
1. Specific binding of [3H]ethylketocyclazocine (EkappaC), a prototype kappa-opiate agonist, to slide-mounted rat striatal sections is increased in the presence of 100 mM NaCl at 4 degrees C. 2. Under similar incubation conditions, binding of mu and delta prototype opiates is reduced to almost undetectable levels. 3. Correlation (P less than 0.01) of the ligand selectivity pattern of [3H]EKC displacement with the potencies of various opiate drugs in inhibiting the contractions of the rabbit vas deferens, a kappa-opiate receptor bioassay, suggests that the binding site under study represents the pharmacologically relevant kappa-opiate receptor. 4. Visualization of these kappa-opiate receptors with tritium-sensitive film reveals a striking, highly discrete brain distribution pattern (e.g., striatal patches, habenular stripe) which is similar to that of [3H]dihydromorphine and [3H]naloxone. 5. Soluble [3H]EKC binding sites obtained from rat membranes also possess a kappa-like ligand selectivity pattern, with bremazocine being a potent displacer while mu and delta ligands are almost inactive. 6. A possible explanation of these data is that the "kappa"-opiate binding site in rat brain is one transitional state of an opiate receptor capable of assuming distinct conformations with characteristic ligand selectivity patterns. Other possibilities such as pre and post-synaptic locations should also be considered. 相似文献
63.
Michelle J. Boyle Prasanna Jagannathan Lila A. Farrington Ijeoma Eccles-James Samuel Wamala Tara I McIntyre Hilary M. Vance Katherine Bowen Felistas Nankya Ann Auma Mayimuna Nalubega Esther Sikyomu Kate Naluwu John Rek Agaba Katureebe Victor Bigira James Kapisi Jordan Tappero Mary K Muhindo Bryan Greenhouse Emmanuel Arinaitwe Grant Dorsey Moses R. Kamya Margaret E. Feeney 《PLoS pathogens》2015,11(7)
FoxP3+ regulatory CD4 T cells (Tregs) help to maintain the delicate balance between pathogen-specific immunity and immune-mediated pathology. Prior studies suggest that Tregs are induced by P. falciparum both in vivo and in vitro; however, the factors influencing Treg homeostasis during acute and chronic infections, and their role in malaria immunopathogenesis, remain unclear. We assessed the frequency and phenotype of Tregs in well-characterized cohorts of children residing in a region of high malaria endemicity in Uganda. We found that both the frequency and absolute numbers of FoxP3+ Tregs in peripheral blood declined markedly with increasing prior malaria incidence. Longitudinal measurements confirmed that this decline occurred only among highly malaria-exposed children. The decline of Tregs from peripheral blood was accompanied by reduced in vitro induction of Tregs by parasite antigen and decreased expression of TNFR2 on Tregs among children who had intense prior exposure to malaria. While Treg frequencies were not associated with protection from malaria, there was a trend toward reduced risk of symptomatic malaria once infected with P. falciparum among children with lower Treg frequencies. These data demonstrate that chronic malaria exposure results in altered Treg homeostasis, which may impact the development of antimalarial immunity in naturally exposed populations. 相似文献
64.
Brooke R Snyder Pei-Hsun Cheng Jinjing Yang Shang-Hsun Yang Anderson HC Huang Anthony WS Chan 《BMC cell biology》2011,12(1):1-8
Background
Activation by extracellular ligands of G protein-coupled (GPCRs) and tyrosine kinase receptors (RTKs), results in the generation of second messengers that in turn control specific cell functions. Further, modulation/amplification or inhibition of the initial signalling events, depend on the recruitment onto the plasma membrane of soluble protein effectors. High throughput methodologies to monitor quantitatively second messenger production, have been developed over the last years and are largely used to screen chemical libraries for drug development. On the contrary, no such high throughput methods are yet available for the other aspect of GPCRs regulation, i.e. protein translocation to the plasma membrane, despite the enormous interest of this phenomenon for the modulation of receptor downstream functions. Indeed, to date, the experimental procedures available are either inadequate or complex and expensive.Results
Here we describe the development of a novel conceptual approach to the study of cytosolic proteins translocation to the inner surface of the plasma membrane. The basis of the technique consists in: i) generating chimeras between the protein of interests and the calcium (Ca2+)-sensitive, luminescent photo-protein, aequorin and ii) taking advantage of the large Ca2+ concentration [Ca2+] difference between bulk cytosolic and the sub-plasma membrane rim.Conclusion
This approach, that keeps unaffected the translocation properties of the signalling protein, can in principle be applied to any protein that, upon activation, moves from the cytosol to the plasma membrane. Thus, not only the modulation of GPCRs and RTKs can be investigated in this way, but that of all other proteins that can be recruited to the plasma membrane also independently of receptor activation. Moreover, its automated version, which can provide information about the kinetics and concentration-dependence of the process, is also applicable to high throughput screening of drugs affecting the translocation process. 相似文献65.
Weiliang Cai Bowen Wu Zhizhong Li Peiheng He Biao Wang Anlie Cai Xiping Zhang 《Journal of cellular biochemistry》2019,120(2):2015-2027
Long noncoding RNAs (lncRNAs) have been identified to have increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. Recent studies have demonstrated that lncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is decreased in several cancers; however, the role of NBR2 in the development of osteosarcoma has not been elucidated. In our study, we found that NBR2 expression was downregulated in osteosarcoma tissues, and osteosarcoma cases with lower NBR2 expression exhibited a shorter overall survival time compared with those with higher NBR2 expression. NBR2 overexpression inhibited osteosarcoma cell proliferation, invasion, and migration but did not increase apoptosis. Furthermore, RNA-binding protein immunoprecipitation assays confirmed that NBR2 directly binds to Notch1 protein. Furthermore, overexpression of Notch1 in NBR2-overexpressing osteosarcoma cells reversed the effects of NBR2 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition. The in vivo results showed that NBR2 overexpression inhibited tumor growth in nude mice that were inoculated with osteosarcoma cells. NBR2 overexpression also suppressed the messenger RNA (mRNA) expression of Notch1, N-cadherin, and vimentin and increased the mRNA expression of E-cadherin in the tumor tissues. These data indicated that NBR2 served as a tumor suppressor gene in osteosarcoma and inhibited osteosarcoma cell proliferation, invasion, and migration. The current study provides a novel insight and treatment strategy for osteosarcoma. 相似文献
66.
1. The trans-epoxide of diethylstilboestrol and its pinacolone were synthesized chemically and the pinacolone shown to be formed from the epoxide by a non-enzymic process. 2. [14C]Diethylstiboestrol epoxide was converted by rat liver microsomal fraction into 4'-hydroxypropiophenone by a new type of cleavage reaction involving mono-oxygenase. Conditions for the formation of this metabolite and also water-soluble products were investigated together with the effect of inhibitors. A sex-difference in the conversion of diethylstilboestrol epoxide into 4'-hydroxypropiophenone and to polar and water-soluble products was observed. 3. Diethylstilboestrol epoxide was found to be a relatively stable compound that did not form a glutathione conjugate readily without further microsomal activation. A purified preparation of epoxide hydratase did not enhance its rate of conversion into the pinacolone. 4. Diethylstilboestrol epoxide was found to have about one-tenth the oestrogenic activity of diethylstilboestrol as measured by the increase in uterine weight or the induction of peroxidase in immature rat uteri. It was inactive as a mutagen when tested for its ability to inhibit bacteriophage phi X174 DNA viral replication. 5. The possible role of diethylstilboestrol epoxide as an intermediate in the metabolism of diethylstilboestrol and in mediating the harmful effects of this synthetic estrogen is discussed. 相似文献
67.
觅食是获取营养物质和能量的重要途经。对于栖息在四季分明地区的灵长类动物而言,低温以及食物资源相对匮乏的冬季是其生存和生长发育的瓶颈期。本研究以安徽黄山的野生藏酋猴(Macaca thibetana)天湖山群为对象,于2019年11月至2020年1月采用瞬时扫描取样法(Instantaneous scan sampling)采集猴群觅食行为数据,并分析其冬季食物组成及食物中各化学成分含量对取食的影响。结果显示,野生藏酋猴在冬季共取食23科31属34种植物,主要包括壳斗科(Fagaceae, 21.62%)、樟科(Lauraceae, 17.57%)、蔷薇科(Rosaceae, 8.11%)的植物,取食部位以叶片(66.22%)和果实(种子)(24.32%)为主。不同取食部位的水分、总糖、淀粉、脂肪、单宁等成分存在显著差异。其中,叶片的水分含量高于果实(种子)、茎和芽,茎和果实(种子)含有较高的总糖,果实(种子)的淀粉和脂肪含量最高,芽的单宁含量最高。此外,取食植物中的总糖含量高于非取食植物。结果表明,野生藏酋猴适应寒冷冬季与食物匮乏的觅食策略是对植物种类、植物部位及其主要营养成分的综合结... 相似文献
68.
Oral administration of methyltestosterone (MT) at 50 mg/dog/day to intact adult male greyhounds for 90 d resulted in decreased (P < 0.05) mean daily sperm output and mean testicular length. Additionally, the mean diameter of seminiferous tubules in MT-treated dogs tended to decrease (P = 0.08). Mean concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) and concentrations of testosterone in serum were also decreased or tended to decrease (P = 0.0003 to 0.059) at various sampling periods during MT treatment, suggesting alterations in spermatogenesis resulted from decreased serum concentrations of gonadotropins and steroids. Mean daily sperm output, mean testicular length, mean seminiferous tubule diameter and mean concentrations of FSH in serum were not decreased (P > 0.05) at the end of a 90-d recovery period. However, mean concentrations of serum LH and concentrations of testosterone were still lower (P < 0.05) during five of six and one of six sampling times, respectively, during the recovery period than the pretreatment levels, suggesting a prolonged effect of MT treatment on the pituitary/gonadal axis. 相似文献
69.
Deeg MA Bowen RF Williams MD Olson LK Kirk EA LeBoeuf RC 《American journal of physiology. Endocrinology and metabolism》2001,281(1):E147-E154
Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is a high-density lipoprotein-associated protein. However, the tissue source(s) for circulating GPI-PLD and whether serum levels are regulated are unknown. Because the diabetic state alters lipoprotein metabolism, and liver and pancreatic islets are possible sources of GPI-PLD, we hypothesized that GPI-PLD levels would be altered in diabetes. GPI-PLD serum activity and liver mRNA were examined in two mouse models of type 1 diabetes, a nonobese diabetic (NOD) mouse model and low-dose streptozotocin-induced diabetes in CD-1 mice. With the onset of hyperglycemia (2- to 5-fold increase over nondiabetic levels), GPI-PLD serum activity and liver mRNA increased 2- to 4-fold in both models. Conversely, islet expression of GPI-PLD was absent as determined by immunofluorescence. Insulin may regulate GPI-PLD expression, because insulin treatment of diabetic NOD mice corrected the hyperglycemia along with reducing serum GPI-PLD activity and liver mRNA. Our data demonstrate that serum GPI-PLD levels are altered in the diabetic state and are consistent with liver as a contributor to circulating GPI-PLD. 相似文献
70.
Sea level fluctuations during glacial cycles affect the distribution of shallow marine biota, exposing the continental shelf on a global scale, and displacing coral reef habitat to steep slopes on oceanic islands. In these circumstances we expect that species inhabiting lagoons should show shallow genetic architecture relative to species inhabiting more stable outer reefs. Here we test this expectation on an ocean-basin scale with four wrasses (genus Halichoeres): H. claudia (N?=?194, with ocean-wide distribution) and H. ornatissimus (N?=?346, a Hawaiian endemic) inhabit seaward reef slopes, whereas H. trimaculatus (N?=?239) and H. margaritaceus (N?=?118) inhabit lagoons and shallow habitats throughout the Pacific. Two mitochondrial markers (cytochrome oxidase I and control region) were sequenced to resolve population structure and history of each species. Haplotype and nucleotide diversity were similar among all four species. The outer reef species showed significantly less population structure, consistent with longer pelagic larval durations. Mismatch distributions and significant negative Fu's F values indicate Pleistocene population expansion for all species, and (contrary to expectations) shallower histories in the outer slope species. We conclude that lagoonal wrasses may persist through glacial habitat disruptions, but are restricted to refugia during lower sea level stands. In contrast, outer reef slope species have homogeneous and well-connected populations through their entire ranges regardless of sea level fluctuations. These findings contradict the hypothesis that shallow species are less genetically diverse as a consequence of glacial cycles. 相似文献