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71.
Small molecule mediated inhibition of RORγ‐dependent gene expression and autoimmune disease pathology in vivo 下载免费PDF全文
72.
Summary An outbreak of acute hemorrhagic conjunctivitis (AHC) was reported in Singapore military camps in the year 2005. A total of
103 conjunctival swab specimens were collected from military personnel diagnosed clinically with AHC. PCR testing on these
conjunctival specimens revealed the presence of an enterovirus, and this was confirmed by virus isolation. Molecular typing
using a partial VP1 gene confirmed a variant of coxsackievirus A24 (CA24v) as the most likely etiological agent for the outbreak.
Full-length genome sequencing was carried out on 2 selected virus strains, DSO-26SIN05 and DSO-52SIN05. Sequence comparison
and phylogenetic analyses of the VP4, VP1 and 3Cpro gene regions were performed, clustering the Singapore CA24v strains with
viruses originating from Asia in the post-2000 era. In addition, we report evolution rates of 4.2 × 10−3 and 1.0 × 10−3 nucleotide/year, respectively, for the VP4 capsid and 3Cpro gene regions. Our result shows a focal evolutionary point around
1965–1966, suggesting that the CA24v virus has been evolving constantly since its emergence in Singapore, nearly 40 years
ago. 相似文献
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Pro-vasopressin mRNA, neurophysin and arginine vasopressin (AVP) were assayed in the mouse anterior pituitary gland, in mouse anterior pituitary cells in culture and in the AtT-20 corticotrophic tumour cell line. Northern blot analysis revealed the presence of an approximately 700 base pair pro-vasopressin mRNA in anterior pituitary and AtT-20 cells. Neurophysin, identified by immunoblots, and AVP, identified by high-performance liquid chromatography and cross-reactivity with AVP antiserum, were detected in anterior pituitary cells and AtT-20 cells. Immunocytochemical staining with anti-neurophysin showed that approximately 40-45% of the dissociated anterior pituitary cells in culture and greater than 95% of the AtT-20 cells were stained. Anterior pituitary cells in culture and AtT-20 cells had a basal level of release of AVP in the 0.01-0.1 nM range. These results indicate that anterior pituitary cells and AtT-20 cells have the ability to synthesize and process pro-vasopressin to AVP and neurophysin, endogenously. 相似文献
76.
Functional analysis of leukemia-associated PTPN11 mutations in primary hematopoietic cells 总被引:7,自引:4,他引:7 下载免费PDF全文
PTPN11 encodes the protein tyrosine phosphatase SHP-2, which relays signals from growth factor receptors to Ras and other effectors. Germline PTPN11 mutations underlie about 50% of Noonan syndrome (NS), a developmental disorder that is associated with an elevated risk of juvenile myelomonocytic leukemia (JMML). Somatic PTPN11 mutations were recently identified in about 35% of patients with JMML; these mutations introduce amino acid substitutions that are largely distinct from those found in NS. We assessed the functional consequences of leukemia-associated PTPN11 mutations in murine hematopoietic cells. Expressing an E76K SHP-2 protein induced a hypersensitive pattern of granulocyte-macrophage colony-forming unit (CFU-GM) colony growth in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3) that was dependent on SHP-2 catalytic activity. E76K SHP-2 expression also enhanced the growth of immature progenitor cells with high replating potential, perturbed erythroid growth, and impaired normal differentiation in liquid cultures. In addition, leukemia-associated SHP-2 mutations conferred a stronger phenotype than a germline mutation found in patients with NS. Mutant SHP-2 proteins induce aberrant growth in multiple hematopoietic compartments, which supports a primary role of hyperactive Ras in the pathogenesis of JMML. 相似文献
77.
Regulation of an opioid-binding protein in NG108-15 cells parallels regulation of delta-opioid receptors. 下载免费PDF全文
C M Lane R Elde H H Loh N M Lee 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(23):11234-11238
An opioid-binding protein has recently been purified from bovine brain and cloned, and its cDNA sequence has been obtained. Indirect evidence suggests that this protein has a role in opioid-receptor function. However, because direct testing of its function by expression of its cDNA has not yet been possible and because its structure bears no resemblance to G protein-coupled receptors, the role of this protein in opioid-receptor activity is still in question. An antibody raised to a portion of the predicted amino acid sequence of opioid-binding cell-adhesion molecule (OBCAM) specifically labeled the surface of NG108-15 cells, as visualized by immunofluorescence with confocal microscopy. Furthermore, chronic treatment of these cells with opioid agonist, which down-regulates opioid receptors, reduced OBCAM immunoreactivity (ir). Down-regulation of both opioid receptors and OBCAM-ir was greatest after chronic treatment of NG108-15 cells with delta-opioid agonists, as well as with nonselective agonists such as etorphine, whereas other agonists including [D-Ala2-N-MePhe4-Gly-ol]enkephalin, morphine, levorphanol, dynorphin A-(1-13), and U-50,488H were less effective or ineffective. Chronic treatment of NG108-15 cells with muscarinic agonists had no effect on OBCAM-ir. Furthermore, NG108-15 cells transfected with an antisense construct to OBCAM have a reduced density of opioid-binding sites as well as reduced OBCAM-ir. Taken together, these results strongly suggest that OBCAM has a role in opioid-receptor function in NG108-15 cells. 相似文献
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J W Holaday E Wei H H Loh C H Li 《Proceedings of the National Academy of Sciences of the United States of America》1978,75(6):2923-2927
Administration of the opiate antagonist naloxone to rats after acute or chronic heat exposure precipitates an increase in colonic temperature, an increase in escape attempts, and a decrease in body weight. These changes are accompanied by signs associated with hyperthermia such as salivation, diarrhea, and an abnormal extended posture. Although brain endorphin involvement is possible, hypophysectomy diminishes the intensity and magnitude of these naloxone effects, indicating that the naloxone effect in intact animals may be due to a functional antagonism of pituitary endorphins. These observations suggest that endorphins attenuate physiological responses to thermal and noxious stimuli triggered in common neuroanatomical pathways by heat. 相似文献
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