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91.
P Saá GF Sferrazza G Ottenberg AM Oelschlegel K Dorsey CI Lasmézas 《Journal of virology》2012,86(19):10494-10504
Several lines of evidence suggest that various cofactors may be required for prion replication. PrP binds to polyanions, and RNAs were shown to promote the conversion of PrP(C) into PrP(Sc) in vitro. In the present study, we investigated strain-specific differences in RNA requirement during in vitro conversion and the potential role of RNA as a strain-specifying component of infectious prions. We found that RNase treatment impairs PrP(Sc)-converting activity of 9 murine prion strains by protein misfolding cyclic amplification (PMCA) in a strain-specific fashion. While the addition of RNA restored PMCA conversion efficiency, the effect of synthetic polynucleotides or DNA was strain dependent, showing a different promiscuity of prion strains in cofactor utilization. The biological properties of RML propagated by PMCA under RNA-depleted conditions were compared to those of brain-derived and PMCA material generated in the presence of RNA. Inoculation of RNA-depleted RML in Tga20 mice resulted in an increased incidence of a distinctive disease phenotype characterized by forelimb paresis. However, this abnormal phenotype was not conserved in wild-type mice or upon secondary transmission. Immunohistochemical and cell panel assay analyses of mouse brains did not reveal significant differences between mice injected with the different RML inocula. We conclude that replication under RNA-depleted conditions did not modify RML prion strain properties. Our study cannot, however, exclude small variations of RML properties that would explain the abnormal clinical phenotype observed. We hypothesize that RNA molecules may act as catalysts of prion replication and that variable capacities of distinct prion strains to utilize different cofactors may explain strain-specific dependency upon RNA. 相似文献
92.
Nitric Oxide Synthase and Breast Cancer: Role of TIMP-1 in NO-mediated Akt Activation 总被引:1,自引:0,他引:1
LA Ridnour KM Barasch AN Windhausen TH Dorsey MM Lizardo HG Yfantis DH Lee CH Switzer RY Cheng JL Heinecke E Brueggemann HB Hines C Khanna SA Glynn S Ambs DA Wink 《PloS one》2012,7(9):e44081
Prediction of therapeutic response and cancer patient survival can be improved by the identification of molecular markers including tumor Akt status. A direct correlation between NOS2 expression and elevated Akt phosphorylation status has been observed in breast tumors. Tissue inhibitor matrix metalloproteinase-1 (TIMP-1) has been proposed to exert oncogenic properties through CD63 cell surface receptor pathway initiation of pro-survival PI3k/Akt signaling. We employed immunohistochemistry to examine the influence of TIMP-1 on the functional relationship between NOS2 and phosphorylated Akt in breast tumors and found that NOS2-associated Akt phosphorylation was significantly increased in tumors expressing high TIMP-1, indicating that TIMP-1 may further enhance NO-induced Akt pathway activation. Moreover, TIMP-1 silencing by antisense technology blocked NO-induced PI3k/Akt/BAD phosphorylation in cultured MDA-MB-231 human breast cancer cells. TIMP-1 protein nitration and TIMP-1/CD63 co-immunoprecipitation was observed at NO concentrations that induced PI3k/Akt/BAD pro-survival signaling. In the survival analysis, elevated tumor TIMP-1 predicted poor patient survival. This association appears to be mainly restricted to tumors with high NOS2 protein. In contrast, TIMP-1 did not predict poor survival in patient tumors with low NOS2 expression. In summary, our findings suggest that tumors with high TIMP-1 and NOS2 behave more aggressively by mechanisms that favor Akt pathway activation. 相似文献
93.
Clete S. Dorsey 《The Western journal of medicine》1959,90(2):155-159
A hitherto unrecognized cause of contact dermatitis in California is the widely cultivated plant known as Algerian ivy. This plant, which grows in California (and its close relative, English ivy) causes a dermatitis which is similar to although milder than that caused by poison oak. Dermatitis from this cause occurs most frequently when persons who have become sensitive to it by previous contact trim the plant back in the spring after its seasonal spurt of growth. For persons whose occupations require repeated contact with the plant, dermatitis from this cause is an occupational hazard. Dermatitis from this plant is easily diagnosed by means of a simple patch test.In a series of 12 cases the only effective treatment was with corticosteroid agents. 相似文献
94.
Background
Clearance of synaptically released glutamate, and hence termination of glutamatergic neurotransmission, is carried out by glutamate transporters, most especially glutamate transporter-1 (GLT-1) and the glutamate-aspartate transporter (GLAST) that are located in astrocytes. It is becoming increasingly well appreciated that changes in the function and expression of GLT-1 and GLAST occur under different physiological and pathological conditions. Here we investigated the plasticity in expression of GLT-1 and GLAST in the spinal dorsal horn using immunohistochemistry following partial sciatic nerve ligation (PSNL) in rats.Results
Animals were confirmed to develop hypersensitivity to mechanical stimulation by 7 days following PSNL. Baseline expression of GLT-1 and GLAST in naive animals was only observed in astrocytes and not in either microglia or neurons. Microglia and astrocytes showed evidence of reactivity to the nerve injury when assessed at 7 and 14 days following PSNL evidenced by increased expression of OX-42 and GFAP, respectively. In contrast, the total level of GLT-1 and GLAST protein decreased at both 7 and 14 days after PSNL. Importantly, the cellular location of GLT-1 and GLAST was also altered in response to nerve injury. Whereas activated astrocytes showed a marked decrease in expression of GLT-1 and GLAST, activated microglia showed de novo expression of GLT-1 and GLAST at 7 days after PSNL and this was maintained through day 14. Neurons showed no expression of GLT-1 or GLAST at any time point.Conclusion
These results indicate that the expression of glutamate transporters in astrocytes and microglia are differentially regulated following nerve injury. 相似文献95.
Charles H. Dorsey 《Experimental parasitology》1975,37(1):37-59
Cercariae of Schistosoma mansoni in daughter sporocysts in Biomphalaria glabrata were studied with the electron microscope to observe the maturing process of their acetabular glands. The undifferentiated acetabular gland displays its enlarged basal area (fundus) and extended narrow process (duct) before other organ systems are recognized. Its fundus contains a prominent nucleus and subcellular organelles typical of active secretory cells.The secretory granules of the postacetabular glands are formed in a milieu of dilated rough endoplasmic reticulum and Golgi. Two morphologically different secretory granules are produced: (1) homogeneously granular ones, and (2) other granular ones with electron dense bodies in their matrices. Mostly, the homogeneously granular ones are produced first in the fundus and are forced into the ducts as the other type is formed.The secretory granules of preacetabular glands are formed from translucent vacuoles which arise from an environment of endoplasmic reticulum and Golgi. Two morphologically different secretory granules are produced: (1) one type has a homogeneous dense matrix, and (2) the other type has a less dense matrix containing electron-lucid bodies.The duct of an undifferentiated acetabular gland has either filamentous material or microtubules dispersed in its cytoplasm. Once microtubules are formed, they persist during the life of the cercaria. The microtubules are believed to have possibly two functions: (1) to support the long duct, and (2) to assist the movement of the secretory granules into the channels of the ducts where they remain until released during host penetration.Few of the subcellular organelles associated with secretory granules formation are seen in the duct except the area in close proximity to the fundus; thus, the few secretory granules produced in the duct are in this region. 相似文献
96.
R Kigozi SM Baxi A Gasasira A Sserwanga S Kakeeto S Nasr D Rubahika G Dissanayake MR Kamya S Filler G Dorsey 《PloS one》2012,7(8):e42857
Background
Recently the use of indoor residual spraying of insecticide (IRS) has greatly increased in Africa; however, limited data exist on the quantitative impacts of IRS on health outcomes in highly malaria endemic areas.Methodology/Principal Findings
Routine data were collected on more than 90,000 patient visits at a single health facility over a 56 month period covering five rounds of IRS using three different insecticides. Temporal associations between the timing of IRS and the probability of a patient referred for microscopy having laboratory confirmed malaria were estimated controlling for seasonality and age. Considering patients less than five years of age there was a modest decrease in the odds of malaria following the 1st round of IRS using DDT (OR = 0.76, p<0.001) and the 2nd round using alpha-cypermethrin (OR = 0.83, p = 0.002). Following rounds 3–5 using bendiocarb there was a much greater decrease in the odds of malaria (ORs 0.34, 0.16, 0.17 respectively, p<0.001 for all comparisons). Overall, the impact of IRS was less pronounced among patients 5 years or older.Conclusions/Significance
IRS was associated with a reduction in malaria morbidity in an area of high transmission intensity in Uganda and the benefits appeared to be greatest after switching to a carbamate class of insecticide. 相似文献97.
Amir Nikou Shauna M. Dorsey Jeremy R. McGarvey Joseph H. Gorman III Jason A. Burdick James J. Pilla 《Computer methods in biomechanics and biomedical engineering》2016,19(16):1714-1720
Computational models are increasingly being used to investigate the mechanical properties of cardiac tissue. While much insight has been gained from these studies, one important limitation associated with computational modeling arises when using in vivo images of the heart to generate the reference state of the model. An unloaded reference configuration is needed to accurately represent the deformation of the heart. However, it is rare for a beating heart to actually reach a zero-pressure state during the cardiac cycle. To overcome this, a computational technique was adapted to determine the unloaded configuration of an in vivo porcine left ventricle (LV). In the current study, in vivo measurements were acquired using magnetic resonance images (MRI) and synchronous pressure catheterization in the LV (N = 5). The overall goal was to quantify the effects of using early–diastolic filling as the reference configuration (common assumption used in modeling) versus using the unloaded reference configuration for predicting the in vivo properties of LV myocardium. This was accomplished by using optimization to minimize the difference between MRI measured and finite element predicted strains and cavity volumes. The results show that when using the unloaded reference configuration, the computational method predicts material properties for LV myocardium that are softer and less anisotropic than when using the early-diastolic filling reference configuration. This indicates that the choice of reference configuration could have a significant impact on capturing the realistic mechanical response of the heart. 相似文献
98.
We used the repetitive character of transposable elements to isolate a
non-LTR retrotransposon in Drosophila subobscura. bilbo, as we have called
it, has homology to TRIM and LOA elements. Sequence analysis showed a 5'
untranslated region (UTR), an open reading frame (ORF) with no RNA-binding
domains, a downstream ORF that had structural homology to that of the I
factor, and, finally, a 3' UTR which ended in several 5-nt repeats. The
results of our phylogenetic and structural analyses shed light on the
evolution of Drosophila non-LTR retrotransposons and support the hypothesis
that an ancestor of these elements was structurally complex.
相似文献
99.
Pacofsky GJ Stafford JA Cox RF Cowan JR Dorsey GF Gonzales SS Kaldor I Koszalka GW Lovell GG McIntyre MS Tidwell JH Todd D Whitesell G Wiard RP Feldman PL 《Bioorganic & medicinal chemistry letters》2002,12(21):3219-3222
The ultrashort-acting benzodiazepine (USA BZD) agonists reported previously have been structurally modified to improve aqueous solubility. Lactam-to-amidine modifications, replacement of the C5-haloaryl ring, and annulation of heterocycles are presented. These analogues retain BZD receptor potency and full agonism profiles. 相似文献
100.
Knee varus position and motion have been correlated with increased medial knee loading during gait. The purpose of this study is to determine whether runners with excessive varus excursion (EVE) at the knee demonstrate frontal plane knee and hip kinetics that are different from those of runners with normal varus excursion (NVE). Twelve runners with EVE were compared with 12 NVE subjects using three-dimensional kinematics and kinetics. Frontal plane angles and moments were compared at the knee and hip. Runners with EVE had significantly greater abductor moment of the knee (p = .004) and lower peak abductor moment of the hip (p = .047). Runners with EVE demonstrate knee and hip mechanics thought to be associated with increased medial tibiofemoral loading. Further understanding of how changing hip abductor moments may affect changes in knee abductor moments during running may potentially lead to interventions that augment long-term risk of injury. 相似文献