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81.
Transmissible spongiform encephalopathies (prion diseases) in animals may be associated with a zoonotic risk potential for humans as shown by the occurrence of variant Creutzfeldt-Jakob disease in the wake of the bovine spongiform encephalopathy epidemic. Thus, the increasing exposure of humans in North America to cervid prions of chronic wasting disease (CWD) in elk and deer has prompted comprehensive risk assessments. The susceptibility of humans to CWD infections is currently under investigation in different studies using macaques as primate models. The necessity for such studies was recently reinforced when disease-associated prion protein and its seeding activity were detected in muscles of clinically inconspicuous CWD-infected white-tailed deer (WTD). Increasing evidence points to the existence of different CWD strains and CWD prions may also change or newly emerge over time. Therefore, CWD isolates examined in macaques should be characterized as precisely as possible for their molecular identity. On this basis other CWD field samples collected in the past, present or future could be systematically compared with macaque-tested inocula in order to assess whether they are covered by the ongoing risk assessments in primates. CWD typing by Fourier transform-infrared spectroscopy of pathological prion protein may provide a method of choice for this purpose. 相似文献
82.
Nora Wender Jan Hegermann Bettina Brunner Brigitte Nuscher Tim Bartels Armin Giese Klaus Beyer Stefan Eimer Konstanze F Winklhofer Christian Haass 《The EMBO journal》2010,29(20):3571-3589
Aggregation of α‐synuclein (αS) is involved in the pathogenesis of Parkinson's disease (PD) and a variety of related neurodegenerative disorders. The physiological function of αS is largely unknown. We demonstrate with in vitro vesicle fusion experiments that αS has an inhibitory function on membrane fusion. Upon increased expression in cultured cells and in Caenorhabditis elegans, αS binds to mitochondria and leads to mitochondrial fragmentation. In C. elegans age‐dependent fragmentation of mitochondria is enhanced and shifted to an earlier time point upon expression of exogenous αS. In contrast, siRNA‐mediated downregulation of αS results in elongated mitochondria in cell culture. αS can act independently of mitochondrial fusion and fission proteins in shifting the dynamic morphologic equilibrium of mitochondria towards reduced fusion. Upon cellular fusion, αS prevents fusion of differently labelled mitochondrial populations. Thus, αS inhibits fusion due to its unique membrane interaction. Finally, mitochondrial fragmentation induced by expression of αS is rescued by coexpression of PINK1, parkin or DJ‐1 but not the PD‐associated mutations PINK1 G309D and parkin Δ1–79 or by DJ‐1 C106A. 相似文献
83.
Taurine transporter is expressed in vascular smooth muscle cells 总被引:2,自引:0,他引:2
Summary. The regulation of vascular smooth muscle cells (VSMCs) function by taurine has been a subject of increasing interest and investigation,
and taurine is taken up into cells through a specific transporter system, the taurine transporter (TAUT). In the present study,
we examined the expression of TAUT in VSMCs and the kinetic parameters of the uptake process of TAUT in VSMCs. RT-PCR and
western blot demonstrated that the mRNA and protein of TAUT was expressed in VSMCs in vitro. Immunohistochemistry using antibody
for TAUT revealed the expression of this protein in rat thoracic aorta. The maximal [3H]taurine uptake rate in VSMCs was 37.75 ± 3.13 pmol/min per mg of protein, with a K
m
value of 5.42 ± 0.81 μM. Thus, VSMCs are able to express a functional taurine transporter. The regulation and detailed function
of taurine and TAUT in VSMCs remain unclear, but our findings suggest a functional role for them in VSMCs metabolism. 相似文献
84.
Species of Borrelia distinguished by restriction site polymorphisms in 16S rRNA genes 总被引:2,自引:0,他引:2
David Ralph Daniele Postic Guy Baranton Charles Pretzman Michael McClelland 《FEMS microbiology letters》1993,111(2-3):239-243
Abstract Three phyletic groups of Borrelia associated with Lyme disease, B. burgdorferi, B. garinii and group VS461 can be distinguished from each other and other species of Borrelia by Bfa I restriction site polymorphisms in PCR amplified 16S rRNA genes. One strain isolated from an Ixodes pacificus tick in California that was previously unclassifiable was distinguishable from B. burgdorferi by an Mnl I restriction site polymorphism. 相似文献
85.
SANDRA ANNE BANACK PAUL ALAN COX fls 《Botanical journal of the Linnean Society. Linnean Society of London》2003,143(2):165-168
BMAA (β-methylamino-L-alanine), a nonprotein amino acid with neurotoxic properties occurs in the cycad Cycas micronesica Hill in Guam. BMAA may have originally played a role as an antiherbivory compound in the plant, but is now of great interest because of its possible link to ALS-PDC, a neurological disease among the Chamorro people of Guam. Biomagnified cycad neurotoxins may play a role because they accumulate in flying foxes of the genus Pteropus that are eaten during traditional feasts. Since flying foxes feed on the seed sarcotesta it is important to understand the distribution of BMAA in the various tissues of the cycad. Using HPLC techniques, we quantified both BMAA and glutamic acid (GLU) in all cycad tissues. Although GLU is distributed randomly throughout the plant, BMAA is concentrated in cycad reproductive organs, with the highest concentrations being found in the immature staminate sporangium and the outmost layer of the sarcotesta. This finding is consistent with the putative evolutionary role of BMAA as an antiherbivory compound, as well as the biomagnification of the compound in flying foxes that ingest the seed sarcotesta. © 2003 The Linnean Society of London, Botanical Journal of the Linnean Society , 2003, 143 , 165–168. 相似文献
86.
Cerebrospinal fluid Th1/Th2 cytokine profiles in children with enterovirus 71‐associated meningoencephalitis 下载免费PDF全文
Huajun Li Shuxian Li Jianfeng Zheng Chunyan Cai Bin Ye Jun Yang Zhimin Chen 《Microbiology and immunology》2015,59(3):152-159
Enterovirus 71 (EV71) infection can cause severe neurological complications including meningoencephalitis (ME) in some patients with hand, foot and mouth disease (HFMD). However, to date no studies have reported changes in cytokine concentrations and their correlations with clinical variables in patients with ME following EV71 infection. In this study, responses of Th1/Th2 cytokine, including IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α and IFN‐γ, in cerebrospinal fluid (CSF) from patients with EV71‐related HFMD with ME and patients with febrile convulsions (FC) were analyzed using cytometric bead array technology. It was found that CSF IL‐6 and IFN‐γ concentrations were significantly higher in patients with EV71‐related ME than in those with FC. Additionally, both CSF IL‐6 and IFN‐γ concentrations were correlated with CSF cytology, fever duration and duration of hospital stay. More interestingly, a positive correlation between CSF IL‐6 and IFN‐γ concentrations was observed. Finally, receiver operating characteristic analysis revealed that when a cutoff value of 9.40 pg/mL was set for IL‐6, the sensitivity and specificity were 84.5% and 85.5%, respectively, for discriminating EV71‐related ME from FC. In conclusion, IL‐6 and IFN‐γ may be associated with EV71‐induced neuropathology. 相似文献
87.
Annelie Eklund Sarron Randall‐Demllo Sergey Shabala Nuri Guven Anthony L Cook Rajaraman D Eri 《Cell biochemistry and function》2013,31(7):603-611
Endoplasmic reticulum (ER) stress and oxidative stress have recently been linked to the pathogenesis of inflammatory bowel diseases. Under physiological conditions, intestinal epithelial cells are exposed to ER and oxidative stress affecting the cellular ionic homeostasis. However, these altered ion flux ‘signatures’ during these stress conditions are poorly characterized. We investigated the kinetics of K+, Ca2+ and H+ ion fluxes during ER and oxidative stress in a colonic epithelial cell line LS174T using a non‐invasive microelectrode ion flux estimation technique. ER and oxidative stress were induced by cell exposure to tunicamycin (TM) and copper ascorbate (CuAsc), respectively, from 1 to 24 h. Dramatic K+ efflux was observed following acute ER stress with peak K+ efflux being ?30·6 and ?138·7 nmolm?2 s?1 for 10 and 50 µg ml?1, respectively (p < 0·01). TM‐dependent Ca2+ uptake was more prolonged with peak values of 0·85 and 2·68 nmol m?2 s?1 for 10 and 50 µg ml?1 TM, respectively (p < 0·02). Ion homeostasis was also affected by the duration of ER stress. Increased duration of TM treatment from 0 to 18 h led to increases in both K+ efflux and Ca2+ uptake. While K+ changes were significantly higher at each time point tested, Ca2+ uptake was significantly higher only after prolonged treatment (18 h). CuAsc also led to an increased K+ efflux and Ca2+ uptake. Functional assays to investigate the effect of inhibiting K+ efflux with tetraethylammonium resulted in increased cell viability. We conclude that ER/oxidative stress in colonic epithelial cells cause dramatic K+, Ca2+ and H+ ion flux changes, which may predispose this lineage to poor stress recovery reminiscent of that seen in inflammatory bowel diseases. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
88.
Average percentages of winter wheat plants with severe take‐all were decreased by up to half by azoxystrobin applied as foliar sprays in four field experiments. Decreased take‐all in three of the experiments was associated with increased grain yield but effects on other diseases may have contributed to these responses. Standard fungicide sprays were ineffective. The effects differed, but not consistently, among different cultivars that were tested in three of the experiments. One, two or three sprays of azoxystrobin or kresoxim‐methyl, in autumn, spring or summer, were tested in the fourth experiment. Unlike azoxystrobin, kresoxim‐methyl had no consistent effects but a smaller amount was applied. Two or three sprays of azoxystrobin were more effective than a single spray but their timing was unimportant. Such control of a root disease by a foliar‐applied fungicide is unusual but may help to explain some of the unexpectedly large yield responses to azoxystrobin that have been reported. This relatively broad‐spectrum fungicide may have the potential to contribute to the practical management of take‐all but further research is needed to determine how best to exploit its effects consistently. 相似文献
89.
M. Flint Beal Ross A. Clevens Geetinder K. Chattha Usha M. MacGarvey Michael F. Mazurek Steven M. Gabriel 《Journal of neurochemistry》1988,51(6):1935-1941
Galanin is a recently isolated neuropeptide that is of particular interest in dementing disorders because of its known colocalization with choline acetyltransferase in magnocellular neurons of the basal nucleus of Meynert. These neurons degenerate in Alzheimer's disease, and there is a corresponding deficiency of cortical choline acetyltransferase activity. In the present study, galanin-like immunoreactivity was measured in the postmortem cerebral cortex and hippocampus of 10 controls and 14 patients who had had Alzheimer's disease. Significant reductions of choline acetyltransferase activity (50-60%) were found in all regions examined; however, there was no significant effect on concentrations of galanin-like immunoreactivity. Similar measurements were made in postmortem tissues of 12 control and 13 demented Parkinsonian patients who had had Alzheimer-type cortical pathology. Choline acetyltransferase activity was again significantly decreased in all regions examined but there were no significant reductions in galanin-like immunoreactivity. Experimental lesions of the fornix in rats produced parallel significantly correlated reductions of both choline acetyltransferase activity and galanin-like immunoreactivity in the hippocampus. Galanin-like immunoreactivity in the human hypothalamus consisted of two molecular-weight species on gel-permeation chromatography, and two forms were resolved by reverse-phase HPLC. The paradoxical preservation of galanin-like immunoreactivity, despite depletion of the activity of choline acetyltransferase, with which it is colocalized, is as yet unexplained. Recent studies have shown that galanin inhibits both acetylcholine release in the hippocampus and memory acquisition; therefore, preserved galanin may exacerbate the cholinergic and cognitive deficits that accompany dementia. 相似文献
90.
Patel S O'Malley S Connolly B Liu W Hargreaves R Sur C Gibson RE 《Journal of neurochemistry》2006,96(1):171-178
Inhibition of gamma-secretase is a potential therapeutic target for Alzheimer's disease (AD). The present studies have characterized the in vitro properties of a radiolabeled small molecule gamma-secretase inhibitor, [3H]compound D (Yan et al., 2004, J. Neurosci.24, 2942-2952) in mammalian brain. [3H]Compound D was shown to bind with nanomolar affinity (Kd = 0.32-1.5 nM) to a single population of saturable sites in rat, rhesus and human brain cortex homogenates, the density of binding sites ranging from 4 to 7 nM across the species. Competition studies with a structurally diverse group of gamma-secretase inhibitors with a wide range of binding affinities showed that the binding affinities of these compounds correlated well with their ability to inhibit gamma-secretase in vitro. Autoradiographic studies showed that the specific binding of [3H]compound D was widely distributed throughout adult rat, rhesus and normal human brain. There did not appear to be any difference in distribution of [3H]compound D specific binding sites in AD cortex compared with control human cortex as measured using tissue section autoradiography, nor any correlation between gamma-secretase binding and plaque burden as measured immunohistochemically. [3H]compound D is a useful tool to probe the expression and pharmacology of gamma-secretase in mammalian brain. 相似文献