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101.
Prions are the infectious agents responsible for prion diseases, which appear to be composed exclusively by the misfolded prion protein (PrP(Sc)). Disease is transmitted by the autocatalytic propagation of PrP(Sc) misfolding at the expense of the normal prion protein. The biggest challenge of the prion hypothesis has been to explain the molecular mechanism by which prions can exist as different strains, producing diseases with distinguishable characteristics. Here, we show that PrP(Sc) generated in vitro by protein misfolding cyclic amplification from five different mouse prion strains maintains the strain-specific properties. Inoculation of wild-type mice with in vitro-generated PrP(Sc) caused a disease with indistinguishable incubation times as well as neuropathological and biochemical characteristics as the parental strains. Biochemical features were also maintained upon replication of four human prion strains. These results provide additional support for the prion hypothesis and indicate that strain characteristics can be faithfully propagated in the absence of living cells, suggesting that strain variation is dependent on PrP(Sc) properties. 相似文献
102.
Combined field surveys and laboratory studies were conducted in two Italian coastal lagoons, which differ for geomorphology,
hydrodynamics and eutrophication degree (Sacca di Goro and Lesina lagoons, Adriatic Sea). Research aimed at assessing with
a rapid technique the potential buffering capacity of sedimentary iron towards sulphides. In Spring and Summer 2004, the main
pools of iron and sulphides were analysed in the uppermost sediment horizon (0–5 cm) at four stations in each lagoon. In parallel,
experiments with laboratory incubations of sediment slurries were carried out at two sites in each lagoon in order to assess
the sediment capacity of binding and retaining sulphides. Sediment slurries were kept stirred and anoxic with N2 purging. Aliquots of dissolved sulphides (DS) were then added and DS concentrations were monitored until they were undetectable.
On average, the total reactive iron (RFe), extracted with 6 N HCl, ranged from 170 to 400 μmol cm−3 in the Sacca di Goro stations, and comprised between 40 and 150 μmol cm−3 in the Lesina sites. The labile iron ferric quota (LFe: extractable with 0.5 N HCl) is considered representative of the microbially
reducible iron fraction and was highest in spring in Sacca di Goro (up to 20 μmol cm−3). Differences among stations evidenced by PCA analysis, can be inferred from RFe, LFe and AVS, which represent the iron buffer
and its saturation status, respectively. The sedimentary DS uptake was 6 μmol cm−3 of fresh sediment in Lesina and 8–12 μmol cm−3 in Sacca di Goro, indicating a direct relationship between DS removal and iron availability.
Guest editors: A. Razinkovas, Z. R. Gasiūnaitė, J. M. Zaldivar & P. Viaroli
European Lagoons and their Watersheds: Function and Biodiversity 相似文献
103.
When protein synthesis is arrested by amino acid starvation, Escherichia coli wild-type strains show stringent control (SC) over stable RNA (sRNA) accumulation as well as a large number of other growth-related processes. One of the events under SC is transport of metabolites. Thus, under amino acid starvation, E. coli fails to accumulate the non-metabolizable glucose analog alpha-methyl-D-glucoside, whereas isogenic relaxed strains continue to take up this glucose analog. Unlike the Bacteria, most wild-type archaeal strains show relaxed control of sRNA accumulation, although a number of stringent strains have been identified. In order to determine whether stringency in the Archaea affects physiological events different from sRNA accumulation, transport of glucose analogs was examined under amino acid starvation in two stringent archaeal strains, Haloferax volcanii and Sulfolobus acidocaldarius. The experiments were performed with 2-deoxy-D-glucose, which was shown to be transported, but metabolized very limitedly. Unlike E. coli, H. volcanii and S. acidocaldarius continued to transport 2-deoxy-D-glucose under amino acid starvation. Thus, in both Archaea glucose analog transport is not under SC, as it is in E. coli. 相似文献
104.
105.
Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research
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106.
The 5′-adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of the cellular energy metabolism and may induce either cell survival or death. We previously reported that in SH-SY5Y human neuroblastoma cells stimulation of muscarinic acetylcholine receptors (mAChRs) activate AMPK by triggering store-operated Ca2+ entry (SOCE). However, whether mAChRs may control AMPK activity by regulating additional mechanisms beyond SOCE remains to be investigated. In the present study we examined the effects of mAChRs on AMPK when SOCE was induced by the sarco–endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin. We found that in SH-SY5Y cells depleted of Ca2+ by thapsigargin, the re-addition Ca2+ to the medium stimulated AMPK phosphorylation at Thr172, which is required for full kinase activity. This response occurred through SOCE, as it was blocked by either the SOCE modulator 2-aminoethoxydiphephenyl borate, knockdown of the SOCE molecular component STIM1, or inhibition of Ca2+/calmodulin (CaM)-dependent protein kinase kinase β (CaMKKβ). In thapsigargin-pretreated cells, stimulation of pharmacologically defined M3 mAChRs potentiated SOCE-induced AMPK activation. This potentiation did not involve an increased Ca2+ influx, but was associated with CaM mobilization from membrane to cytosol, increased CaM/CaMKKβ interaction, and enhanced CaMKK stimulation by thapsigargin-induced SOCE. In thapsigargin-pretreated cells Ca2+ re-addition stimulated glucose uptake and increased the membrane expression of the glucose transporter GLUT1. Both responses were significantly potentiated by mAChRs. These data indicate that in human neuroblastoma cells mAChRs up-regulate AMPK and the downstream glucose uptake by triggering not only SOCE but also CaM translocation and enhanced formation of active CaM/CaMKKβ complexes. 相似文献
107.
108.
Structure and absolute stereochemistry of vanillosmin,a guaianolide from Vanillosmopsis erythropappa
Attilio Corbrella Pierluigi Gariboldi Giancarlo Jommi Fulvia Orsini Giorgio Ferrari 《Phytochemistry》1974,13(2):459-465
The structure and absolute stereochemistry of vanillosmin were established by chemical and spectral evidence and by comparison with O-acetyl-isophoto-α-santonic lactone and tetrahydroartabsin “C”. 相似文献
109.
QUANTITATIVE AUTORADIOGRAPHIC STUDY OF LABELED RNA IN RABBIT OPTIC NERVE AFTER INTRAOCULAR INJECTION OF [3H]URIDINE 总被引:1,自引:1,他引:0
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Pierluigi Gambetti Lucila Autilio-Gambetti Brenda Shafer LaDorna Pfaff 《The Journal of cell biology》1973,59(3):677-684
The distribution of labeled RNA in the optic nerve of the rabbit was studied by quantitative ultrastructural autoradiography after the intraocular injection of [3H]uridine. The highest density of silver grains related to [3H]RNA (27–40 grains/100 µm2) was found in glial cell perikarya; a slightly lower density was present in the glial nuclei (19–20 grains/100 µm2). Axons (4–5 grains/100 µm2) and myelin (2–3 grains/100 µm2) had the lowest grain densities. 74–83% of all counted grains were located outside the axons. By comparing the grain density distribution over the axon with that expected in the case of an exclusive labeling of the surrounding myelin and glial cell processes, it was concluded that the axons contained a number of grains representing [3H]RNA significantly higher than that expected to scatter from myelin and glial processes. Most of these grains were concentrated at the periphery of the axon and were not related to axonal mitochondria. 相似文献
110.
THE FINE STRUCTURE OF PUROMYCIN-INDUCED CHANGES IN MOUSE ENTORHINAL CORTEX 总被引:8,自引:2,他引:6
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Pierluigi Gambetti Nicholas K. Gonatas Louis B. Flexner 《The Journal of cell biology》1968,36(2):379-390
Bitemporal intracerebral injections of puromycin in mice suppress indefinitely expression of memory of avoidance-discrimination learning. Ultrastructural studies of the entorhinal cortex of puromycin-treated mice revealed the following: (a) Abnormalities were not observed in presynaptic terminals and synaptic clefts; many postsynaptic dendrites or somas contained swollen mitochondria. (b) Dispersion of polyribosomes into single units or condensation of ribosomes into irregular aggregates with loss of "distinctiveness" was noted in a few neurons 7–27 hr after puromycin treatment. (c) Cytoplasmic aggregates of granular or amorphous material were frequently noted within otherwise normal neuronal perikarya. (d) Mitochondria in many neuronal perikarya and dendrites were swollen. Mitochondria in axons, presynaptic terminals, and glial cells were unaltered. The relationships between these lesions and the effect of puromycin on protein synthesis and memory are examined. It is suggested that the disaggregation of polysomes is too limited to explain the effect of puromycin on memory. Special emphasis is given to the swelling of mitochondria. The possible mechanisms and the significance of this lesion are discussed. 相似文献