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991.
Broccolini A Gidaro T De Cristofaro R Morosetti R Gliubizzi C Ricci E Tonali PA Mirabella M 《Journal of neurochemistry》2008,105(3):971-981
Autosomal recessive hereditary inclusion-body myopathy (h-IBM) is caused by mutations of the UDP- N -acetylglucosamine 2-epimerase/ N -acetylmannosamine kinase gene, a rate-limiting enzyme in the sialic acid metabolic pathway. Previous studies have demonstrated an abnormal sialylation of glycoproteins in h-IBM. h-IBM muscle shows the abnormal accumulation of proteins including amyloid-β (Aβ). Neprilysin (NEP), a metallopeptidase that cleaves Aβ, is characterized by the presence of several N-glycosylation sites, and changes in these sugar moieties affect its stability and enzymatic activity. In the present study, we found that NEP is hyposialylated and its expression and enzymatic activity reduced in all h-IBM muscles analyzed. In vitro , the experimental removal of sialic acid by Vibrio Cholerae neuraminidase in cultured myotubes resulted in reduced expression of NEP. This was most likely because of a post-translational modification consisting in an abnormal sialylation of the protein that leads to its reduced stability. Moreover, treatment with Vibrio Cholerae neuraminidase was associated with an increased immunoreactivity for Aβ mainly in the form of distinct cytoplasmic foci within myotubes. We hypothesize that, in h-IBM muscle, hyposialylated NEP has a role in hampering the cellular Aβ clearing system, thus contributing to its abnormal accumulation within vulnerable fibers and possibly promoting muscle degeneration. 相似文献
992.
Serotonin-1A (5-HT1A ) receptors in the dorsal raphe nucleus (DRN) function as somatodendritic autoreceptors, and therefore play a critical role in controlling serotonergic cell firing and serotonergic neurotransmission. We hypothesized that a decrease in the capacity of 5-HT1A receptors to activate G proteins was a general mechanism by which 5-HT1A receptors in the DRN are desensitized following chronic administration of selective serotonin reuptake inhibitors (SSRIs). Using in vivo microdialysis, we found that the ability of the 5-HT1A receptor agonist 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT) (0.025 mg/kg, s.c.) to decrease extracellular 5-HT levels in striatum was attenuated following chronic treatment of rats with the SSRIs sertraline or fluoxetine. This apparent desensitization of somatodendritic 5-HT1A autoreceptor function was not accompanied by a decrease in 5-HT1A receptor sites in the coupled, high-affinity agonist state as measured by the binding of [3H]8-OH-DPAT. In marked contrast to what was observed following chronic administration of fluoxetine, 5-HT1A receptor-stimulated [35 S]GTPγS binding in the DRN was not altered following chronic sertraline treatment. Thus, desensitization of 5-HT1A somatodendritic autoreceptor function following chronic sertraline administration appears not to be due to a decrease in the capacity 5-HT1A receptors to activate G proteins in the DRN. Our findings suggest that the SSRIs may not be a homogeneous class of antidepressant drug with regard to the mechanism by which the function of somatodendritic 5-HT1A autoreceptors is regulated. 相似文献
993.
994.
Herbivory can induce changes in plant traits that may involve both tolerance mechanisms that compensate for biomass loss and
resistance traits that reduce herbivore preference. Seagrasses are marine vascular plants that possess many attributes that
may favour tolerance and compensatory growth, and they are also defended with mechanisms of resistance such as toughness and
secondary metabolites. We quantified phenotypic changes induced by herbivore damage on the temperate seagrass Posidonia oceanica in order to identify specific compensatory and resistance mechanisms in this plant, and to assess any potential trade-offs
between these two strategies of defence. We simulated three natural levels of fish herbivory by repeatedly clipping seagrass
leaves during the summer period of maximum herbivory. Compensatory responses were determined by measuring shoot-specific growth,
photosynthetic rate, and the concentration of nitrogen and carbon resources in leaves and rhizomes. Induced resistance was
determined by measuring the concentration of phenolic secondary metabolites and by assessing the long-term effects of continued
clipping on herbivore feeding preferences using bioassays. Plants showed a significant ability to compensate for low and moderate
losses of leaf biomass by increasing aboveground growth of damaged shoots, but this was not supported by an increase in photosynthetic
capacity. Low levels of herbivory induced compensatory growth without any measurable effects on stored resources. In contrast,
nitrogen reserves in the rhizomes played a crucial role in the plant’s ability to compensate and survive herbivore damage
under moderate and high levels of herbivory, respectively. We found no evidence of inducibility of long-term resistance traits
in response to herbivory. The concentration of phenolics decreased with increasing compensatory growth despite all treatments
having similar carbon leaf content, suggesting reallocation of these compounds towards primary functions such as cell-wall
construction. 相似文献
995.
Calés C Román-Trufero M Pavón L Serrano I Melgar T Endoh M Pérez C Koseki H Vidal M 《Molecular and cellular biology》2008,28(3):1018-1028
Polycomb group (PcG) proteins act as positive regulators of cell proliferation. Ring1B is a PcG gene essential for embryonic development, but its contribution to cell turnover in regenerating tissues in not known. Here, we have generated a conditional mouse mutant line to study the Ring1B role in adult hematopoiesis. Mutant mice developed a hypocellular bone marrow that paradoxically contained an enlarged, hyperproliferating compartment of immature cells, with an intact differentiation potential. These alterations were associated with differential upregulation of cyclin D2, which occurred in all mutant bone marrow cells, and of p16Ink4a, observed only in the differentiated compartment. Concurrent inactivation of Ink4a rescued the defective proliferation of maturing cells but did not affect the hyperproliferative activity of progenitors and resulted in a shortening of the onset of lymphomas induced by Ink4a inactivation. These data show that Ring1B restricts the progenitors' proliferation and promotes the proliferation of their maturing progeny by selectively altering the expression pattern of cell cycle regulators along hematopoietic differentiation. The novel antiproliferative role of Ring1B's downregulation of a cell cycle activator may play an important role in the tight control of hematopoietic cell turnover. 相似文献
996.
997.
998.
Laska M Persson Suorra J Bautista RM Hernandez Salazar LT 《American journal of primatology》2008,70(9):839-847
The purpose of this study was to determine taste difference thresholds for monosodium glutamate (MSG) and sodium chloride (NaCl) in pigtail macaques (Macaca nemestrina) and spider monkeys (Ateles geoffroyi). Using a two-bottle preference test of brief duration, three animals of each species were presented with four different reference concentrations of 50, 100, 200, and 400 mM of a tastant and tested for their ability to discriminate these from lower concentrations of the same tastant. The just noticeable differences (JNDs), expressed as Weber ratios (DeltaI/I), were found to range from 0.1 to 0.5 for MSG and 0.2 to 0.45 for NaCl in the pigtail macaques, with a significant tendency for higher Weber ratios with higher reference concentrations. In the spider monkeys, JNDs ranged from 0.15 to 0.4 for MSG and 0.1 to 0.25 for NaCl, with Weber ratios staying fairly constant across the reference concentrations tested. Thus, the JNDs were found to be generally similar in both species and to be at least as low as those found in humans for MSG and NaCl, as well as those found in spider monkeys for sucrose. The results support the assumption that both pigtail macaques and spider monkeys may use differences in perceived intensity of MSG and NaCl as a criterion for food selection. 相似文献
999.
Because there is a paucity of information on the mineral requirements of free-ranging deer, data are needed from clinically healthy deer to provide a basis for the diagnosis of mineral deficiencies. To our knowledge, no reports are available on baseline hepatic mineral concentrations from sympatric white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) using different habitats in the Northern Great Plains. We assessed variation in hepatic minerals of female white-tailed deer (n = 42) and mule deer (n = 41). Deer were collected in February and August 2002 and 2003 from study areas in Custer and Pennington Counties, South Dakota, in and adjacent to a wildfire burn. Hepatic samples were tested for levels (parts per million; ppm) of aluminum (Al), antimony (Sb), arsenic (As), barium (Ba), boron (B), cadmium (Cd), calcium (Ca), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), magnesium (Mg), manganese (Mn), mercury (Hg), molybdenum (Mo), nickel (Ni), phosphorus (P), potassium (K), selenium (Se), sodium (Na), sulfur (S), thalium (Tl), and zinc (Zn). We predicted that variability in element concentrations would occur between burned and unburned habitat due to changes in plant communities and thereby forage availability. We determined that Zn, Cu, and Ba values differed (P 相似文献
1000.
Polyamidoamino (PAMAM) dendrimer of generation 3.5 (G3.5) specific interactions with rat liver mitochondria were studied. Selected parameters of mitochondria (transmembrane potential and uptake of Ca2+ ions) were investigated after the exposure to G3.5 used at the concentration of 10, 30 and 50 microM and Ca2+ ions used at 1mM. The times of preincubation of isolated liver mitochondria with dendrimer were 5, 15 and 30 min at room temperature. The mitochondrial membrane potential was monitored spectrofluorimetrically by fluorescence quenching of Rhodamine 123 (Rh 123). The changes in calcium homeostasis upon dendrimer exposure were detected using flow cytometric analysis with Fluo-3. On the one hand the obtained results revealed an impact of the tested chemical on rat liver mitochondrial function. We found that dendrimer G3.5 in a concentration above 10 microM contributes to the reduction in the transmembrane potential and hinders in the influx of Ca2+ ions to mitochondria added externally, or accelerates their efflux from mitochondria. The most effective preincubation time was observed to be 15 min for all tested concentrations. On the other hand the combined treatment of dendrimer G3.5 with Ca2+ demonstrated the protective effect of G3.5 against mitochondrial depolarization caused by calcium ions. These preliminary studies suggest that tested dendrimer can significantly affect the mitochondria and modulate their functionality. 相似文献