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131.
132.
Ingemar Björkhem Angel Cedazo-Minguez Valerio Leoni Steve Meaney 《Molecular aspects of medicine》2009,30(3):171-179
In contrast to their parent molecule cholesterol, two of its side-chain oxidized metabolites are able to cross the blood–brain barrier. There is a concentration-driven flux of 24S-hydroxycholesterol (24S-OHC) from the brain into the circulation, which is of major importance for elimination of excess cholesterol from the brain. The opposite flux of 27-hydroxycholesterol (27-OHC) from the circulation into the brain may regulate a number of key enzymes within the brain. In vitro experiments suggest that the balance between the levels of these two molecules may be of importance for the generation of β-amyloid peptides. In primary cultures of rat hippocampal cells 27-OHC is able to suppress expression of the activity regulated cytoskeleton-associated protein (Arc), a protein important in memory consolidation which is reduced in patients with Alzheimer’s disease (AD). In the present work we explore the possibility that the flux of 27-OHC from the circulation into the brain represents the missing link between AD and hypercholesterolemia, and discuss the possibility that modification of this flux may be a therapeutic strategy. Lastly, we discuss the use of oxysterols as diagnostic markers in neurodegenerative disease. 相似文献
133.
Idalia Kasprzyk 《International journal of biometeorology》2009,53(4):345-353
Forecasting the time when the atmospheric pollen season of allergenic plants begins is particularly important for doctors
and their patients. The aim of this paper is to determine whether it is possible to forecast the start of the oak (Quercus) pollen season in Rzeszów, Poland. In the elaboration of the most effective model, various forecasting techniques were tested:
growth degree days (GDD°C); meteorological factors; bioclimatic factors; and indicator taxon. The aerobiological monitoring
was carried out in 1997–2005 and 2007 in Rzeszów (SE Poland). In the presented investigation, three methods defining the start
of the Quercus pollen season were selected on the basis of accumulated sums of pollen or the constant occurrence of pollen grains in air.
Despite the application of different combinations of GDD°C methods and threshold temperatures, the correlation coefficients
between the expected and obtained values were low. In some cases, however, they proved highly effective for the test years
(2005, 2007) with the accuracy of a few days. For GDD°C methods, the best threshold temperatures range between 5 and 6°C.
Models based on bioclimatic indices and meteorological variables were not satisfactory. On the basic of the 10 years of results,
the method of indicator species were good for forecast the start of oak pollen season. Birch was the best indicator taxa. 相似文献
134.
Romano Silvestri Alessia Ligresti Giuseppe La Regina Francesco Piscitelli Valerio Gatti Antonella Brizzi Serena Pasquini Antonio Lavecchia Marco Allarà Noemi Fantini Mauro Antonio Maria Carai Ettore Novellino Giancarlo Colombo Vincenzo Di Marzo Federico Corelli 《Bioorganic & medicinal chemistry》2009,17(15):5549-5564
New substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized by replacing the 2,4-dichlorobenzyl and cyclohexyl moieties at the 3-carboxamide nitrogen of the previously reported CB1 receptor antagonists/inverse agonists 4 and 5. Several ligands showed potent affinity for the hCB1 receptor, with Ki concentrations comparable to the reference compounds 1, 4 and 5, and exhibited CB1 selectivity comparable to 1 and 2. Docking experiments and molecular dynamics (MD) simulations explained the potent hCB1 binding affinity of compounds 31 and 37. According to our previous studies, 31 and 37 formed a H-bond with K3.28(192), which accounted for the high affinity for the receptor inactive state and the inverse agonist activity. The finding of inhibition of food intake following their acute administration to rats, supported the concept that the CB1 selective compounds 4 and 52 act as antagonists/inverse agonists. 相似文献
135.
Background
Synesthesia is a condition in which the stimulation of one sense elicits an additional experience, often in a different (i.e., unstimulated) sense. Although only a small proportion of the population is synesthetic, there is growing evidence to suggest that neurocognitively-normal individuals also experience some form of synesthetic association between the stimuli presented to different sensory modalities (i.e., between auditory pitch and visual size, where lower frequency tones are associated with large objects and higher frequency tones with small objects). While previous research has highlighted crossmodal interactions between synesthetically corresponding dimensions, the possible role of synesthetic associations in multisensory integration has not been considered previously.Methodology
Here we investigate the effects of synesthetic associations by presenting pairs of asynchronous or spatially discrepant visual and auditory stimuli that were either synesthetically matched or mismatched. In a series of three psychophysical experiments, participants reported the relative temporal order of presentation or the relative spatial locations of the two stimuli.Principal Findings
The reliability of non-synesthetic participants'' estimates of both audiovisual temporal asynchrony and spatial discrepancy were lower for pairs of synesthetically matched as compared to synesthetically mismatched audiovisual stimuli.Conclusions
Recent studies of multisensory integration have shown that the reduced reliability of perceptual estimates regarding intersensory conflicts constitutes the marker of a stronger coupling between the unisensory signals. Our results therefore indicate a stronger coupling of synesthetically matched vs. mismatched stimuli and provide the first psychophysical evidence that synesthetic congruency can promote multisensory integration. Synesthetic crossmodal correspondences therefore appear to play a crucial (if unacknowledged) role in the multisensory integration of auditory and visual information. 相似文献136.
Anna Ghelli Anna Maria Porcelli Claudia Zanna Sara Vidoni Stefano Mattioli Anna Barbieri Luisa Iommarini Maria Pala Alessandro Achilli Antonio Torroni Michela Rugolo Valerio Carelli 《PloS one》2009,4(11)
Leber''s hereditary optic neuropathy (LHON) is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA) point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778/ND4 and 14484/ND6 mutations. Recently it was also documented that the professional exposure to n-hexane might act as an exogenous trigger for LHON. Therefore, we here investigate the effect of the n-hexane neurotoxic metabolite 2,5-hexanedione (2,5-HD) on cell viability and mitochondrial function of different cell models (cybrids and fibroblasts) carrying the LHON mutations on different mtDNA haplogroups. The viability of control and LHON cybrids and fibroblasts, whose mtDNAs were completely sequenced, was assessed using the MTT assay. Mitochondrial ATP synthesis rate driven by complex I substrates was determined with the luciferine/luciferase method. Incubation with 2,5-HD caused the maximal loss of viability in control and LHON cells. The toxic effect of this compound was similar in control cells irrespective of the mtDNA background. On the contrary, sensitivity to 2,5-HD induced cell death was greatly increased in LHON cells carrying the 11778/ND4 or the 14484/ND6 mutation on haplogroup J, whereas the 11778/ND4 mutation in association with haplogroups U and H significantly improved cell survival. The 11778/ND4 mutation on haplogroup U was also more resistant to inhibition of complex I dependent ATP synthesis by 2,5-HD. In conclusion, this study shows that mtDNA haplogroups modulate the response of LHON cells to 2,5-HD. In particular, haplogroup J makes cells more sensitive to its toxic effect. This is the first evidence that an mtDNA background plays a role by interacting with an environmental factor and that 2,5-HD may be a risk element for visual loss in LHON. This proof of principle has broad implications for other neurodegenerative disorders such as Parkinson''s disease. 相似文献
137.
Liliana Milani Fabrizio Ghiselli Marco Pellecchia Valerio Scali Marco Passamonti 《BMC evolutionary biology》2010,10(1):258
Background
Phasmids show noteworthy abilities to overcome species-specific reproductive isolation mechanisms, including hybridization, polyploidy, parthenogenesis, hybridogenesis and androgenesis. From an evolutionary standpoint, such tangled reproductive interactions lead to the complex phyletic relationships known as "reticulate evolution". Moroccan stick insects of the genus Clonopsis include one bisexual (C. felicitatis) and two closely related parthenogenetic forms (C. gallica, C. soumiae), which represent a polyploid series in chromosome number, but with apparent diploid karyotypes. Moreover, two Clonopsis strains of ameiotic males have been described, C. androgenes-35 and C. androgenes-53. As a consequence, Clonopsis stick insects may have experienced complex micro-evolutionary events, which we try to disentangle in this study. 相似文献138.
Hanessian S Vinci V Auzzas L Marzi M Giannini G 《Bioorganic & medicinal chemistry letters》2006,16(18):4784-4787
Analogues of suberoylanilide hydroxamic acid (SAHA) were prepared by replacing the Zn-binding group with squaric acid, N-hydroxyurea, and 4-hydroxymethyl oxazoline units, also varying the length of the aliphatic chain. No inhibitory activity on HDAC was observed below 1.0 microM and no cytotoxic activity on different tumor cell lines was seen below 20.0 microM. 相似文献
139.
Alessandra Basso Patrizia Spizzo Valerio Ferrario Lorena Knapic Nina Savko Paolo Braiuca Cynthia Ebert Emanuele Ricca Vincenza Calabrò Lucia Gardossi 《Biotechnology progress》2010,26(2):397-405
Three‐dimensional models of exoinulinase from Bacillus stearothermophilus and endoinulinase from Aspergillus niger were built up by means of homology modeling. The crystal structure of exoinulinase from Aspergillus awamori was used as a template, which is the sole structure of inulinase resolved so far. Docking and molecular dynamics simulations were performed to investigate the differences between the two inulinases in terms of substrate selectivity. The analysis of the structural differences between the two inulinases provided the basis for the explanation of their different regio‐selectivity and for the understanding of enzyme‐substrate interactions. Surface analysis was performed to point out structural features that can affect the efficiency of enzymes also after immobilization. The computational analysis of the three‐dimensional models proved to be an effective tool for acquiring information and allowed to formulate an optimal immobilized biocatalyst even more active that the native one, thus enabling the full exploitation of the catalytic potential of these enzymes. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 相似文献
140.
Early childhood arts education in the United States: A special issue of Arts Education Policy Review
ABSTRACTIn this introduction to Early Childhood Arts Education in the United States, a special issue of Arts Education Policy Review, the editors provide a platform for stakeholders' increased awareness and understandings of the need to ensure children's rights to arts education. They summarize the five articles comprising this issue, and invite stakeholders to consider example action steps to apply content from this Issue to arts interactions with young children. 相似文献