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We previously found that BDNF-dependent retrograde trafficking is impaired in AD transgenic mouse neurons. Utilizing a novel microfluidic culture chamber, we demonstrate that Aβ oligomers compromise BDNF-mediated retrograde transport by impairing endosomal vesicle velocities, resulting in impaired downstream signaling driven by BDNF/TrkB, including ERK5 activation, and CREB-dependent gene regulation. Our data suggest that a key mechanism mediating the deficit involves ubiquitin C-terminal hydrolase L1 (UCH-L1), a deubiquitinating enzyme that functions to regulate cellular ubiquitin. Aβ-induced deficits in BDNF trafficking and signaling are mimicked by LDN (an inhibitor of UCH-L1) and can be reversed by increasing cellular UCH-L1 levels, demonstrated here using a transducible TAT-UCH-L1 strategy. Finally, our data reveal that UCH-L1 mRNA levels are decreased in the hippocampi of AD brains. Taken together, our data implicate that UCH-L1 is important for regulating neurotrophin receptor sorting to signaling endosomes and supporting retrograde transport. Further, our results support the idea that in AD, Aβ may down-regulate UCH-L1 in the AD brain, which in turn impairs BDNF/TrkB-mediated retrograde signaling, compromising synaptic plasticity and neuronal survival.  相似文献   
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Thalli of Xanthoria parietina have been grown in cultures in the natural environment. In early phases of development the fungus associates with foreign algae and only later forms a symbiosis with Pseudotrebouxia . The lichen is shown to have a very effective mechanism for distribution by sexual spores followed by relichenization.  相似文献   
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We examined the intra-tree foraging behavior of individually-released, wild-population Mediterranean fruit flies (medflies), Ceratitis capitata (Wiedemann), on field-caged host trees bearing each of three different densities (0, 3, or 12 per tree) of non-infested host fruit (kumquat) or each of two levels of fruit quality (12 non-infested fruit or 12 fruit infested with eggs and covered with host marking pheromone). With increasing density of non-infested fruit, medflies tended to remain longer in trees, visit more fruit before leaving, oviposit more often, accept a proportionately smaller number of fruit visited, and emigrate sooner after the last egg was laid (i.e. have a shorter Giving-Up-Time). Medflies spent much less time, oviposited much less often, and exhibited a longer Giving-Up-Time on trees harboring pheromone-marked fruit than non-infested fruit. Variation in temperature within the range at which experiments were conducted (25–36°C) had little detectable influence on foraging behavior. We compare our findings with published findings on the intra-tree foraging behavior of another tephritid fly, Rhagoletis pomonella (Walsh), and with current foraging behavior theory. We discuss implications of our findings with respect to medfly management strategies, particularly fruit stripping in eradication programs and use of synthetic marking pheromone for control.
Résumé Nous avons étudié le comportement de prospection dans un arbre, de femelles d'une population sauvage de C. capitata, libérées individuellement à l'intérieur de cages contenant des Eriobotrya japonica (kumquat), portant chacun 3 densités différentes de fruits no contaminés (0, 3, 12 par arbre) et chacun 2 niveaux de qualité de fruits: 12 fruits non infestés ou 12 fruits contaminés par des oeufs et recouverts de phéromone de marquage de l'hôte. C. capitata avait terndance à rester plus longtemps dans les arbres, à visiter plus de fruits avant le quitter, à pondre plus souvent, à accepter proportionnellement un nombre plus réduit de fruits déjà visités, à émigrer plus tôt après la ponte du dernier oeuf (c'est-à-dire à présenter un temps d'abandon plus bref), quand la densité des fruits non contaminés augmentait. C. capitata a dépensé beaucoup moins de temps, pondu beaucoup moins souvent, et présenté un temps d'abandon plus long sur les arbres portant des fruits marqués par la phéromone que sur ceux ayant des fruits non contaminés. Les variations de température dans la gamme de cells où les observations ont eu lieu (23–36°C) n'ont eu qu'une faible influence décelable sur le comportement de prospection. Nous avons comparé nos résultats avec ceux publiés sur la prospection à l'intérieur de l'arbre par une autre téphritide (Rhagoletis pomonella) et avec la théorie dominante sur le comportement de prospection. Nous discutons les conséquences de nos résultats sur les stratégies de lutte contre C. capitata, en particulier l'élimination des fruits dans les plans d'erradication et l'utilisation de phéromone synthétique de marquage.
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A 7-generation kindred with the HLA-linked form of spinocerebellar ataxia (SCA1) was studied to determine whether the SCA1 gene maps centromeric or telomeric to the HLA loci. The DNA markers flanking the HLA-(A-B) region were used for polymorphism studies and multilocus linkage analysis. These two markers are the cDNA for the beta-subunit of HLA-DP, which is centromeric to HLA-(A-B), and the cDNA for coagulation factor XIIIa (F13A), which is telomeric to HLA-(A-B). Haplotypes were constructed using multiple polymorphisms for these two DNA markers, and pairwise linkage analysis revealed a maximum lod score of 2.18 for SCA1 versus HLA-DP at a recombination fraction of .05 and a maximum lod score of 0 for SCA1 versus F13A at a recombination fraction of .50. A possible crossover between HLA-(A-B) and HLA-DP was identified, but lack of samples from key individuals hampered the analysis. To clarify the phase and improve the analysis, the two chromosomes 6 for the crossover individual were separated in somatic cell hybrids. The results strongly favored the probability that the crossover occurred between HLA-(A-B-DR) and HLA-DP with SCA1 segregating with HLA-DP, consistent with a location centromeric to HLA-(A-B). Multilocus linkage analysis was used to evaluate further the location of SCA1 relative to F13A, HLA-(A-B), and HLA-DP; the results indicated that the SCA1 gene locus is centromeric to HLA-DP with odds of 46:1 favoring this most likely location over the second most likely location, i.e., telomeric to HLA-(A-B) between the HLA complex and F13A.  相似文献   
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Regulation of cardiac sarcoplasmic reticulum (Ca2+ + Mg2+)-ATPase   总被引:2,自引:0,他引:2  
Summary The two high affinity calcium binding sites of the cardiac (Ca2+ + Mg2+)-ATPase have been identified with the use of Eu3+. Eu3+ competes for the two high affinity calcium sites on the enzyme. With the use of laser-pulsed fluorescent spectroscopy, the environment of the two sites appear to be heterogeneous and contain different numbers of H2O molecules coordinated to the ion. The ion appears to be occluded even further in the presence of ATP. Using non-radiative energy transfer studies, we were able to estimate the distance between the two Ca2+ sites to be between 9.4 to 10.2 A in the presence of ATP. Finally, from the assumption that the calcium site must contain four carboxylic side chains to provide the 6–8 ligands needed to coordinate calcium, and based on our recently published data, we predict the peptidic backbone of the two sites.  相似文献   
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Prolonged submaximal exercise and L-carnitine in humans   总被引:1,自引:0,他引:1  
Changes in the main physiological parameters and circulating indicators of carbohydrate, protein, lipid (and ketone body) metabolism were measured in ten exercising subjects before L-carnitine (L-carn) loading, after 4 weeks of daily loading with 2 g L-carn, and 6-8 weeks after terminating L-carn administration. Measurements were made on venous blood samples collected during each experiment at fixed time intervals over an initial rest of 45 min, 60 min bicycle exercise performed near 50% VO2max and 120 min recovery. Free and total plasma carnitine levels reached a plateau corresponding to an average rise of 25% for both fractions, 9-10 days after the beginning of the L-carn diet. These levels returned to their initial values 6-8 weeks after cessation of the supply. Generally L-carn supplementation did not significantly modify the physiological parameters and circulating metabolites. No distinct increase of the relative participation of endogenous lipids in the fuel supply of prolonged submaximal exercise was observed. In normal human subjects the increased demand for fatty acid oxidation resulting from exercise seems to be adequately supported by endogenous levels of carnitine.  相似文献   
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