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111.
Apoptosis in transgenic mice expressing the P301L mutated form of human tau   总被引:3,自引:0,他引:3  
The rTg4510 mouse is a tauopathy model, characterized by massive neurodegeneration in Alzheimer's disease (AD)-relevant cortical and limbic structures, deficits in spatial reference memory, and progression of neurofibrillary tangles (NFT). In this study, we examined the role of apoptosis in neuronal loss and associated tau pathology. The results showed that DNA fragmentation and caspase-3 activation are common in the hippocampus and frontal cortex of young rTg4510 mice. These changes were associated with cleavage of tau into smaller intermediate fragments, which persist with age. Interestingly, active caspase-3 was often co-localized with cleaved tau. In vitro, fibrillar Abeta(1-42) resulted in nuclear fragmentation, caspase activation, and caspase-3-induced cleavage of tau. Notably, incubation with the antiapoptotic molecule tauroursodeoxycholic acid abrogated apoptosis-mediated cleavage of tau in rat cortical neurons. In conclusion, caspase-3-cleaved intermediate tau species occurred early in rTg54510 brains and preceded cell loss in Abeta-exposed cultured neurons. These results suggest a potential role of apoptosis in neurodegeneration.  相似文献   
112.

Background  

Large multigene sequence alignments have over recent years been increasingly employed for phylogenomic reconstruction of the eukaryote tree of life. Such supermatrices of sequence data are preferred over single gene alignments as they contain vastly more information about ancient sequence characteristics, and are thus more suitable for resolving deeply diverging relationships. However, as alignments are expanded, increasingly numbers of sites with misleading phylogenetic information are also added. Therefore, a major goal in phylogenomic analyses is to maximize the ratio of information to noise; this can be achieved by the reduction of fast evolving sites.  相似文献   
113.
    
We carried out Hartree–Fock (HF) and density functional theory calculations on the conjugated bases of phenols and alcohols for 23 compounds and analysed their acid–base behaviour using molecular orbital (MO) energies and their dependence on solvent effects. Despite the well-known correlation between highest-occupied MO (HOMO) energies and proton affinity (PA), we observed that HOMO energies are inadequate to describe the acid–base behaviour of these compounds. Therefore, we established a criterion to identify the best frontier MO for describing PA values and also to understand why the HOMO approach fails. The MO that fits our criterion provided very good correlations with PA values, much better than those obtained by the HOMO energies. Since the frontier MOs are those which drive the acid–base reactions in each compound, they were called frontier effective-for-reaction MOs, or FERMOs. By using the FERMO concept, the reactions that are HOMO driven, and those that are not, can be better explained, independent of the calculation method used, since both HF and Kohn–Sham methodologies lead to the same FERMO.  相似文献   
114.
T-20 (also known as enfuvirtide) is a fusion inhibitor peptide known to have some effectiveness in the control of progression of HIV infection by inhibiting the fusion of the HIV envelope with the target cell membrane. Recent results indicate that T-20 is able to interact with membranes in the liquid disordered state but not with membranes in an ordered state, which could be linked to its effectiveness. A detailed molecular picture of the interaction of these molecules with membranes is still lacking. To this effect, extensive molecular dynamics simulations (100 ns) were carried out to investigate the interaction between T-20 and bilayers of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and POPC/cholesterol (1:1). Membrane properties such as area/lipid, density profiles, order parameters and membrane thickness were studied. It was observed that T-20 has the ability to interact to different extents with both model membranes in this study and that peptide interaction with the bilayer surface has a local effect on membrane structure. The formation of hydrogen bonding between certain peptide residues and the POPC phosphate group was observed. However, T-20 showed a more limited extent of interaction with model membranes when compared with other, more efficient, peptides (such as T-1249). This effect is most notable in POPC/Chol membranes in which interaction is especially weak, owing to less peptide residues acting as H bond donors to POPC and virtually no H bonds being formed between T-20 and cholesterol. This lower ability to interact with membranes is probably correlated with its smaller inhibitory efficiency.  相似文献   
115.
Mechanisms of energy dissipation in peanut under water stress   总被引:1,自引:0,他引:1  
Effect of drought on the mechanisms of energy dissipation was evaluated in two-month-old Arachis hypogaea cvs. 57–422, 73–30, and GC 8–35. Plants were submitted to three treatments: control (C), mild water stress (S1), and severe water stress (S2). Photosynthetic performance was evaluated as the Hill and Mehler reactions. These activities were correlated with the contents of the low and high potential forms of cytochrome (cyt) b 559, plastoquinone, cyt b 563, and cyt f. Additionally, the patterns of carotenoids and chlorophylls (Chls), as well as the alterations of Chl a fluorescence parameters were studied. Under mild water stress the regulatory mechanism at the antennae level was effective for 57–422 and GC 8–35, while in the cv. 73–30 an overcharge of photosynthetic apparatus occurred. Relative to this cv., under S1 the stability of carotene and the dissipative cycle around photosystem (PS) 2 became an important factor for the effective protection of the PS2 reaction centres. The cyclic electron flow around PS1 was important for energy dissipation under S1 only for the cvs. 57–422 and 73–30.  相似文献   
116.
    
Recent studies have revealed multiple mechanisms that can lead to heterogeneity in ribosomal composition. This heterogeneity can lead to preferential translation of specific panels of mRNAs, and is defined in large part by the ribosomal protein (RP) content, amongst other things. However, it is currently unknown to what extent ribosomal composition is heterogeneous across tissues, which is compounded by a lack of tools available to study it. Here we present dripARF, a method for detecting differential RP incorporation into the ribosome using Ribosome Profiling (Ribo-seq) data. We combine the ‘waste’ rRNA fragment data generated in Ribo-seq with the known 3D structure of the human ribosome to predict differences in the composition of ribosomes in the material being studied. We have validated this approach using publicly available data, and have revealed a potential role for eS25/RPS25 in development. Our results indicate that ribosome heterogeneity can be detected in Ribo-seq data, providing a new method to study this phenomenon. Furthermore, with dripARF, previously published Ribo-seq data provides a wealth of new information, allowing the identification of RPs of interest in many disease and normal contexts. dripARF is available as part of the ARF R package and can be accessed through https://github.com/fallerlab/ARF.  相似文献   
117.
    
Rates of photosynthesis and leaf conductance of the leaves of carob trees ( Ceratonia siliqua L.) growing in natural conditions were measured during the course of the seasons to define the effects of the main climatic factors limiting growth in the region: temperature during the winter and water in the summer. The highest photosynthetic rates were measured in spring and autumn and could reach 25 μmol m−2 s−1 with optimal temperature and available water. Due to lower temperatures (4 to 6°C in the night) these values were frequently around 15 μmol m−2 s−1 during winter, but the strongest depression was due to prolonged drought in summer. However a reduction in photosynthesis rate down to 5 μmol m−2 s−1 occurred only after depletion of all the available water in the soil layer up to a depth of 50 cm. In the end of the summer, leaf conductance and water potential were in the order of 20 mmol m−2 s−1 and −3 MPa respectively. Compared to other trees that make up the Mediterranean sclerophyll forest, the photosynthetic activity of carob is high, and the tree tolerates a considerable depletion of soil water.  相似文献   
118.
Drought was induced in chickpea (Cicer arietinum L.) genotypes (ChK 3226 and ILC 3279) differing in yield capacity. Water stress (S1, RWC around 55–50%; S2, RWC ≤ 40%) drastically reduced stomatal conductance (g s) and net photosynthetic rate (P N) in both genotypes. ILC 3279 showed greater photosynthetic capacity (A max) decreases. Maximum PSII photochemical efficiency (Fv/Fm), photochemical quenching (qP), total chlorophylls (Chls) and carotenoids (Cars) content showed stability in both genotypes under stress, but in S2 ILC 3279 presented an increase in basal fluorescence (F0) and a greater reduction in estimation of quantum yield of linear electron transport (Φe) than ChK 3226. Membrane damage evaluated by electrolyte leakage occurred earlier and was greater in ILC 3279. It also presented a decrease of total fatty acids (TFA) along drought, while in ChK 3226 greater amounts of TFA were observed in S1. In rehydration, P N of S1 plants completely recovered (ILC 3279) or remained slightly below control (ChK 3226). As regards S2 plants, ILC 3279 showed stronger P N and g s reductions than ChK 3226, despite both genotypes totally recovered A max and chlorophyll (Chl) a fluorescence. ChK 3226 recovered more efficiently from membrane damage. Under control conditions, greater amounts of most of the studied soluble metabolites occurred in ChK 3226 plants. Malate and citrate decreased with water stress (S2) in both genotypes. Sucrose and pinitol (that had a higher concentration than sucrose in both genotypes) increased in ILC 3279 (S1 and S2), and decreased in ChK 3226 (S2). In ILC 3279 proline and asparagine followed similar patterns. Genotypes showed a similar shoot dry mass (DM) in control plants, but root DM was higher in ChK 3226. Drought reduced root and shoot DM in ChK 3226 already under S1, while in ILC 3279 root DM was unaffected by drought and shoot biomass decreased only in S2. Root/shoot ratio was always higher in ChK 3226 but tended to decrease under stress, while the opposite was observed in ILC 3279. No pods were obtained from control plants of both genotypes, or droughted ILC 3279 plants. ChK 3226 produced pods under S1 (higher yield) and S2. Under stress conditions, ChK 3226 was less affected in photosynthetic activity and membrane integrity, showing a better tolerance to drought. This agrees with the better yield of this genotype under water stress. Distinct strategies seem to underlie the different physiological responses of the two genotypes to water deficit. In spite of its significant solutes accumulation, ILC 3279 was more affected in photosynthetic activity and membrane integrity during water stress than ChK 3226, which showed better yield under drought. A relation could not be established between solutes accumulation of ILC 3279 and yield.  相似文献   
119.
Background: Helicobacter pylori is mainly acquired in childhood. Although adult studies reported a high prevalence of H. pylori infection in Portugal, the actual rate in children remains unknown. This study aimed to determine the prevalence and the incidence of H. pylori infection in an asymptomatic pediatric population of the Lisbon area and to correlate prevalence with sociodemographic determinants. Materials and Methods: Helicobacter pylori infection was determined by stool antigen test in 844 asymptomatic children (age 0–15 years; 49.4% boys). For the incidence study, H. pylori‐negative children in the prevalence study were followed‐up every 6 months over a 3‐year period. Results: The global prevalence of H. pylori infection was 31.6%, increasing with age (19.9, 37.0 and 51.5%, in age groups 0–5, 6–10, and 11–15, respectively), but was similar among genders (34.5% in boys and 28.4% in girls). Older age and attendance of nursery/kindergarten during preschool constituted independent risk factors. The overall estimated incidence was 11.6 per 100 child‐years (CY). Although 47.5% of children acquired H. pylori infection before 5 years of age, the mean age of acquisition was 6.3. The incidence of infection was similar among the three age groups (11.5, 13.0, and 10.5 per 100 CY, in age groups 0–5, 6–10, and 11–15, respectively). Conclusions: The prevalence of H. pylori infection in the Portuguese pediatric population is still high. Although this study confirmed that the highest acquisition rate occurs at young age, it showed that in high‐prevalence populations, older children can also acquire H. pylori infection at a rate similar to that of young children.  相似文献   
120.
The coordination of iron(III) ion to hyaluronic acid (Hyal) in aqueous solutions and solid state was accomplished by potentiometric titrations and infrared spectroscopy. The potentiometric titration studies provided the binding constants for the complexes found in the systems and the speciation of these species according to the variation of pH values. The complexes found presented a complexing ability through both the chelating moieties of Hyal (via the N-glucosamine and D-glucoronic acid), showing no special preference for either one while in solid state, but when in aqueous solution the complexation via the N-glucosamine moiety was the preferred, forming two complexed species, ML and ML(2) (log K(ML)=8.2 and log K(ML2)=7.9). The presence of a mu-oxo complex via the D-glucoronic acid was also detected in both aqueous (log K=6.7) and solid states via the N-glucosamine and D-glucoronic acid simultaneously linked to two Hyal chains. A structure for this latter complex was suggested. The results indicated that these complexes could be used in eliminating the excess iron(III) in living organisms.  相似文献   
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