Synaptic failure and adenosine triphosphate imbalance induced by amyloid-ß aggregates are prevented by blueberry-enriched polyphenols extract.

The potential neuroprotective properties of fruits have been widely recognized. In this study, we evaluated the protective properties of a blueberry extract (BB-4), rich in polyphenols, in a neurodegenerative model induced by amyloid-ß peptide (Aß). Chronic treatment with Aß drastically reduced synaptic transmission and the extent of secretory vesicles, which were recovered partially with BB-4. Also, the extract recovered Ca(2+) transients in hippocampal neurons preincubated with Aß (0.5 and 5 µM) by about 25% ± 3% and 30% ± 2, respectively. In this work, we demonstrate a novel effect of the BB-4 extract on Aß-induced ATP leakage, in which this extract was able to antagonize the acute ATP leakage but not chronic ATP depletion. On the other hand, BB-4 prevented the uncoupling of mitochondrial function induced by FCCP by about 85%, but it was unable to modify the uncoupling induced by Aß. The present results strongly indicate that BB-4 plays a role in the process of Aß aggregation by reducing the toxic species (i.e., 40 kDa). These findings suggest that a blueberry extract can protect neuronal tissue from Aß toxicity mainly through its antiaggregation property, and its antioxidant properties and mitochondrial membrane potential capacities are secondary mechanisms important in chronic stages. Our work suggests that BB-4 could be an important nutritional complement to neuronal health as well as a potential nutraceutical formulation useful as a dietary supplement in the elderly.

Cathepsin L inhibitor I blocks mitotic chromosomes decondensation during cleavage cell cycles of sea urchin embryos.

We have previously reported that sperm histones (SpH) degradation after fertilization is catalyzed by a cystein-protease (SpH-protease). Its inhibition blocks the degradation of SpH in vivo and also aborts sea urchin development at the initial embryonic cell cycles. It remains unknown if this effect is a consequence of the persistence of SpH on zygotic chromatin, or if this protease is involved per-se in the progression of the embryonic cell cycles. To discriminate among these two options we have inhibited this protease at a time when male chromatin remodeling was completed and the embryos were engaged in the second cell cycle of the cleavage divisions. The role of this enzyme in cell cycle was initially analyzed by immuno-inhibiting its SpH degrading activity in one of the two blastomeres after the initial cleavage division, while the other blastomere was used as a control. We found that in the blastomere injected with the anti-SpH-protease antibodies the cytokinesis was arrested, the chromatin failed to decondense after mitosis and BrdU incorporation into DNA was blocked. Since the N-terminal sequence and the SpH protease was homologous to the cathepsin L (Cat L) family of proteases, we subsequently investigated if the deleterious effect of the inhibition of this protease is related to its Cat L activity. In this context we analyzed the effect of Cat L inhibitor I (Z-Phe-Phe-CH(2)F) on embryonic development. We found that the addition of 100 uM of this inhibitor to the embryos harvested at the time of the initial cleavage division (80 min p.i.) mimics perfectly the effects of the immuno-inhibition of this enzyme obtained by microinjecting the anti-SpH-protease antibodies. Taken together these results indicate that the activity of this protease is required for embryonic cell cycle progression. Interestingly, we observed that when this protease was inhibited the chromatin decondensation after mitosis was abolished indicating that the inhibition of this enzyme affects chromosomes decondensation after mitosis.

User-centered evaluation of Arizona BioPathway: an information extraction, integration, and visualization system.

Explosive growth in biomedical research has made automated information extraction, knowledge integration, and visualization increasingly important and critically needed. The Arizona BioPathway (ABP) system extracts and displays biological regulatory pathway information from the abstracts of journal articles. This study uses relations extracted from more than 200 PubMed abstracts presented in a tabular and graphical user interface with built-in search and aggregation functionality. This paper presents a task-centered assessment of the usefulness and usability of the ABP system focusing on its relation aggregation and visualization functionalities. Results suggest that our graph-based visualization is more efficient in supporting pathway analysis tasks and is perceived as more useful and easier to use as compared to a text-based literature-viewing method. Relation aggregation significantly contributes to knowledge-acquisition efficiency. Together, the graphic and tabular views in the ABP Visualizer provide a flexible and effective interface for pathway relation browsing and analysis. Our study contributes to pathway-related research and biological information extraction by assessing the value of a multiview, relation-based interface that supports user-controlled exploration of pathway information across multiple granularities.

Microinjection of an antibody against the cysteine-protease involved in male chromatin remodeling blocks the development of sea urchin embryos at the initial cell cycle.

We reported recently that the inhibition of cysteine-proteases with E-64-d disturbs DNA replication and prevents mitosis of the early sea urchin embryo. Since E-64-d is a rather general inhibitor of thiol-proteases, to specifically target the cysteine-protease previously identified in our laboratory as the enzyme involved in male chromatin remodeling after fertilization, we injected antibodies against the N-terminal sequence of this protease that were able to inhibit the activity of this enzyme in vitro. We found that injection of these antibodies disrupts the initial zygotic cell cycle. As shown in this report in injected zygotes a severe inhibition of DNA replication was observed, the mitotic spindle was not correctly bipolarized the embryonic development was aborted at the initial cleavage division. Consequently, the injection of these antibodies mimics perfectly the effects previously described for E-64-d, indicating that the effects of this inhibitor rely mainly on the inhibition of the cysteine-protease involved in male chromatin remodeling after fertilization. These results further support the crucial role of this protease in early embryonic development.