Effects of a Copper-Deficient Diet on the Biochemistry,Neural Morphology and Behavior of Aged Mice

Copper dyshomeostasis has been suggested as an aetiological risk factor for some neurodegenerative diseases, such as Alzheimer’s disease. However, the precise mechanism at the base of this involvement is still obscure. In this work, we show the effects of a copper-deficient diet in aged CD1 mice and the influence of such a diet on: a) the concentration of various metal ions (aluminium, copper, iron, calcium, zinc) in the main organs and in different brain areas; b) the alteration of metallothioneins I-II and tyrosine hydroxylase immunopositivity in the brain; c) behavioural tests (open field, pole, predatory aggression, and habituation/dishabituation smell tests). Our data suggested that the copper-deficiency was able to produce a sort of “domino effect” which altered the concentration of the other tested metal ions in the main organs as well as in the brain, without, however, significantly affecting the animal behaviour.     

Effects of lipid composition on the membrane activity and lipid phase behaviour of Vibrio sp. DSM14379 cells grown at various NaCl concentrations

The membrane lipid composition of living cells generally adjusts to the prevailing environmental and physiological conditions. In this study, membrane activity and lipid composition of the Gram-negative bacterium Vibrio sp. DSM14379, grown aerobically in a peptone-yeast extract medium supplemented with 0.5, 1.76, 3, 5 or 10% (w/v) NaCl, was determined. The ability of the membrane to reduce a spin label was studied by EPR spectroscopy under different salt concentrations in cell suspensions labeled with TEMPON. For lipid composition studies, cells were harvested in a late exponential phase and lipids were extracted with chloroform-methanol-water, 1:2:0.8 (v/v). The lipid polar head group and acyl chain compositions were determined by thin-layer and gas-liquid chromatographies. ³¹P-NMR spectroscopy was used to study the phase behaviour of the cell lipid extracts with 20 wt.% water contents in a temperature range from −10 to 50 °C. The results indicate that the ability of the membrane to reduce the spin label was highest at optimal salt concentrations. The composition of both polar head groups and acyl chains changed markedly with increasing salinity. The fractions of 16:0, 16:1 and 18:0 acyl chains increased while the fraction of 18:1 acyl chains decreased with increasing salinity. The phosphatidylethanolamine fraction correlated inversely with the lysophosphatidylethanolamine fraction, with phosphatidylethanolamine exhibiting a minimum, and lysophosphatidylethanolamine a maximum, at the optimum growth rate. The fraction of lysophosphatidylethanolamine was surprisingly high in the lipid extracts. This lipid can form normal micellar and hexagonal phases and it was found that all lipid extracts form a mixture of lamellar and normal isotropic liquid crystalline phases. This is an anomalous behaviour since the nonlamellar phases formed by total lipid extracts are generally of the reversed type.     

A measure of explained variation for event history data

Summary There is no shortage of proposed measures of prognostic value of survival models in the statistical literature. They come under different names, including explained variation, correlation, explained randomness, and information gain, but their goal is common: to define something analogous to the coefficient of determination R² in linear regression. None however have been uniformly accepted, none have been extended to general event history data, including recurrent events, and many cannot incorporate time‐varying effects or covariates. We present here a measure specifically tailored for use with general dynamic event history regression models. The measure is applicable and interpretable in discrete or continuous time; with tied data or otherwise; with time‐varying, time‐fixed, or dynamic covariates; with time‐varying or time‐constant effects; with single or multiple event times; with parametric or semiparametric models; and under general independent censoring/observation. For single‐event survival data with neither censoring nor time dependency it reduces to the concordance index. We give expressions for its population value and the variance of the estimator and explore its use in simulations and applications. A web link to R software is provided.     

Visualization-based cancer microarray data classification analysis

MOTIVATION: Methods for analyzing cancer microarray data often face two distinct challenges: the models they infer need to perform well when classifying new tissue samples while at the same time providing an insight into the patterns and gene interactions hidden in the data. State-of-the-art supervised data mining methods often cover well only one of these aspects, motivating the development of methods where predictive models with a solid classification performance would be easily communicated to the domain expert. RESULTS: Data visualization may provide for an excellent approach to knowledge discovery and analysis of class-labeled data. We have previously developed an approach called VizRank that can score and rank point-based visualizations according to degree of separation of data instances of different class. We here extend VizRank with techniques to uncover outliers, score features (genes) and perform classification, as well as to demonstrate that the proposed approach is well suited for cancer microarray analysis. Using VizRank and radviz visualization on a set of previously published cancer microarray data sets, we were able to find simple, interpretable data projections that include only a small subset of genes yet do clearly differentiate among different cancer types. We also report that our approach to classification through visualization achieves performance that is comparable to state-of-the-art supervised data mining techniques. AVAILABILITY: VizRank and radviz are implemented as part of the Orange data mining suite (http://www.ailab.si/orange). SUPPLEMENTARY INFORMATION: Supplementary data are available from http://www.ailab.si/supp/bi-cancer.     

Protein Corona Prevents TiO2 Phototoxicity

Background & Aim

TiO₂ nanoparticles have generally low toxicity in the in vitro systems although some toxicity is expected to originate in the TiO₂-associated photo-generated radical production, which can however be modulated by the radical trapping ability of the serum proteins. To explore the role of serum proteins in the phototoxicity of the TiO₂ nanoparticles we measure viability of the exposed cells depending on the nanoparticle and serum protein concentrations.

Methods & Results

Fluorescence and spin trapping EPR spectroscopy reveal that the ratio between the nanoparticle and protein concentrations determines the amount of the nanoparticles’ surface which is not covered by the serum proteins and is proportional to the amount of photo-induced radicals. Phototoxicity thus becomes substantial only at the protein concentration being too low to completely coat the nanotubes’ surface.

Conclusion

These results imply that TiO₂ nanoparticles should be applied with ligands such as proteins when phototoxic effects are not desired - for example in cosmetics industry. On the other hand, the nanoparticles should be used in serum free medium or any other ligand free medium, when phototoxic effects are desired – as for efficient photodynamic cancer therapy.     

Peptides and pseudopeptides incorporating D-Phe-Pro-Arg and Arg-Gly-Asp lead sequences as potential antithrombotic agents.

Peptide leads D-Phe-Pro-Arg for thrombin inhibition and Arg-Gly-Asp for antagonistic activity on fibrinogen receptor were combined in one molecule in order to produce compounds capable of acting both as thrombin inhibitors and as fibrinogen receptor antagonists. Peptide conjugate 7 possessing both leads joined by a tetraglycine linker as well as tripeptides and peptidomimetics with highly overlapped D-Phe-Pro-Arg and Arg-Gly-Asp pharmacophore groups were prepared. Conjugate 7 was found to possess antagonistic activity on fibrinogen receptor, but was unexpectedly inactive as thrombin inhibitor. Compound 9 comprising of highly integrated D-Phe-Pro-Arg and Arg-Gly-Asp pharmacophore groups was found to possess a moderate but well balanced thrombin inhibitory and fibrinogen receptor antagonistic activity. Copyright (c) 2008 European Peptide Society and John Wiley & Sons, Ltd.     

Potential pathogenic role of beta-amyloid(1-42)-aluminum complex in Alzheimer's disease

The etiopathogenesis of Alzheimer's disease is far from being clearly understood. However, the involvement of metal ions as a potential key factor towards conformational modifications and aggregation of amyloid is widely recognized. The aim of the present study is to shed some light on the relationship between metal ions, amyloid conformation/aggregation, and their potential relationship with the conformational aspects of AD. We compare the effects of beta-amyloid(1-42) and its various metal complexes (beta-amyloid-Al, beta-amyloid-Zn, beta-amyloid-Cu, beta-amyloid-Fe) in human neuroblastoma cells in terms of cell viability, membrane structure properties, and cell morphology. No significant toxic effects were observed in neuroblastoma cells after 24h treatment both with beta-amyloid and beta-amyloid-metals (beta-amyloid-Zn, beta-amyloid-Cu, beta-amyloid-Fe); on the other hand, there was a marked reduction of cellular viability after treatment with beta-amyloid-Al complex. In addition, treatment with beta-amyloid-Al increased membrane fluidity much more than other beta-amyloid-metal complexes, whose contribution was negligible. Furthermore, the cellular morphology, as observed by electron microscopy, was deeply altered by beta-amyloid-Al. Importantly, beta-amyloid-Al toxicity is closely and significantly associated with a great difference in the structure/aggregation of this complex with respect to that of beta-amyloid alone and other beta-amyloid-metal complexes. In addition, beta-amyloid, as a consequence of Al binding, becomes strongly hydrophobic in character. These findings show a significant involvement of Al, compared to the other metal ions used in our experiments, in promoting a specific amyloid(1-42) aggregation, which is able to produce marked toxic effects on neuroblastoma cells, as clearly demonstrated for the first time in this study.     

F-Like Plasmid Sequences in Enteric Bacteria of Diverse Origin, with Implication of Horizontal Transfer and Plasmid Host Range

Seventy-eight bacterial isolates from human, animal, and plant hosts, representing eight species of the family Enterobacteriaceae, were screened for F-like plasmid sequences. Of the examined human Escherichia coli strains, 28% harbored one or two of the three F-like, RepFI replication regions, while 35% of the examined animal and all phytopathogenic strains harbored RepFIA-specific sequences. Comparative analysis of Salmonella, Shigella, Erwinia, and E. coli plasmid RepFI sequences showed 100% or very high homology, indicating frequent and recent interspecies gene transfer. The high incidence of RepFIA sequences in enteric bacterial species, including Klebsiella and Erwinia, showed that F-like plasmids are successful in avoiding natural barriers to establishment of horizontally transferred DNA and that in the natural environment conjugal transfer is efficient in diverse ecological niches. Received: 26 March 2001 / Accepted 12 July 2001