Bioluminescence imaging reveals inhibition of tumor cell proliferation by Alzheimer's amyloid β protein

Background  

Cancer and Alzheimer's disease (AD) are two seemingly distinct diseases and rarely occur simultaneously in patients. To explore molecular determinants differentiating pathogenic routes towards AD or cancer, we investigate the role of amyloid β protein (Aβ) on multiple tumor cell lines that are stably expressing luciferase (human glioblastoma U87; human breast adenocarcinoma MDA-MB231; and mouse melanoma B16F).     

Tobamovirus evolution: gene overlaps, recombination, and taxonomic implications

Tobamoviruses, mostly isolated from solanaceous plants, may represent ancient virus lineages that have codiverged with their hosts. Recently completed nucleotide sequences of six nonsolanaceous tobamoviruses allowed assessment of the codivergence hypothesis and support a third subgroup within tobamoviruses. The genomic sequences of 12 tobamoviruses and the partial sequences of 11 others have been analyzed. Comparisons of the predicted protein sequences revealed three clusters of tobamoviruses, corresponding to those infecting solanaceous species (subgroup 1), those infecting cucurbits and legumes (subgroup 2), and those infecting crucifers. The orchid-infecting odontoglossum ringspot tobamovirus was associated with subgroup 1 genomes by its coat and movement protein sequences, but with the crucifer-pathogenic tobamoviruses by the remainder of its genome, suggesting that it is the progeny of a recombinant. For four of five genomic regions, subgroup 1 and 3 genomes were equidistant from a subgroup 2 genome chosen for comparison, suggesting uniform rates of evolution. A phylogenetic tree of plant families based on the tobamoviruses they harbor was congruent with that based on rubisco sequences but had a different root, suggesting that codivergence was tempered by rare events of viruses of one family colonizing another family. The proposed subgroup 3 viruses probably have an origin of virion assembly in the movement protein gene, a large (25-codon) overlap of movement and coat protein open reading frames, and a comparably shorter genome. Codon-position- dependent base compositions and codon prevalences suggested that the coat protein frame of the overlap region was ancestral. Bootstrapped parsimony analysis of the nucleotides in the overlap region and of the sequences translated from the -1 frame (the subgroup 3 movement protein frame) of this region produced trees inconsistent with those deduced from other regions. The results are consistent with a model in which a no or short overlap organization was ancestral. Despite encoding of subgroup 2 and 3 movement protein C-termini by nonhomologous nucleotides, weak similarities between their amino acid sequences suggested convergent sequence evolution.      

Xenotransplantation: a problematic world behind a glamorous facade

The discussion about the ethics of xenotransplantation seems to focus upon the benefits for individual patients and the potential risks for human society, in general, to contract a newly emerging retrovirus. In these risk-benefit considerations, the moral concern for the research animals involved appears to be absent. This is remarkable, because the presumed successful xenograft is not expected very soon. A lot of basic problems in pig and primate xenotransplantations still need solving. These new experiments in our own biomedical laboratories raise questions regarding animal welfare and ethical justification in the light of possible alternative strategies. In this article, I discuss some of the moral issues related to preclinical, fundamental xenotransplantation research.     

Ethics and Embryo/Foetus Research

Research with embryos and foetuses raise moral problems. In this article the origins of these moral intuitions are analyzed and discussed at four levels: moral problems regarding the treatment of the foetus and the mother animal; ethical problems experienced by the moral actor (researcher); ethical problems related to a justification based upon a balance between means and goals; and ethical problems raised by society.     

New embedding medium for sectioning undecalcified bone

Methylmethacrylate (MMA) is the most commonly used embedding medium for sectioning undecalcified bone; however, a number of problems exist with its use in a research laboratory. MMA requires a long infiltration time and temperature control, and it reacts with many polymers. We used Kleer Set resin™ as an alternative embedding medium for sectioning undecalcified bone specimens. Fluorochrome labeled bone specimens were sectioned transversely using a ground section technique and longitudinally on a sledge macrotome. The slides were viewed using both transmitted light and epifluorescence microscopy. High quality sections were obtained using Kleer Set resin™ for both sectioning techniques. We have shown that this new embedding medium is simpler, safer, quicker to use and does not interfere with visualization of fluorochromes.     

Crotaline pit organs analyzed as warm receptors

Afferent impulses from single-fiber preparations of the trigeminal nerve in Agkistrodon blomhoffi brevicauduswere recorded during steady and dynamic temperature stimulation of the sensory membrane in the facial pit. The thermoreceptors of the pit showed high sensitivity to the rate of change in receptor temperature. Changing the heat capacity of the pit membrane (a drop of water in the pit in the case of the laser and halogen lamp, and a drop of water covered by a plastic film in the case of flowing water) changed the pattern of response. When the heat capacity of the pit membrane is increased, responses approach those obtained in other warm receptors. The spatial gradient theory of Williams, whereby a reversal of heat energy flow is supposed to produce a reverse of response, was shown to be inapplicable to the pit receptors. Reversal of heat energy flow in the pits produced neither off-silence nor depression of response, and therefore direction of heat flow is not an important component of the stimulus for these receptors. This research was made possible by aid from The Netherlands Organization for Advancement of Pure Research (ZWO).