Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability

Genetic evidence predicts a causative role for amyloid-beta (A beta) in Alzheimer's disease. Recent debate has focused on whether fibrils (amyloid) or soluble oligomers of A beta are the active species that contribute to neurodegeneration and dementia. We developed two aggregation protocols for the consistent production of stable oligomeric or fibrillar preparations of A beta-(1-42). Here we report that oligomers inhibit neuronal viability 10-fold more than fibrils and approximately 40-fold more than unaggregated peptide, with oligomeric A beta-(1-42)-induced inhibition significant at 10 nm. Under A beta-(1-42) oligomer- and fibril-forming conditions, A beta-(1-40) remains predominantly as unassembled monomer and had significantly less effect on neuronal viability than preparations of A beta-(1-42). We applied the aggregation protocols developed for wild type A beta-(1-42) to A beta-(1-42) with the Dutch (E22Q) or Arctic (E22G) mutations. Oligomeric preparations of the mutations exhibited extensive protofibril and fibril formation, respectively, but were not consistently different from wild type A beta-(1-42) in terms of inhibition of neuronal viability. However, fibrillar preparations of the mutants appeared larger and induced significantly more inhibition of neuronal viability than wild type A beta-(1-42) fibril preparations. These data demonstrate that protocols developed to produce oligomeric and fibrillar A beta-(1-42) are useful in distinguishing the structural and functional differences between A beta-(1-42) and A beta-(1-40) and genetic mutations of A beta-(1-42).     

Auxin action on proton influx in corn roots and its correlation with growth

At concentrations inhibitory to the elongation of corn (Zea mays L.) roots, the auxins, indole-3-acetic acid (IAA) and α-naphthaleneacetic acid (α-NAA), cause an increase in the pH of the bathing medium; this increase occurs with an average latent period shorter than the latent period for the inhibitory effect of these auxins on elongation. Indole-2-carboxylic acid, an inactive structural analogue of IAA, and β-naphthaleneacetic acid, an inactive analogue of α-NAA, affect neither growth nor the pH of the medium. Since acid pH is known to promote and basic pH to inhibit root elongation, the data are consistent with the hypothesis that hormone-induced modification of cell-wall pH plays a role in the control of elongation of roots, as has been proposed for elongation of stems and coleoptiles.     

CO2 adsorption on polar surfaces of ZnO

Physical and chemical adsorption of CO₂ on ZnO surfaces were studied by means of two different implementations of periodic density functional theory. Adsorption energies were computed and compared to values in the literature. In particular, it was found that the calculated equilibrium structure and internuclear distances are in agreement with previous work. CO₂ adsorption was analyzed by inspection of the density of states and electron localization function. Valence bands, band gap and final states of adsorbed CO₂ were investigated and the effect of atomic displacements analyzed. The partial density of states (PDOS) of chemical adsorption of CO₂ on the ZnO(0001) surface show that the p orbitals of CO₂ were mixed with the ZnO valence band state appearing at the top of the valence band and in regions of low-energy conduction band.

Characterization of Butyrate Uptake by Nontransformed Intestinal Epithelial Cell Lines

Butyrate (BT) is one of the main end products of anaerobic bacterial fermentation of dietary fiber within the human colon. Among its recognized effects, BT inhibits colon carcinogenesis. Our aim was to characterize uptake of BT by two nontransformed intestinal epithelial cell lines: rat small intestinal epithelial (IEC-6) and fetal human colonic epithelial (FHC) cells. Uptake of ¹⁴C-BT by IEC-6 cells was (1) time- and concentration-dependent; (2) pH-dependent; (3) Na⁺-, Cl⁻- and energy-dependent; (4) inhibited by BT structural analogues; (5) sensitive to monocarboxylate transporter 1 (MCT1) inhibitors; and (6) insensitive to DIDS and amiloride. IEC-6 cells express both MCT1 and Na⁺-coupled monocarboxylate transporter 1 (SMCT1) mRNA. We conclude that ¹⁴C-BT uptake by IEC-6 cells mainly involves MCT1, with a small contribution of SMCT1. Acute exposure to ethanol, acetaldehyde, indomethacin, resveratrol and quercetin reduced ¹⁴C-BT uptake. Chronic exposure to resveratrol and quercetin reduced ¹⁴C-BT uptake but had no effect on either MCT1 or SMCT1 mRNA levels. Uptake of ¹⁴C-BT by FHC cells was time- and concentration-dependent but pH-, Na⁺-, Cl⁻- and energy-independent and insensitive to BT structural analogues and MCT1 inhibitors. Although MCT1 (but not SMCT1) mRNA expression was found in FHC cells, the characteristics of ¹⁴C-BT uptake by FHC cells did not support either MCT1 or SMCT1 involvement. In conclusion, uptake characteristics of ¹⁴C-BT differ between IEC-6 and FHC cells. IEC-6 cells demonstrate MCT1- and SMCT1-mediated transport, while FHC cells do not.     

Aster self-organization at meiosis: a conserved mechanism in insect parthenogenesis?

Unfertilized eggs usually lack maternal centrosomes and cannot develop without sperm contribution. However, several insect species lay eggs that develop to adulthood as unfertilized in the absence of a preexisting centrosome. We report that the oocyte of the parthenogenetic viviparous pea aphid Acyrthosiphon pisum is able to self-organize microtubule-based asters, which in turn interact with the female chromatin to form the first mitotic spindle. This mode of reproduction provides a good system to investigate how the oocyte can assemble new centrosomes and how their number can be exactly monitored. We propose that the cooperative interaction of motor proteins and randomly nucleated surface microtubules could lead to the formation of aster-like structures in the absence of pre-existing centrosomes. Recruitment of material along the microtubules might contribute to the accumulation of pericentriolar material and centriole precursors at the focus of the asters, thus leading to the formation of true centrosomes. The appearance of microtubule asters at the surface of activated oocytes could represent a possible common mechanism for centrosome formation during insect parthenogenesis.