Mutations in mitochondrial-encoded cytochrome c oxidase subunits I, II, and III genes detected in Alzheimer's disease using single-strand conformation polymorphism

A "mitochondrial hypothesis" of late onset Alzheimer's disease (AD) has been proposed. Biochemical studies indicate that there is a significant decrease in cytochrome oxidase (CO) activity as well as perturbed CO I and CO III mRNA levels in platelets and brain tissue from Alzheimer's patients. Using the electrophoretic mutation detection technique SSCP and DNA sequencing, we have identified 20 point mutations in the mitochondrial-encoded CO subunits (CO I, II, and III) in AD and age-matched control brain samples. Eight of the mutations are new variants of the mitochondrial genome. The efficiency of SSCP in detecting mutations in the CO subunits was estimated to be 80% when compared to dideoxy sequencing. One of the mutations (at position 9,861) results in a phenylalanine-->leucine substitution at a highly conserved residue in CO III. CO activity was reduced by an average of 35% in all AD brains compared to age-matched control samples, which agrees with previous reports. CO activity in one of the AD brain samples carrying the 9,861 mutation decreased by 80% relative to control brain samples, suggesting that the phenotypic expression of this mutation may result in reduced CO activity and compromised mitochondrial function.     

Hole transfer dynamics from dye molecules to p-type NiO nanoparticles: effects of processing conditions

Hole transfer dynamics of Atto647N sensitized p-type NiO nanoparticle (NP) thin films is investigated using both ensemble-averaged and single-molecule spectroscopy techniques. The rate of hole transfer is dependent on the processing conditions and is enhanced when the NiO is pre-annealed in air as compared to vacuum. This is possibly due to an upward shift of the valence band of the semiconductor and an increase in the free energy for hole transfer as more Ni(2)O(3) are formed in the presence of air. The stretched exponential fluorescence decay profile of Atto647N on NiO NP suggests the presence of a distribution of hole transfer rates. This is in agreement with the observed emission lifetime and intensity fluctuations and non-monoexponential fluorescence decays for individual Atto647N molecules on NiO NP films. A plausible explanation for the heterogeneous hole transfer rates is an inhomogeneous distribution of (defect) sites on the metal oxide due to the processing conditions and a fluctuation in the intermolecular interaction.     

Unconventional multiple ring structure formation from evaporation-induced self-assembly of polymers

The formation of multiring deposits of poly(2-vinylpyridine) (P2VP) from the evaporation of a P2VP-(2,6-lutidine + water) drop on a glass substrate does not conform to the conventional pinning-depinning mechanism. Instead, ringlike deposits are formed when the droplet undergoes several cycles of spreading and receding where, for each spreading event, a P2VP ridge is formed at the contact line when the polymer flows toward the outward advancing edge. The complex interplay between an outward solutal-Marangoni flow due to a higher concentration of the polymer at the contact line and an inward solvent-Marangoni flow arising from the differences in volatilities and surface tensions of the pure solvent components plays an important role in enhancing the droplet spreading rate. The newly discovered surface patterning mechanism has important implications in the development of novel techniques for inducing self-assembly of functional materials from evaporating drops.     

2-O-alkylated para-benzamide α-helix mimetics: the role of scaffold curvature

The design and synthesis of a new 2-O-alklyated benzamide α-helix mimetic is described. Comparison with regioisomeric 3-O-alkylated benzamides permits a preliminary evaluation of the role that mimetic curvature has in determining molecular recognition properties.     

Gut microbiota, diet, and heart disease

Modulation of the gut microbiota is an area of growing interest, particularly for its link to improving and maintaining the systemic health of the host. It has been suggested to have potential to reduce risk factors associated with chronic diseases, such as elevated cholesterol levels in coronary heart disease (CHD). Diets of our evolutionary ancestors were largely based on plant foods, high in dietary fiber and fermentable substrate, and our gut microbiota has evolved against a background of such diets. Therapeutic diets that mimic plant-based diets from the early phases of human evolution may result in drug-like cholesterol reductions. In contrast, typical Western diets low in dietary fiber and fermentable substrate, and high in saturated and trans fatty acids, are likely contributors to the increased need for pharmacological agents for cholesterol reduction. The gut microbiota of those consuming a Western diet are likely underutilized and depleted of metabolic fuels, resulting in a less than optimal gut microbial profile. As a result, this diet is mismatched to our archaic gut microbiota and, therefore, to our genome, which has changed relatively little since humans first appeared. While the exact mechanism by which the gut microbiota may modulate cholesterol levels still remains uncertain, end products of bacterial fermentation, particularly the short chain fatty acids (i.e., propionate), have been suggested as potential candidates. While more research is required to clarify the potential link between gut microbiota and CHD risk reduction, consuming a therapeutic diet rich in plant foods, dietary fiber, and fermentable substrate would be a useful strategy for improving systemic health, possibly by altering the gut microbiota.     

Processing the capillary viscometry data of fluids with yield stress

The capillary viscometer is used to measure the shear stress-shear rate relationship of a wide range of purely viscous fluids. It is however not considered as an appropriate instrument for obtaining the yield stress and the post-yield behaviour of fluids that have a yield stress. This is partly because conventional methods of processing the capillary viscometry data of purely viscous fluids cannot be applied to similar data of fluids with yield stress. The unavoidable experimental noise in the capillary data, particularly at low shear rates, also makes it difficult to obtain a reliable estimate of the yield stress from capillary data. In this investigation the problem of converting the capillary viscometry data of yield stress fluids into a shear stress-shear rate curve and a yield stress is formulated as a Volterra integral equation of the first kind. This is an ill-posed problem i.e. noise in the data will be amplified by inappropriate methods of data processing. A method, based on Tikhonov regularisation that takes into account the ill-posed nature of the problem, is then developed to solve this problem for fluids with yield stress. The performance of this method is assessed by applying it to a set of “synthetic” capillary viscometry data with added random noise and to a set of experimental data for a concentrated suspension of TiO₂ taken from the literature. In both cases Tikhonov regularisation was able to extract the complete shear properties of these fluids from capillary viscometry data alone. Received: 22 November 1999/Accepted: 17 December 1999     

Accuracy of radial basis function interpolation and derivative approximations on 1-D infinite grids

Radial basis function (RBF) interpolation can be very effective for scattered data in any number of dimensions. As one of their many applications, RBFs can provide highly accurate collocation-type numerical solutions to several classes of PDEs. To better understand the accuracy that can be obtained, we survey here derivative approximations based on RBFs using a similar Fourier analysis approach that has become the standard way for assessing the accuracy of finite difference schemes. We find that the accuracy is directly linked to the decay rate, at large arguments, of the (generalized) Fourier transform of the radial function. Three different types of convergence rates can be distinguished as the node density increases – polynomial, spectral, and superspectral, as exemplified, for example, by thin plate splines, multiquadrics, and Gaussians respectively. Bengt Fornberg: The work was supported by NSF grants DMS-9810751 (VIGRE), DMS-0073048 and DMS-0309803.Natasha Flyer: The work was supported by the NSF grant DMS-9810751 (VIGRE).