ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients

Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects.     

Thalamocortical inputs show post-critical-period plasticity

Experience-dependent plasticity in the adult brain has clinical potential for functional rehabilitation following central and peripheral nerve injuries. Here, plasticity induced by unilateral infraorbital (IO) nerve resection in 4-week-old rats was mapped using MRI and synaptic mechanisms were elucidated by slice electrophysiology. Functional MRI demonstrates a cortical potentiation compared to thalamus 2 weeks after IO nerve resection. Tracing thalamocortical (TC) projections with manganese-enhanced MRI revealed circuit changes in the spared layer 4 (L4) barrel cortex. Brain slice electrophysiology revealed TC input strengthening onto L4 stellate cells due to an increase in postsynaptic strength and the number of functional synapses. This work shows that the TC input is a site for robust plasticity after the end of the previously defined critical period for this input. Thus, TC inputs may represent a major site for adult plasticity in contrast to the consensus that adult plasticity mainly occurs at cortico-cortical connections.     

Effects of contrasting soil fertility on root mass, root growth, root decomposition and soil carbon under a New Zealand perennial ryegrass/white clover pasture

The contribution of below ground plant root tissue to soil carbon (C) pools is attracting considerable interest in the context of greenhouse gas mitigation options. A field experiment was conducted on a perennial ryegrass/white clover pasture in the Manawatu, New Zealand, to examine the effect of differing soil nitrogen (N) and phosphorus (P) fertility status on root dynamics. Root standing mass, shoot and root dry matter (DM) accumulation and root tissue decomposition were measured at 6–8 week intervals over one year at moderate (Olsen P?=?24, no added N) and high (Olsen P?=?49, 400 kgN ha^?1y^?1 added N) soil fertility levels. Shoot production was significantly greater in the high fertility treatment (2550 cf. 1890 gDM m^?2y^?1) but differences in root dynamics were confined to two periods in spring and winter. In late spring the pattern was for lower root mass (183 cf. 231 gDM m^?2 between 0–80 mm depth) and higher root production (0.71 cf. 0.52 gDM m^?2 d^?1 between 0–120 mm depth) under higher fertility. In winter the reverse was observed. There is some evidence that the soil type used in the root in-growth cores underestimated root production values for this site by a factor of approx. one third. Short-term differences between the two fertiity treatments in standing root mass and root production did not lead to treatment differences in topsoil C and N changes over four years. This may reflect insufficient separation in the two soil fertility treatments and a low overall root tissue input to soil organic matter.     

Area per lipid and acyl length distributions in fluid phosphatidylcholines determined by (2)H NMR spectroscopy

Deuterium ((2)H) NMR spectroscopy provides detailed information regarding the structural fluctuations of lipid bilayers, including both the equilibrium properties and dynamics. Experimental (2)H NMR measurements for the homologous series of 1, 2-diacyl-sn-glycero-3-phosphocholines with perdeuterated saturated chains (from C12:0 to C18:0) have been performed on randomly oriented, fully hydrated multilamellar samples. For each lipid, the C-D bond order parameters have been calculated from de-Paked (2)H NMR spectra as a function of temperature. The experimental order parameters were analyzed using a mean-torque potential model for the acyl chain segment distributions, and comparison was made with the conventional diamond lattice approach. Statistical mechanical principles were used to relate the measured order parameters to the lipid bilayer structural parameters: the hydrocarbon thickness and the mean interfacial area per lipid. At fixed temperature, the area decreases with increasing acyl length, indicating increased van der Waals attraction for longer lipid chains. However, the main effect of increasing the acyl chain length is on the hydrocarbon thickness rather than on the area per lipid. Expansion coefficients of the structural parameters are reported and interpreted using an empirical free energy function that describes the force balance in fluid bilayers. At the same absolute temperature, the phosphatidylcholine (PC) series exhibits a universal chain packing profile that differs from that of phosphatidylethanolamines (PE). Hence, the lateral packing of phospholipids is more sensitive to the headgroup methylation than to the acyl chain length. A fit to the area per lipid for the PC series using the empirical free energy function shows that the PE area represents a limiting value for the packing of fluid acyl chains.     

State ranks of incident cancer burden due to overweight and obesity in the United States, 2003

Objective: Given links between obesity and cancer, we estimated incident cancer burden due to overweight and obesity at the state level in the United States. Methods and Procedures: Using state rankings by per capita burden of incident cancer cases diagnosed in 2003 that were related to overweight and obesity, we examined the frequency with which states ranked in the highest and lowest quintiles of weight‐related burden for cancers of the postmenopausal breast, endometrium, kidney, colon, and prostate. In this study, data from the Behavioral Risk Factor Surveillance System (BRFSS), US Census, US Mortality Public Use Data Tapes, and National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program were used. Results: Western states had the lowest weight‐related cancer burden for both sexes. Iowa, South Dakota, and West Virginia had the highest burden for all three types of male cancers. West Virginia is the only state that ranked in the quintile of highest weight‐related burden for all four cancers considered in women. Discussion: For certain cancers, including endometrial, postmenopausal breast, and colon cancers, states with high burdens clustered in geographic regions, warranting further inquiry. Although state ranks for the total cancer burden and the prevalence of overweight and obesity correlated with state ranks for weight‐related incident cancer burden, they often served poorly as its proxy. Such a finding cautions against simply targeting states with high overweight and obesity or high total burdens of cancers for which overweight and obesity are risk factors, as this approach may not reach areas of unrecognized burden.     

Monte Carlo Study of the Buckingham Exponential-six Fluid

Abstract

In this paper we report the results of extensive Monte Carlo simulations of a pure fluid of Buckingham modified exponential-six molecules. Data are presented for the configurational energy and pressure covering a wide range of temperatures and densities. These data are interpreted using the generalized van der Waals partition function with a novel separation into free volume and mean potential terms. We find, surprisingly, that the Buckingham fluid is described by a simple van der Waals-like equation of state provided that the b parameter is temperature dependent and chosen in a theoretically correct manner.     

Orientation of commissural axons in vitro in response to a floor plate-derived chemoattractant

Developing axons are guided to their targets by molecular cues in their local environment. Some cues are short-range, deriving from cells along axonal pathways. There is also increasing evidence for longer-range guidance cues, in the form of gradients of diffusible chemoattractant molecules, which originate from restricted populations of target cells. The guidance of developing commissural axons within the spinal cord depends on one of their intermediate cellular targets, the floor plate. We have shown previously that floor plate cells secrete a diffusible factor(s) that can alter the direction of commissural axon growth in vitro. Here we show that the factor is an effective chemoattractant for commissural axons. It can diffuse considerable distances through a collagen gel matrix and through dorsal and ventral neural epithelium in vitro to reorient the growth of virtually all commissural axons. The orientation of axons occurs in the absence of detectable effects on the survival of commissural neurons or on the rate of commissural axon extension. The regionally restricted expression of the factor suggests that it is present in the embryonic spinal cord in a gradient with its high point at the floor plate. These observations support the idea that the guidance of commissural axons to the ventral midline of the spinal cord results in part from the secretion of a chemoattractant by the floor plate.     

The use of toluidine blue for in situ detection of micro-organisms in foods

The use of toluidine blue to stain cryosections of food samples to detect sites of microbial growth was examined. The method successfully detected colonies and single cells of both yeasts and bacteria at magnifications of x 400 or below in the majority of foods studied. The method demonstrates great potential for studying the micro-environments in which micro-organisms grow.     

Bacterial community structure and location in Stilton cheese

The microbial diversity occurring in Stilton cheese was evaluated by 16S ribosomal DNA analysis with PCR-denaturing gradient gel electrophoresis. DNA templates for PCR experiments were directly extracted from the cheese as well as bulk cells harvested from a variety of viable-count media. The variable V3 and V4-V5 regions of the 16S genes were analyzed. Closest relatives of Lactococcus lactis, Enterococcus faecalis, Lactobacillus plantarum, Lactobacillus curvatus, Leuconostoc mesenteroides, Staphylococcus equorum, and Staphylococcus sp. were identified by sequencing of the DGGE fragments. Fluorescently labeled oligonucleotide probes were developed to detect Lactococcus lactis, Lactobacillus plantarum, and Leuconostoc mesenteroides in fluorescence in situ hybridization (FISH) experiments, and their specificity for the species occurring in the community of Stilton cheese was checked in FISH experiments carried out with reference cultures. The combined use of these probes and the bacterial probe Eub338 in FISH experiments on Stilton cheese sections allowed the assessment of the spatial distribution of the different microbial species in the dairy matrix. Microbial colonies of bacteria showed a differential location in the different parts of the cheese examined: the core, the veins, and the crust. Lactococci were found in the internal part of the veins as mixed colonies and as single colonies within the core. Lactobacillus plantarum was detected only underneath the surface, while Leuconostoc microcolonies were homogeneously distributed in all parts observed. The combined molecular approach is shown to be useful to simultaneously describe the structure and location of the bacterial flora in cheese. The differential distribution of species found suggests specific ecological reasons for the establishment of sites of actual microbial growth in the cheese, with implications of significance in understanding the ecology of food systems and with the aim of achieving optimization of the fermentation technologies as well as preservation of traditional products.     

The ultrastructural localization of acid phosphatase,alkaline phosphatase and adenosine triphosphatase in induced goitres of Xenopus laevis Daudin tadpoles

Summary Tadpoles of Xenopus laevis were maintained in solutions of potassium perchlorate, potassium thiocyanate, thiourea and propyl-thiouracil (0.005% w/v). Metamorphosis was inhibited and within a short time large well-vascularized goitres developed. The localization of certain phosphatases at the ultrastructural level in these goitres is described and the possible roles played by these enzymes is discussed. Acid phosphatase was localized in follicle epithelial cells in dense droplets thought to be lysosomes or cytolysomes. Alkaline phosphatase and a Mg⁺⁺-activated ATP-ase were found on the outer surfaces of the membranes of follicular cells and on the walls of capillary blood vessels.This work was carried out during the tenure by one of us (R.C.) of a Medical Research Council Scholarship and forms part of a programme of research in amphibian thyroid physiology supported by a grant from the Medical Research Council, which we gratefully acknowledge.