Inter-relationships between small, dense low-density lipoprotein (LDL), plasma triacylglycerol and LDL apoprotein B in an atherogenic lipoprotein phenotype in free-living subjects

A predominance of small, dense low-density lipoprotein (LDL) is a major component of an atherogenic lipoprotein phenotype, and a common, but modifiable, source of increased risk for coronary heart disease in the free-living population. While much of the atherogenicity of small, dense LDL is known to arise from its structural properties, the extent to which an increase in the number of small, dense LDL particles (hyper-apoprotein B) contributes to this risk of coronary heart disease is currently unknown. This study reports a method for the recruitment of free-living individuals with an atherogenic lipoprotein phenotype for a fish-oil intervention trial, and critically evaluates the relationship between LDL particle number and the predominance of small, dense LDL. In this group, volunteers were selected through local general practices on the basis of a moderately raised plasma triacylglycerol (triglyceride) level (>1.5 mmol/l) and a low concentration of high-density-lipoprotein cholesterol (<1.1 mmol/l). The screening of LDL subclasses revealed a predominance of small, dense LDL (LDL subclass pattern B) in 62% of the cohort. As expected, subjects with LDL subclass pattern B were characterized by higher plasma triacylglycerol and lower high-density lipoprotein cholesterol (<1.1 mmol/l) levels and, less predictably, by lower LDL cholesterol and apoprotein B levels (P<0.05; LDL subclass A compared with subclass B). While hyper-apoprotein B was detected in only five subjects, the relative percentage of small, dense LDL-III in subjects with subclass B showed an inverse relationship with LDL apoprotein B (r=-0.57; P<0.001), identifying a subset of individuals with plasma triacylglycerol above 2.5 mmol/l and a low concentration of LDL almost exclusively in a small and dense form. These findings indicate that a predominance of small, dense LDL and hyper-apoprotein B do not always co-exist in free-living groups. Moreover, if coronary risk increases with increasing LDL particle number, these results imply that the risk arising from a predominance of small, dense LDL may actually be reduced in certain cases when plasma triacylglycerol exceeds 2.5 mmol/l.

Using zero-norm constraint for sparse probability density function estimation

A new sparse kernel probability density function (pdf) estimator based on zero-norm constraint is constructed using the classical Parzen window (PW) estimate as the target function. The so-called zero-norm of the parameters is used in order to achieve enhanced model sparsity, and it is suggested to minimize an approximate function of the zero-norm. It is shown that under certain condition, the kernel weights of the proposed pdf estimator based on the zero-norm approximation can be updated using the multiplicative nonnegative quadratic programming algorithm. Numerical examples are employed to demonstrate the efficacy of the proposed approach.

Association between dietary phyto-oestrogens and bone density in men and postmenopausal women

Phyto-oestrogens have been associated with a decreased risk for osteoporosis, but results from intervention and observational studies in Western countries have been inconsistent. In the present study, we investigated the association between habitual phyto-oestrogen intake and broadband ultrasound attenuation (BUA) of the calcanaeum as a marker of bone density. We collected 7 d records of diet, medical history and demographic and anthropometric data from participants (aged 45–75 years) in the European Prospective Investigation into Cancer-Norfolk study. Phyto-oestrogen (biochanin A, daidzein, formononetin; genistein, glycitein; matairesinol; secoisolariciresinol; enterolactone; equol) intake was determined using a newly developed food composition database. Bone density was assessed using BUA of the calcanaeum. Associations between bone density and phyto-oestrogen intake were investigated in 2580 postmenopausal women who were not on hormone replacement therapy and 4973 men. Median intake of total phyto-oestrogens was 876 (interquartile range 412) μg/d in postmenopausal women and 1212 (interquartile range 604) μg/d in men. The non-soya isoflavones formononetin and biochanin A were marginally significant or significantly associated with BUA in postmenopausal women (β = 1·2; P < 0·1) and men (β = 1·2; P < 0·05), respectively; enterolignans and equol were positively associated with bone density in postmenopausal women, but this association became non-significant when dietary Ca was added to the model. In the lowest quintile of Ca intake, soya isoflavones were positively associated with bone density in postmenopausal women (β = 1·4; P < 0·1). The present results therefore suggest that non-soya isoflavones are associated with bone density independent of Ca, whereas the association with soya or soya isoflavones is affected by dietary Ca.

A study of the atmospherically relevant reaction between molecular chlorine and dimethylsulfide (DMS): establishing the reaction intermediate and measurement of absolute photoionization cross-sections

In a study using UV photoelectron spectroscopy (PES) of the atmospherically relevant reaction CH3SCH3 + Cl2 → CH3SCH2Cl + HCl bands associated with a reaction intermediate have been observed. These have been assigned to ionization of the covalently bound molecule (CH3)2SCl2 on the basis of the intensity of the observed bands as a function of reaction time, molecular orbital calculations of vertical ionization energies and evidence from infrared spectroscopy. A method has also been developed, with the flow-tube/PE spectrometer combination used, to measure photoionization cross-sections of the reagents and products at the photon energy utilized and this has allowed the photoionization cross-section of the intermediate to be estimated. This work augments an earlier study in which the rate constant of the reaction between CH3SCH3 (DMS) and Cl2 has been measured at room temperature.

Stomatal conductance and not stomatal density determines the long-term reduction in leaf transpiration of poplar in elevated CO2

Using a free-air CO2 enrichment (FACE) experiment, poplar trees (Populus · euramericana clone I214) were exposed to either ambient or elevated [CO2] from planting, for a 5-year period during canopy development, closure, coppice and re-growth. In each year, measurements were taken of stomatal density (SD, number mm2) and stomatal index (SI, the proportion of epidermal cells forming stomata). In year 5, measurements were also taken of leaf stomatal conductance (gs, lmol m2 s1), photosynthetic CO2 fixation (A, mmol m2 s1), instantaneous water-use efficiency (A/E) and the ratio of intercellular to atmospheric CO2 (Ci:Ca). Elevated [CO2] caused reductions in SI in the first year, and in SD in the first 2 years, when the canopy was largely open. In following years, when the canopy had closed, elevated [CO2] had no detectable effects on stomatal numbers or index. In contrast, even after 5 years of exposure to elevated [CO2], gs was reduced, A/E was stimulated, and Ci:Ca was reduced relative to ambient [CO2]. These outcomes from the long-term realistic field conditions of this forest FACE experiment suggest that stomatal numbers (SD and SI) had no role in determining the improved instantaneous leaf-level efficiency of water use under elevated [CO2]. We propose that altered cuticular development during canopy closure may partially explain the changing response of stomata to elevated [CO2], although the mechanism for this remains obscure.

Amphioxus type I keratin cDNA and the evolution of intermediate filament genes

We report the cloning of an intermediate filament (IF) cDNA from the cephalochordate amphioxus that encodes a protein assignable to the type I keratin group. This is the first type I keratin reported from an invertebrate. Molecular phylogenetic analyses reveal that amphioxus also possesses a type II keratin, and that the genes encoding short-rod IF proteins underwent different patterns of duplication in vertebrates and their closest relatives, the cephalochordates. Extensive IF gene duplication and divergence may have facilitated the origin of new specialised cell types in vertebrates.

Alkenyl derivatives of the metals. Oxidative addition to intermediate tin(II) alkenyls; isolation, and crystal and molecular structure of n-butyltris(triphenylethenyl)tin(IV)

Reaction of tin(II) chloride with Li(CPhCPh2) at –78 °C in diethyl ether–hexane–tetrahydrofuran affords a deep red solution whose colour fades on warming, and which we believe contains the (unstable) first dialkenyltin(II) species. The latter survives long enough at low temperatures to undergo intermolecular oxidative addition, and one such adduct leads ultimately to the formation of Sn(CPhCPh2)3Bun, which has been fully characterised including a crystal and molecular structure study. The mechanism of formation of the final product has been examined and results are reported.

Initial distribution spread: A density forecasting approach

Ensemble forecasting of nonlinear systems involves the use of a model to run forward a discrete ensemble (or set) of initial states. Data assimilation techniques tend to focus on estimating the true state of the system, even though model error limits the value of such efforts. This paper argues for choosing the initial ensemble in order to optimise forecasting performance rather than estimate the true state of the system. Density forecasting and choosing the initial ensemble are treated as one problem. Forecasting performance can be quantified by some scoring rule. In the case of the logarithmic scoring rule, theoretical arguments and empirical results are presented. It turns out that, if the underlying noise dominates model error, we can diagnose the noise spread.

The key role of the western boundary in linking the AMOC strength to the north-south pressure gradient

A key idea in the study of the Atlantic meridional overturning circulation (AMOC) is that its strength is proportional to the meridional density gradient, or more precisely, to the strength of the meridional pressure gradient. A physical basis that would tell us how to estimate the relevant meridional pressure gradient locally from the density distribution in numerical ocean models to test such an idea, has been lacking however. Recently, studies of ocean energetics have suggested that the AMOC is driven by the release of available potential energy (APE) into kinetic energy (KE), and that such a conversion takes place primarily in the deep western boundary currents. In this paper, we develop an analytical description linking the western boundary current circulation below the interface separating the North Atlantic Deep Water (NADW) and Antarctic Intermediate Water (AAIW) to the shape of this interface. The simple analytical model also shows how available potential energy is converted into kinetic energy at each location, and that the strength of the transport within the western boundary current is proportional to the local meridional pressure gradient at low latitudes. The present results suggest, therefore, that the conversion rate of potential energy may provide the necessary physical basis for linking the strength of the AMOC to the meridional pressure gradient, and that this could be achieved by a detailed study of the APE to KE conversion in the western boundary current.

Analysis of the intermediate housing market mechanism in the UK

Government policies have backed intermediate housing market mechanisms like shared equity, intermediate rented and shared ownership (SO) as potential routes for some households, who are otherwise squeezed between the social housing and the private market. The rhetoric deployed around such housing has regularly contained claims about its social progressiveness and role in facilitating socio-economic mobility, centring on a claim that SO schemes can encourage people to move from rented accommodation through a shared equity phase and into full owner-occupation. SO has been justified on the grounds of it being transitional state, rather than a permanent tenure. However SO buyers may be laden with economic cost-benefit structures that do not stack up evenly and as a consequence there may be little realistic prospect of ever reaching a preferred outcome. Such behaviours have received little empirical attention as yet despite, the SO model arguably offers a sub-optimal solution towards homeownership, or in terms of wider quality of life. Given the paucity of rigorous empirical work on this issue, this paper delineates the evidence so far and sets out a research agenda. Our analysis is based on a large dataset of new shared owners, observing an information base that spans the past decade. We then set out an agenda to further examine the behaviours of the SO occupants and to examine the implications for future public policy based on existing literature and our outline findings. This paper is particularly opportune at a time of economic uncertainty and an overriding ‘austerity’ drive in public funding in the UK, through which SO schemes have enjoyed support uninterruptedly thus far.

Gut microbial catabolism of grape seed flavan-3-ols by human faecal microbiota. Targetted analysis of precursor compounds, intermediate metabolites and end-products.

In vitro batch culture fermentations were conducted with grape seed polyphenols and human faecal microbiota, in order to monitor both changes in precursor flavan-3-ols and the formation of microbial-derived metabolites. By the application of UPLC-DAD-ESI-TQ MS, monomers, and dimeric and trimeric procyanidins were shown to be degraded during the first 10 h of fermentation, with notable inter-individual differences being observed between fermentations. This period (10 h) also coincided with the maximum formation of intermediate metabolites, such as 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone and 4-hydroxy-5-(3′,4′-dihydroxyphenyl)-valeric acid, and of several phenolic acids, including 3-(3,4-dihydroxyphenyl)-propionic acid, 3,4-dihydroxyphenylacetic acid, 4-hydroxymandelic acid, and gallic acid (5–10 h maximum formation). Later phases of the incubations (10–48 h) were characterised by the appearance of mono- and non-hydroxylated forms of previous metabolites by dehydroxylation reactions. Of particular interest was the detection of γ-valerolactone, which was seen for the first time as a metabolite from the microbial catabolism of flavan-3-ols. Changes registered during fermentation were finally summarised by a principal component analysis (PCA). Results revealed that 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone was a key metabolite in explaining inter-individual differences and delineating the rate and extent of the microbial catabolism of flavan-3-ols, which could finally affect absorption and bioactivity of these compounds.