Gene-nutrient interactions in the metabolic syndrome: single nucleotide polymorphisms in ADIPOQ and ADIPOR1 interact with plasma saturated fatty acids to modulate insulin resistance

Background: Progression of the metabolic syndrome (MetS) is determined by genetic and environmental factors. Gene-environment interactions may be important in modulating the susceptibility to the development of MetS traits. Objective: Gene-nutrient interactions were examined in MetS subjects to determine interactions between single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) and plasma fatty acid composition and their effects on MetS characteristics. Design: Plasma fatty acid composition, insulin sensitivity, plasma adiponectin and lipid concentrations, and ADIPOQ, ADIPOR1, and ADIPOR2 SNP genotypes were determined in a cross-sectional analysis of 451 subjects with the MetS who participated in the LIPGENE (Diet, Genomics, and the Metabolic Syndrome: an Integrated Nutrition, Agro-food, Social, and Economic Analysis) dietary intervention study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX (SUpplementation en VItamines et Mineraux AntioXydants) case-control study (http://www.ucd.ie/lipgene). Results: Single SNP effects were detected in the cohort. Triacylglycerols, nonesterified fatty acids, and waist circumference were significantly different between genotypes for 2 SNPs (rs266729 in ADIPOQ and rs10920533 in ADIPOR1). Minor allele homozygotes for both of these SNPs were identified as having degrees of insulin resistance, as measured by the homeostasis model assessment of insulin resistance, that were highly responsive to differences in plasma saturated fatty acids (SFAs). The SFA-dependent association between ADIPOR1 rs10920533 and insulin resistance was replicated in cases with MetS from a separate independent study, which was an association not present in controls. Conclusions: A reduction in plasma SFAs could be expected to lower insulin resistance in MetS subjects who are minor allele carriers of rs266729 in ADIPOQ and rs10920533 in ADIPOR1. Personalized dietary advice to decrease SFA consumption in these individuals may be recommended as a possible therapeutic measure to improve insulin sensitivity. This trial was registered at clinicaltrials.

The prompt hypothesis: clarification requests as corrective input for grammatical errors

The potential of clarification questions (CQs) to act as a form of corrective input for young children's grammatical errors was examined. Corrective responses were operationalized as those occasions when child speech shifted from erroneous to correct (E -> C) contingent on a clarification question. It was predicted that E -> C sequences would prevail over shifts in the opposite direction (C -> E), as can occur in the case of nonerror-contingent CQs. This prediction was tested via a standard intervention paradigm, whereby every 60s a sequence of two clarification requests (either specific or general) was introduced into conversation with a total of 45 2- and 4-year-old children. For 10 categories of grammatical structure, E -> C sequences predominated over their C -> E counterparts, with levels of E -> C shifts increasing after two clarification questions. Children were also more reluctant to repeat erroneous forms than their correct counterparts, following the intervention of CQs. The findings provide support for Saxton's prompt hypothesis, which predicts that error-contingent CQs bear the potential to cue recall of previously acquired grammatical forms.

Input and output modality effects in immediate serial recall

In immediate recall tasks, visual recency is substantially enhanced when output interference is low (Cowan, Saults, Elliott, & Moreno, 2002; Craik, 1969) whereas auditory recency remains high even under conditions of high output interference. Ibis auditory advantage has been interpreted in terms of auditory resistance to output interference (e.g., Neath & Surprenant, 2003). In this study the auditory-visual difference at low output interference re-emerged when ceiling effects were accounted for, but only with spoken output. With written responding the auditory advantage remained significantly larger with high than with low output interference. These new data suggest that both superior auditory encoding and modality-specific output interference contribute to the classic auditory-visual modality effect.

Input constraints handling in an MPC/feedback linearization scheme

The combination of model predictive control based on linear models (MPC) with feedback linearization (FL) has attracted interest for a number of years, giving rise to MPC+FL control schemes. An important advantage of such schemes is that feedback linearizable plants can be controlled with a linear predictive controller with a fixed model. Handling input constraints within such schemes is difficult since simple bound contraints on the input become state dependent because of the nonlinear transformation introduced by feedback linearization. This paper introduces a technique for handling input constraints within a real time MPC/FL scheme, where the plant model employed is a class of dynamic neural networks. The technique is based on a simple affine transformation of the feasible area. A simulated case study is presented to illustrate the use and benefits of the technique.

Design of a minimum variance multiple input-multiple output neuro self-tuning proportional-integral-derivative controller for non-linear dynamic systems

In this study a minimum variance neuro self-tuning proportional-integral-derivative (PID) controller is designed for complex multiple input-multiple output (MIMO) dynamic systems. An approximation model is constructed, which consists of two functional blocks. The first block uses a linear submodel to approximate dominant system dynamics around a selected number of operating points. The second block is used as an error agent, implemented by a neural network, to accommodate the inaccuracy possibly introduced by the linear submodel approximation, various complexities/uncertainties, and complicated coupling effects frequently exhibited in non-linear MIMO dynamic systems. With the proposed model structure, controller design of an MIMO plant with n inputs and n outputs could be, for example, decomposed into n independent single input-single output (SISO) subsystem designs. The effectiveness of the controller design procedure is initially verified through simulations of industrial examples.

ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat.

Acetyl-CoA carboxylase β (ACC2) plays a key role in fatty acid synthesis and oxidation pathways. Disturbance of these pathways is associated with impaired insulin responsiveness and metabolic syndrome (MetS). Gene-nutrient interactions may affect MetS risk. This study determined the relationship between ACC2 polymorphisms (rs2075263, rs2268387, rs2284685, rs2284689, rs2300453, rs3742023, rs3742026, rs4766587, and rs6606697) and MetS risk, and whether dietary fatty acids modulate this in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754). Minor A allele carriers of rs4766587 had increased MetS risk (OR 1.29 [CI 1.08, 1.58], P = 0.0064) compared with the GG homozygotes, which may in part be explained by their increased body mass index (BMI), abdominal obesity, and impaired insulin sensitivity (P < 0.05). MetS risk was modulated by dietary fat intake (P = 0.04 for gene-nutrient interaction), where risk conferred by the A allele was exacerbated among individuals with a high-fat intake (>35% energy) (OR 1.62 [CI 1.05, 2.50], P = 0.027), particularly a high intake (>5.5% energy) of n-6 polyunsaturated fat (PUFA) (OR 1.82 [CI 1.14, 2.94], P = 0.01; P = 0.05 for gene-nutrient interaction). Saturated and monounsaturated fat intake did not modulate MetS risk. Importantly, we replicated some of these findings in an independent cohort. In conclusion, the ACC2 rs4766587 polymorphism influences MetS risk, which was modulated by dietary fat, suggesting novel gene-nutrient interactions.

A nutrient increment method for reducing bias in global biogeochemical models

Assimilation of physical variables into coupled physical/biogeochemical models poses considerable difficulties. One problem is that data assimilation can break relationships between physical and biological variables. As a consequence, biological tracers, especially nutrients, are incorrectly displaced in the vertical, resulting in unrealistic biogeochemical fields. To prevent this, we present the idea of applying an increment to the nutrient field within a data assimilating model to ensure that nutrient-potential density relationships are maintained within a water column during assimilation. After correcting the nutrients, it is assumed that other biological variables rapidly adjust to the corrected nutrient fields. We applied this method to a 17 year run of the 2° NEMO ocean-ice model coupled to the PlankTOM5 ecosystem model. Results were compared with a control with no assimilation, and with a model with physical assimilation but no nutrient increment. In the nutrient incrementing experiment, phosphate distributions were improved both at high latitudes and at the equator. At midlatitudes, assimilation generated unrealistic advective upwelling of nutrients within the boundary currents, which spread into the subtropical gyres resulting in more biased nutrient fields. This result was largely unaffected by the nutrient increment and is probably due to boundary currents being poorly resolved in a 2° model. Changes to nutrient distributions fed through into other biological parameters altering primary production, air-sea CO2 flux, and chlorophyll distributions. These secondary changes were most pronounced in the subtropical gyres and at the equator, which are more nutrient limited than high latitudes.

The full-spectrum correlated-k method for longwave atmospheric radiative transfer using an effective Planck function

The correlated k-distribution (CKD) method is widely used in the radiative transfer schemes of atmospheric models and involves dividing the spectrum into a number of bands and then reordering the gaseous absorption coefficients within each one. The fluxes and heating rates for each band may then be computed by discretizing the reordered spectrum into of order 10 quadrature points per major gas and performing a monochromatic radiation calculation for each point. In this presentation it is shown that for clear-sky longwave calculations, sufficient accuracy for most applications can be achieved without the need for bands: reordering may be performed on the entire longwave spectrum. The resulting full-spectrum correlated k (FSCK) method requires significantly fewer monochromatic calculations than standard CKD to achieve a given accuracy. The concept is first demonstrated by comparing with line-by-line calculations for an atmosphere containing only water vapor, in which it is shown that the accuracy of heating-rate calculations improves approximately in proportion to the square of the number of quadrature points. For more than around 20 points, the root-mean-squared error flattens out at around 0.015 K/day due to the imperfect rank correlation of absorption spectra at different pressures in the profile. The spectral overlap of m different gases is treated by considering an m-dimensional hypercube where each axis corresponds to the reordered spectrum of one of the gases. This hypercube is then divided up into a number of volumes, each approximated by a single quadrature point, such that the total number of quadrature points is slightly fewer than the sum of the number that would be required to treat each of the gases separately. The gaseous absorptions for each quadrature point are optimized such that they minimize a cost function expressing the deviation of the heating rates and fluxes calculated by the FSCK method from line-by-line calculations for a number of training profiles. This approach is validated for atmospheres containing water vapor, carbon dioxide, and ozone, in which it is found that in the troposphere and most of the stratosphere, heating-rate errors of less than 0.2 K/day can be achieved using a total of 23 quadrature points, decreasing to less than 0.1 K/day for 32 quadrature points. It would be relatively straightforward to extend the method to include other gases.

Gene-nutrient interactions with dietary fat modulate the association between genetic variation of the ACSL1 gene and metabolic syndrome

Long-chain acyl CoA synthetase 1 (ACSL1) plays an important role in fatty acid metabolism and triacylglycerol (TAG) synthesis. Disturbance of these pathways may result in dyslipidemia and insulin resistance, hallmarks of the metabolic syndrome (MetS). Dietary fat is a key environmental factor that may interact with genetic determinants of lipid metabolism to affect MetS risk. We investigated the relationship between ACSL1 polymorphisms (rs4862417, rs6552828, rs13120078, rs9997745, and rs12503643) and MetS risk and determined potential interactions with dietary fat in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1,754). GG homozygotes for rs9997745 had increased MetS risk {odds ratio (OR) 1.90 [confidence interval (CI) 1.15, 3.13]; P = 0.01}, displayed elevated fasting glucose (P = 0.001) and insulin concentrations (P = 0.002) and increased insulin resistance (P = 0.03) relative to the A allele carriers. MetS risk was modulated by dietary fat, whereby the risk conferred by GG homozygosity was abolished among individuals consuming either a low-fat (<35% energy) or a high-PUFA diet (>5.5% energy). In conclusion, ACSL1 rs9997745 influences MetS risk, most likely via disturbances in fatty acid metabolism, which was modulated by dietary fat consumption, particularly PUFA intake, suggesting novel gene-nutrient interactions.

Twentieth century secular decrease in the atmospheric potential gradient

Current flowing in the global atmospheric electrical circuit (AEC) substantially decreased during the twentieth century. Fair-weather potential gradient (PG) observations in Scotland and Shetland show a previously unreported annual decline from 1920 to 1980, when the measurements ceased. A 25% reduction in PG occurred in Scotland 1920–50, with the maximum decline during the winter months. This is quantitatively explained by a decrease in cosmic rays (CR) increasing the thunderstorm-electrosphere coupling resistance, reducing the ionospheric potential VI. Independent measurements of VI also suggest a reduction of 27% from 1920–50. The secular decrease will influence fair weather atmospheric electrical parameters, including ion concentrations and aerosol electrification. Between 1920–50, the PG showed a negative correlation with global temperature, despite the positive correlation found recently between surface temperature and VI. The 1980s stabilisation in VI may arise from compensation of the continuing CR-induced decline by increases in global temperature and convective electrification.

The global atmospheric electrical circuit and climate

Evidence is emerging for physical links among clouds, global temperatures, the global atmospheric electrical circuit and cosmic ray ionisation. The global circuit extends throughout the atmosphere from the planetary surface to the lower layers of the ionosphere. Cosmic rays are the principal source of atmospheric ions away from the continental boundary layer: the ions formed permit a vertical conduction current to flow in the fair weather part of the global circuit. Through the (inverse) solar modulation of cosmic rays, the resulting columnar ionisation changes may allow the global circuit to convey a solar influence to meteorological phenomena of the lower atmosphere. Electrical effects on non-thunderstorm clouds have been proposed to occur via the ion-assisted formation of ultra-fine aerosol, which can grow to sizes able to act as cloud condensation nuclei, or through the increased ice nucleation capability of charged aerosols. Even small atmospheric electrical modulations on the aerosol size distribution can affect cloud properties and modify the radiative balance of the atmosphere, through changes communicated globally by the atmospheric electrical circuit. Despite a long history of work in related areas of geophysics, the direct and inverse relationships between the global circuit and global climate remain largely quantitatively unexplored. From reviewing atmospheric electrical measurements made over two centuries and possible paleoclimate proxies, global atmospheric electrical circuit variability should be expected on many timescales