Self-assembly of a model amphiphilic oligopeptide incorporating an arginine headgroup

The self-assembly in aqueous solution of the alanine-rich peptide A12R2 containing twelve alanine residues and two arginine residues has been investigated. This oligomeric peptide was synthesized via NCA-polymerization methods. The surfactant-like peptide is found via FTIR to form antiparallel dimers which aggregate into twisted fibrils, as revealed by cryogenic-transmission electron microscopy. The fibril substructure is probed via detailed X-ray scattering experiments, and are uniquely comprised of twisted tapes only 5 nm wide, set by the width of the antiparallel A12R2 dimers. The packing of the alanine residues leads to distinct “b-sheet” spacings compared to those for amyloid-forming peptides. For this peptide, b-sheet structure coexists with some a-helical content. These ultrafine amyloid fibrils present arginine at high density on their surfaces, and this may lead to applications in nanobiotechnology.

Information-based data selection for ensemble data assimilation

Ensemble-based data assimilation is rapidly proving itself as a computationally-efficient and skilful assimilation method for numerical weather prediction, which can provide a viable alternative to more established variational assimilation techniques. However, a fundamental shortcoming of ensemble techniques is that the resulting analysis increments can only span a limited subspace of the state space, whose dimension is less than the ensemble size. This limits the amount of observational information that can effectively constrain the analysis. In this paper, a data selection strategy that aims to assimilate only the observational components that matter most and that can be used with both stochastic and deterministic ensemble filters is presented. This avoids unnecessary computations, reduces round-off errors and minimizes the risk of importing observation bias in the analysis. When an ensemble-based assimilation technique is used to assimilate high-density observations, the data-selection procedure allows the use of larger localization domains that may lead to a more balanced analysis. Results from the use of this data selection technique with a two-dimensional linear and a nonlinear advection model using both in situ and remote sounding observations are discussed.

Polar cap patch segmentation of the tongue of ionization in the morning convection cell

Two types of poleward moving plasma concentration enhancements (PMPCEs) were observed during a sequence of pulsed reconnection events, both in the morning convection cell: Type L (low density) was associated with a cusp flow channel and seems likely to have been produced by ionization associated with particle precipitation, while Type H (high density) appeared to originate from the segmentation of the tongue of ionization by the processes which produced the Type L events. As a result, the Type L and Type H PMPCEs were interspersed, producing a complex density structure which underlines the importance of cusp flow channels as a mechanism for segmenting and structuring electron density in the cusp and shows the necessity of differentiating between at least two classes of electron density patches.

Fireball models for flares in AE Aquarii

We examine the flaring behaviour of the cataclysmic variable AE Aqr in the context of the `magnetic propeller' model for this system. The flares are thought to arise from collisions between high-density regions in the material expelled from the system after interaction with the rapidly rotating magnetosphere of the white dwarf. We calculate the first quantitative models for the flaring and calculate the time-dependent emergent optical spectra from the resulting hot, expanding ball of gas. We compare the results under different assumptions to observations and derive values for the mass, length-scale and temperature of the material involved in the flare. We see that the fits suggest that the secondary star in this system has Population II composition.

REVIEW: Fireballs, Flares and Flickering

We review our understanding of the prototype ``Propeller'' system AE Aqr and we examine its flaring behaviour in detail. The flares are thought to arise from collisions between high density regions in the material expelled from the system after interaction with the rapidly rotating magnetosphere of the white dwarf. We show calculations of the time-dependent emergent optical spectra from the resulting hot, expanding ball of gas and derive values for the mass, lengthscale and temperature of the material involved. We see that the fits suggest that the secondary star in this system has reduced metal abundances and that, counter-intuitively, the evolution of the fireballs is best modelled as isothermal.

Assessing the benefits of crop albedo bio-geoengineering

It has been proposed that growing crop varieties with higher canopy albedo would lower summer-time temperatures over North America and Eurasia and provide a partial mitigation of global warming ('bio-geoengineering') (Ridgwell et al 2009 Curr. Biol. 19 1–5). Here, we use a coupled ocean–atmosphere–vegetation model (HadCM3) with prescribed agricultural regions, to investigate to what extent the regional effectiveness of crop albedo bio-geoengineering might be influenced by a progressively warming climate as well as assessing the impacts on regional hydrological cycling and primary productivity. Consistent with previous analysis, we find that the averted warming due to increasing crop canopy albedo by 0.04 is regionally and seasonally specific, with the largest cooling of ~1 °C for Europe in summer whereas in the low latitude monsoonal SE Asian regions of high density cropland, the greatest cooling is experienced in winter. In this study we identify potentially important positive impacts of increasing crop canopy albedo on soil moisture and primary productivity in European cropland regions, due to seasonal increases in precipitation. We also find that the background climate state has an important influence on the predicted regional effectiveness of bio-geoengineering on societally-relevant timescales (ca 100 years). The degree of natural climate variability and its dependence on greenhouse forcing that are evident in our simulations highlights the difficulties faced in the detection and verification of climate mitigation in geoengineering schemes. However, despite the small global impact, regionally focused schemes such as crop albedo bio-geoengineering have detection advantages.

Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS)

The first genome-wide association study for BMI identified a polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 (INSIG2) transcription start site, as the most significantly associated variant in children and adults. Subsequent studies, however, showed inconsistent association of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender, maturity and country. Interactions were tested by including the interaction terms in the model. Despite having sufficient power (98%) to detect the previously reported effect size for association with BMI, we did not find significant effects of rs7566605 on BMI (additive, P = 0.68; recessive, P = 0.24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender-specific (P = 0.55), age-group-specific (P = 0.63) or country-specific (P = 0.56) effects. There was also no evidence of interaction between genotype and physical activity (P = 0.95). Despite an adequately powered study, our findings suggest that rs7566605 is not associated with obesity-related traits and lipids in the EYHS.

Association of low adiponectin levels with the metabolic syndrome--the Chennai Urban Rural Epidemiology Study (CURES-4)

The aim of the study was to assess the relation of adiponectin levels with the metabolic syndrome in Asian Indians, a high-risk group for diabetes and premature coronary artery disease. The study was conducted on 100 (50 men and 50 women) type 2 diabetic subjects and 100 age and sex matched subjects with normal glucose tolerance selected from the Chennai Urban Rural Epidemiology Study, an ongoing population study in Chennai in southern India. Metabolic syndrome was defined using modified Adult Treatment Panel III (ATPIII) guidelines. Adiponectin values were significantly lower in diabetic subjects (men: 5.2 vs 8.3 microg/mL, P=.00l; women: 7.6 vs 11.1 microg/mL, P<.00l) and those with the metabolic syndrome (men: 5.0 vs 6.8 microg/mL, P=.01; women: 6.5 vs 9.9 microg/mL, P=.001) compared with those without. Linear regression analysis revealed adiponectin to be associated with body mass index (P<.05), waist circumference (P<.01), fasting plasma glucose (P=.001), glycated hemoglobin (P<.001), triglycerides (P<.00l), high-density lipoprotein (HDL) cholesterol (P<.001), cholesterol/HDL ratio (P<.00l), and insulin resistance measured by homeostasis assessment model (P<.00l). Factor analysis identified 2 factors: factor 1, negatively loaded with adiponectin and HDL cholesterol and positively loaded with triglycerides, waist circumference, and insulin resistance measured by homeostasis assessment model; and factor 2, with a positive loading of waist circumference and systolic and diastolic blood pressure. Logistic regression analysis revealed adiponectin to be negatively associated with metabolic syndrome (odds ratio [OR], 0.365; P<.001) even after adjusting for age (OR, 0.344; P<.00l), sex (OR, 0.293; P<.001), and body mass index (OR, 0.292; P<.00l). Lower adiponectin levels are associated with the metabolic syndrome per se and several of its components, particularly, diabetes, insulin resistance, and dyslipidemia in this urban south Indian population.

Shovel ready? An empirical investigation of stalled residential sites.

Drawing upon a national database of unimplemented planning permissions and 18 in-depth case studies, this paper provides both a quantitative and qualitative analysis of the phenomenon of stalled sites in England. The practical and conceptual difficulties of classifying sites as stalled are critically reviewed. From the literature, it is suggested that planning permission may not be implemented due to lack of financial viability, strategic behaviour by landowners and house-builders and other problems associated with the development process. Consistent with poor viability, the analysis of the national database indicates that a substantial proportion of the stalled sites is high density apartment development and/or is located in low house value areas. The case studies suggest that a combination of interlinked issues may need to be resolved before a planning permission can be implemented. These include; the sale of the land to house-builders, re-negotiation of the planning permission and, most importantly, improvement in housing market conditions.

Interactions between lipid-free apolipoprotein-AI and a lipopeptide incorporating the RGDS cell adhesion motif

The interaction of a designed bioactive lipopeptide C16-GGGRGDS, comprising a hexadecyl lipid chain attached to a functional heptapeptide, with the lipid-free apoliprotein, Apo-AI, is examined. This apolipoprotein is a major component of high density lipoprotein and it is involved in lipid metabolism and may serve as a biomarker for cardiovascular disease and Alzheimers’ disease. We find via isothermal titration calorimetry that binding between the lipopeptide and Apo-AI occurs up to a saturation condition, just above equimolar for a 10.7 μM concentration of Apo-AI. A similar value is obtained from circular dichroism spectroscopy, which probes the reduction in α-helical secondary structure of Apo-AI upon addition of C16-GGGRGDS. Electron microscopy images show a persistence of fibrillar structures due to self-assembly of C16-GGGRGDS in mixtures with Apo-AI above the saturation binding condition. A small fraction of spheroidal or possibly “nanodisc” structures was observed. Small-angle X-ray scattering (SAXS) data for Apo-AI can be fitted using a published crystal structure of the Apo-AI dimer. The SAXS data for the lipopeptide/ Apo-AI mixtures above the saturation binding conditions can be fitted to the contribution from fibrillar structures coexisting with flat discs corresponding to Apo-AI/lipopeptide aggregates.

TNF-α influences the lateral dynamics of TNF receptor I in living cells

In mammalian cells, inflammation is mainly mediated by the binding of tumor necrosis factor alpha to tumor necrosis factor receptor 1. In this study, we investigated lateral dynamics of TNF-R1 before and after ligand binding using high-density single-particle tracking in combination with photoactivated localization microscopy. Our single-molecule data indicates the presence of tumor necrosis factor receptor 1 with different mobilities in the plasma membrane, suggesting different molecular organizations. Cholesterol depletion led to a decrease of slow receptor species and a strong increase in the average diffusion coefficient. Moreover, as a consequence of tumor necrosis factor-alpha treatment, the mean diffusion coefficient moderately increased while its distribution narrowed. Based on our observation, we propose a refined mechanism on the structural arrangement and activation of tumor necrosis factor receptor 1 in the plasma membrane.

Structural stability of the synthetic thermoelectric ternary and nickel-substituted tetrahedrite phases

The purity and structural stability of the high thermoelectric performance Cu12Sb4S13 and Cu10.4Ni1.6Sb4S13 tetrahedrite phases, synthesized by solid–liquid–vapor reaction and Spark Plasma Sintering, were studied at high temperature by Rietveld refinement using high resolution X-ray powder diffraction data, DSC/TG measurements and high resolution transmission electron microscopy. In a complementary study, the crystal structure of Cu10.5Ni1.5Sb4S13 as a function of temperature was investigated by powder neutron diffraction. The temperature dependence of the structural stability of ternary Cu12Sb4S13 is markedly different to that of the nickel-substituted phases, providing clear evidence for the significant and beneficial role of nickel substitution on both sample purity and stability of the tetrahedrite phase. Moreover, kinetic effects on the phase stability/decomposition have been identified and discussed in order to determine the maximum operating temperature for thermoelectric applications. The thermoelectric properties of these compounds have been determined for high density samples (>98%) prepared by Spark Plasma Sintering and therefore can be used as reference values for tetrahedrite samples. The maximum ZT of 0.8 was found for Cu10.4Ni1.6Sb4S13 at 700 K.

Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study

Background: Public health strategies to lower cardiovascular disease (CVD) risk involve reducing dietary saturated fatty acid (SFA) intake to ≤10% of total energy (%TE). However, the optimal type of replacement fat is unclear. Objective: We investigated the substitution of 9.5-9.6%TE dietary SFA with either monounsaturated (MUFA) or n-6 polyunsaturated fatty acids (PUFA) on vascular function and other CVD risk factors. Design: Using a randomized, controlled, single-blind, parallel group dietary intervention, 195 men and women aged 21-60 y with moderate CVD risk (≥50% above the population mean) from the United Kingdom followed one of three 16-wk isoenergetic diets (%TE target compositions, total fat:SFA:MUFA:n-6 PUFA): SFA-rich (36:17:11:4, n = 65), MUFA-rich (36:9:19:4, n = 64) or n-6 PUFA-rich (36:9:13:10, n = 66). The primary outcome measure was flow-mediated dilatation (%FMD); secondary outcome measures included fasting serum lipids, microvascular reactivity, arterial stiffness, ambulatory blood pressure, and markers of insulin resistance, inflammation and endothelial activation. Results: Replacing SFA with MUFA or n-6 PUFA did not significantly impact on %FMD (primary endpoint) or other measures of vascular reactivity. Of the secondary outcome measures, substitution of SFA with MUFA attenuated the increase in night systolic blood pressure (-4.9 mm Hg, P = 0.019) and reduced E-selectin (-7.8%, P = 0.012). Replacement with MUFA or n-6 PUFA lowered fasting serum total cholesterol (TC; -8.4% and -9.2%, respectively), low-density lipoprotein cholesterol (-11.3% and -13.6%) and TC to high-density lipoprotein cholesterol ratio (-5.6% and -8.5%) (P ≤ 0.001). These changes in low-density lipoprotein cholesterol equate to an estimated 17-20% reduction in CVD mortality. Conclusions: Substitution of 9.5-9.6%TE dietary SFA with either MUFA or n-6 PUFA did not impact significantly on %FMD or other measures of vascular function. However, the beneficial effects on serum lipid biomarkers, blood pressure and E-selectin offer a potential public health strategy for CVD risk reduction.

Cannabinoids and tremor induced by motor-related disorders: friend or foe?

Tremor arises from an involuntary, rhythmic muscle contraction/relaxation cycle and is a common disabling symptom of many motor-related diseases such as Parkinson disease, multiple sclerosis, Huntington disease, and forms of ataxia. In the wake of anecdotal, largely uncontrolled, observations claiming the amelioration of some symptoms among cannabis smokers, and the high density of cannabinoid receptors in the areas responsible for motor function, including basal ganglia and cerebellum, many researchers have pursued the question of whether cannabinoid-based compounds could be used therapeutically to alleviate tremor associated with central nervous system diseases. In this review, we focus on possible effects of cannabinoid-based medicines, in particular on Parkinsonian and multiple sclerosis-related tremors and the common probable molecular mechanisms. While, at present, inconclusive results have been obtained, future investigations should extend preclinical studies with different cannabinoids to controlled clinical trials to determine potential benefits in tremor.

Revisiting the ‘Venturi effect’ in passage ventilation between two non-parallel buildings

A recent study conducted by Blocken et al. (Numerical study on the existence of the Venturi effect in passages between perpendicular buildings. Journal of Engineering Mechanics, 2008,134: 1021-1028) challenged the popular view of the existence of the ‘Venturi effect’ in building passages as the wind is exposed to an open boundary. The present research extends the work of Blocken et al. (2008a) into a more general setup with the building orientation varying from 0° to 180° using CFD simulations. Our results reveal that the passage flow is mainly determined by the combination of corner streams. It is also shown that converging passages have a higher wind-blocking effect compared to diverging passages, explained by a lower wind speed and higher drag coefficient. Fluxes on the top plane of the passage volume reverse from outflow to inflow in the cases of α=135°, 150° and 165°. A simple mathematical expression to explain the relationship between the flux ratio and the geometric parameters has been developed to aid wind design in an urban neighborhood. In addition, a converging passage with α=15° is recommended for urban wind design in cold and temperate climates since the passage flow changes smoothly and a relatively lower wind speed is expected compared with that where there are no buildings. While for the high-density urban area in (sub)tropical climates such as Hong Kong where there is a desire for more wind, a diverging passage with α=150° is a better choice to promote ventilation at the pedestrian level.