Inhibition of food intake in obese subjects by peptide YY3-36

Background: The gut hormone fragment peptide YY3-36 (PYY) reduces appetite and food intake when infused into subjects of normal weight. In common with the adipocyte hormone leptin, PYY reduces food intake by modulating appetite circuits in the hypothalamus. However, in obesity there is a marked resistance to the action of leptin, which greatly limits its therapeutic effectiveness. We investigated whether obese subjects were also resistant to the anorectic effects of PYY.Methods: We compared the effects of PYY infusion on appetite and food intake in 12 obese and 12 lean subjects in a double-blind, placebo-controlled, crossover study. The plasma levels of PYY, ghrelin, leptin, and insulin were also determined.Results: Caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30 percent in the obese subjects (P<0.001) and 31 percent in the lean subjects (P<0.001). PYY infusion also caused a significant decrease in the cumulative 24-hour caloric intake in both obese and lean subjects. PYY infusion reduced plasma levels of the appetite-stimulatory hormone ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects (the mean [+/-SE] fasting PYY levels were 10.2+/-0.7 pmol per liter in the obese group and 16.9+/-0.8 pmol per liter in the lean group, P<0.001). Furthermore, the fasting PYY levels correlated negatively with the body-mass index (r=-0.84, P<0.001).Conclusions: We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity

The dependence of metal-silicate partitioning of moderately volatile elements on oxygen fugacity and Si contents of Fe metal: Implications for their valence states in silicate liquids

The volatile siderophile elements are important tracers of the delivery of volatile elements to the Earth. Their concentrations in the bulk silicate Earth are a function of the relative timing of their accretion and their sequestration into the core: a comprehensive understanding of their metal-silicate partitioning behaviour is therefore required in order to infer the volatile element accretion history. We present new partitioning data between liquid metal and liquid silicate at 11 GPa for a suite of volatile siderophile elements: Ag, As, Au, Cu, Ge, P, Pb, Sb, Sn. We focus particularly on determining their valence states and the effects of Si on partitioning, which are required in order to extrapolate from experimental conditions to core-formation conditions. It was found that all elements have weak to strong positive interaction parameters with Si. At low fO2, redox equilibria dictate that the siderophile elements should become more siderophile. However, at low fO2, Si also partitions more strongly into the metal. Given the repulsive nature of the interaction between Si and the elements of interest, the increased Si concentration at low fO2 will counteract the expected increase in the partition coefficient, making these elements less siderophile than expected at very reducing conditions. This causes the linear relationship between fO2 and log(D) to become non-linear at low fO2, which we account for by fitting an interaction parameter between Si and the elements of interest. This has implications for the interpretation of experimental results, because the valence cannot be determined from the slope of log(D) vs. logfO2 if low fO2, high Si metal compositions are employed without applying an activity correction. This also has implications for the extrapolation of experimental partitioning data to core-formation conditions: reducing conditions in the early stages of core formation do not necessarily result in complete or even strong depletion of siderophile elements when Si is present as a light element in the core-forming metal phase

Transformation textures in post-perovskite: Understanding mantle flow in the D '' layer of the Earth

Deformation and texture formation in (Mg, Fe)SiO3 post perovskite (ppv) is a potential explanation for the strong seismic anisotropy that is found in the D '' layer of the Earth. However, different experimental approaches have resulted in different lattice preferred orientations (LPO) in deformed ppv that have led to ambiguity in the interpretation of deformation in the lowermost mantle. Here, we show that deformation of the analogue substance CaIrO3 during a phase transformation from perovskite to ppv leads to a transformation texture that differs from the CaIrO3 ppv deformation texture but resembles the results from ppv deformation experiments in diamond anvil cells. Assuming material spreading parallel to the core-mantle boundary, our results predict a widespread shear wave splitting with fast horizontal S-waves, which is compatible with seismic studies. Downwelling material that undergoes a phase transformation may develop a transformation texture that would locally result in vertically polarized fast S-waves. Citation: Walte, N. P., F. Heidelbach, N. Miyajima, D. J. Frost, D. C. Rubie, and D. P. Dobson (2009), Transformation textures in post-perovskite: Understanding mantle flow in the D '' layer of the Earth, Geophys. Res. Lett., 36, L04302, doi: 10.1029/2008GL036840

Weight management: a comparison of existing dietary approaches in a work-site setting

&lt;b&gt;OBJECTIVES:&lt;/b&gt; (1) To compare the effectiveness a 2512 kJ (600 kcal) daily energy deficit diet (ED) with a 6279 kJ (1500 kcal) generalized low-calorie diet (GLC) over a 24 week period (12 weeks weight loss plus 12 weeks weight maintenance). (2) To determine if the inclusion of lean red meat at least five times per week as part of a slimming diet is compatible with weight loss in comparison with a diet that excludes lean red meat. DESIGN: Randomized controlled trial. &lt;b&gt;SETTING:&lt;/b&gt; Large petrochemical work-site. &lt;b&gt;PARTICIPANTS:&lt;/b&gt; One-hundred and twenty-two men aged between 18 and 55 y. &lt;b&gt;MAIN OUTCOME MEASURES:&lt;/b&gt; Weight loss and maintenance of weight loss. &lt;b&gt;INTERVENTION:&lt;/b&gt; Eligible volunteers were randomized to one of the four diet=meat combinations (ED meat, ED no meat, GLC meat, GLC no meat). One-third of subjects in each diet/meat combination were randomized to an initial control period prior to receiving dietary advice. All subjects attended for review every 2 weeks during the weight loss period. For the 12 week structured weight maintenance phase, individualized energy prescriptions were re-calculated for the ED group as 1.4 (activity factor)x basal metabolic rate. Healthy eating advice was reviewed with subjects in the GLC group. All subjects were contacted by electronic mail at 2 week intervals and anthropometric and dietary information requested. &lt;b&gt;RESULTS:&lt;/b&gt; No difference was evident between diet groups in mean weight loss at 12 weeks (4.3 (s.d. 3.4) kg ED group vs 5.0 (s.d. 3.5) kg GLC group, P=0.34). Mean weight loss was closer to the intended weight loss in the 2512 kJ (600 kcal) ED group. The dropout rate was also lower than the GLC group. The inclusion of lean red meat in the diet on at least five occasions per week did not impair weight loss. Mean weight gain following 12 weeks weight maintenance was þ1.1 (s.d. 1.8) kg, P&lt;0.0001. No differences were found between groups. &lt;b&gt;CONCLUSIONS:&lt;/b&gt; This study has shown that the individualized 2512 kJ (600 kcal) ED approach was no more effective in terms of weight loss than the 6279 kJ (1500 kcal) GLC approach. However the ED approach might be considered preferable as compliance was better with this less demanding prescription. In terms of weight loss the elimination of red meat from the diet is unnecessary. The weight maintenance intervention was designed as a low-input approach, however weight regain was significant and weight maintenance strategies require further development

Metal–silicate partitioning of W and Mo and the role of carbon in controlling their abundances in the bulk silicate earth

The liquid metal–liquid silicate partitioning of molybdenum and tungsten during core formation must be well-constrained in order to understand the evolution of Earth and other planetary bodies, in particular because the Hf–W isotopic system is used to date early planetary evolution. The partition coefficients DMo and DW have been suggested to depend on pressure, temperature, silicate and metal compositions, although previous studies have produced varying and inconsistent models. Additionally, the high cationic charges of W and Mo in silicate melts make their partition coefficients particularly sensitive to oxygen fugacity. We combine 48 new high pressure and temperature experimental results with a comprehensive database of previous experiments to re-examine the systematics of Mo and W partitioning, and produce revised partitioning models from the large combined dataset. W partitioning is particularly sensitive to silicate and metallic melt compositions and becomes more siderophile with increasing temperature. We show that W has a 6+ oxidation state in silicate melts over the full experimental fO2 range of ΔIW −1.5 to −3.5. Mo has a 4+ oxidation state, and its partitioning is less sensitive to silicate melt composition but also depends on metallic melt composition. DMo stays approximately constant with increasing depth in Earth. Both W and Mo become more siderophile with increasing C content of the metal: we therefore performed experiments with varying C concentrations and fit epsilon interaction parameters:  = −7.03 ± 0.30 and  = −7.38 ± 0.57. W and Mo along with C are incorporated into a combined N-body accretion and core–mantle differentiation model, which already includes the major rock-forming elements as well as S, and moderately and highly siderophile elements. In this model, oxidation and volatility gradients extend through the protoplanetary disk so that Earth accretes heterogeneously. These gradients, as well as the metal–silicate equilibration pressure, are fitted using a least squares optimisation so that the model Earth-like planet reproduces the composition of the bulk silicate Earth (BSE) in terms of 17 simulated element concentrations (Mg, Fe, Si, Ni, Co, Nb, Ta, V, Cr, S, Pt, Pd, Ru, Ir, W, Mo, and C). The effects of the interaction of W and Mo with Si, S, O, and C in metal are included. Using this model with six separate terrestrial planet accretion simulations, we show that W and Mo require the early accreting Earth to be sulfur-depleted and carbon-enriched so that W and Mo are efficiently partitioned into Earth’s core and do not accumulate in the mantle. When this is the case, the produced Earth-like planets possess mantle compositions matching the BSE for all simulated elements. However, there are two distinct groups of estimates of the bulk mantle’s C abundance in the literature: low (∼100 ppm) and high (∼800 ppm), and all six models are consistent with the higher estimated carbon abundance. The low BSE C abundance would be achievable when the effects of the segregation of dispersed metal droplets produced in deep magma oceans by the disproportionation of Fe2+ to Fe3+ plus metallic Fe is included

Quantitative characterization of plastic deformation of single diamond crystals: A high pressure high temperature (HPHT) experimental deformation study combined with electron backscatter diffraction (EBSD)

We report the results of a high-pressure high-temperature (HPHT) experimental investigation into the deformation of diamonds using the D-DIA apparatus. Electron backscatter diffraction (EBSD) data confirm that well-defined 300–700 nm wide {111} slip lamellae are in fact deformation micro-twins with a 60° rotation around a axis. Such twins formed at high confining pressures even without any apparatus-induced differential stress; mechanical anisotropy within the cell assembly was sufficient for their formation with very little subsequent lattice bending ( slip system dominates as expected for the face-centred cubic (FCC) structure of diamond. Slip occurs on multiple {111} planes resulting in rotation around axes. Deformation microstructure characteristics depend on the orientation of the principal stress axes and finite strain but are independent of confining pressure and nitrogen content. All of the uniaxially deformed samples took on a brown colour, irrespective of their initial nitrogen characteristics. This is in contrast to the two quasi-hydrostatic experiments, which retained their original colour (colourless for nitrogen free diamond, yellow for single substitutional nitrogen, Type Ib diamond) despite the formation of {111} twin lamellae. Comparison of our experimental data with those from two natural brown diamonds from Finsch mine (South Africa) shows the same activation of the dominant slip system. However, no deformation twin lamellae are present in the natural samples. This difference may be due to the lower strain rates experienced by the natural samples investigated. Our study shows the applicability and potential of this type of analysis to the investigation of plastic deformation of diamonds under mantle conditions

Single crystal elasticity of majoritic garnets: Stagnant slabs and thermal anomalies at the base of the transition zone

The elastic properties of two single crystals of majoritic garnet (Mg3.24Al1.53Si3.23O12 and Mg3.01Fe0.17Al1.68Si3.15O12), have been measured using simultaneously single-crystal X-ray diffraction and Brillouin spectroscopy in an externally heated diamond anvil cell with Ne as pressure transmitting medium at conditions up to ∼30 GPa and ∼600 K. This combination of techniques makes it possible to use the bulk modulus and unit-cell volume at each condition to calculate the absolute pressure, independently of secondary pressure calibrants. Substitution of the majorite component into pyrope garnet lowers both the bulk (Ks) and shear modulus (G). The substitution of Fe was found to cause a small but resolvable increase in Ks that was accompanied by a decrease in ∂Ks/∂P, the first pressure derivative of the bulk modulus. Fe substitution had no influence on either the shear modulus or its pressure derivative. The obtained elasticity data were used to derive a thermo-elastic model to describe Vs and Vp of complex garnet solid solutions. Using further elasticity data from the literature and thermodynamic models for mantle phase relations, velocities for mafic, harzburgitic and lherzolitic bulk compositions at the base of Earth's transition zone were calculated. The results show that Vs predicted by seismic reference models are faster than those calculated for all three types of lithologies along a typical mantle adiabat within the bottom 150 km of the transition zone. The anomalously fast seismic shear velocities might be explained if laterally extensive sections of subducted harzburgite-rich slabs pile up at the base of the transition zone and lower average mantle temperatures within this depth range

Single-crystal elasticity of majoritic garnets: stagnant slabs and thermal anomalies at the base of the transition zone

The elastic properties of two single crystals of majoritic garnet (Mg3.24Al1.53Si3.23O12 and Mg3.01Fe0.17Al1.68Si3.15O12), have been measured using simultaneously single-crystal X-ray diffraction and Brillouin spectroscopy in an externally heated diamond anvil cell with Ne as pressure transmitting medium at conditions up to 3c30 GPa and 3c600 K. This combination of techniques makes it possible to use the bulk modulus and unit-cell volume at each condition to calculate the absolute pressure, independently of secondary pressure calibrants. Substitution of the majorite component into pyrope garnet lowers both the bulk (Ks) and shear modulus (G). The substitution of Fe was found to cause a small but resolvable increase in Ks that was accompanied by a decrease in 02Ks/ 02P, the first pressure derivative of the bulk modulus. Fe substitution had no influence on either the shear modulus or its pressure derivative. The obtained elasticity data were used to derive a thermo-elastic model to describe Vs and Vp of complex garnet solid solutions. Using further elasticity data from the literature and thermodynamic models for mantle phase relations, velocities for mafic, harzburgitic and lherzolitic bulk compositions at the base of Earth's transition zone were calculated. The results show that Vs predicted by seismic reference models are faster than those calculated for all three types of lithologies along a typical mantle adiabat within the bottom 150 km of the transition zone. The anomalously fast seismic shear velocities might be explained if laterally extensive sections of subducted harzburgite-rich slabs pile up at the base of the transition zone and lower average mantle temperatures within this depth range

Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis.

BACKGROUND: Many of the established risk factors for breast cancer implicate circulating hormone levels in the aetiology of the disease. Increased levels of postmenopausal endogenous oestradiol (E2) have been found to increase the risk of breast cancer, but no such association has been confirmed in premenopausal women. We carried out a meta-analysis to summarise the available evidence in women before the menopause. METHODS: We identified seven prospective studies of premenopausal endogenous E2 and breast cancer risk, including 693 breast cancer cases. From each study we extracted odds ratios of breast cancer between quantiles of endogenous E2, or for unit or s.d. increases in (log transformed) E2, or (where odds ratios were unavailable) summary statistics for the distributions of E2 in breast cancer cases and unaffected controls. Estimates for a doubling of endogenous E2 were obtained from these extracted estimates, and random-effect meta-analysis was used to obtain a pooled estimate across the studies. RESULTS: Overall, we found weak evidence of a positive association between circulating E2 levels and the risk of breast cancer, with a doubling of E2 associated with an odds ratio of 1.10 (95% CI: 0.96, 1.27). CONCLUSION: Our findings are consistent with the hypothesis of a positive association between premenopausal endogenous E2 and breast cancer risk

Implementation of Web-Based Respondent-Driven Sampling among Men who Have Sex with Men in Vietnam

Objective: Lack of representative data about hidden groups, like men who have sex with men (MSM), hinders an evidence-based response to the HIV epidemics. Respondent-driven sampling (RDS) was developed to overcome sampling challenges in studies of populations like MSM for which sampling frames are absent. Internet-based RDS (webRDS) can potentially circumvent limitations of the original RDS method. We aimed to implement and evaluate webRDS among a hidden population. Methods and Design: This cross-sectional study took place 18 February to 12 April, 2011 among MSM in Vietnam. Inclusion criteria were men, aged 18 and above, who had ever had sex with another man and were living in Vietnam. Participants were invited by an MSM friend, logged in, and answered a survey. Participants could recruit up to four MSM friends. We evaluated the system by its success in generating sustained recruitment and the degree to which the sample compositions stabilized with increasing sample size. Results: Twenty starting participants generated 676 participants over 24 recruitment waves. Analyses did not show evidence of bias due to ineligible participation. Estimated mean age was 22 year and 82% came from the two large metropolitan areas. 32 out of 63 provinces were represented. The median number of sexual partners during the last six months was two. The sample composition stabilized well for 16 out of 17 variables. Conclusion: Results indicate that webRDS could be implemented at a low cost among Internet-using MSM in Vietnam. WebRDS may be a promising method for sampling of Internet-using MSM and other hidden groups. Key words: Respondent-driven sampling, Online sampling, Men who have sex with men, Vietnam, Sexual risk behavio