Crowding effect on helix-coil transition: beyond entropic stabilization

We report circular dichroism measurements on the helix-coil transition of poly(L-glutamic acid) in solution with polyethylene glycol (PEG) as a crowding agent. Using small angle neutron scattering, PEG solutions have been characterized and found to be well described by the picture of a transient network of mesh size $\xi$, usual for semi-diluted chains in good solvent. We show that the increase of PEG concentration stabilizes the helices and increases the transition temperature. But more unexpectedly we also notice that the increase of crowding agent concentration reduces the mean helix extent at the transition, or in other words reduces its cooperative feature. This result cannot be accounted for by an entropic stabilization mechanism. Comparing the mean length of helices at the transition and the mesh size of the PEG network, our results strongly suggest two regimes: helices shorter or longer than the mesh size

Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed N-nitrosation

<b>Background</b>: The major potential site of acid nitrosation is the proximal stomach, an anatomical site prone to a rising incidence of metaplasia and adenocarcinoma. Nitrite, a pre-carcinogen present in saliva, can be converted to nitrosating species and N-nitroso compounds by acidification at low gastric pH in the presence of thiocyanate. <b>Aims</b>: To assess the effect of lipid and ascorbic acid on the nitrosative chemistry under conditions simulating the human proximal stomach. <b>Methods</b>: The nitrosative chemistry was modelled in vitro by measuring the nitrosation of four secondary amines under conditions simulating the proximal stomach. The N-nitrosamines formed were measured by gas chromatography–ion-trap tandem mass spectrometry, while nitric oxide and oxygen levels were measured amperometrically. <b>Results</b>: In absence of lipid, nitrosative stress was inhibited by ascorbic acid through conversion of nitrosating species to nitric oxide. Addition of ascorbic acid reduced the amount of N-nitrosodimethylamine formed by fivefold, N-nitrosomorpholine by .1000-fold, and totally prevented the formation of N-nitrosodiethylamine and N-nitrosopiperidine. In contrast, when 10% lipid was present, ascorbic acid increased the amount of Nnitrosodimethylamine, N-nitrosodiethylamine and N-nitrosopiperidine formed by approximately 8-, 60- and 140-fold, respectively, compared with absence of ascorbic acid. <b>Conclusion</b>: The presence of lipid converts ascorbic acid from inhibiting to promoting acid nitrosation. This may be explained by nitric oxide, formed by ascorbic acid in the aqueous phase, being able to regenerate nitrosating species by reacting with oxygen in the lipid phase

Dark matter annihilation and decay in dwarf spheroidal galaxies: The classical and ultrafaint dSphs

Dwarf spheroidal (dSph) galaxies are prime targets for present and future gamma-ray telescopes hunting for indirect signals of particle dark matter. The interpretation of the data requires careful assessment of their dark matter content in order to derive robust constraints on candidate relic particles. Here, we use an optimised spherical Jeans analysis to reconstruct the `astrophysical factor' for both annihilating and decaying dark matter in 21 known dSphs. Improvements with respect to previous works are: (i) the use of more flexible luminosity and anisotropy profiles to minimise biases, (ii) the use of weak priors tailored on extensive sets of contamination-free mock data to improve the confidence intervals, (iii) systematic cross-checks of binned and unbinned analyses on mock and real data, and (iv) the use of mock data including stellar contamination to test the impact on reconstructed signals. Our analysis provides updated values for the dark matter content of 8 `classical' and 13 `ultrafaint' dSphs, with the quoted uncertainties directly linked to the sample size; the more flexible parametrisation we use results in changes compared to previous calculations. This translates into our ranking of potentially-brightest and most robust targets---viz., Ursa Minor, Draco, Sculptor---, and of the more promising, but uncertain targets---viz., Ursa Major 2, Coma---for annihilating dark matter. Our analysis of Segue 1 is extremely sensitive to whether we include or exclude a few marginal member stars, making this target one of the most uncertain. Our analysis illustrates challenges that will need to be addressed when inferring the dark matter content of new `ultrafaint' satellites that are beginning to be discovered in southern sky surveys.Comment: 19 pages, 14 figures, submitted to MNRAS. Supplementary material available on reques

Dark matter annihilation and decay profiles for the Reticulum II dwarf spheroidal galaxy

The dwarf spheroidal galaxies (dSph) of the Milky Way are among the most attractive targets for indirect searches of dark matter. In this work, we reconstruct the dark matter annihilation (J-factor) and decay profiles for the newly discovered dSph Reticulum II. Using an optimized spherical Jeans analysis of kinematic data obtained from the Michigan/Magellan Fiber System (M2FS), we find Reticulum II's J-factor to be among the largest of any Milky Way dSph. We have checked the robustness of this result against several ingredients of the analysis. Unless it suffers from tidal disruption or significant inflation of its velocity dispersion from binary stars, Reticulum II may provide a unique window on dark matter particle properties.Comment: 5 pages, 4 figures. Match the ApJL accepted versio

New perspectives on bioactivity of olive oil: evidence from animal models, human interventions and the use of urinary proteomic biomarkers

Olive oil (OO) is the primary source of fat in the Mediterranean diet and has been associated with longevity and a lower incidence of chronic diseases, particularly CHD. Cardioprotective effects of OO consumption have been widely related with improved lipoprotein profile, endothelial function and inflammation, linked to health claims of oleic acid and phenolic content of OO. With CVD being a leading cause of death worldwide, a review of the potential mechanisms underpinning the impact of OO in the prevention of disease is warranted. The current body of evidence relies on mechanistic studies involving animal and cell-based models, epidemiological studies of OO intake and risk factor, small- and large-scale human interventions, and the emerging use of novel biomarker techniques associated with disease risk. Although model systems are important for mechanistic research nutrition, methodologies and experimental designs with strong translational value are still lacking. The present review critically appraises the available evidence to date, with particular focus on emerging novel biomarkers for disease risk assessment. New perspectives on OO research are outlined, especially those with scope to clarify key mechanisms by which OO consumption exerts health benefits. The use of urinary proteomic biomarkers, as highly specific disease biomarkers, is highlighted towards a higher translational approach involving OO in nutritional recommendations

Iodine status during pregnancy in India and related neonatal and infant outcomes

Objective: To document iodine status in Indian pregnancies, associations with maternal diet and demographics, and offspring developmental measures. Design: Longitudinal study following mothers through pregnancy and offspring up to 24 months. Setting: Rural health-care centre (Vadu) and urban antenatal clinic (Pune) in the Maharashtra region of India. Subjects: Pregnant mothers at 17 (n 132) and 34 weeks’ (n 151) gestation and their infants from birth to the age of 24 months. Results: Median urinary iodine concentration (UIC) was 203 and 211 μg/l at 17 and 34 weeks of pregnancy, respectively (range 26–800 μg/l). Using the UIC distribution adjusted for within-person variation, extreme UIC quartiles were compared for predictors and outcomes. There was no correlation between UIC at 17 and 34 weeks, but 24 % of those with UIC in the lowest quartile at 17 weeks had UIC in the same lowest quartile at 34 weeks. Maternal educational, socio-economic status and milk products consumption (frequency) were different between the lowest and highest quartile of UIC at 34 weeks. Selected offspring developmental outcomes differed between the lowest and highest UIC quartiles (abdominal circumference at 24 months, subscapular and triceps skinfolds at 12 and 24 months). However, UIC was only a weak predictor of subscapular skinfold at 12 months and of triceps skinfold at 24 months. Conclusions: Median UIC in this pregnant population suggested adequate dietary provision at both gestational stages studied. Occasional high results found in spot samples may indicate intermittent consumption of iodine-rich foods. Maternal UIC had limited influence on offspring developmental outcomes

Klotho, ageing and the failing kidney

Klotho has been recognised as a gene involved in the ageing process in mammals for over thirty years, where it regulates phosphate homeostasis and the activity of members of the fibroblast growth factor (FGF) family. The α -Klotho protein is the receptor for Fibroblast Growth Factor-23 (FGF23), regulating phosphate homeostasis and vitamin D metabolism. Phosphate toxicity is a hallmark of mammalian ageing and correlates with diminution of Klotho levels with increasing age. As such, modulation of Klotho activity is an attractive target for therapeutic intervention in the diseasome of ageing; in particular for chronic kidney disease (CKD), where Klotho has been implicated directly in the pathophysiology. A range of senotherapeutic strategies have been developed to directly or indirectly influence Klotho expression, with varying degrees of success. These include administration of exogenous Klotho, synthetic and natural Klotho agonists and indirect approaches, via modulation of the foodome and the gut microbiota. All these approaches have significant potential to mitigate loss of physiological function and resilience accompanying old age and to improve outcomes within the diseasome of ageing

Dark matter profiles and annihilation in dwarf spheroidal galaxies: prospectives for present and future γ-ray observatories - I. The classical dwarf spheroidal galaxies

Due to their large dynamical mass-to-light ratios, dwarf spheroidal galaxies (dSphs) are promising targets for the indirect detection of dark matter (DM) in γ-rays. We examine their detectability by present and future γ-ray observatories. The key innovative features of our analysis are as follows: (i) we take into account the angular size of the dSphs; while nearby objects have higher γ-ray flux, their larger angular extent can make them less attractive targets for background-dominated instruments; (ii) we derive DM profiles and the astrophysical J-factor (which parametrizes the expected γ-ray flux, independently of the choice of DM particle model) for the classical dSphs directly from photometric and kinematic data. We assume very little about the DM profile, modelling this as a smooth split-power-law distribution, with and without subclumps; (iii) we use a Markov chain Monte Carlo technique to marginalize over unknown parameters and determine the sensitivity of our derived J-factors to both model and measurement uncertainties; and (iv) we use simulated DM profiles to demonstrate that our J-factor determinations recover the correct solution within our quoted uncertainties. Our key findings are as follows: (i) subclumps in the dSphs do not usefully boost the signal; (ii) the sensitivity of atmospheric Cherenkov telescopes to dSphs within ∼20 kpc with cored haloes can be up to ∼50 times worse than when estimated assuming them to be point-like. Even for the satellite-borne Fermi-Large Area Telescope (Fermi-LAT), the sensitivity is significantly degraded on the relevant angular scales for long exposures; hence, it is vital to consider the angular extent of the dSphs when selecting targets; (iii) no DM profile has been ruled out by current data, but using a prior on the inner DM cusp slope 0 ≤γprior≤ 1 provides J-factor estimates accurate to a factor of a few if an appropriate angular scale is chosen; (iv) the J-factor is best constrained at a critical integration angle αc= 2rh/d (where rh is the half-light radius and d is the distance from the dwarf) and we estimate the corresponding sensitivity of γ-ray observatories; (v) the ‘classical' dSphs can be grouped into three categories: well constrained and promising (Ursa Minor, Sculptor and Draco), well constrained but less promising (Carina, Fornax and Leo I), and poorly constrained (Sextans and Leo II); and (vi) observations of classical dSphs with the Fermi-LAT integrated over the mission lifetime are more promising than observations with the planned Cherenkov Telescope Array for DM particle mass ≲ 700 GeV. However, even the Fermi-LAT will not have sufficient integrated signal from the classical dwarfs to detect DM in the ‘vanilla' Minimal Supersymmetric Standard Model. Both the Galactic Centre and the ‘ultrafaint' dwarfs are likely to be better targets and will be considered in future wor

Coincidence measurement of residues and light particles in the reaction 56Fe+p at 1 GeV per nucleon with SPALADIN

The spallation of $^{56}$Fe in collisions with hydrogen at 1 A GeV has been studied in inverse kinematics with the large-aperture setup SPALADIN at GSI. Coincidences of residues with low-center-of-mass kinetic energy light particles and fragments have been measured allowing the decomposition of the total reaction cross-section into the different possible de-excitation channels. Detailed information on the evolution of these de-excitation channels with excitation energy has also been obtained. The comparison of the data with predictions of several de-excitation models coupled to the INCL4 intra-nuclear cascade model shows that only GEMINI can reasonably account for the bulk of collected results, indicating that in a light system with no compression and little angular momentum, multifragmentation might not be necessary to explain the data.Comment: 4 pages, 5 figures, revised version accepted in Phys. Rev. Let