Mechanisms underlying the association between breastfeeding and obesity

Decades of epidemiological research have established that breastfeeding is associated with a modest reduction in risk of later overweight and obesity. However, no systematic effort has been made to delineate the mechanisms that may explain this association. This review summarizes evidence from a variety of disciplines to understand the potential mechanisms underlying this association. One possibility is that this association is spurious and that confounding factors fully or partially explain this association. Additionally, breastfeeding could confer protection by: encouraging the infant\u27s emerging capabilities of self-regulation of intake; reducing problematic feeding behaviors on the part of caregivers that interfere with the infant\u27s self-regulation of intake; and providing bioactive factors that regulate energy intake, energy expenditure, and cellular chemistry. These three protective effects may promote slower growth and lower body fat levels in breastfed infants, which reduce risk of overweight and obesity later in life

Thermodynamics of CuPt nanoalloys.

The control of structural and chemical transitions in bimetallic nanoalloys at finite temperatures is one of the challenges for their use in advanced applications. Comparing Nested Sampling and Molecular Dynamics simulations, we investigate the phase changes of CuPt nanoalloys with the aim to elucidate the role of kinetic effects during their solidification and melting processes. We find that the quasi-thermodynamic limit for the nucleation of (CuPt)309 is 965 ± 10 K, but its prediction is increasingly underestimated when the system is cooled faster than 109 K/s. The solidified nanoparticles, classified following a novel tool based on Steinhardt parameters and the relative orientation of characteristic atomic environments, are then heated back to their liquid phase. We demonstrate the kinetic origin of the hysteresis in the caloric curve as (i) it closes for rates slower than 108 K/s, with a phase change temperature of 970 K ± 25 K, in very good agreement with its quasi-thermodynamic limit; (ii) the process happens simultaneously in the inner and outer layers; (iii) an onion-shell chemical order - Cu-rich surface, Pt-rich sub-surface, and mixed core - is always preserved

Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds

Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin containing four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve potential therapeutic use of the toxin, we have designed a double substituted analog, [N17A/F32T]-AnTx, which showed comparable Kv1.3 affinity to the wild-type peptide, but also a 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chemical synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace, by chemical synthesis, all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly, the key pharmacological properties of the Sec-[N17A/F32T]-AnTx are retained since the peptide is functionally active. We also propose here a combined experimental and theoretical approach including NOE- and Se-77-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-[N17A/F32T]-AnTx. Using this combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed characterization of the conformational dynamics around each disulfide/diselenide bridge

Historical fog climate dataset for Carpathian Basin from 1886 to 1919

This paper presents the historical fog climate dataset from 1886 to 1919 for Hungary and its neighbouring countries in the Carpathian Basin. The dataset was obtained from the yearbooks of the Royal Hungarian Central Institute of Meteorology and Earth Magnetism (RHCIMEM) established in 1870 to investigate the climatic features of Hungary during the time of the Austro-Hungarian Monarchy. Monthly observations were recorded from 1871 and daily observations were recorded from 1886. The yearbooks contain daily meteorological records of temperature, relative humidity, rainfall, pressure, wind speed and direction, cloudiness and surface weather conditions along with monthly summaries for 24 meteorological stations. The daily weather observations were recorded three times a day, namely at 07:00, 14:00 and 21:00 local time. Station information (location, environment, instrumentation, observations etc.) can also be found in the yearbooks as metadata. For example, the definition of fog in the case of historical observations is the same as that of today, i.e., fog is detected if the maximum horizontal visibility is less than 1 km. In this way fog observations are easily comparable to today's observations without requiring further data correction and homogenisation. The longest 13 continuously recorded fog observation datasets have the length between 15 and 34 years. The stations are located in 5 countries of the Carpathian Basin at present. These datastests are suitable for conducting historical climatic investigations and can also serve as reference datasets. The historical dataset can be used to study the annual and seasonal changes in frequency and duration of fog events in the Carpathian Basin as a reference, thus facilitating research in the field of fog climatology and forecast

IP3 receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer

Contact sites of endoplasmic reticulum (ER) and mitochondria locally convey calcium signals between the IP3 receptors (IP3R) and the mitochondrial calcium uniporter, and are central to cell survival. It remains unclear whether IP3Rs also have a structural role in contact formation and whether the different IP3R isoforms have redundant functions. Using an IP3R-deficient cell model rescued with each of the three IP3R isoforms and an array of super-resolution and ultrastructural approaches we demonstrate that IP3Rs are required for maintaining ER-mitochondrial contacts. This role is independent of calcium fluxes. We also show that, while each isoform can support contacts, type 2 IP3R is the most effective in delivering calcium to the mitochondria. Thus, these studies reveal a non-canonical, structural role for the IP3Rs and direct attention towards the type 2 IP3R that was previously neglected in the context of ER-mitochondrial calcium signaling

Study of the first paramagnetic to ferromagnetic transition in as prepared samples of Mn-Fe-P-Si magnetocaloric compounds prepared by different synthesis routes

International audienceMagnetocaloric materials with composition of Mn 1.3 Fe 0.65 P 0.5 Si 0.5 have been prepared by ball milling and solid-state reaction methods and consolidated using powder annealing, and conventional and spark plasma sintering. Magnetic and calorimetric measurements show remarkable differences upon first cooling, and slight differences on second and further coolings between the samples prepared by different synthesis routes. Further measurements using Hall probe imaging in high magnetic field have been also carried out. As-prepared samples have been cooled down just above the critical temperature, and the first phase transition has been induced by application of a magnetic field. Bulk samples show staircase isothermal magnetization curves whereas powders show smoother transition curves

Opportunities for the Primary Prevention of Obesity during Infancy

Are chubby babies healthy babies? Whereas most seem well during infancy, evidence is increasing that heavier babies have a poorer long-term health trajectory than their trimmer counterparts. Data have emerged over the past 2 decades that early life growth patterns and behaviors play an important role in the etiology of obesity, yet there has been very little focus on the primary prevention of obesity during infancy by the medical, behavioral health, and public health communities. A recent report from the National Health and Nutrition Examination Survey (NHANES) highlighted the need for very early intervention when it revealed that between 2003 and 2006, a staggering 24.4% of children aged 2 to 5 years already were overweight or obese (body mass index [BMI; calculated as the weight in kilograms divided by height in meters squared] 85th–94th and ≥95th percentiles, respectively) [1]. NHANES data also have described obesity (weight-for-length/height ≥95th percentile) among infants younger than 2 years ( Fig. 1). Between the late 1970s and 2000, the prevalence of obesity among infants 6 to 23 months old increased by more than 60% [2]. Reports from the Centers for Disease Control and Prevention (CDC) Pediatric Nutrition Surveillance System [3] and a Massachusetts Health Maintenance Organization [4] similarly showed significant increases in the prevalence of overweight for infants and toddlers for all age groups since the 1980

Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds

Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin containing four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve potential therapeutic use of the toxin, we have designed a double substituted analog, N17A/F32T-AnTx{,} which showed comparable Kv1.3 affinity to the wild-type peptide{,} but also a 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chemical synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace{,} by chemical synthesis{,} all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly{,} the key pharmacological properties of the Sec-N17A/F32T-AnTx are retained since the peptide is functionally active. We also propose here a combined experimental and theoretical approach including NOE- and 77Se-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-N17A/F32T-AnTx. Using this combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed characterization of the conformational dynamics around each disulfide/diselenide bridge

An engineered scorpion toxin analogue with improved Kv1.3 selectivity displays reduced conformational flexibility

The voltage-gated Kv1.3 K(+) channel plays a key role in the activation of T lymphocytes. Kv1.3 blockers selectively suppress immune responses mediated by effector memory T cells, which indicates the great potential of selective Kv1.3 inhibitors in the therapy of certain autoimmune diseases. Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin is a high affinity blocker of Kv1.3, but also blocks Kv1.2 with similar potency. We designed and produced three AnTx variants: ([F32T]-AnTx, [N17A]-AnTx, [N17A/F32T]-AnTx) using solid-phase synthesis with the goal of improving the selectivity of the toxin for Kv1.3 over Kv1.2 while keeping the high affinity for Kv1.3. We used the patch-clamp technique to determine the blocking potency of the synthetic toxins on hKv1.3, mKv1.1, hKv1.2 and hKCa3.1 channels. Of the three variants [N17A/F32T]-AnTx maintained the high affinity of the natural peptide for Kv1.3 but became more than 16000-fold selective over Kv1.2. NMR data and molecular dynamics simulations suggest that the more rigid structure with restricted conformational space of the double substituted toxin compared to the flexible wild-type one is an important determinant of toxin selectivity. Our results provide the foundation for the possibility of the production and future therapeutic application of additional, even more selective toxins targeting various ion channels