Numerical study of linear and circular model DNA chains confined in a slit: metric and topological properties

Advanced Monte Carlo simulations are used to study the effect of nano-slit confinement on metric and topological properties of model DNA chains. We consider both linear and circularised chains with contour lengths in the 1.2--4.8 $\mu$m range and slits widths spanning continuously the 50--1250nm range. The metric scaling predicted by de Gennes' blob model is shown to hold for both linear and circularised DNA up to the strongest levels of confinement. More notably, the topological properties of the circularised DNA molecules have two major differences compared to three-dimensional confinement. First, the overall knotting probability is non-monotonic for increasing confinement and can be largely enhanced or suppressed compared to the bulk case by simply varying the slit width. Secondly, the knot population consists of knots that are far simpler than for three-dimensional confinement. The results suggest that nano-slits could be used in nano-fluidic setups to produce DNA rings having simple topologies (including the unknot) or to separate heterogeneous ensembles of DNA rings by knot type.Comment: 12 pages, 10 figure

Adult Height in Patients with Advanced CKD Requiring Renal Replacement Therapy during Childhood.

BACKGROUND AND OBJECTIVES: Growth and final height are of major concern in children with ESRD. This study sought to describe the distribution of adult height of patients who started renal replacement therapy (RRT) during childhood and to identify determinants of final height in a large cohort of RRT children. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 1612 patients from 20 European countries who started RRT before 19 years of age and reached final height between 1990 and 2011 were included. Linear regression analyses were performed to calculate adjusted mean final height SD score (SDS) and to investigate its potential determinants. RESULTS: The median final height SDS was -1.65 (median of 168 cm in boys and 155 cm in girls). Fifty-five percent of patients attained an adult height within the normal range. Adjusted for age at start of RRT and primary renal diseases, final height increased significantly over time from -2.06 SDS in children who reached adulthood in 1990-1995 to -1.33 SDS among those reaching adulthood in 2006-2011. Older age at start of RRT, more recent period of start of RRT, cumulative percentage time on a functioning graft, and greater height SDS at initiation of RRT were independently associated with a higher final height SDS. Patients with congenital anomalies of the kidney and urinary tract and metabolic disorders had a lower final height than those with other primary renal diseases. CONCLUSIONS: Although final height remains suboptimal in children with ESRD, it has consistently improved over time

Nature of Cations Critically Affects Water at the Negatively Charged Silica Interface

[Image: see text] Understanding the collective behavior of ions at charged surfaces is of paramount importance for geological and electrochemical processes. Ions screen the surface charge, and interfacial fields break the centro-symmetry near the surface, which can be probed using second-order nonlinear spectroscopies. The effect of electrolyte concentration on the nonlinear optical response has been semi-quantitatively explained by mean-field models based on the Poisson–Boltzmann equation. Yet, to explain previously reported ion-specific effects on the spectroscopic response, drastic ion-specific changes in the interfacial properties, including surface acidities and dielectric permittivities, or strong ion adsorption/desorption had to be invoked. Here, we use sum-frequency generation (SFG) spectroscopy to probe the symmetry-breaking of water molecules at a charged silica surface in contact with alkaline metal chloride solutions (LiCl, NaCl, KCl, and CsCl) at various concentrations. We find that the water response varies with the cation: the SFG response is markedly enhanced for LiCl compared to CsCl. We show that within mean-field models, neither specific ion–surface interactions nor a reduced dielectric constant of water near the interface can account for the variation of spectral intensities with cation nature. Molecular dynamics simulations confirm that the decay of the electrochemical potential only weakly depends on the salt type. Instead, the effect of different salts on the optical response is indirect, through the reorganization of the interfacial water: the salt-type-dependent alignment of water directly at the interface can explain the observations

Energy transfer within the hydrogen bonding network of water following resonant terahertz excitation

Energy dissipation in water is very fast and more efficient than in many other liquids. This behavior is commonly attributed to the intermolecular interactions associated with hydrogen bonding. Here, we investigate the dynamic energy flow in the hydrogen bond network of liquid water by a pump-probe experiment. We resonantly excite intermolecular degrees of freedom with ultrashort single-cycle terahertz pulses and monitor its Raman response. By using ultrathin sample cell windows, a background-free bipolar signal whose tail relaxes monoexponentially is obtained. The relaxation is attributed to the molecular translational motions, using complementary experiments, force field, and ab initio molecular dynamics simulations. They reveal an initial coupling of the terahertz electric field to the molecular rotational degrees of freedom whose energy is rapidly transferred, within the excitation pulse duration, to the restricted translational motion of neighboring molecules. This rapid energy transfer may be rationalized by the strong anharmonicity of the intermolecular interactions

Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies

With a growing number of prospective cohort studies, an updated dose-response meta-analysis of milk and dairy products with all-cause mortality, coronary heart disease (CHD) or cardiovascular disease (CVD) have been conducted. PubMed, Embase and Scopus were searched for articles published up to September 2016. Random-effect meta-analyses with summarised dose-response data were performed for total (high-fat/low-fat) dairy, milk, fermented dairy, cheese and yogurt. Non-linear associations were investigated using the spine models and heterogeneity by subgroup analyses. A total of 29 cohort studies were available for meta-analysis, with 938,465 participants and 93,158 mortality, 28,419 CHD and 25,416 CVD cases. No associations were found for total (high-fat/low-fat) dairy, and milk with the health outcomes of mortality, CHD or CVD. Inverse associations were found between total fermented dairy (included sour milk products, cheese or yogurt; per 20 g/day) with mortality (RR 0.98, 95% CI 0.97-0.99; I2 = 94.4%) and CVD risk (RR 0.98, 95% CI 0.97-0.99; I2 = 87.5%). Further analyses of individual fermented dairy of cheese and yogurt showed cheese to have a 2% lower risk of CVD (RR 0.98, 95% CI 0.95-1.00; I2 = 82.6%) per 10 g/day, but not yogurt. All of these marginally inverse associations of totally fermented dairy and cheese were attenuated in sensitivity analyses by removing one large Swedish study. This meta-analysis combining data from 29 prospective cohort studies demonstrated neutral associations between dairy products and cardiovascular and all-cause mortality. For future studies it is important to investigate in more detail how dairy products can be replaced by other foods

European chronic kidney disease registries for children not on kidney replacement therapy: tools for improving health systems and patient-centred outcomes

Chronic kidney disease (CKD) in children, from birth to late adolescence, is a unique and highly challenging condition that requires epidemiological research and large-scale, prospective cohort studies. Since its first launch in 2007, the European Society for Paediatric Nephrology/European Renal Association (ESPN/ERA) Registry has collected data on patients on kidney replacement therapy (KRT). However, slowing the progression of CKD is of particular importance and thus the possibility to extend the current registry dataset to include patients in CKD stages 4–5 should be a priority. A survey was sent to the national representatives within the ESPN/ERA Registry to collect information on whether they are running CKD registries. All the representatives from the 38 European countries involved in the ESPN/ERA Registry participated in the survey. Eight existing CKD registries have been identified. General characteristics of the national registry and detailed data on anthropometry, laboratory tests and medications at baseline and at follow-up were collected. Results provided by this survey are highly promising regarding the establishment of an ESPN CKD registry linked to the ESPN/ERA KRT registry and subsequently linking it to the ERA Registry with the same patient identifier, which would allow us to monitor disease progression in childhood and beyond. It is our belief that through such linkages, gaps in patient follow-up will be eliminated and patient-centred outcomes may be improved

Unraveling the origin of the apparent charge of zwitterionic lipid layers

The structure of water molecules in contact with zwitterionic lipid molecules is of great biological relevance, because biological membranes are largely composed of such lipids. The interaction of the interfacial water molecules with the amphiphilic lipid molecules drives the formation of membranes and greatly influences various processes at the membrane surface, as the field that arises from the aligned interfacial water molecules masks the charges of the lipid headgroups from the approaching metabolites. To increase our understanding of the influence of water molecules on biological processes we study their structure at the interface using sum-frequency generation spectroscopy and molecular dynamics simulations. Interestingly, we find that water molecules at zwitterionic lipid molecules are mainly oriented by the field arising between the two oppositely charged molecular moieties within the lipid headgroups

Whole body composition analysis by the BodPod air-displacement plethysmography method in children with phenylketonuria shows a higher body fat percentage

BACKGROUND: Phenylketonuria (PKU) causes irreversible central nervous system damage unless a phenylalanine (PHE) restricted diet with amino acid supplementation is maintained. To prevent growth retardation, a protein/amino acid intake beyond the recommended dietary protein allowance is mandatory. However, data regarding disease and/or diet related changes in body composition are inconclusive and retarded growth and/or adiposity is still reported. The BodPod whole body air-displacement plethysmography method is a fast, safe and accurate technique to measure body composition. AIM: To gain more insight into the body composition of children with PKU. METHODS: Patients diagnosed with PKU born between 1991 and 2001 were included. Patients were identified by neonatal screening and treated in our centre. Body composition was measured using the BodPod system (Life Measurement Incorporation©). Blood PHE values determined every 1–3 months in the year preceding BodPod analysis were collected. Patients were matched for gender and age with data of healthy control subjects. Independent samples t tests, Mann–Whitney and linear regression were used for statistical analysis. RESULTS: The mean body fat percentage in patients with PKU (n = 20) was significantly higher compared to healthy controls (n = 20) (25.2% vs 18.4%; p = 0.002), especially in girls above 11 years of age (30.1% vs 21.5%; p = 0.027). Body fat percentage increased with rising body weight in patients with PKU only (R = 0.693, p = 0.001), but did not correlate with mean blood PHE level (R = 0.079, p = 0.740). CONCLUSION: Our data show a higher body fat percentage in patients with PKU, especially in girls above 11 years of age