Non-Brownian diffusion in lipid membranes: Experiments and simulations

Metzler, R.,Jeon, J.H.,Cherstvy, A.G. Elsevier Pub. Co 2016 Biochimica et biophysica acta, Biomembranes Vol.1858 No.10

The dynamics of constituents and the surface response of cellular membranes-also in connection to the binding of various particles and macromolecules to the membrane-are still a matter of controversy in the membrane biophysics community, particularly with respect to crowded membranes of living biological cells. We here put into perspective recent single particle tracking experiments in the plasma membranes of living cells and supercomputing studies of lipid bilayer model membranes with and without protein crowding. Special emphasis is put on the observation of anomalous, non-Brownian diffusion of both lipid molecules and proteins embedded in the lipid bilayer. While single component, pure lipid bilayers in simulations exhibit only transient anomalous diffusion of lipid molecules on nanosecond time scales, the persistence of anomalous diffusion becomes significantly longer ranged on the addition of disorder-through the addition of cholesterol or proteins-and on passing of the membrane lipids to the gel phase. Concurrently, experiments demonstrate the anomalous diffusion of membrane embedded proteins up to macroscopic time scales in the minute time range. Particular emphasis will be put on the physical character of the anomalous diffusion, in particular, the occurrence of ageing observed in the experiments-the effective diffusivity of the measured particles is a decreasing function of time. Moreover, we present results for the time dependent local scaling exponent of the mean squared displacement of the monitored particles. Recent results finding deviations from the commonly assumed Gaussian diffusion patterns in protein crowded membranes are reported. The properties of the displacement autocorrelation function of the lipid molecules are discussed in the light of their appropriate physical anomalous diffusion models, both for non-crowded and crowded membranes. In the last part of this review we address the upcoming field of membrane distortion by elongated membrane-binding particles. We discuss how membrane compartmentalisation and the particle-membrane binding energy may impact the dynamics and response of lipid membranes. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog.

Microflora Management in the Gastrointestinal Tract of Piglets

Metzler, B.,Bauer, E.,Mosenthin, R. Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.9

The stressful physiological and environmental conditions around weaning often promote the proliferation of pathogens in the digestive tract of piglets resulting in diarrhoea and reduced daily weight gain. Typical dietary practices to maintain growth performance and health have led to an increased use of antimicrobial growth promoters. Due to the advanced ban of antibiotics in pig production, new concepts have been developed to secure animal health and growth performance, feed efficiency, and product quality as well. Several naturally occurring compounds seem to beneficially affect the composition and activity of the microflora in the gastrointestinal tract (GIT) of pigs. These are, among others, organic acids, probiotics, prebiotics, and enzymes. Organic acids are already widely used, especially in pigs, due to their positive effects on GIT health and growth performance. Probiotics have been shown to be effective against diarrhoea though effects may be dependent on diet composition and environmental conditions. Prebiotics may influence composition and activity of the intestinal microflora. Additionally, pre- and probiotics may exert positive influences on immune response, whereas enzymes may enhance feed digestibility by breaking down anti-nutritional factors. In the following, the focus will be directed to the role of organic acids, probiotics, prebiotics, and feeding enzymes as potential modulators of GIT health.

A Review of Interactions between Dietary Fiber and the Gastrointestinal Microbiota and Their Consequences on Intestinal Phosphorus Metabolism in Growing Pigs

Metzler, B.U.,Mosenthin, R. Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.4

Dietary fiber is an inevitable component in pig diets. In non-ruminants, it may influence many physiological processes in the gastrointestinal tract (GIT) such as transit time as well as nutrient digestion and absorption. Moreover, dietary fiber is also the main substrate of intestinal bacteria. The bacterial community structure is largely susceptible to changes in the fiber content of a pig's diet. Indeed, bacterial composition in the lower GIT will adapt to the supply of high levels of dietary fiber by increased growth of bacteria with cellulolytic, pectinolytic and hemicellulolytic activities such as Ruminococcus spp., Bacteroides spp. and Clostridium spp. Furthermore, there is growing evidence for growth promotion of beneficial bacteria, such as lactobacilli and bifidobacteria, by certain types of dietary fiber in the small intestine of pigs. Studies in rats have shown that both phosphorus (P) and calcium (Ca) play an important role in the fermentative activity and growth of the intestinal microbiota. This can be attributed to the significance of P for the bacterial cell metabolism and to the buffering functions of Ca-phosphate in intestinal digesta. Moreover, under P deficient conditions, ruminal NDF degradation as well as VFA and bacterial ATP production are reduced. Similar studies in pigs are scarce but there is some evidence that dietary fiber may influence the ileal and fecal P digestibility as well as P disappearance in the large intestine, probably due to microbial P requirement for fermentation. On the other hand, fermentation of dietary fiber may improve the availability of minerals such as P and Ca which can be subsequently absorbed and/or utilized by the microbiota of the pig's large intestine.

Anomalous diffusion models and their properties: non-stationarity, non-ergodicity, and ageing at the centenary of single particle tracking

Metzler, Ralf,Jeon, Jae-Hyung,Cherstvy, Andrey G.,Barkai, Eli The Royal Society of Chemistry 2014 Physical chemistry chemical physics Vol.16 No.44

<P>Modern microscopic techniques following the stochastic motion of labelled tracer particles have uncovered significant deviations from the laws of Brownian motion in a variety of animate and inanimate systems. Such anomalous diffusion can have different physical origins, which can be identified from careful data analysis. In particular, single particle tracking provides the entire trajectory of the traced particle, which allows one to evaluate different observables to quantify the dynamics of the system under observation. We here provide an extensive overview over different popular anomalous diffusion models and their properties. We pay special attention to their ergodic properties, highlighting the fact that in several of these models the long time averaged mean squared displacement shows a distinct disparity to the regular, ensemble averaged mean squared displacement. In these cases, data obtained from time averages cannot be interpreted by the standard theoretical results for the ensemble averages. Here we therefore provide a comparison of the main properties of the time averaged mean squared displacement and its statistical behaviour in terms of the scatter of the amplitudes between the time averages obtained from different trajectories. We especially demonstrate how anomalous dynamics may be identified for systems, which, on first sight, appear to be Brownian. Moreover, we discuss the ergodicity breaking parameters for the different anomalous stochastic processes and showcase the physical origins for the various behaviours. This Perspective is intended as a guidebook for both experimentalists and theorists working on systems, which exhibit anomalous diffusion.</P> <P>Graphic Abstract</P><P>This Perspective summarises the properties of a variety of anomalous diffusion processes and provides the necessary tools to analyse and interpret recorded anomalous diffusion data. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cp03465a'> </P>

The Effects of Cellulose, Pectin and Starch on Standardized Ileal and Apparent Total Tract Amino Acid Digestibilities and Bacterial Contribution of Amino Acids in Feces of Growing Pigs

Ma, Q.G.,Metzler, B.U.,Eklund, M.,Ji, C.,Mosenthin, R. Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.6

Eight ileally cannulated pigs (BW $35.9{\pm}0.9kg$) were randomly allotted according to a $4{\times}3$ Latin square design to determine the effects of cellulose, pectin and starch on standardized ileal digestibility (SID) and apparent total tract digestibility (ATTD) of crude protein (CP) and amino acids (AA) as well as on the bacterial AA contribution in feces. The pigs were fed the control diet (20.2% CP, % dry matter (DM)) or one of the three experimental diets in which 25% of the control diet was substituted by cellulose, starch or pectin. Due to this substitution, dietary CP levels were lower in the cellulose (15.5% CP, % DM), pectin (15.4% CP, % DM) and starch diet (15.2% CP, % DM). Following a 15-d adaptation period, feces were collected for 5 d and ileal digesta for a total of 24 h. Starch increased SID of CP, while cellulose and pectin had no significant effect on the digestibility of CP. Overall, starch supplementation resulted in higher (p<0.05) SID values of histidine, isoleucine, threonine, alanine, aspartic acid, cysteine, glycine and serine compared with cellulose, while pectin decreased (p<0.05) SID of valine and proline compared with the starch and control diet. Both cellulose and pectin reduced (p<0.05) the ATTD of CP and AA, while starch decreased (p<0.05) ATTD of phenylalanine, alanine, proline and serine compared with the control. With regard to bacterial AA composition of the fecal mixed bacterial mass (MBM), cellulose supplementation increased (p<0.05) its content of N and almost all AA, except for valine, while pectin caused higher contents of arginine, histidine and proline compared with the control (p<0.05). The bacterial contribution of arginine in feces was higher (p<0.05) in the cellulose treatment, while pectin reduced (p<0.05) the bacterial contribution of leucine, alanine, glutamic acid and proline in feces compared with the control. In conclusion, the effects of cellulose, starch and pectin on SID were rather small. Bacterial activity in the large intestine can only explain the reduced ATTD values for arginine in the cellulose treatment, but not for the other AA in the cellulose and pectin treatments, suggesting higher endogenous losses of these AA in the large intestine.

An old problem with a new solution: Cost-effective, easy correction of rhinophyma using a disposable razor

Evi M. Morandi,Ralph Verstappen,Julia Metzler,Peter Kronberger,Gerhard Pierer,Gabriel Djedovic 대한성형외과학회 2018 Archives of Plastic Surgery Vol.45 No.5

Geometry controlled anomalous diffusion in random fractal geometries: looking beyond the infinite cluster

Mardoukhi, Yousof,Jeon, Jae-Hyung,Metzler, Ralf The Royal Society of Chemistry 2015 Physical chemistry chemical physics Vol.17 No.44

<P>We investigate the ergodic properties of a random walker performing (anomalous) diffusion on a random fractal geometry. Extensive Monte Carlo simulations of the motion of tracer particles on an ensemble of realisations of percolation clusters are performed for a wide range of percolation densities. Single trajectories of the tracer motion are analysed to quantify the time averaged mean squared displacement (MSD) and to compare this with the ensemble averaged MSD of the particle motion. Other complementary physical observables associated with ergodicity are studied, as well. It turns out that the time averaged MSD of individual realisations exhibits non-vanishing fluctuations even in the limit of very long observation times as the percolation density approaches the critical value. This apparent non-ergodic behaviour concurs with the ergodic behaviour on the ensemble averaged level. We demonstrate how the non-vanishing fluctuations in single particle trajectories are analytically expressed in terms of the fractal dimension and the cluster size distribution of the random geometry, thus being of purely geometrical origin. Moreover, we reveal that the convergence scaling law to ergodicity, which is known to be inversely proportional to the observation time <I>T</I> for ergodic diffusion processes, follows a power-law ∼<I>T</I><SUP>−<I>h</I></SUP> with <I>h</I> < 1 due to the fractal structure of the accessible space. These results provide useful measures for differentiating the subdiffusion on random fractals from an otherwise closely related process, namely, fractional Brownian motion. Implications of our results on the analysis of single particle tracking experiments are provided.</P> <P>Graphic Abstract</P><P>We study the strongly non-ergodic effects of a random walk on a percolation geometry below, at, and above the percolation threshold. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c5cp03548a'> </P>

An old problem with a new solution: Cost-effective, easy correction of rhinophyma using a disposable razor

Morandi, Evi M.,Verstappen, Ralph,Metzler, Julia,Kronberger, Peter,Pierer, Gerhard,Djedovic, Gabriel Korean Society of Plastic and Reconstructive Surge 2018 Archives of Plastic Surgery Vol.45 No.5

Fluctuations of random walks in critical random environments

Mardoukhi, Yousof,Jeon, Jae-Hyung,Chechkin, Aleksei V.,Metzler, Ralf The Royal Society of Chemistry 2018 Physical chemistry chemical physics Vol.20 No.31

<P>Percolation networks have been widely used in the description of porous media but are now found to be relevant to understand the motion of particles in cellular membranes or the nucleus of biological cells. Random walks on the infinite cluster at criticality of a percolation network are asymptotically ergodic. On any finite size cluster of the network stationarity is reached at finite times, depending on the cluster's size. Despite of this we here demonstrate by combination of analytical calculations and simulations that at criticality the disorder and cluster size average of the ensemble of clusters leads to a non-vanishing variance of the time averaged mean squared displacement, regardless of the measurement time. Fluctuations of this relevant experimental quantity due to the disorder average of such ensembles are thus persistent and non-negligible. The relevance of our results for single particle tracking analysis in complex and biological systems is discussed.</P>

Available phosphorus levels modulate gene expression related to intestinal calcium and phosphorus absorption and bone parameters differently in gilts and barrows

Vötterl Julia Christiane,Klinsoda Jutamat,Koger Simone,Hennig-Pauka Isabel,Verhovsek Doris,Metzler-Zebeli Barbara U. 아세아·태평양축산학회 2023 Animal Bioscience Vol.36 No.5

Objective: Dietary phytase increases bioavailability of phytate-bound phosphorus (P) in pig nutrition affecting dietary calcium (Ca) to P ratio, intestinal uptake, and systemic utilization of both minerals, which may contribute to improper bone mineralization. We used phytase to assess long-term effects of two dietary available P (aP) levels using a one-phase feeding system on gene expression related to Ca and P homeostasis along the intestinal tract and in the kidney, short-chain fatty acids in stomach, cecum, and colon, serum, and bone parameters in growing gilts and barrows. Methods: Growing pigs (37.9±6.2 kg) had either free access to a diet without (Con; 75 gilts and 69 barrows) or with phytase (650 phytase units; n = 72/diet) for 56 days. Samples of blood, duodenal, jejunal, ileal, cecal, and colonic mucosa and digesta, kidney, and metacarpal bones were collected from 24 pigs (6 gilts and 6 barrows per diet). Results: Phytase decreased daily feed intake and average daily gain, whereas aP intake increased with phytase versus Con diet (p<0.05). Gilts had higher colonic expression of TRPV5, CDH1, CLDN4, ZO1, and OCLN and renal expression of TRPV5 and SLC34A3 compared to barrows (p<0.05). Phytase increased duodenal expression of TRPV5, TRPV6, CALB1, PMCA1b, CDH1, CLDN4, ZO1, and OCLN compared to Con diet (p<0.05). Furthermore, phytase increased expression of SCL34A2 in cecum and of FGF23 and CLDN4 in colon compared to Con diet (p<0.05). Alongside, phytase decreased gastric propionate, cecal valerate, and colonic caproate versus Con diet (p<0.05). Phytase reduced cortical wall thickness and index of metacarpal bones (p<0.05). Conclusion: Gene expression results suggested an intestinal adaptation to increased dietary aP amount by increasing duodenal trans- and paracellular Ca absorption to balance the systemically available Ca and P levels, whereas no adaption of relevant gene expression in kidney occurred. Greater average daily gain in barrows related to higher feed intake.