In human airways diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), host defense is compromised and airways inflammation and infection often result. Mucus clearance and trapping of inhaled pathogens constitute key elements of host defense. Clearance rates are governed by mucus viscous and elastic moduli at physiological driving frequencies, whereas transport of trapped pathogens in mucus layers is governed by diffusivity. There is a clear need for simple and effective clinical biomarkers of airways disease that correlate with these properties. We tested the hypothesis that mucus solids concentration, indexed as weight percent solids (wt%), is such a biomarker. Passive microbead rheology was employed to determine both diffusive and viscoelastic properties of mucus harvested from human bronchial epithelial (HBE) cultures. Guided by sputum from healthy (1.5–2.5 wt%) and diseased (COPD, CF; 5 wt%) subjects, mucus samples were generated in vitro to mimic in vivo physiology, including intermediate range wt% to represent disease progression. Analyses of microbead datasets showed mucus diffusive properties and viscoelastic moduli scale robustly with wt%. Importantly, prominent changes in both biophysical properties arose at ∼4 wt%, consistent with a gel transition (from a more viscous-dominated solution to a more elastic-dominated gel). These findings have significant implications for: (1) penetration of cilia into the mucus layer and effectiveness of mucus transport; and (2) diffusion vs. immobilization of micro-scale particles relevant to mucus barrier properties. These data provide compelling evidence for mucus solids concentration as a baseline clinical biomarker of mucus barrier and clearance functions.
This study compared the flesh quality of farmed and wild sources of British Columbia (BC) salmon with respect to concentrations of polychlorinated biphenyl compounds, polychlorinated dibenzodioxins/dibenzofurans and their associated toxic equivalents, total mercury (THg), methylmercury (MeHg), and selected fatty acids of known importance for human health viz., omega-3 (n-3) highly unsaturated fatty acids (n-3 HUFAs) and (n-6) fatty acids. Skinned fillets from known sources of farmed Atlantic, coho, and chinook salmon (n = 110) and wild coho, chinook, chum, sockeye, and pink salmon (n = 91) were examined. Atlantic salmon contained higher PCB concentrations (means, 28-38 ng/g) than farmed coho or chinook salmon, and levels in these latter species were similar to those in wild counterparts (means, 2.8-13.7 ng/g). PCB levels in Atlantic salmon flesh were, nevertheless, 53-71-fold less than the level of concern for human consumption of fish, i.e., 2000 ng/g as established by Health Canada and the U.S. Food and Drug Administration (US-FDA). Similarly, THg and MeHg levels in all samples were well below the Health Canada guideline (0.5 microg/g) and the US-FDA action level (1.0 microg/g). On average, THg in farmed salmon (0.021 microg/g) was similar to or lower than wild salmon (0.013-0.077 microg/g). Atlantic salmon were a richer source (mean, 2.34 g/100 g fillet) of n-3 HUFAs than the other farmed and wild sources of salmon examined (means, 0.39-1.17 g/100 g). The present findings support the recommended weekly consumption guidelines for oily fish species (includes all BC salmon sources) for cardio-protective benefits as made by the American Heart Association and the UK Food Standards Agency.
SynopsisThis paper is motivated by experiments in which time series of tracer particles in viscoelastic liquids are recorded using advanced microscopy. The experiments seek to infer either viscoelastic properties of the sample ͓Mason and Weitz, Phys. Rev. Lett. 74, 1250-1253 ͑1995͔͒ or diffusive properties of the specific tracer particle in the host medium ͓Suh et al., Adv. Drug Delivery Rev. 57, 63-78 ͑2005͒; Matsui et al., Proc. Natl. Acad. Sci. U.S.A. 103, 18131-18136 ͑2006͒; Lai et al., Proc. Natl. Acad. Sci. U.S.A. 104, 1482-1487 ͑2007͒; Fricks et al., SIAM J. Appl. Math. 69, 1277-1308 ͑2009͔͒. Our focus is the latter. Experimentalists often fit data to transient anomalous diffusion: a sub-diffusive power law scaling ͑t , with 0 Ͻ Ͻ 1͒ of mean-squared displacement ͑MSD͒ over a finite time interval, with longtime viscous scaling ͑t 1 ͒. The time scales of sub-diffusion and exponents are observed to vary with particle size, particle surface chemistry, and viscoelastic properties of the host material. Until now, explicit models for transient subdiffusive MSD scaling behavior ͓Doi and Edwards, The Theory of Polymer Physics ͑Oxford University Press, New York, 1986͒; Kremer and Grest, J. Chem. Phys. 92, 5057-5086 ͑1990͒; Rubinstein and Colby, Polymer Physics ͑Oxford University Press, New York, 2003͔͒ are limited to precisely three exponents: monomer diffusion in Rouse chain melts ͑t 1/2 ͒, in Zimm chain solutions ͑t 2/3 ͒, and in reptating chains ͑t 1/4 ͒. In this paper, we present an explicit parametrized family of stochastic processes ͑generalized Langevin equations with prescribed memory kernels͒ and derive their closed-form solutions which ͑1͒ span the complete range of transient sub-diffusive behavior and ͑2͒ possess the flexibility to tune both the time window of sub-diffusive scaling and the power law exponent . These results establish a robust family of sub-diffusive models, for which the inverse problem of parameter inference from experimental data ͓Fricks et al., SIAM J. Appl. Math. I. DIFFUSION IN A VISCOELASTIC MEDIUM A. The generalized Langevin equationOver the past half-century, the molecular theory of polymer dynamics ͓Rouse ͑1953͒; Zimm ͑1956͒; Kubo ͑1985͒; Kremer and Grest ͑1990͒; Levine and Lubensky ͑2001͔͒ has developed the correspondence between diffusive dynamics and linear viscoelastic relaxation of polymer melts and solutions. Excellent accounts of the sources and scaling properties of diffusive time scales and associated normal modes of stress relaxation are given in the monographs of Doi and Edwards ͑1986͒ and Rubinstein and Colby ͑2003͒. Stochastic models were likewise developed to understand atomic and molecular fluctuation spectra in media where viscous and elastic collisions are comparable ͓Mori ͑1965͒; Zwanzig and Bixon ͑1970͔͒.A standard model for diffusion in a viscoelastic medium is a generalized Langevin equation ͑GLE͒. Following Mori ͑1965͒, Zwanzig and Bixon ͑1970͒, and Mason and Weitz ͑1995͒, the Stokes drag law is generalized by convolution of the velocity with a memory func...
This review examines the nutritional factors that influence the growth and survival of larval bivalves. Factors considered include feed form (live phytoplankton, preserved phytoplankton and artificial feeds) and feed biochemical composition (protein, lipid, carbohydrate and essential fatty acids). These factors, as they relate to larval production, are discussed in terms of growth and survival rates. To facilitate comparisons among larval studies, growth rates and feeding rates are standardized to common units. In addition, the standardized results for larvae of the Pacific oyster (Crassostrea gigas Thunberg) are analysed using linear regression techniques to determine the strength of the correlations between daily doses of biochemical feed components and daily growth rates. Piecewise linear spline modelling is used to determine maximum effective dose response, the point where feeding additional biochemical components to the larvae yields no significant improvements in growth. Derived from these analyses are suggested daily rations of lipid, protein, carbohydrate, eicosapentanoic acid, docosahexanoic acid and energy for larvae of C. gigas.
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