500 MHz H-NMR studies of bile salt-phosphatidylcholine mixed micelles and vesicles Evidence for differential motional restraint on bile salt and phosphatidylcholine resonances

¹H nuclear magnetic resonance (NMR) spectra at 500 MHz have been obtained for taurocholate/egg phosphatidylcholine mixtures of varying composition. The excellent chemical shift dispersion permits identification of most resonances for each component. This high-resolution character of the NMR spectra is retained until the phosphatidylcholine (PC) mole fraction exceeds 60–70% (the exact limit depends on ionic strength). ¹H linewidths have been monitored as a function of solute composition in order to evaluate trends in local molecular mobility of each component as the distribution of aggregate particles is varied, and to examine the effects of added NaCl in altering micellar size and shape. Although prior light scattering studies (Mazer, N.A., Benedek, G.B. and Carey, M.C. (1980) Biochemistry 19, 601–615) and our own work indicate a 6-fold increase in particle hydrodynamic radius from pure taurocholate micelles to 1 : 1 taurocholate/PC mixtures containing 150 mM NaCl, both lipid components retain substantial motional freedom and exhibit narrow NMR signals in this compositional region. As the solubilization limit for PC is approached (approx. 2:1 PC:taurocholate), differential behavior is observed for the two components: the motion of taurocholate becomes preferentially restricted, while polar portions of the PC remain mobile until large multilayers predominate.     

Quantitation of model digestive mixtures by 13C NMR.

13C nuclear magnetic resonance (NMR) spectra were obtained at 50.3 and 100.5 MHz for methanolic and aqueous mixtures of sodium taurocholate, 1-monocapryloyl-rac-glycerol, and caprylic acid. Distortionless Enhancement by Polarization Transfer (DEPT) was used to improve spectral sensitivity and resolution, and to generate calibration curves for quantitative determinations of each lipid in methanol. Alternatively, the heights for nonoverlapping peaks in a 13C NMR spectrum acquired with inverse-gated decoupling provide reliable quantitative estimates for each component of the mixture, particularly when the data are obtained in methanol. These experiments also demonstrate the feasibility of detailed NMR structural investigations in model systems for glyceride digestion.     

Inhibition of Photosynthetic Energy Conversion by Cupric Ion : EVIDENCE FOR Cu-COUPLING FACTOR 1 INTERACTION

This study describes a specific Cu²⁺ and light-dependent inhibition of spinach (Spinacia oleracea L.) chloroplast reactions involving coupling factor 1 function. A primary effect is an inhibition of photophosphorylation induced by illumination of Class II chloroplasts with micromolar Cu²⁺ and pyocyanine in the absence of ADP, Mg²⁺, and HPO₄²⁻. The inhibition, which is dependent on free Cu²⁺ as indicated by protection by ethylene diamine tetraacetic acid and dithiothreitol, requires illumination (electron flow) for establishment of the specific inhibition to be noted. Protection is also afforded by uncouplers and some partial protection is provided by micromolar concentrations of ADP and ATP. The data strongly suggest that Cu²⁺ causes an O₂-independent oxidation of sulfhydryl groups on coupling factor 1, which are essential to catalytic function. This conclusion is supported by the reduction of energy-dependent ³H-N-ethylmaleimide labeling of the γ subunit of coupling factor 1 by the Cu²⁺-light pretreatment.     

Network resonance can be generated independently at distinct levels of neuronal organization

Resonance is defined as maximal response of a system to periodic inputs in a limited frequency band. Resonance may serve to optimize inter-neuronal communication, and has been observed at multiple levels of neuronal organization. However, it is unknown how neuronal resonance observed at the network level is generated and how network resonance depends on the properties of the network building blocks. Here, we first develop a metric for quantifying spike timing resonance in the presence of background noise, extending the notion of spiking resonance for in vivo experiments. Using conductance-based models, we find that network resonance can be inherited from resonances at other levels of organization, or be intrinsically generated by combining mechanisms across distinct levels. Resonance of membrane potential fluctuations, postsynaptic potentials, and single neuron spiking can each be generated independently of resonance at any other level and be propagated to the network level. At all levels of organization, interactions between processes that give rise to low- and high-pass filters generate the observed resonance. Intrinsic network resonance can be generated by the combination of filters belonging to different levels of organization. Inhibition-induced network resonance can emerge by inheritance from resonance of membrane potential fluctuations, and be sharpened by presynaptic high-pass filtering. Our results demonstrate a multiplicity of qualitatively different mechanisms that can generate resonance in neuronal systems, and provide analysis tools and a conceptual framework for the mechanistic investigation of network resonance in terms of circuit components, across levels of neuronal organization.     

A Pilot Randomized Controlled Trial of a Clinic and Home‐Based Behavioral Intervention to Decrease Obesity in Preschoolers

We evaluated the efficacy of a 6‐month clinic and home‐based behavioral intervention (Learning about Activity and Understanding Nutrition for Child Health; LAUNCH) to reduce obesity in preschool children ≥95th BMI percentile compared to enhanced standard of care (Pediatrician Counseling; PC). LAUNCH was a family‐based behavioral intervention that taught parents to use child behavior management strategies to increase healthy eating and activity for their children and themselves. PC presented the same diet and activity recommendations, but was delivered in a one‐time PC session. Eighteen children aged 2–5 years (mean 4.71 ± 1.01) with an average BMI percentile of 98 (±1.60) and an overweight parent were randomized to LAUNCH or PC. Assessments were conducted at baseline, 6 months (end of LAUNCH treatment) and 12 months (6 months following LAUNCH treatment). LAUNCH showed a significantly greater decrease on the primary outcomes of child at month 6 (post‐treatment) BMI z (?0.59 ± 0.17), BMI percentile (?2.4 ± 1.0), and weight gain (?2.7 kg ± 1.2) than PC and this difference was maintained at follow‐up (month 12). LAUNCH parents also had a significantly greater weight loss (?5.5 kg ± 0.9) at month 6 and 12 (?8.0 kg ± 3.5) than PC parents. Based on the data from this small sample, an intensive intervention that includes child behavior management strategies to improve healthy eating and activity appears more promising in reducing preschool obesity than a low intensity intervention that is typical of treatment that could be delivered in primary care.     

Local spatial and temporal processes of influenza in Pennsylvania, USA: 2003-2009

Background

Influenza is a contagious respiratory disease responsible for annual seasonal epidemics in temperate climates. An understanding of how influenza spreads geographically and temporally within regions could result in improved public health prevention programs. The purpose of this study was to summarize the spatial and temporal spread of influenza using data obtained from the Pennsylvania Department of Health''s influenza surveillance system.

Methodology and Findings

We evaluated the spatial and temporal patterns of laboratory-confirmed influenza cases in Pennsylvania, United States from six influenza seasons (2003–2009). Using a test of spatial autocorrelation, local clusters of elevated risk were identified in the South Central region of the state. Multivariable logistic regression indicated that lower monthly precipitation levels during the influenza season (OR = 0.52, 95% CI: 0.28, 0.94), fewer residents over age 64 (OR = 0.27, 95% CI: 0.10, 0.73) and fewer residents with more than a high school education (OR = 0.76, 95% CI: 0.61, 0.95) were significantly associated with membership in this cluster. In addition, time series analysis revealed a temporal lag in the peak timing of the influenza B epidemic compared to the influenza A epidemic.

Conclusions

These findings illustrate a distinct spatial cluster of cases in the South Central region of Pennsylvania. Further examination of the regional transmission dynamics within these clusters may be useful in planning public health influenza prevention programs.