Resolving intertracer inconsistencies in soil ingestion estimation.

In this article we explore sources and magnitude of positive and negative error in soil ingestion estimates for children on a subject-week and trace element basis. Errors varied among trace elements. Yttrium and zirconium displayed predominantly negative error; titanium and vanadium usually displayed positive error. These factors lead to underestimation of soil ingestion estimates by yttrium and zirconium and a large overestimation by vanadium. The most reliable tracers for soil ingestion estimates were aluminum, silicon, and yttrium. However, the most reliable trace element for a specific subject-day (or week) would be the element with the least error during that time period. The present analysis replaces our previous recommendations that zirconium and titanium are the most reliable trace elements in estimating soil ingestion by children. This report identifies limitations in applying the biostatistical model based on data for adults to data for children. The adult-based model used data less susceptible to negative bias and more susceptible to source error (positive bias) for titanium and vanadium than the data for children. These factors contributed significantly to inconsistencies in model predictions of soil ingestion rates for children. Correction for error at the subject-day level provides a foundation for generation of subject-specific daily soil ingestion distributions and for linking behavior to soil ingestion

Longitudinal evaluation, acceptability and long-term retention of knowledge on a horizontally integrated organic and functional systems course

Undergraduate medical education is moving from traditional disciplinary basic science courses into more integrated curricula. Integration models based on organ systems originated in the 1950s, but few longitudinal studies have evaluated their effectiveness. This article outlines the development and implementation of the Organic and Functional Systems (OFS) courses at the University of Minho in Portugal, using evidence collected over 10 years. It describes the organization of content, student academic performance and acceptability of the courses, the evaluation of preparedness for future courses and the retention of knowledge on basic sciences. Students consistently rated the OFS courses highly. Physician tutors in subsequent clinical attachments considered that students were appropriately prepared. Performance in the International Foundations of Medicine examination of a self-selected sample of students revealed similar performances in basic science items after the last OFS course and 4 years later, at the moment of graduation. In conclusion, the organizational and pedagogical approaches of the OFS courses achieve high acceptability by students and result in positive outcomes in terms of preparedness for subsequent training and long-term retention of basic science knowledge

Minute ventilation of cyclists, car and bus passengers: an experimental study

<p>Abstract</p> <p>Background</p> <p>Differences in minute ventilation between cyclists, pedestrians and other commuters influence inhaled doses of air pollution. This study estimates minute ventilation of cyclists, car and bus passengers, as part of a study on health effects of commuters' exposure to air pollutants.</p> <p>Methods</p> <p>Thirty-four participants performed a submaximal test on a bicycle ergometer, during which heart rate and minute ventilation were measured simultaneously at increasing cycling intensity. Individual regression equations were calculated between heart rate and the natural log of minute ventilation. Heart rates were recorded during 280 two hour trips by bicycle, bus and car and were calculated into minute ventilation levels using the individual regression coefficients.</p> <p>Results</p> <p>Minute ventilation during bicycle rides were on average 2.1 times higher than in the car (individual range from 1.3 to 5.3) and 2.0 times higher than in the bus (individual range from 1.3 to 5.1). The ratio of minute ventilation of cycling compared to travelling by bus or car was higher in women than in men. Substantial differences in regression equations were found between individuals. The use of individual regression equations instead of average regression equations resulted in substantially better predictions of individual minute ventilations.</p> <p>Conclusion</p> <p>The comparability of the gender-specific overall regression equations linking heart rate and minute ventilation with one previous American study, supports that for studies on the group level overall equations can be used. For estimating individual doses, the use of individual regression coefficients provides more precise data. Minute ventilation levels of cyclists are on average two times higher than of bus and car passengers, consistent with the ratio found in one small previous study of young adults. The study illustrates the importance of inclusion of minute ventilation data in comparing air pollution doses between different modes of transport.</p

Photoreceptor spectral sensitivities of the Small White butterfly Pieris rapae crucivora interpreted with optical modeling

The compound eye of the Small White butterfly, Pieris rapae crucivora, has four classes of visual pigments, with peak absorption in the ultraviolet, violet, blue and green, but electrophysiological recordings yielded eight photoreceptors classes: an ultraviolet, violet, blue, double-peaked blue, green, blue-suppressed-green, pale-red and deep-red class. These photoreceptor classes were identified in three types of ommatidia, distinguishable by the different eye shine spectra and fluorescence; the latter only being present in the eyes of males. We present here two slightly different optical models that incorporate the various visual pigments, the light-filtering actions of the fluorescent, pale-red and deep-red screening pigment, located inside or adjacent to the rhabdom, and the reflectance spectrum of the tapetum that abuts the rhabdom proximally. The models serve to explain the photoreceptor spectral sensitivities as well as the eye shine

Adult Circadian Behavior in Drosophila Requires Developmental Expression of cycle, But Not period

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex

Wolbachia infections that reduce immature insect survival: Predicted impacts on population replacement

<p>Abstract</p> <p>Background</p> <p>The evolutionary success of <it>Wolbachia </it>bacteria, infections of which are widespread in invertebrates, is largely attributed to an ability to manipulate host reproduction without imposing substantial fitness costs. Here, we describe a stage-structured model with deterministic immature lifestages and a stochastic adult female lifestage. Simulations were conducted to better understand <it>Wolbachia </it>invasions into uninfected host populations. The model includes conventional <it>Wolbachia </it>parameters (the level of cytoplasmic incompatibility, maternal inheritance, the relative fecundity of infected females, and the initial <it>Wolbachia </it>infection frequency) and a new parameter termed relative larval viability (<it>RLV</it>), which is the survival of infected larvae relative to uninfected larvae.</p> <p>Results</p> <p>The results predict the <it>RLV </it>parameter to be the most important determinant for <it>Wolbachia </it>invasion and establishment. Specifically, the fitness of infected immature hosts must be close to equal to that of uninfected hosts before population replacement can occur. Furthermore, minute decreases in <it>RLV </it>inhibit the invasion of <it>Wolbachia </it>despite high levels of cytoplasmic incompatibility, maternal inheritance, and low adult fitness costs.</p> <p>Conclusions</p> <p>The model described here takes a novel approach to understanding the spread of <it>Wolbachia </it>through a population with explicit dynamics. By combining a stochastic female adult lifestage and deterministic immature/adult male lifestages, the model predicts that even those <it>Wolbachia </it>infections that cause minor decreases in immature survival are unlikely to invade and spread within the host population. The results are discussed in relation to recent theoretical and empirical studies of natural population replacement events and proposed applied research, which would use <it>Wolbachia </it>as a tool to manipulate insect populations.</p

Regulation of BMAL1 Protein Stability and Circadian Function by GSK3β-Mediated Phosphorylation

Circadian rhythms govern a large array of physiological and metabolic functions. To achieve plasticity in circadian regulation, proteins constituting the molecular clock machinery undergo various post-translational modifications (PTMs), which influence their activity and intracellular localization. The core clock protein BMAL1 undergoes several PTMs. Here we report that the Akt-GSK3beta signaling pathway regulates BMAL1 protein stability and activity.GSK3beta phosphorylates BMAL1 specifically on Ser 17 and Thr 21 and primes it for ubiquitylation. In the absence of GSK3beta-mediated phosphorylation, BMAL1 becomes stabilized and BMAL1 dependent circadian gene expression is dampened. Dopamine D2 receptor mediated signaling, known to control the Akt-GSK3beta pathway, influences BMAL1 stability and in vivo circadian gene expression in striatal neurons.These findings uncover a previously unknown mechanism of circadian clock control. The GSK3beta kinase phosphorylates BMAL1, an event that controls the stability of the protein and the amplitude of circadian oscillation. BMAL1 phosphorylation appears to be an important regulatory step in maintaining the robustness of the circadian clock

Functional Interactions between KCNE1 C-Terminus and the KCNQ1 Channel

The KCNE1 gene product (minK protein) associates with the cardiac KvLQT1 potassium channel (encoded by KCNQ1) to create the cardiac slowly activating delayed rectifier, IKs. Mutations throughout both genes are linked to the hereditary cardiac arrhythmias in the Long QT Syndrome (LQTS). KCNE1 exerts its specific regulation of KCNQ1 activation via interactions between membrane-spanning segments of the two proteins. Less detailed attention has been focused on the role of the KCNE1 C-terminus in regulating channel behavior. We analyzed the effects of an LQT5 point mutation (D76N) and the truncation of the entire C-terminus (Δ70) on channel regulation, assembly and interaction. Both mutations significantly shifted voltage dependence of activation in the depolarizing direction and decreased IKs current density. They also accelerated rates of channel deactivation but notably, did not affect activation kinetics. Truncation of the C-terminus reduced the apparent affinity of KCNE1 for KCNQ1, resulting in impaired channel formation and presentation of KCNQ1/KCNE1 complexes to the surface. Complete saturation of KCNQ1 channels with KCNE1-Δ70 could be achieved by relative over-expression of the KCNE subunit. Rate-dependent facilitation of K+ conductance, a key property of IKs that enables action potential shortening at higher heart rates, was defective for both KCNE1 C-terminal mutations, and may contribute to the clinical phenotype of arrhythmias triggered by heart rate elevations during exercise in LQTS mutations. These results support several roles for KCNE1 C-terminus interaction with KCNQ1: regulation of channel assembly, open-state destabilization, and kinetics of channel deactivation

Adult Circadian Behavior in Drosophila Requires Developmental Expression of cycle, But Not period

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex