Numerical evaluation of the fields induced by body motion in or near high-field MRI scanners

In modern magnetic resonance imaging , both patients and health care workers are exposed to strong, non-uniform static magnetic fields inside and outside of the scanner, in which body movement may be able to induce electric currents in tissues which could be potentially harmful. This paper presents theoretical investigations into the spatial distribution of induced E-fields in a tissue-equivalent human model when moving at various positions around the magnet. The numerical calculations are based on an efficient, quasi-static, finite-difference scheme. Three-dimensional field profiles from an actively shielded 4 T magnet system are used and the body model projected through the field profile with normalized velocity. The simulation shows that it is possible to induce E-fields/currents near the level of physiological significance under some circumstances and provides insight into the spatial characteristics of the induced fields. The methodology presented herein can be extrapolated to very high field strengths for the evaluation of the effects of motion at a variety of field strengths and velocities.     

Plasma fatty acids and [13C]linoleic acid metabolism in preterm infants fed a formula with medium-chain triglycerides

Most preterm infant formulas contain medium-chain triacylglycerols (MCT), but the effects of MCT on polyunsaturated fatty acid status and metabolism are controversial. Thus, we studied the effects of MCT on linoleic acid metabolism using stable isotopes. Enterally fed preterm infants were randomized to receive for 7 days 40% of fat as MCT (n = 10) or a formula without MCT (n = 9). At study day 5, infants received orally 2 mg/kg body weight of (13)C-labeled linoleic acid. Fatty acids in plasma lipid classes and (13)C enrichment of phospholipid fatty acids were measured and tracer oxidation was monitored. Compared with the control group, the MCT group showed lower breath (13)CO(2) and higher plasma triacylglycerol contents of octanoic acid, of decanoic acid, and of total long-chain polyunsaturated fatty acids (57.1 +/- 4.4 micro mol/l vs. 37.9 +/- 4.8 micro mol/l, P < 0.01). Concentrations of several polyunsaturated fatty acids in plasma phospholipids and non esterified fatty acids were higher in the MCT group. (13)C concentrations in phospholipid n-6 fatty acids indicated no difference in the relative conversion of linoleic to arachidonic acid. We conclude that oral MCT effectively reduce polyunsaturated fatty acid and long chain polyunsaturated fatty acid oxidation in preterm infants without compromising endogenous n-6 long chain polyunsaturated fatty acid synthesis.     

Population and colony genetic structure of the primitive termite Mastotermes darwiniensis

The termite Mastotermes darwiniensis is the sole extant member of its family and occupies the basal position in the phylogeny of the eusocial order Isoptera. In this study, we investigated the micro- and macrogeographic genetic structure of M. darwiniensis in its native range in Australia. A total of 1591 workers were sampled from 136 infested trees in 24 locales. Each locale was separated by 2-350 km, and these locales were found within two broader geographic regions approximately 1500 km apart. The multilocus genotypes of all termites were assayed at six polymorphic microsatellite loci. The genetic data indicated that colonies typically fed on multiple trees within locales and extended over linear distances of up to 320 m. Single colonies were frequently headed by multiple reproductives. Workers were highly related (r = 0.40) and substantially inbred (f = 0.10). Thus, M. darwiniensis colonies are characterized by the input of alleles from multiple reproductives, which sometimes engage in consanguineous matings. Our analyses of population genetic structure above the level of the colony indicated that locales and regions were significantly differentiated (theta(locale) = 0.50, theta(region) = 0.37). Moreover, locales showed a pattern of genetic isolation by distance within regions. Thus, M. darwiniensis populations display restricted gene flow over moderate geographic distances. We suggest that the genetic patterns displayed by M. darwiniensis result primarily from selective pressures acting to maintain high relatedness among colonymates while allowing colonies to grow rapidly and dominate local habitats.     

AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling

AMP-activated protein kinase (AMPK) is viewed as an energy sensor that acts to modulate glucose uptake and fatty acid oxidation in skeletal muscle. Given that protein synthesis is a high energy-consuming process, it may be transiently depressed during cellular energy stress. Thus, the intent of this investigation was to examine whether AMPK activation modulates the translational control of protein synthesis in skeletal muscle. Injections of 5-aminoimidazole-4-carboxamide 1-beta-d-ribonucleoside (AICAR) were used to activate AMPK in male rats. The activity of alpha1 AMPK remained unchanged in gastrocnemius muscle from AICAR-treated animals compared with controls, whereas alpha2 AMPK activity was significantly increased (51%). AICAR treatment resulted in a reduction in protein synthesis to 45% of the control value. This depression was associated with decreased activation of protein kinases in the mammalian target of rapamycin (mTOR) signal transduction pathway as evidenced by reduced phosphorylation of protein kinase B on Ser(473), mTOR on Ser(2448), ribosomal protein S6 kinase on Thr(389), and eukaryotic initiation factor eIF4E-binding protein on Thr(37). A reduction in eIF4E associated with eIF4G to 10% of the control value was also noted. In contrast, eIF2B activity remained unchanged in response to AICAR treatment and therefore would not appear to contribute to the depression in protein synthesis. This is the first investigation to demonstrate changes in translation initiation and skeletal muscle protein synthesis in response to AMPK activation.     

Beta -oxidation of free fatty acids is required to maintain translational control of protein synthesis in heart

The study described herein investigated the role of free fatty acids (FFAs) in the maintenance of protein synthesis in vivo in rat cardiac and skeletal muscle. Suppression of FFA beta-oxidation by methyl palmoxirate caused a marked reduction in protein synthesis in the heart. The effect on protein synthesis was mediated in part by changes in the function of eukaryotic initiation factors (eIFs) involved in the initiation of mRNA translation. The guanine nucleotide exchange activity of eIF2B was repressed, phosphorylation of the alpha-subunit of eIF2 was enhanced, and phosphorylation of eIF4E-binding protein-1 and ribosomal protein S6 kinase was reduced. Similar changes in protein synthesis and translation initiation were not observed in the gastrocnemius following treatment with methyl palmoxirate. In heart, repressed beta-oxidation of FFA correlated, as demarcated by changes in the ATP/AMP ratio and phosphorylation of AMP-activated kinase, with alterations in the energy status of the tissue. Therefore, the activation state of signal transduction pathways that are responsive to cellular energy stress represents one mechanism whereby translation initiation may be regulated in cardiac muscle.     

Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression

PSD-95 is a major scaffolding protein of the postsynaptic density, tethering NMDA- and AMPA-type glutamate receptors to signaling proteins and the neuronal cytoskeleton. Here we show that PSD-95 is regulated by the ubiquitin-proteasome pathway. PSD-95 interacts with and is ubiquitinated by the E3 ligase Mdm2. In response to NMDA receptor activation, PSD-95 is ubiquitinated and rapidly removed from synaptic sites by proteasome-dependent degradation. Mutations that block PSD-95 ubiquitination prevent NMDA-induced AMPA receptor endocytosis. Likewise, proteasome inhibitors prevent NMDA-induced AMPA receptor internalization and synaptically induced long-term depression. This is consistent with the notion that PSD-95 levels are an important determinant of AMPA receptor number at the synapse. These data suggest that ubiquitination of PSD-95 through an Mdm2-mediated pathway is critical in regulating AMPA receptor surface expression during synaptic plasticity.     

How environment supports a state: molecular dynamics simulations of two states in bacteriorhodopsin suggest lipid and water compensation

The light-driven proton pump bacteriorhodopsin (bR) is a transmembrane protein that uses large conformational changes for proton transfer from the cytoplasmic to the extracellular regions. Crystal structures, due to their solvent conditions, do not resolve the effect of lipid molecules on these protein conformational changes. To begin to understand the molecular details behind such large conformational changes, we simulated two conformations of wild-type bacteriorhodopsin, one of the dark-adapted state and the second of an intermediate (M(O)) state, each within an explicit dimyristoyl-phosphatidylcholine (DMPC) lipid bilayer. The simulations included all-hydrogen and all-atom representations of protein, lipid, and water and were performed for 20 ns. We investigate the equilibrium properties and the dynamic motions of the two conformations in the lipid setting. We note that the conformational state of the M(O) intermediate bR remains markedly different from the dark-adapted bR state in that the M(O) intermediate shows rearrangement of the cytoplasmic portions of helices C, F, and G, and nearby loops. This difference in the states remained throughout the simulations, and the results are stable on the molecular dynamics timescale and provide an illustration of the changes in both lipid and water that help to stabilize a particular state. Our analysis focuses on how the environment adjusts to these two states and on how the dynamics of the helices, loops, and water molecules can be related to the pump mechanism of bacteriorhodopsin. For example, water generally behaves in the same manner on the extracellular sides of both simulations but is decreased in the cytoplasmic region of the M(O) intermediate. We suspect that the different water behavior is closely related to the fluctuations of microcavities volume in the protein interior, which is strongly coupled to the collective motion of the protein. Our simulation result suggests that experimental observation can be useful to verify a decreased number of waters in the cytoplasmic regions of the late-intermediate stages by measuring the rate of water exchange with the interior of the protein.     

RELATEDNESS AND POPULATION STRUCTURE OF THE PRIMITIVELY EUSOCIAL BEE LASIOGLOSSUM ZEPHYRUM (HYMENOPTERA: HALICTIDAE) IN KANSAS

Lasioglossum zephyrum is a primitively eusocial bee, which nests in small colonies of up to 20 individuals. The nests occur in patchily distributed aggregations of from a few to over 1,000 nests along periodically disturbed stream and river banks in eastern North America. We used five polymorphic allozyme loci to test for geographic structure and estimate relatedness in eight patches of nests from five aggregations in Douglas Co., Kansas. Autocorrelation analysis of gene frequencies, plus a multilocus G test, revealed a low but significant tendency for differentiation among nests within patches, among patches within aggregations, and among aggregations. Small numbers of nests restricted estimation of relatedness to three patches, of which only one had a sample size large enough to yield confidence limits narrow enough to be informative. The limits from this patch of 20 nests are 0.64 < 0.8245 < 1.01. While these limits are consistent with the true value being 0.75 (that expected under male-haploidy if each nest results from the reproduction of a single, once-mated female), the occurrence of some nests with three or more genotypes shows that nest makeup is more complex than this, so that a lower value, say 0.7, is more plausible. This value is sufficiently high to indicate that kin selection is probably important in these populations.     

Diel oxygen uptake rhythms in diapausing pupae of Pieris brassicae and Papilio machaon

Diel rhythms of oxygen uptake are described for P. brassicae and P. machaon. The rhythms are bimodal in both species at 10°C, with a main midday peak, a smaller peak in the afternoon or early evening and low nocturnal uptake rates under natural and artificial (LD 9:15) light regimes. In P. brassicae, the rhythm of oxygen uptake is linked with a diel rhythm of the incidence of short-term oxygen uptake cycles. Summated batch curves for both species contain significant elements of individual variation. In P. machaon, the timing of daily peaks in oxygen uptake is related directly to the level of metabolism.