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Combined DC and ELF magnetic fields can alter cell proliferation.

Effects of extremely-low-frequency (ELF) electromagnetic fields on proliferation of rabbit-ligament fibroblasts were examined. Markedly different effects, ranging from inhibition to stimulation of proliferation, were obtained, depending on the signal parameters of amplitude, frequency, and DC magnetic field. These results demonstrate that simple, single-frequency signals can have dramatic effects on ligament cells, which may be useful for bioelectrical stimulation of growth and repair. Also, the range of frequencies examined in this study covered those commonly used in transmission of electrical energy (50 or 60 Hz), which indicates that further study of possible effects of exposure to fields generated by power transmission equipment is warranted.

Animals↗

Electric fields and surface charges induced by ELF magnetic fields.

A method is described for evaluating electric fields induced by ELF magnetic fields into electrically inhomogeneous, low-conductivity (less than 5 S/m) structures. It is applied to cylinders and spheres, and numerical results are given for electrical properties that are representative of some tissues, or of cells embedded either in saline solution or a tissue matrix. Surface currents on spherical cell boundaries are estimated and compared with thermal noise due to ion motion.

Electromagnetic Fields↗

Optimal experimental design for in vitro studies with ELF magnetic fields.

An experimental arrangement is described that maximized the dosimetric information that can be obtained during in vitro studies with ELF magnetic fields. The arrangement enables researchers to distinguish between a purely magnetic-field effect and one that also involves the electric fields and currents induced by the magnetic field.

Electromagnetic Fields↗

A dosimeter for assessment of exposures to ELF fields.

There are currently no biological indicators of electromagnetic field exposure to aid investigation of the biological effects of ELF fields, but this hiatus is partly compensated for by the ease with which the external fields can be measured. The subject of this report is a small electronic instrument that can log electric-, magnetic-, and transient-field intensities of individual subjects for a duration of two weeks, thus allowing exposure to be assessed in considerable detail. A preliminary survey conducted with the instrument has shown clear differences in domestic and occupational exposures of specific groups. Simple analytical models can be fitted to the field-exposure data by adjusting a few parameters such as current, intensity, and distance. Such modeling may be increasingly useful as the data base on exposures expands.

Electromagnetic Fields↗

Threshold for inhibition of Na, K-ATPase by ELF alternating currents.

Alternating currents can increase or decrease the ATP-splitting activity of the membrane enzyme Na,K-ATPase. Either change depends on the AC frequency, and the greatest effect appears to be in the ELF range at about 100 Hz. The threshold for enzyme inhibition by AC was determined, and it is estimated to be an internal electric field circa 5 microV/cm. The corresponding current-density threshold approximates 8 nA/cm2.

Animals↗

Misclassification of ELF occupational exposure resulting from spatial variation of the magnetic field.

The adequacy of a single hip- or chest-worn magnetic field dosimeter to reliably classify subjects with respect to their occupational ELF magnetic field exposure is investigated. Hip-worn dosimeters consistently underestimate both whole-body average exposure and head exposure, tentatively regarded here as two possible definitions of the "true" exposure measurement. The approximate resulting bias in the relative risk estimate in hypothetical case-control studies is evaluated. A chest-worn dosimeter is found to be generally superior to a hip-worn one in assessing exposure during the occupational tasks considered here.

Electromagnetic Fields↗

Do ELF magnetic fields affect human reaction time?

Two double-blind studies were run in an attempt to confirm the finding that a 0.2 Hz magnetic field affects simple reaction time (RT) in humans, whereas a 0.1 Hz field does not. In the first experiment, 12 volunteer subjects were exposed to a continuous 0.2 Hz, 0.1 Hz, or sham field in a fully counterbalanced, within-subjects design. Subjects were run singly for one condition each day over 3 consecutive days with a field strength of 1.1 mT and a daily exposure duration of 5 min. Neither magnetic field had any effect on RT at any time during the exposure. One condition of a second study, using a new group of 24 volunteer subjects, also failed to find any field effects at 0.2 Hz. Additionally, the second study failed to show any effects when the frequency, flux density, and field orientation were set according to parametric resonance theory. It is suggested that, although ELF magnetic field effects on human behaviour may be elusive, future research can improve detection rates by paying greater attention to reducing error variance and increasing statistical power.

Adult↗

Fast topological analysis of 2D and 3D grids of data: application to the atoms in molecule (AIM) and the electron localization function (ELF).

The topological analysis of grids of data is used for determination of surfaces or volumes around maxima. The volumes are then related to chemical information such as atoms or bonds, and can be used for integration of local properties such as electronic population. The problem of global connectivity is reversed into the question of local connectivity yielding a linear scaling partition algorithm. Two packages are developed for a very fast analysis and partition of 2D or 3D grids of data, applications being made to C2H2, C2H4, C6H6, H2CO, and H2CS molecules using the Atoms in Molecule (AIM) or Electron Localization Function (ELF).

Journal Article↗

The suppressive effect of myeloid Elf-1-like factor (MEF) in osteogenic differentiation.

Myeloid Elf-1 like factor (MEF) is a member of the Ets transcription factor family. Ets family proteins control the expression of genes that are critical for biological processes such as proliferation, differentiation, and cell death. Some of Ets factors are also known to regulate bone development. In this study, we investigated the role of MEF in osteoblast differentiation. MEF expression was highest early in the differentiation of MC3T3-E1 osteoblasts and was reduced by treatment with BMP-2. The expression of MEF suppressed the alkaline phosphatase activity and expression induced by BMP-2 stimulation and mediated by Runx2. The expression of MEF also reduces osteocalcin mRNA levels, and mineralization in MC3T3-E1 cells. We found that the MEF-mediated suppression of osteogenic differentiation was critically related to Runx2 regulation. The MEF and Runx2 proteins physically interact to form a complex, and this interaction interferes with Runx2 binding to the cis-acting element OSE2 derived from the osteocalcin promoter. Co-transfection of MEF inhibited the 6xOSE2-luciferase reporter activity induced by Runx2. In addition, MEF stimulated the transcription of a negative mediator Msx2, and a transcriptional repressor, Mab21L1, and suppressed the transcription of a positive mediator, Dlx5 in osteoblast differentiation. MEF overexpression stimulated C2C12 cell proliferation. Together, our findings suggest that MEF promotes cell proliferation and functions as a negative regulator of osteogenic differentiation by directly interacting with Runx2 and suppressing its transcriptional activity.

Alkaline Phosphatase↗

Extremely low frequency (ELF) pulsed-gradient magnetic fields inhibit malignant tumour growth at different biological levels.

Extremely low frequency (ELF) pulsed-gradient magnetic field (with the maximum intensity of 0.6-2.0 T, gradient of 10-100 T.M(-1), pulse width of 20-200 ms and frequency of 0.16-1.34 Hz treatment of mice can inhibit murine malignant tumour growth, as seen from analyses at different hierarchical levels, from organism, organ, to tissue, and down to cell and macromolecules. Such magnetic fields induce apoptosis of cancer cells, and arrest neoangiogenesis, preventing a supply developing to the tumour. The growth of sarcomas might be amenable to such new method of treatment.

Animals↗

BLyS BINDS TO B CELLS WITH HIGH AFFINITY AND INDUCES ACTIVATION OF THE TRANSCRIPTION FACTORS NF-kappaB AND ELF-1.

B lymphocyte stimulator (BLyS) is a novel member of the TNF family of proteins expressed by myeloid cells as membrane-bound and soluble forms. BLyS was shown to act specifically on B cells, inducing proliferation and immunoglobulin production both in vitro and in vivo. The present study was undertaken to characterize binding of radiolabeled BLyS to its cognate receptor on human B lymphocytes and examine intracellular events initiated by BLyS binding. Similar to other TNF family members, BLyS is present in solution as a homotrimer as determined by gel filtration chromatography and light scattering analysis. BLyS binding to B cells is specific as other TNF family members tested did not compete for(125)I-BLyS binding. Analysis of equilibrium binding of(125)I-labeled BLyS to purified human tonsillar B cells demonstrated saturable binding. Scatchard analysis of the binding data revealed a single class of high-affinity binding on human B cells with approximately 2600 binding sites per cell and an apparent dissociation constant (K(D)) of about 0.1 nM. In addition we report that BLyS binding to B cells results in the activation of NF-kappaB and the Ets family transcription factor, ELF-1, and in the induction of mRNA for Polo-like kinase (PLK).

B-Cell Activating Factor↗

Weak ELF magnetic field effects on hippocampal rhythmic slow activity.

Several investigations have revealed that electrical activity within the central nervous system (CNS) can be affected by exposure to weak extremely-low-frequency (ELF) magnetic fields. Many of these studies have implicated CNS structures exhibiting endogenous oscillation and synchrony as optimal sites for field coupling. A particularly well characterized structure in this regard is the rat hippocampus. Under urethane anesthesia, synchronous bursting among hippocampal pyramidal neurons produces a large-amplitude quasi-sinusoidal field potential oscillation, termed "rhythmic slow activity" (RSA) or "theta." Using this in vivo model, we investigated the effect of exposure to an externally applied sinusoidal magnetic field (16.0 Hz; 28.9 microT(rms)) on RSA. During a 60-min exposure interval, the probability of RSA decaying to a less coherent mode of oscillation, termed "large irregular-amplitude activity" (LIA), was increased significantly. Moreover, this instability persisted for up to 90 min postexposure. These results are consistent with the hypothesis that endogenous CNS oscillators are uniquely susceptible to field-mediated perturbation and suggest that the sensitivity of these networks to such fields may be far greater than had previously been assumed. This sensitivity may reflect nonlinearities inherent to these networks which permit amplification of endogenous fields mediating the initiation and propagation of neuronal synchrony.

Animals↗

Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor.

The NS1 protein of influenza A virus binds not only to poly(A) and a stem-bulge region in U6 small nuclear RNA (snRNA), but also to double-stranded (ds) RNA. Binding assays with NS1 protein mutants established that the previously identified RNA-binding domain of the NS1 protein is required for binding to ds RNA as well as for binding to poly(A) and U6 snRNA. In addition, dsRNA competed with U6 snRNA for binding to the NS1 protein, consistent with both RNAs sharing the same binding site on the protein. As a consequence of its binding to dsRNA, the NS1 protein blocks the activation of the dsRNA-activated protein kinase (PKR) in vitro. This kinase phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (elF-2 alpha), leading to a decrease in the rate of initiation of translation. Assays using purified PKR and purified elF2 demonstrated that the NS1 protein blocks the dsRNA activation of PKR, and experiments using reticulocyte extracts showed that the NS1 protein blocks the inhibition of translation caused by dsRNA activation of PKR. The implications of these results for control mechanisms occurring in influenza virus-infected cells are discussed.

Animals↗

Induction of ELF transmembrane potentials in relation to power-frequency electric field bioeffects in a plant root model system. I. Relationship between applied field strength and cucurbitaceous root growth rates.

Seminal roots of Cucumis sativus and Cucurbita maxima were exposed to 60 Hz electric fields of 100-500 V X m-1 in a conducting aqueous inorganic growth medium. Root growth rates were measured to produce a dose-response relationship for each species. The species were selected for study because of their familial relationship, reported sensitivity to 60 Hz, 360 V X m-1 electric fields, and differing average root cell sizes. The latter characteristic influences the magnitude of ELF membrane potentials induced by constant-strength applied electric fields, but does not affect the magnitude of the electric field strength tangent to the cell surface. The difference in average root cell size between C. sativus (smaller cells) and C. maxima (larger cells) was used to evaluate two alternate hypotheses that the observed effect on root growth is stimulated by the electric field tangent to the cell surface, or a field-induced perturbation in the normal transmembrane potential of the cells. The results of the dose-response relationship studies are qualitatively consistent with the hypothesis that the effect is elicited by induced transmembrane potentials. The smaller-celled roots showed a substantially higher response threshold [C. sativus; E0TH approximately 330 V X m-1] than did the larger-celled species [C. maxima; E0TH approximately 200 V X m-1]. At field strengths above the response thresholds in both species, the growth rate of C. sativus roots was less affected than that of C. maxima roots exposed to the same field strength.

Cell Division↗

Matching between theoretical and experimental data for ELF ion transport effects.

In recent years, several studies have been focused on the problem of nonthermal interaction between extremely low-frequency (ELF) electromagnetic fields and cell environment at membrane level. In the paper, to analyse the dynamic effects of weak static and harmonic fields on charged particles, some new considerations have been developed, based on the Lorentz model. The authors have reached a suitable formulation so that the data processing has led expressly to the evaluation of ionic-velocity components against magnetic-field amplitudes and frequencies, as well as a viscosity parameter. Even through a direct and rough comparison, the results of the authors' investigation have demonstrated an interesting agreement with some experimental data relative to ionic fluxes through cell membranes. Indeed, by means of an algorithm based on the techniques of the inversion theory, the author's have found definite values of the viscosity parameter for which the expected resonant behaviours (amplitude and frequency windows) fit existing experiments well. It seems worthy of interest that such viscosity values fall within a consistent, narrow range of low amplitude.

Animals↗

SUMO down-regulates the activity of Elf4/myeloid Elf-1-like factor.

Myeloid elf-1-like factor (MEF) or Elf4 is an ETS protein known to regulate the basal expression of the anti-microbial peptides, lysozyme and human beta-defensin-2, in epithelial cells and activate the transcription of perforin in natural killer cells. The numerous target genes of MEF and its biological functions signify the importance of this Ets transcription factor. Here we show that MEF is modified by conjugation with SUMO-1/-2 (small ubiquitin-related modifier) both in mammalian cells and in Escherichia coli overexpressing human SUMO-1/-2. We identified by point mutation that lysine 657 of MEF is the site for sumoylation. This modification down-regulated MEF activity on lysozyme and perforin promoters, and decreased the lysozyme mRNA expression. Chromatin immuno-precipitation analysis revealed that SUMO-conjugation diminished the recruitment of MEF to the lysozyme promoter, which partly explains the down-regulation of MEF activity by SUMO. These findings contribute to our understanding of the regulation of the ETS factor MEF.

Amino Acid Substitution↗

Effects of time-variant extremely low-frequency (ELF) electromagnetic fields (EMF) on cholinesterase activity in Dictyostelium discoideum (Protista).

Recently, we detected propionylcholinesterase (PrChE) activity in single-cell amoebae of Dictyostelium discoideum using cytochemical, electrophoretic, and spectrophotometric methods. The involvement of this enzyme activity in cell-cell and cell-environment interactions was suggested. In this work, we found that exposure of single-cell amoebae to an extremely low-frequency electromagnetic fields (ELF-EMF) of 300 microT, 50 Hz, from 1 h up to 48 h at 21 +/- 1 degrees C affected PrChE activity.

Animals↗

Sp1-dependent regulation of Myeloid Elf-1 like factor in human epithelial cells.

Myeloid Elf-1 like factor (MEF) is an ETS protein, which activates the promoters of granulocyte macrophage colony-stimulating factor, interleukin-3, lysozyme, human beta defensin-2 and perforin. In spite of its many known functions, little is known about MEF transcriptional regulation. Here, we cloned the 5'-flanking region of human MEF gene and identified a TATA-less promoter region at -204/-54 which contains 4 putative binding sites for Sp1, two of which are essential in up-regulating MEF activity. These were proven by EMSA and blocking Sp1 using RNAi or mithramycin A treatment of HEK293 cells. Our results suggest that Sp1 constitutively regulates the MEF gene.

Base Sequence↗