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PubMed2003

Electron probability distribution in AIM and ELF basins.

The probabilities of finding a certain number of electrons enclosed in a given volume is calculated and discussed for a series of molecules. Two different methodologies to do the partition of the molecular space in separate volumes are investigated: the Atoms in the Molecules, AIM, topologic analysis of the density, and the topologic analysis of the Electron Localization Function (ELF). The formulas to calculate the probability distribution are reviewed and the way to implement them shortly explained. For a series of molecules, we present how the probability distribution complement the chemical information about the localization of the electrons in certain regions of the space. The calculations show that the probability of finding Z electrons in the AIM atomic basin associated to an atom of atomic number Z is, in general, low, even when the average number of electrons is close to Z. The probability distribution on the ELF basins associated to bonds yields new insight about the nature of the respective bond.

Journal Article↗

PubMed2005

Electron pairing and chemical bonds. Electron fluctuation and pair localization in ELF domains.

This article reports the numerical comparison of the quantities characterizing the extent of electron fluctuation and pair localization in the domains determined by the direct minimization of electron fluctuation with the domains resulting from the partitioning of the molecules based on the topological analysis of the so-called electron localization function (ELF). Such a comparison demonstrates that the ELF partitioning can be regarded as a feasible alternative to computationally much more demanding direct optimization of minimum fluctuation domains. This opened the possibility of the systematic scrutiny of the electron pair model of the chemical bond, and as it was demonstrated, the previous pessimistic claims about the applicability of this model are not completely justified.

Journal Article↗

PubMed1990

Incidence of leukaemia and brain tumours in Finnish workers exposed to ELF magnetic fields.

The relative incidence of leukaemia, acute myeloid leukaemia (AML) and central nervous system (CNS) tumours among workers presumably exposed to extremely low frequency (ELF) magnetic fields (MFs) was studied. The study population consisted of all male industrial workers in Finland aged 25 to 64 years during 1971-1980 according to the Population Census in 1970. The occupations were grouped into three exposure categories according to the probability of exposure. The category of "probable" exposure included electrical occupations and the category of "possible" exposure included occupations where electric motors or welding are common. All other occupations were included to the category of "no exposure". Cancer incidence rates in different occupational groups during 1971-1980 were obtained after linking the census records with the national death certificates and the files of the Finnish Cancer Registry. The adjusted relative risks (with 95% confidence limits) in the categories of "probable" and "possible" exposure were for all leukaemia 1.9 (1.0-3.5) and 1.4 (1.1-1.8), for AML 1.5 (0.5-4.7) and 1.4 (0.9-2.1), and for CNS tumours 1.3 (0.7-2.3) and 1.3 (1.0-1.6), respectively. The results are concordant with earlier studies suggesting elevated risk among workers exposed to ELF magnetic fields.

Adult↗

PubMed1986

Induction of ELF transmembrane potentials in relation to power-frequency electric field bioeffects in a plant root model system. II. The effect of 60 Hz electric fields on the growth of different regions of the cucurbit root elongation zone.

The region of elongation in Cucumis sativus and Cucurbita maxima roots was marked at increasing distances from the apex to provide an analog of increasing cell size. These roots were exposed/sham-exposed to 60 Hz electric fields and the growth rates of the root segments measured. The growth rate effect magnitude varied with increasing distance from the root tip at constant field strength, and with increasing applied field strength. These results provide strong, qualitative support for the postulate that ELF transmembrane potential induction is involved in the stimulation of ELF electric field effects in the plant root model system.

Cell Division↗

PubMed1977

Phosphorylation of initiation factor elF-2 and the control of reticulocyte protein synthesis.

When rabbit reticulocyte lysates are incubated in the absence of hemin or in the presence of low concentrations of double-stranded RNA, the rate of initiation of protein synthesis is severely reduced after a lag period in which control rates are observed. This reduced initiation rate is due to inhibition of the binding of Methionyl-tRNAf to native 40S ribosomal subunits and is caused by a macromolecular inhibitor which is activated under these conditions. This paper shows that the inhibitors activated in these two situations appear to be different entities, but that in both cases, the inhibitor has an associated protein kinase activity which is highly selective for the small subunit of elF-2, the initiation factor which catalyzes binding of Methionyl-tRNAf to 40S subunits. We present several lines of evidence in support of the hypothesis that the phosphorylation of elF-2 by these kinases is basis of the control of initiation in lysates incubated under these conditions.

Adenosine Triphosphate↗

PubMed1996

Cloning and expression of the murine Elf-1 cDNA.

The Ets family of transcription factors has been implicated in the etiology of several types of cancer. We cloned and characterized the gene encoding the murine homologue of one Ets family member, Elf-1 (mElf-1), in order to gain insight into its cellular physiology. We examined mElf-1 mRNA expression in normal mouse tissues and in several murine and human cell lines. Expression of mElf-1, although highest in lymphocytes, was observed in a number of hematopoietic cell lineages, including the myeloid, macrophages and erythroid lineages, and was lowest in the murine fibroblast cell line, NIH3T3. Analysis of human and fetal tissue mRNAs confirmed that mElf-1 is expressed in a variety of cell lineages, principally in hematopoietic cells. Western blot analysis using antiserum generated to a synthetic C-terminal peptide of mElf-1, and extracts prepared from cell lines that expressed the mElf-1 mRNA identified multiple mElf-1 species that migrated near the 97-kDa molecular weight marker. Site selection analysis indicated that the binding site preferred by mElf-1 is very similar to that of the Drosophila melanogaster homologue, E74, and to that of Fli-1, another Ets family member. We conclude that the expression of mElf-1 is not restricted to the lymphoid lineage, and suggest that Elf-1 may regulate the transcription of a broad spectrum of genes.

Amino Acid Sequence↗

PubMedDate not supplied

Phospholipase C-dependent phosphoinositide breakdown induced by ELF-EMF in Peganum harmala calli.

With the aim of examining the response of plant cells to extremely low frequency (ELF) electromagnetic fields (EMF), we investigated the behaviour of the phosphatidylinositol 4,5 bisphosphate (PtdIns 4,5-P(2)) molecule (the precursor of the phosphoinositide signal transduction cascade) by exposing callus cells from Peganum harmala to 50 Hz, 1 gauss EMF for 10 min and by examining the level and the fatty acid composition of PtdIns 4,5-P(2) after the exposure. Our results evidenced a statistically significant decrease in PtdIns 4,5-P(2) concentrations and a different involvement of the constituting fatty acids in the induced breakdown. The manipulation of the lipid-based signalling pathway by phosphoinositide-phospholipase C (PI-PLC) inhibitors (i.e., neomycin, U-73122 and ET-18-OCH(3)) seems to support the hypothesis that, as in animals, also in plants, the cell membrane is the primary impact site of ELF electromagnetic stimulus and that this interaction could probably involve the activation of PI signal transduction pathway including a heterotrimeric G protein.

Antioxidants↗

PubMed2006

Extremely low-frequency electromagnetic field (ELF-EMF) does not affect the expression of alpha3, alpha5 and alpha7 nicotinic receptor subunit genes in SH-SY5Y neuroblastoma cell line.

Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in a number of functional processes, including cognition, learning and memory, and alterations in their expression and/or activity have been implicated in various neurological disorders such as Alzheimer's disease (AD), Parkinson's disease and schizophrenia. Epidemiological studies have shown that exposure to electromagnetic fields (EMF) may contribute to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. Given the role of nAChRs in physiological and pathological conditions, we wondered whether an extremely low-frequency electromagnetic field (ELF-EMF) may affect the expression of the molecules involved in neurodegenerative processes. In order to investigate this possibility, we studied the expression of alpha3, alpha5 and alpha7 nicotinic subunits upon exposure of the SH-SY5Y human neuroblastoma cell line to a 50 Hz power-line magnetic field in a "blind trial" system; various magnetic flux densities and exposure times were applied. Our studies show that the expression of some relevant components of the cholinergic nicotinic system, which is one of the most affected neurotransmission systems in AD, did not undergo any change at molecular level by environmental exposure to ELF-EMF.

Blotting, Northern↗

PubMed1997

The inhibitory effect on neurite outgrowth of motoneurons exerted by the ligands ELF-1 and RAGS.

Eph-related receptor tyrosine kinases and ligands are expressed at high levels in the developing nervous system, giving rise to the proposal that they are involved in neuronal connection. Cek8 was found to be predominantly expressed on a subset of motoneurons innervating limb but not body muscles during motoneuron axonal growth. Here we show that the ligands RAGS and ELF-1 were expressed in limb buds and that they activated Cek8 when presented in membrane-bound or clustered forms of Fc chimeric proteins but not in unclustered soluble forms. When chick embryonic motoneurons enriched by panning were cultured on clustered forms of RAGS-Fc and ELF-1-Fc, the neutrite growth of motoneurons expressing Cek8 was inhibited. Our results show a relationship between receptor phosphorylation and neurite growth inhibition and suggest that Eph-related kinases and ligands have a regulatory effect on the axon growth of motoneurons during development.

Animals↗

PubMed1998

Transcriptional regulation of the stem cell leukemia gene by PU.1 and Elf-1.

The SCL gene, also known as tal-1, encodes a basic helix-loop-helix transcription factor that is pivotal for the normal development of all hematopoietic lineages. SCL is expressed in committed erythroid, mast, and megakaryocytic cells as well as in hematopoietic stem cells. Nothing is known about the regulation of SCL transcription in mast cells, and in other lineages GATA-1 is the only tissue-specific transcription factor recognized to regulate the SCL gene. We have therefore analyzed the molecular mechanisms underlying SCL expression in mast cells. In this paper, we demonstrate that SCL promoter 1a was regulated by GATA-1 together with Sp1 and Sp3 in a manner similar to the situation in erythroid cells. However, SCL promoter 1b was strongly active in mast cells, in marked contrast to the situation in erythroid cells. Full activity of promoter 1b was dependent on ETS and Sp1/3 motifs. Transcription factors PU.1, Elf-1, Sp1, and Sp3 were all present in mast cell extracts, bound to promoter 1b and transactivated promoter 1b reporter constructs. These data provide the first evidence that the SCL gene is a direct target for PU.1, Elf-1, and Sp3.

Animals↗

PubMed1999

A potential role for Elf-1 in CD4 promoter function.

The control of CD4 gene expression is believed to be linked directly to the signaling events that mediate T cell development and is directly dependent on the CD4 promoter. We have previously determined that this promoter contains four factor-binding sites important for its function. One of these sites, referred to as the P4 site, contains an Ets consensus recognition sequence. Using functional and biochemical analyses, we determine that Elf-1 binds to this site and specifically activates the CD4 promoter, indicating that Elf-1 is playing an important role in CD4 promoter function. In addition, a second nuclear factor binds to this region. Although there are consensus recognition sites for other factors, we demonstrate that none of these factors binds to the P4 site, nor do other known members of the Ets family. Thus, a novel transcription factor may bind to the CD4 promoter and help mediate its function.

Animals↗

PubMedDate not supplied

Comparison of personal exposure meter placement for the determination of office worker ELF magnetic field exposures.

This article compares extremely low frequency (ELF) magnetic field exposures measured by placing EMDEX Lite personal exposure meters (PEMs) at the head, chest, and waist level for a group of office workers. Twenty-three volunteers were solicited to wear three PEMs simultaneously; one was attached to a baseball cap worn on the head, one was attached to a band and worn around the neck (positioned on the chest), and one was worn in a belted pouch around the waist (positioned on the right side of the hip). The effect of PEM placement was evaluated by comparing full-shift average exposures and daily maximum or peak exposure. The results of this investigation indicate that time-weighted average magnetic field exposures determined at the hip provide the highest mean exposure estimates. Averages of the full-shift mean magnetic field measurements taken at hip and head levels were statistically greater than measurements taken at the chest level by 33 and 22%, respectively. Comparisons of the maximum or peak magnetic field exposures by body position indicate that the hip position produced an average exposure estimate that was 136% greater than the average head-level measurement. Results suggest that for office workers PEM meter placement on the body does not produce large differences in full-shift average ELF magnetic flux density exposures. However, the hip position produced the largest daily maximum or peak exposures. It is recommended that PEMs be placed on the hip for exposure assessments in office environments, because this placement is the most commonly used, the most convenient, and resulted in the highest magnetic field exposures.

Electromagnetic Fields↗

PubMed2001

A model of the electrical volume conductor in the region of the eye in the ELF range.

Electrical and magnetic phosphenes are irritations of the eye caused by electric currents or magnetic fields. These are well known effects initially investigated in the early 1900s. Available estimations of the current densities in the eye, based on the assumption of a homogeneous volume conductor, show low thresholds. These outdated thresholds are still an important cornerstone when justifying today's limit values for extremely low-frequency (ELF) fields specified by statutory regulations. In vitro measurements of the complex conductivity of cattle eye are carried out for the ELF range (5-2000 Hz) separated for the different tissues of the eyeball. They do not show peculiarities at 20 Hz which is the threshold minimum for the phosphene generation. The reported conductivity data of the eye region show variations of two orders of magnitude regarding the electrical conductivity of the individual tissue layers. Starting with these new data, a model of the orbita is introduced describing the eye and its periphery as an electrically inhomogeneous volume conductor. This model contains small-scale structures which are expected to behave as good electrical conductors yielding regions of higher field values within the eye. Therefore, earlier models assuming a homogeneous volume conductor can be regarded as oversimplistic.

Animals↗

PubMed2001

Outdoor background ELF magnetic fields in an urban environment.

Classification of 'exposed/non-exposed' subjects in epidemiological studies concerning the possible cancer risk associated with ELF magnetic field exposure is based on the a priori assumption of magnetic field value cut-off points that, often, are defined equal to minimum exposure levels typical of a population residing near high voltage facilities (0.1-4.2 microT), but in some cases an environmental magnetic field level not associated with transmission lines can exist. The results of an ELF magnetic field survey in an Italian urban area (about 1 million inhabitants) are presented: average field levels are correlated with population density of different districts. Exposure indexes are obtained, which are compared with those evaluated in studies regarding domestic exposure: background average levels result in comparable to cut-off points in epidemiological studies, but in some districts with high population density, they are much higher. This shows that knowledge of background magnetic field level in urban areas can assume a significant role in exposure assessment.

Background Radiation↗

PubMed2004

Assessing occupational and domestic ELF magnetic field exposure in the uk adult brain tumour study: results of a feasibility study.

The feasibility of measuring exposure to extremely low frequency magnetic fields (ELF MF) in the UK Adult Brain Tumour Study (UKABTS) was examined. During the study, 81 individuals and 30 companies were approached with 79 individuals and 25 companies agreeing to participate. Exposure data were collected using EMDEX II dosemeters worn by the participants for 3-4 consecutive days. Data were collected over a total of 321 d, including non-occupational periods. The results showed occupational exposure to be the main determinant of overall exposure. Moderate to strong correlations were found between arithmetic mean exposure and all other metrics with the possible exception of maximum exposure. Significant differences in exposure were found between job categories with large variability in certain categories. Highest average exposures were found for security officers (arithmetic mean, AM: 0.78 micro T), secretaries (AM: 0.48 micro T) and dentists (AM: 0.42 micro T). Welding and working near high-voltage power lines were associated with elevated exposure. In summary, acceptably precise measures of ELF MF exposure are feasible at relatively moderate cost. The results were used to develop a protocol for data collection from subjects in the UKABTS.

Activities of Daily Living↗

PubMed1993

Activation of the human T-cell leukemia virus type I enhancer is mediated by binding sites for Elf-1 and the pets factor.

Infection with human T-cell leukemia virus type I (HTLV-I) is associated with adult T-cell lymphoma/leukemia. This disease occurs in only a small minority of people infected with HTLV-I and manifests itself many years after infection. Therefore, it appears that a fine balance exists between HTLV-I and the host T-cell factors with which it interacts. HTLV-I encodes a transactivating protein, Tax, which activates viral transcription via cellular mechanisms which are incompletely understood. As viral gene expression is negligible during latency, it is doubtful that Tax controls the initial transition to the replicative state. Tax-independent cellular factors which control HTLV-I transcription, and presumably latency, have received little study. Recently, the product of the chicken proto-oncogene ets-1 has been shown to bind to the HTLV-I enhancer and modestly activate transcription in certain cell types (S. C. Gitlin, R. Bosselut, A. Gégonne, J. Ghysdael, and J. N. Brady, J. Virol. 65:5513-5523, 1991). However, the functional significance of the ets-binding site in the intact enhancer has not previously been shown. We now demonstrate that site-specific mutation of the purine-rich ets-binding site significantly diminishes inducible enhancer function, but not Tax response, in the human Jurkat T-cell line. Similarly, mutation of the peri-ets (pets) site, not previously noted in the HTLV-I enhancer, markedly inhibits inducible enhancer function but not Tax response. Further, we show that the predominant protein binding the purine-rich HTLV-I enhancer element in human T cells is not ets-1 but Elf-1, a member of the ets family which is very similar to the Drosophila morphogen E74. Regulation of HTLV-I through Elf-1/pets enhancer motifs resembles that seen with human immunodeficiency virus type 2 (D. M. Markovitz, M. Smith, J. Hilfinger, M. C. Hannibal, B. Petryniak, and G. J. Nabel, J. Virol. 66:5479-5484, 1992; J. M. Leiden, C.-W. Wang, B. Petryniak, M. Smith, D. M. Markovitz, G. J. Nabel, and C. B. Thompson, J. Virol. 66:5890-5897, 1992), another human pathogenic retrovirus with a relatively long incubation period.

Animals↗

PubMed1996

Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene.

The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is a key regulator of lymphocyte proliferation. IL-2R alpha is rapidly and potently induced in T cells in response to mitogenic stimuli. Interleukin 2 (IL-2) stimulates IL-2R alpha. transcription, thereby amplifying expression of its own high-affinity receptor. IL-2R alpha transcription is at least in part controlled by two positive regulatory regions, PRRI and PRRII. PRRI is an inducible proximal enhancer, located between nucleotides -276 and -244, which contains NF-kappaB and SRE/CArG motifs. PRRII is a T-cell-specific enhancer, located between nucleotides -137 and -64, which binds the T-cell-specific Ets protein Elf-1 and HMG-I(Y) proteins. However, none of these proximal regions account for the induction of IL-2R alpha transcription by IL-2. To find new regulatory regions of the IL-2R alpha gene, 8.5 kb of the 5' end noncoding sequence of the IL-2R alpha gene have been sequenced. We identified an 86-nucleotide fragment that is 90% identical to the recently characterized murine IL-2-responsive element (mIL-2rE). This putative human IL-2rE, designated PRRIII, confers IL-2 responsiveness on a heterologous promoter. PRRIII contains a Stat protein binding site that overlaps with an EBS motif (GASd/EBSd). These are essential for IL-2 inducibility of PRRIII/CAT reporter constructs. IL-2 induced the binding of Stat5a and b proteins to the human GASd element. To confirm the physiological relevance of these findings, we carried out in vivo footprinting experiments which showed that stimulation of IL-2R alpha expression correlated with occupancy of the GASd element. Our data demonstrate a major role of the GASd/EBSd element in IL-2R alpha regulation and suggest that the T-cell-specific Elf-1 factor can serve as a transcriptional repressor.

Animals↗

PubMed2002

Possible attenuation of the G2 DNA damage cell cycle checkpoint in HeLa cells by extremely low frequency (ELF) electromagnetic fields.

BACKGROUND: The issue remains unresolved as to whether low frequency magnetic fields can affect cell behaviour, with the possibility that they may be in part responsible for the increased incidence of leukaemia in parts of the population exposed to them. METHODS: Combined treatment of HeLa cells with gamma-irradiation (1, 3 and 5 Grays) and extra low frequency magnetic fields of ~50 Hz was carried out under rigorously controlled conditions. RESULTS: Synchronised cells progressing from S-phase arrived at mitosis on average marginally ahead of irradiation controls not exposed to ELF. In no instance out of a total of twenty separate experiments did this "double-insult" further delay entry of cells into mitosis, as had been anticipated. CONCLUSION: This apparently "non-genotoxic" agent (ELF) appears to be capable of affecting cells that would normally arrest for longer in G2, suggesting a weakening of the stringency of the late cycle (G2) checkpoint.

Journal Article↗