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PubMed1988

The interaction of nuclear proteins with essential promoter element of the chicken cardiac myosin light chain 2 gene is involved in muscle-specific transcription.

A quantitative microinjection procedure has been developed to demonstrate muscle-specific transcription of the myosin light chain 2-A (MLC2-A) promoter in differentiated chicken primary breast muscle cells. Nuclear protein binds to the distal region of the required promoter sequence but not to a mutated version of this sequence. The functional significance of this specific DNA-protein interaction for the promoter activity is demonstrated by 'in vivo' competition of microinjected MLC-CAT reporter construct together with excess of synthetic oligonucleotides encompassing the protein binding sites.

Animals↗
PubMed1984

Concentrations of four essential trace elements in breast milk of mothers from two socio-economic groups: preliminary observations.

Concentrations are reported for Cu, Mn, Mo and Zn in human milk samples obtained from mothers belonging to low and middle per capita family income groups. The trace element levels in milk of both groups are compared for samples obtained at two stages, viz. 3-5 days and 4-6 weeks post partum. Although the Mn level during the first stage appears to be lower in samples from the low income group, the difference is not statistically significantly (p less than or equal to 0.01). However, at 4-6 weeks post partum, Zn is significantly lower (p less than or equal to 0.01) in milk of mothers belonging to this group.

Copper↗
PubMed1988

Carcinogenesis as the result of the deficiency of some essential trace elements.

"Energetic" biological trace elements [gallium (III), germanium (IV), silicon (silica), arsenic (V) and selenium (IV)] occurring in DNA of eukaryotic cells may improve the semiconductor properties of DNA and may influence the mechanisms that control genetic expression at the electronic level. Their roles are postulated as follows: (i) to maintain the level and direction of free sliding electrons in DNA, (ii) to modulate the electron conductivity and hole conductivity of DNA. This specific electronic nature of DNA take the form of magnetic pigeonholes in which an electric pulse is (0), or is not (1) stored as an area of local magnetisation. These types of conductivity occurring in different parts of DNA of different cells could participate in the switch on and switch off of genetic information in gene expression. This model may help to elucidate the mechanism of action of these naturally occurring antitumor agents and may help in understanding the role of trace elements in charge transport of DNA and in carcinogenesis.

Animals↗
PubMed2005

Maternal and umbilical cord blood levels of mercury, lead, cadmium, and essential trace elements in Arctic Canada.

Maternal and umbilical cord blood levels of mercury (Hg), lead (Pb), cadmium (Cd), and the trace elements copper (Cu), zinc (Zn), and selenium (Se) are reported for Inuit, Dene/Métis, Caucasian, and Other nonaboriginal participants from Arctic Canada. This is the first human tissue monitoring program covering the entire Northwest Territories and Nunavut for multiple contaminants and establishes a baseline upon which future comparisons can be made. Results for chlorinated organic pesticides and PCBs for these participants have been reported elsewhere. Between May 1994 and June 1999, 523 women volunteered to participate by giving their written informed consent, resulting in the collection of 386 maternal blood samples, 407 cord samples, and 351 cord:maternal paired samples. Geometric mean (GM) maternal total mercury (THg) concentrations ranged from 0.87 microg/L (SD = 1.95) in the Caucasian group of participants (n = 134) to 3.51 microg/L (SD = 8.30) in the Inuit group (n = 146). The GM of the Inuit group was 2.6-fold higher than that of the Dene/Métis group (1.35 microg/L, SD = 1.60, n = 92) and significantly higher than those of all other groups (P<0.0001). Of Inuit women participants, 3% (n = 4) were within Health Canada's level of concern range (20-99 microg/L) for methylmercury (MeHg) exposure. Of Inuit and Dene/Métis cord samples, 56% (n = 95) and 5% (n = 4), respectively, exceeded 5.8 microg/L MeHg, the revised US Environmental Protection Agency lower benchmark dose. GM maternal Pb was significantly higher in Dene/Métis (30.9 microg/L or 3.1 microg/dL; SD = 29.1 microg/L) and Inuit (31.6 microg/L, SD = 38.3) participants compared with the Caucasian group (20.6 microg/L, SD = 17.9) (P < 0.0001). Half of all participants were smokers. GM blood Cd in moderate smokers (1-8 cigarettes/day) and in heavy smokers (> 8 cigarettes/day) was 7.4-fold higher and 12.5-fold higher, respectively, than in nonsmokers. The high percentage of smokers among Inuit (77%) and Dene/Métis (48%) participants highlights the need for ongoing public health action directed at tobacco prevention, reduction, and cessation for women of reproductive age. Pb and THg were detected in more than 95% of all cord blood samples, with GMs of 21 microg/L and 2.7 microg/L, respectively, and Cd was detected in 26% of all cord samples, with a GM of 0.08 microg/L. Cord:maternal ratios from paired samples ranged from 0.44 to 4.5 for THg, from 0.5 to 10.3 for MeHg, and 0.1 to 9.0 for Pb. On average, levels of THg, MeHg, and Zn were significantly higher in cord blood than in maternal blood (P < 0.0001), whereas maternal Cd, Pb, Se, and Cu levels were significantly higher than those in cord blood (P < 0.0001). There was no significant relationship between methylmercury and selenium for the range of MeHg exposures in this study. Ongoing monitoring of populations at risk and traditional food species, as well as continued international efforts to reduce anthropogenic sources of mercury, are recommended.

Adult↗
PubMed2004

The plasmids of Borrelia burgdorferi: essential genetic elements of a pathogen.

The spirochete Borrelia burgdorferi, the causative agent of Lyme disease, has an unusual genome comprised of a linear chromosome and the largest plasmid complement of any characterized bacterium. Certain plasmid-encoded elements are required for virulence and viability, both in vitro and in vivo. The genetic tools to manipulate B. burgdorferi are sufficiently developed for precise molecular genetic investigations. B. burgdorferi now represents a prime system with which to address basic questions of plasmid biology and plasmid contributions to bacterial virulence and disease pathogenesis.

Animals↗
PubMed2005

Biofortifying crops with essential mineral elements.

Humans require more than 22 mineral elements, which can all be supplied by an appropriate diet. However, the diets of populations subsisting on cereals, or inhabiting regions where soil mineral imbalances occur, often lack Fe, Zn, Ca, Mg, Cu, I or Se. Traditional strategies to deliver these minerals to susceptible populations have relied on supplementation or food fortification programs. Unfortunately, these interventions have not always been successful. An alternative solution is to increase mineral concentrations in edible crops. This is termed 'biofortification'. It can be achieved by mineral fertilization or plant breeding. There is considerable genetic variation in crop species that can be harnessed for sustainable biofortification strategies. Varieties with increased mineral concentrations in their edible portions are already available, and new genotypes with higher mineral densities are being developed.

Crops, Agricultural↗
PubMed1997

Detecting subclinical deficiency of essential trace elements in children with special reference to zinc and selenium.

OBJECTIVE: This article reviews situations in which we should be alert to the risk of trace element deficiencies, and the difficulties of assessing trace element status, as illustrated by states of potential subclinical deficiency of zinc and selenium in infants. CONCLUSION: Deficiency states of many trace elements have been documented in infants, and there is probably an underdiagnosed group of infants with subclinical deficiency, from which however the great majority are protected by effective regulatory systems. Specific, sensitive, and reliable methods are needed for the detection of trace element imbalances.

Child↗
PubMed1999

Numerical simulation of nonlinear feedback model of saccade generation circuit implemented in the LabView graphical programming language.

The object-oriented graphical programming language LabView was used to implement the numerical solution to a computational model of saccade generation in primates. The computational model simulates the activity and connectivity of anatomical strictures known to be involved in saccadic eye movements. The LabView program provides a graphical user interface to the model that makes it easy to observe and modify the behavior of each element of the model. Essential elements of the source code of the LabView program are presented and explained. A copy of the model is available for download from the internet.

Animals↗
PubMed1997

Tissue-specific methylation occurs in the essential promoter element of the tyrosine hydroxylase gene.

Expression of tyrosine hydroxylase (TH) is regulated in a tissue-specific manner by multiple mechanisms. In catecholaminergic cells, the expression of TH-mRNA is up-regulated by forskolin (FK) and is suppressed by retinoic acid (RA). We have previously provided evidence that, in N-18 cells, the expression of TH-mRNA is suppressed by DNA methylation of the TH gene itself. In the present study, using a catecholaminergic cell line, N1E-115, we performed deletional and mutational analyses on the 5'-flanking region of the mouse TH gene. The results indicate that a cAMP response element (CRE) mediates constitutive transcription of the TH gene, as well as responsiveness to FK and RA. Using bisulfite sequencing methods, we analyzed the methylation status of the TH gene 5'-flanking region in various cell lines and rat tissues. We found that three cytosine residues in the domain surrounding the CRE of the TH gene promoter were specifically methylated in N-18 cells and TH non-expressing rat tissues. In contrast, these cytosines were undermethylated in TH expressing cell lines and tissues. The inverse correlation between the frequency of cytosine methylation at these specific sites and the levels of TH expression supports a role for DNA methylation in the regulation of tissue-specific gene expression.

Animals↗
PubMed1985

Physiology and metabolism of essential trace elements: an outline.

Man depends on at least nine trace elements--iron, zinc, copper, manganese, iodine, chromium, selenium, molybdenum and cobalt--for optimum metabolic function. These elements serve a variety of functions including catalytic, structural and regulatory activities in which they interact with macromolecules such as enzymes, pro-hormones, pre-secretory granules and biological membranes. These micronutrients are involved, therefore, in all major metabolic pathways at levels which are so fundamental that the features of deficiency of many of them are protean and non-specific. In considering the metabolism of the elements themselves, they fall into two groups: those which exist normally as cations and those present as anions. The latter group are absorbed relatively easily and whole-body homeostasis is mediated mainly by renal excretion. The cations need specific pathways for absorption and their homeostasis is effected by gastrointestinal and biliary secretion. Some elements are absorbed more efficiently as organic complexes. The net achievement of the metabolic pathways for each element is to deliver it to its functional site(s) by exploiting its physicochemical characteristics to avoid interactions with other inorganic nutrients.

Animals↗
PubMed1997

Essential promoter elements are located within the 5' untranslated region of human insulin-like growth factor-I exon I.

Multiple mechanisms regulate insulin-like growth factor-I (IGF-I) gene expression in mammals, including transcription from two promoters, alternative RNA splicing, and differential RNA polyadenylation. In previous studies we demonstrated that IGF-I promoter 1, the major human promoter, initiated transcription within a dispersed 158 nt segment of exon 1, and showed that full promoter activity required the entire 322 nt 5' untranslated region (UTR) of exon 1. We now have examined the functional significance of this highly conserved region by testing the activity of hybrid promoter-reporter genes containing various portions of the 5' UTR after transient transfection into the IGF-I-producing SK-N-MC cell line. Recombinant plasmids containing the entire 322 nt 5' UTR of exon 1 and a 1630 nt segment of 5' flanking sequence stimulated luciferase activity nearly 70 times higher than a promoterless control plasmid. Truncation to +198 had little effect on promoter function, while subsequent 3' deletions (to +111. +51, and +5) led to a stepwise decrease in reporter gene expression. Internal deletions of nt +6 to +50, +52 to +110, and +112 to +197 led to 65, 25, and less than 10% decreases in promoter function, respectively. Removal of the entire segment from +6 to +197 caused a complete loss of activity. Analysis for DNA-protein interactions by in vitro DNase-I footprinting identified a broad region of protection extending from nt -12 to +38. Further characterization by gel mobility shift assays indicated that several specific DNA-protein complexes could be formed in this region with nuclear protein extracts from SK-N-MC cells. Substitution mutations within the footprinted segment had deleterious effects on promoter function, and one mutation involving nt +10 to +20 resulted in a greater than 70% decline in reporter gene expression. Our results demonstrate that the initial portion of the 5' UTR of human IGF-I exon 1 is required for high level basal transcription of promoter 1 and provide a starting point for defining the nuclear factors regulating this component of IGF-I gene expression.

Base Sequence↗
PubMed1997

Availability of essential trace elements in Ayurvedic Indian medicinal herbs using instrumental neutron activation analysis.

Specific parts of several plants (fruits, leaves, stem, bark, and roots) often used as medicines in the Indian Ayurvedic system have been analysed for 20 elements (As, Ba, Br, Ca, Cl, Co, Cr, Cu, Fe, K, Mn, Mo, Na, P, Rb, Sb, Sc, Se, Sr and Zn) by employing instrumental neutron activation analysis (INAA). The samples were irradiated with thermal neutrons in a nuclear reactor and the induced activity was counted using high resolution gamma ray spectrometry. Most of the medicinal herbs have been found to be rich in one or more of the elements under study.

Humans↗
PubMed2000

Systematic circular permutation of an entire protein reveals essential folding elements.

The importance of chain connectivity in determining protein function and stability can be examined by breaking the peptide backbone using a technique such as circular permutation. Cleavage at certain positions results in a complete loss of the ability of the protein to fold. When such cleavage sites occur sequentially in the primary structure, we call the region a 'folding element', a new concept that could assist in our understanding of the protein folding problem. The folding elements of dihydrofolate reductase have been assigned by conducting a systematic circular permutation analysis in which the peptide backbone was sequentially broken between every pair of residues in the protein. The positions of folding elements do not appear to correspond to secondary structure motifs, substrate or coenzyme binding sites, or accessible surface area. However, almost all of the amino acid residues known to be involved in early folding events are located within the folding elements.

Binding Sites↗
PubMed2003

[Status of essential trace elements in untreated carcinomas of the head and neck].

BACKGROUND: The changed mineral status is well known in different tumor types. This phenomenon has influenced the redox potential of patients suffering from solid cancers. A prospective trial was conducted to evaluate the specifics for untreated head and neck cancer patients. MATERIAL AND METHODS: We included 100 patients with advanced squamous cell carcinoma of the head and neck region before each kind of treatment. Following serum-concentrations were measured by atom absorption spectrometry: selenium, copper, zinc, and ferrum. Additionally we evaluated the activity of glutathion peroxidase and the concentration of malondialdehyde of the serum. RESULTS: 66 % of all patients have shown a decreased serum-concentration of selenium. These patients were additionally characterized by decreased activities of endogenous glutathionperoxiase. A third of all patients had decreased zinc and iron levels. Copper was found enhanced in 30 %. In trend the malondialdehyde was increasing due to decreasing selenium levels. CONCLUSIONS: Head neck cancer patients show the same characteristic trace element status as other solid tumors: decreased selenium, zinc and iron, increased copper. The therapeutic consequences of these observations are still unclear.

Adult↗