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PubMed1998

Review of the scientific basis for establishing the essentiality of trace elements.

The recent Expert Consultation of World Health Organization (WHO)/Food and Agricultural Organization (FAO)/International Atomic Energy Agency (IAEA) defined essentiality of a trace element as follows: "An element is considered essential to an organism when reduction of its exposure below a certain limit results consistently in a reduction in a physiologically important function, or when the element is an integral part of an organic structure performing a vital function in the organism." This definition omits a previous postulate that the mechanism of action of an essential trace element should be well defined; it also supersedes another criterion, once suggested for essentiality, a normal, rather than log-normal distribution of an element's tissue concentrations. The Expert Consultation offers no generally applicable criteria for the physiological importance of functions, and that determination is left to expert groups charged with setting national and other nutritional recommendations. The use of the term "physiological" rather than "biochemical" strongly implies that neither changes of an element's concentration nor of a specific enzyme function alone are proof of essentiality. Among physiologically important functions are growth, reproduction, longevity, and all metabolic and hormonal functions that bear a clear, inverse relation to disease risk. Finally, the term "consistent" states the need for independent confirmation of the original data, before an element can be recognized as essential. These definitions will be discussed as background for further discussions of our present knowledge of boron (B).

Animals↗

PubMed2003

Maintenance and regulation of mRNA stability of the Saccharomyces cerevisiae OLE1 gene requires multiple elements within the transcript that act through translation-independent mechanisms.

The Saccharomyces cerevisiae OLE1 gene encodes a membrane-bound Delta-9 fatty acid desaturase, whose expression is regulated by unsaturated fatty acids through both transcriptional and mRNA stability controls. In fatty acid-free medium, the mRNA has a half-life of 10 +/- 1.5 min (basal stability) that drops to 2 +/- 1.5 min when cells are exposed to unsaturated fatty acids (regulated stability). A deletion analysis of elements within the transcript revealed that the sequences within the protein-coding region that encode transmembrane sequences and a part of the cytochrome b5 domain are essential for the basal stability of the transcript. Deletion of any of the three essential elements produced unstable transcripts and loss of regulated instability. By contrast, substitution of the 3'-untranslated region with that of the stable PGK1 gene did not affect the basal stability of the transcript and did not block regulated decay. Given that Ole1p is a membrane-bound protein whose activities are a major determinant of membrane fluidity, we asked whether membrane-associated translation of the protein was essential for basal and regulated stability. Insertion of stop codons within the transcript that blocked either translation of the entire protein or parts of the protein required for co-translation insertion of Ole1p had no effect. We conclude that the basal and regulated stability of the OLE1 transcript is resistant to the nonsense-mediated decay pathway and that the essential protein-encoding elements for basal stability act cooperatively as stabilizing sequences through RNA-protein interactions via a translation-independent mechanism.

3' Untranslated Regions↗

PubMed1995

Structure and role of the terminal repeats of Epstein-Barr virus in processing and packaging of virion DNA.

The linear virion Epstein-Barr virus (EBV) DNA is terminated at both ends by a variable number of direct, tandemly arranged terminal repeats (TRs) which are approximately 500 bp in size The number of TRs at each terminus can vary. After infection of host cells, the EBV DNA circularizes via the TRs by an unknown mechanism, and replication of the viral DNA during the lytic phase of the EBV life cycle leads to large DNA concatemers which need to be cleaved into virion DNA units, eventually. This cleavage event occurs at an unknown locus within the TRs of EBV, which are the cis-acting elements essential for cleavage of the concatemers and encapsidation of the virion DNA. To investigate the mechanism of DNA processing during genome circularization and cleavage of concatemeric DNA, the genomic termini of EBV were cloned, sequenced, and analyzed by direct labeling of the virion DNA. Both termini ended with identical 11-bp elements; the right end has acquired an additional 9-bp stretch that seemed to originate from the leftmost unique sequences. The left terminus is blunt, whereas the right terminus appears to have a 3' single-base extension. In a transient packaging assay, a single terminal repeat was found to be sufficient for encapsidation of plasmid DNA, and mutagenesis of the TR element defined a region of 159 bp, including the 11-bp element, which is essential for packaging. These results indicate that the genomic termini of EBV are not generated by a simple cut of a hypothetical terminase. The mechanism for cleavage of concatemers seems to involve recombination events.

Base Sequence↗

PubMed2005

Health information system reform in South Africa: developing an essential data set.

Health services are increasingly under pressure to develop information systems that are responsive to changing health needs and appropriate to service objectives. Developing an essential data set provides managers with a clearly defined set of indicators for monitoring and evaluating services. This article describes a process that resulted in the creation of an essential data set at district level. This had a significant impact on neighbouring districts and resulted in the development of a regional essential data set, which in turn helped to influence the creation of a provincial and then national essential data set. Four key lessons may be drawn from the process. The development of an essential data set both requires and can contribute to a process that allows the reporting requirements to be adjusted over time in response to changing circumstances. In addition, it contributes to (and requires) the integration of programme reporting requirements into a coherent information system. While the case study describes a bottom-up approach, a top-down consultative process is advocated because it establishes a framework within which information needs can be reviewed. Lastly, the use of surveys can aid efforts to keep the essential elements to a minimum. In conclusion, the development of an essential data set contributes to strengthening health services because it necessitates dialogue between programme managers and defines indicators to be monitored by them.

Community Health Services↗

PubMed1995

The status of trace elements in staple foods. II. Some effects of cereal and potato processing.

The effects of food processing on some cereal and potato products are discussed with respect to the status of 11 trace elements. The influences of milling, bread making and cooking of potatoes on the contents of trace elements are demonstrated. It is shown that these recently obtained results are quite representative for the former federal Republic of Germany (FRG) as compared with results published previously. Average intake levels of undesired elements such as cadmium and lead, as well as of essential elements such as calcium, copper, iron, magnesium, manganese, molybdenum, nickel, selenium and zinc via consumption of cereal and potato products are calculated.

Edible Grain↗

PubMed1997

Iron, copper, and zinc absorption and turnover; the use of stable isotopes.

This overview demonstrates the increasing use of low natural abundance stable isotopes in the investigation of mineral metabolism. There are many practical problems associated with their use and analysis and their expense has limited their application in some areas such as studies in adults. Undoubtedly we will have to assess our ideas and protocols as the practical problems and their metabolic implications become better appreciated but none the less, the use of such isotopes will certainly refine our understanding of the way the body uses elements such as zinc, copper, iron and selenium and other essential elements and will enable us to determine our dietary requirements for these nutrients and to find ways of detecting more efficiently early deficiency and toxicity states.

Biological Availability↗

PubMed2000

Assessment of reference values for elements in human hair of urban schoolboys.

Hair samples of youngsters (3-15 years of age) from several urban areas of Rome were analyzed to determine the content of 19 minor and trace elements with the aim of assessing Reference Values (RVs). Thirteen essential elements were taken into account, Ca, Co, Cr, Cu, Fe, Mg, Mn, Mo, Ni, P, Se, V and Zn. On the other hand, Al, As, Cd, Pb, Sr and Ti were also evaluated on the basis of their potential toxicity. Procedures were developed for the collection, storage and pre-analytical treatment of samples. Measurements were performed by inductively coupled plasma atomic emission spectrometry. Subgroups were formed according to age and sex. Significant differences were found for certain elements depending on age and sex. This was the case, e.g., for Ca which showed a mean value of 336 mg/kg for males and of 537 mg/kg for females. The sex-dependent pattern for this element was also apparent when the three age subgroups of 3-6, 7-10 and 11-15 years were compared. The overall RVs obtained (mg/kg) are as follows Al, 10.2; As, 0.09; Ca, 450; Cd, 0.23; Co, 0.67; Cr, 0.99; Cu, 22.1; Fe, 19.0; Mg, 28.0; Mn, 0.35; Mo, 0.43; Ni, 1.49; P, 195; Pb, 7.11; Se, 0.77; Sr, 1.20; Ti, 0.79; V, 1.22; and Zn 150.

Adolescent↗

PubMed2000

Setting up a multidisciplinary clinic.

Chronic pelvic pain can be a perplexing and complex problem, frustrating to both clinicians and patients. The traditional medical and surgical model does not always relieve symptoms, and many patients suffer years of pain and undergo multiple surgical procedures without long-term benefit. The biopsychosocial model for chronic pelvic pain gives clinicians the opportunity to broaden the scope for management. A multidisciplinary team can offer simultaneous assessment and management of somatic, behavioural and psychosocial components of the pain. Key members of the team are identified and their roles explored. Practical aspects of operating a multidisciplinary clinic are discussed. A multidisciplinary approach comprises many elements. Further research is needed to identify which are the essential elements to secure optimum outcome for the individual patient.

Chronic Disease↗

PubMedDate not supplied

Iron and chronic viral hepatitis: emerging evidence for an important interaction.

Iron is an essential element for cell survival; it serves as a cofactor for essential enzymes in oxidative metabolism and (in the form of heme) as the major oxygen transporter in most forms of life on earth. Both deficiency and excess of iron often lead to disease. Iron is necessary for the proliferation of microorganisms and neoplastic cells. The presence of iron overload facilitates infection, as evidenced by the increased risk of persons with hemochromatosis to certain infections and by the fact that patients with lesser amounts of hepatic iron appear to respond better to interferon therapy for chronic viral hepatitis than those with larger amounts of hepatic iron. Viral hepatitis is a common cause of morbidity and mortality. Recent studies suggest that there is a key link between iron metabolism and the pathophysiology of viral hepatitis. The lobular and cellular distribution of iron in the liver may be as important as the total quantity of iron present. Whether iron removal will prove useful in the long-term management of chronic viral hepatitis is an issue in need of further well-designed, randomized, controlled trials.

Chronic Disease↗

PubMed1992

A yeast chromosomal origin of DNA replication defined by multiple functional elements.

Although it has been demonstrated that discrete origins of DNA replication exist in eukaryotic cellular chromosomes, the detailed organization of a eukaryotic cellular origin remains to be determined. Linker substitution mutations were constructed across the entire Saccharomyces cerevisiae chromosomal origin, ARS1. Functional studies of these mutants revealed one essential element (A), which includes a match to the ARS consensus sequence, and three additional elements (B1, B2, and B3), which collectively are also essential for origin function. These four elements arranged exactly as in ARS1, but surrounded by completely unrelated sequence, functioned as an efficient origin. Element B3 is the binding site for the transcription factor-origin binding protein ABF1. Other transcription factor binding sites substitute for the B3 element and a trans-acting transcriptional activation domain is required. The multipartite nature of a chromosomal replication origin and the role of transcriptional activators in its function present a striking similarity to the organization of eukaryotic promoters.

Amino Acid Sequence↗

PubMed2000

Essentiality of selenium in the human body: relationship with different diseases.

In the present review different aspects related to the essential element selenium in the human organism are considered. A large number of human studies have been performed in order to improve knowledge on the influence of this element in the origin and development of several degenerative diseases. Selenium deficiencies among human beings as well as animals are being recognized worldwide to be related to a number of pathologies. This element has also the special characteristic that the range between its essential and toxic character is very close, and consequently daily dietary intake should be appropriately monitored in individuals. Nevertheless, nowadays there is still a lot of controversy about the optimum dietary level of this element in order to cure or to prevent the appearance of diseases such as cirrhosis, cancer, diabetes, or cardiovascular pathologies. Results obtained in several animal and epidemiological studies have indicated that Se could constitute a dietary factor with protective action against several degenerative diseases.

Biological Availability↗

PubMed1992

Two promoter elements are necessary and sufficient for expression of the sea urchin U1 snRNA gene.

The essential elements of the sea urchin L. variegatus U1 snRNA promoter were mapped by microinjection of a U1 maxigene into sea urchin zygotes. Two elements are required for expression: a distal sequence element (DSE) located between -318 and -300 and a proximal sequence element (PSE) centered at -55. Removal or alteration of other sequences conserved in different sea urchin snRNA U1 genes, including deletion of all sequence between -90 and -273, did not affect the expression. Sequences around the start site were not required for expression. Deletion of nucleotides between the PSE and the start site resulted in initiation inside the U1 coding region, suggesting that the PSE determines the start site of transcription. There is no obvious similarity between the sequences required for the sea urchin U1 snRNA expression and the sequences required for the expression of other sea urchin snRNAs.

Animals↗

PubMed1984

Nickel as a "newer trace element" in the nutrition of domestic animals.

Evidence is reviewed that indicates Ni is an essential element for the chick, rat, pig, sheep and goat. Although a number of possible functions for Ni have been proposed based on in vitro and in vivo studies, the physiological role of Ni in the mammalian or avian system is presently unknown. Rumen bacterial urease has been shown to be a Ni-dependent enzyme and Ni is a component of factor F430 present in methanogenic bacteria. Nickel can interact or influence the metabolism of a number of minerals. Interactions of Ni and Fe, Zn and Cu are discussed. The requirement for Ni is low (50 to 60 ppb) in chicks fed semipurified diets. Insufficient data are available to estimate the Ni requirement of swine. In ruminants, the Ni requirement appears to be higher than that for other animal species. Nickel supplementation to practical diets has increased gain, feed efficiency and ruminal urease activity in ruminants, but performance results have been inconsistent. Level of crude protein and urea are two factors that influence ruminant responses to dietary Ni. The greatest responses have been observed in ruminants fed low protein diets. Little is known concerning levels, forms and bioavailability of Ni in different feedstuffs. Nickel is homeostatically controlled in the animal's body and high levels of Ni are required to cause toxicity.

Animal Nutritional Physiological Phenomena↗

PubMedDate not supplied

Trace element content in fingernails and hair of a nonindustrialized US control population.

The concentrations of 17 elements in the nail and hair of 117 subjects from a nonindustrialized environment were determined by instrumental neutron activation analysis (INAA). A new method of statistical treatment that allows for more meaningful use of detection limit values was used to process the concentration data. Geometric means and standard errors are presented for each element, along with a summary of the effects of age, sex, and treatment on the concentration of each element. For nails, these data represent the first comprehensive study for several important elements. Correlations for each element between hair and nail were determined. With few exceptions, concentrations of nonessential trace elements were positively correlated in hair and nail, whereas concentrations of essential elements showed no correlations. The factors affecting concentrations and control levels must be considered in studying alterations in disease states.

Adolescent↗

PubMed1987

The abundance and in vitro DNA binding of three cellular proteins interacting with the adenovirus EIIa early promoter are not modified by the EIa gene products.

Specific protein binding on the EIa-inducible adenovirus EIIa early (EIIaE) promoter was analyzed by the sensitive electrophoretic band-shift assay and by protection against DNase I digestion. Three factors were identified, and precise mapping of the cognate-binding sites revealed their correspondence to promoter elements essential for constitutive EIIaE transcription. One binds to the major upstream element located between -82 and -64 (with respect to the major EIIaE cap site), another appears to interact with sequences on either side of this region, and the last one binds to an element located further upstream. Comparison of the binding activities of the factors present in extracts from cells infected with wild-type adenovirus (adenovirus type 5) or with the EIa deletion mutant dl312 did not reveal striking differences. Not only were the general binding patterns indistinguishable, but the concentration of each of the identified factors as well as their affinity for the cognate-binding sites were unchanged. Our results suggest that the EIa-mediated activation of the EIIaE transcription complexes involves appropriate interactions between transcription factors, rather than their increased binding to DNA.

Adenovirus Early Proteins↗

PubMed1993

RNA regulatory element BLE1 directs the early steps of bicoid mRNA localization.

Deployment of the bicoid morphogen gradient in early Drosophila embryos requires the prelocalization of bicoid mRNA to the anterior pole of the egg. This anterior localization is mediated by a cis-acting localization signal contained within the 3' untranslated region of the bicoid mRNA. Here we use a series of bicoid transgenes carrying small deletions in the 3' untranslated region to survey for functional elements that constitute the localization signal. We identify and characterize one essential element, BLE1, which specifically directs the early steps of localization. In addition, we find that many deletions within the bicoid mRNA 3' untranslated region impair but do not prevent localization. One such deletion specifically interferes with a later step in localization. Thus the bicoid mRNA localization signal appears to consist of multiple different elements, each responsible for different steps in the localization process.

Animals↗

PubMed2003

Trace elements in human physiology and pathology: zinc and metallothioneins.

Zinc is one of the most abundant nutritionally essential elements in the human body. It is found in all body tissues with 85% of the whole body zinc in muscle and bone, 11% in the skin and the liver and the remaining in all the other tissues. In multicellular organisms, virtually all zinc is intracellular, 30-40% is located in the nucleus, 50% in the cytoplasm, organelles and specialized vesicles (for digestive enzymes or hormone storage) and the remainder in the cell membrane. Zinc intake ranges from 107 to 231 micromol/d depending on the source, and human zinc requirement is estimated at 15 mg/d. Zinc has been shown to be essential to the structure and function of a large number of macromolecules and for over 300 enzymic reactions. It has both catalytic and structural roles in enzymes, while in zinc finger motifs, it provides a scaffold that organizes protein sub-domains for the interaction with either DNA or other proteins. It is critical for the function of a number of metalloproteins, inducing members of oxido-reductase, hydrolase ligase, lyase family and has co-activating functions with copper in superoxide dismutase or phospholipase C. The zinc ion (Zn(++)) does not participate in redox reactions, which makes it a stable ion in a biological medium whose potential is in constant flux. Zinc ions are hydrophilic and do not cross cell membranes by passive diffusion. In general, transport has been described as having both saturable and non-saturable components, depending on the Zn(II) concentrations involved. Zinc ions exist primarily in the form of complexes with proteins and nucleic acids and participate in all aspects of intermediary metabolism, transmission and regulation of the expression of genetic information, storage, synthesis and action of peptide hormones and structural maintenance of chromatin and biomembranes.

Animals↗

PubMed1996

Adequacy of dialysis: trace elements in dialysis fluids.

A number of considerations suggest that trace element disturbances might occur in dialysed patients. These must at least in part be ascribed to the dialysis treatment itself during which these constituents may either be transferred to or removed from the patient. Tap water must be considered as the main source of dialysate trace metal contamination. These can adequately be removed during water treatment provided that, in addition to softening and deionization, reverse osmosis is available. However, even in the presence of the latter devices the possibility of serious contamination of the dialysis fluids leading to either chronic or acute intoxications still exists. The addition of chemical concentrates may also contribute to the increased concentrations of a number of trace metals. The toxic effects of aluminium in dialysis patients are well known and at the present time the element is still responsible for the greater part of trace metal-related problems in dialysis patients. Hence, the need for regular monitoring of aluminium cannot be ruled out at present. Strategies for diagnosis and treatment of aluminium overload have been updated. Recent studies demonstrated the efficacy of low desferrioxamine doses in diagnosis and treatment of aluminium overload, and optimal schedules for administration of the chelator and duration of treatment have been presented. Recently, in an epidemiological survey serum silicon concentrations in dialysis patients were found to be increased up to 100-fold compared to subjects with normal renal function. Moreover, it was noted that silicon concentrations in the dialysis population differ from one centre to another and that increased levels are due to either the use of silicon-contaminated dialysis fluids or an increased oral intake of the element originating from a high silicon content in the drinking water. Besides aluminium and silicon, a transfer towards the patients during dialysis has also been reported for a number of other elements including copper, zinc, nickel, strontium and chromium. The possible consequences of dialysate contamination with these elements will briefly be dealt with in the present paper. In contrast to trace metal accumulation, removal of trace metals during dialysis may at least in part contribute to the relative deficiency of particular essential elements. Selenium deficiency has repeatedly been observed. In view of the element's well-known essential role in glutathion peroxidase activity and the association of its deficiency with the development of some malignant diseases, further studies on the clinical impact of decreased serum selenium in dialysis patients are worthwhile. In conclusion, trace metal dialysate contamination/ depletion may contribute to the disturbed trace element concentration in dialysis patients. Aluminium accumulation is still an important problem in clinical nephrology. The clinical importance of the accumulation/ deficiency of trace elements other than aluminium is not yet fully understood and deserves further investigation.

Aluminum↗