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PubMed1985

The suitability of transfer coefficients used for stochastic calculations in radioecology.

In radioecology, stochastic calculations are used to an increasing extent. It is shown that transfer coefficients which are defined as concentration ratios are not suited for stochastic calculations, at least for essential elements and their antagonists. The reason is that essential elements are regulated in plants and animals whereby their concentrations vary within narrow limits, rather independent of the concentrations in the source compartment. For a more accurate description of the transfer of radionuclides, it is proposed to include the concentrations of the essential elements in the source and target compartments into the transfer equation which leads to the specific activity model. This model has already been proposed by Comar et al. in 1956. It seems to work accurately for the transfer into animals and their products as well as into plants. Examples of its applicability are presented and discussed. Furthermore stochastic calculations seem to be more reasonable with this model.

Animals↗
PubMed1995

Risk assessment of essential trace elements: new approaches to setting recommended dietary allowances and safety limits.

By definition, every essential trace element must have a range of intakes safe from toxicity but adequate enough to meet nutrition requirements. That range is part of the total dose-response curve and its lower and upper limits are delineated on the basis of nutrition and toxicology data, respectively. Close coordination of activities to set these limits is necessary to avoid recommendations that are either impractical (narrow zones of safe and adequate intakes) or contradictory (overlapping limits, i.e., no zones of safe and adequate intakes).

Biological Availability↗
PubMed1986

Silicon as an essential trace element in animal nutrition.

Within the last decade silicon has been recognized as participating in the normal metabolism of higher animals and as being an essential trace element. Silicon is found to perform an important role in connective tissue, especially in bone and cartilage. Bone and cartilage abnormalities are associated with a reduction in matrix components, resulting in the establishment of a requirement for silicon in collagen and glycosaminoglycan formation. Silicon's primary effect in bone and cartilage is on the matrix, with formation of the organic matrix appearing to be more severely affected by silicon deficiency than the mineralization process. Additional support for silicon's metabolic role in connective tissue is provided by the finding that silicon is a major ion of osteogenic cells and is present in especially high concentrations in the metabolically active state of the cell; furthermore, silicon reaches relatively high levels in the mitochondria of these cells. Further studies also indicate that silicon participates in the biochemistry of the subcellular enzyme-containing structures. Silicon also forms important interrelationships with other elements. Although it is clear from the body of recent work that silicon performs a specific metabolic function, a structural role has also been proposed for it in connective tissue. A relationship established between silicon and ageing probably relates to glycosaminoglycan changes.

Animals↗
PubMed1995

Requirements and toxicity of essential trace elements, illustrated by zinc and copper.

Early signs of toxicity of essential trace elements are important. Some trace elements are available over-the-counter (OTC) and/or are present at industrial waste sites. Physicochemically similar trace elements compete for ligands, impairing functions, which is exemplified by the zinc-copper antagonism described long ago by Van Campen, Hill and Matrone, and Klevay. Intestinal absorption of copper is inhibited by zinc. Thus risk of copper deficiency is increased when the molar ratio of zinc to copper (Zn:Cu) is high. As shown by experiments, copper deficiency can occur in humans. Manifestations include decreased erythrocyte copper-zinc superoxide dismutase, increased low-density-lipoprotein cholesterol, decreased high-density-lipoprotein cholesterol, decreased glucose clearance, decreased methionine and leucine enkephalins, and abnormal cardiac function. Calculation of a preliminary reference dose for OTC zinc that assumed high bioavailability and uncertain copper intakes established 9 mg as a safe amount for 60-kg adults.

Animals↗
PubMed1995

The NF-kappa B-like site in the TNF-alpha repressor element is essential for its repressor function.

We have previously identified a repressor element in the TNF-alpha promoter (-280 to -172) by deletion analysis. When this 108 bp repressor element was placed in front of a heterologous promoter containing an NF-kappa B binding site, less repression was observed. When this element was dimerized and placed in front of the positive element (-125 to -102) of the TNF-alpha promoter, instead of repression, activation was observed. There is an NF-kappa B-like site in the 108 bp repressor region (-211 to -202) and our gel retardation analysis showed that this site and a known NF-kappa B binding site both could compete for one of the specific protein complexes formed on the 108 bp probe. To test the functionality of this NF-kappa B-like site, we mutagenized the critical GGGG sequence to ATCC. Contrary to our prediction, such a mutation blocked the repressor function of the 108 bp element. This suggests that the NF-kappa B-like site is an essential sequence for the repressor function of the 108 bp repressor element.

Base Sequence↗
PubMed1989

[Effects of total parenteral nutrition containing essential trace elements on their concentrations in rats].

Twenty-four rats were equally divided into 4 groups and maintained for 1 week as follows: Group A (normal control) with a synthetic normal diet and distilled water, group B with conventional total parenteral nutrition (TPN), i.e., TPN without essential trace elements (ETE), group C with TPN supplemented with a usual dose of ETE solution (TE-5), and group D with TPN supplemented with 3 times the usual dose of TE-5. Body weight, trace element concentrations in various tissues and certain blood biochemical parameters were determined in these rats. The results were as follows: 1) No significant differences in body weight were observed among the groups. 2) The iron concentrations in plasma and tibia decreased significantly in group B as compared with group A. The addition of TE-5 prevented these decreases, but dose-dependent increases in the concentrations of iron were observed in liver, spleen and kidney (groups C and D). 3) The zinc concentrations in plasma, whole blood, brain, heart, kidney and tibia decreased significantly in group B as compared with group A. The addition of TE-5 prevented these decreases dose-dependently (groups C and D). 4) The copper concentrations in plasma, whole blood, liver, spleen, kidney, testis and tibia decreased significantly in group B as compared with group A. The addition of TE-5 resulted in a tendency for these decreases to diminish (groups C and D). 5) The manganese concentrations of whole blood in group B decreased significantly as compared with group A. The addition of TE-5 caused the manganese concentrations of various tissues in groups C and D to increase significantly as compared with group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Lethal and temperature-sensitive mutations and their suppressors identify an essential structural element in U2 small nuclear RNA.

U2 snRNA is an essential component of the splicing apparatus in eukaryotic cells. Three possible secondary structures for the highly conserved 5' half of U2 snRNA are consistent with U2 phylogenetic sequence variation. To distinguish among these models and to test the function of U2 structural elements, we made greater than 35 mutations in the yeast U2 snRNA gene. Some of the mutations were designed in pairs so that combinations could be made that would restore base-pairing to differentiate helix requirements from primary sequence requirements. The mutations identify an essential stem-and-loop structure adjacent to the branchpoint interaction region. A conserved complementarity to the loop just upstream of the Sm site and an additional conserved stem-loop are dispensable for U2 function, even in the background of a previously identified large internal deletion. Non-Watson-Crick base appositions at the 53-62 base pair in the essential stem lead to a variety of temperature and KCl-sensitive phenotypes, as well as an accumulation of unspliced precursors in vivo. Chemical structure probing of U2 RNA in vivo reveals that the bulk of U2 in a yeast cell adopts a structure in good agreement with that deduced from genetic results. We suggest that this stem-loop is not a binding site for an intrinsic U2 snRNP protein but may interact with other factors during spliceosome assembly or splicing.

Base Sequence↗
PubMed1992

A transcriptionally active tRNA gene interferes with nucleosome positioning in vivo.

Incorporation into a positioned nucleosome of a cis-acting element essential for replication in Saccharomyces cerevisiae disrupts the function of the element in vivo [R. T. Simpson, Nature (London) 343:387-389, 1990]. Furthermore, nucleosome positioning has been implicated in repression of transcription by RNA polymerase II in yeast cells. We have now asked whether the function of cis-acting elements essential for transcription of a gene transcribed by RNA polymerase III can be similarly affected. A tRNA gene was fused to either of two nucleosome positioning signals such that the predicted nucleosome would incorporate near its center the tRNA start site and essential A-box element. These constructs were then introduced into yeast cells on stably maintained, multicopy plasmids. Competent tRNA genes were transcribed in vivo and were not incorporated into positioned nucleosomes. Mutated, inactive tRNA genes were incorporated into nucleosomes whose positions were as predicted. This finding demonstrates that the transcriptional competence of the tRNA gene determined its ability to override a nucleosome positioning signal in vivo and establishes that a hierarchy exists between cis-acting elements and nucleosome positioning signals.

Base Sequence↗
PubMed1987

Simultaneous determination of Pt and essential trace elements in plasma by energy dispersive x-ray fluorescence (EDXRF).

Energy dispersive x-ray fluorescence allows the simultaneous determination of platinum and essential trace-elements in plasma and filtered plasma. Pharmacokinetics of platinum and the variations of trace-elements levels with respect to the normal mean values before and during the treatment are reported. Particularly during the treatment we observed that total iron concentration clearly increases in plasma, which suggests a hemolytic effect of the drug. However we can exclude this hypothesis by the simultaneous determination of potassium and rubidium levels, which do not increase as greatly as in hemolysed samples.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Lethal mutations in a yeast U6 RNA gene B block promoter element identify essential contacts with transcription factor-IIIC.

The B block promoter element is the primary binding site for the RNA polymerase III transcription initiation factor TFIIIC. It is always located within the transcript coding region, except in the Saccharomyces cerevisiae U6 RNA gene (SNR6), in which the B block lies 120 base pairs downstream of the terminator. We have exploited the unique location of the SNR6 B block to examine the sequence specificity of its interaction with TFIIIC. The in vitro and in vivo effects of all possible single base pair substitutions in the 9-base pair core of the B block were determined. Five mutant alleles are recessive lethal when present at a low copy number; these alleles identify crucial contacts between TFIIIC and the B block promoter element. Transcript analysis reveals that lethal B block substitutions reduce U6 RNA synthesis at least 10-fold in vivo and 20-fold in vitro. One viable B block mutant strain has one-third the wild type amount of U6 RNA and exhibits reduced levels of the U4-U6 RNA complex required for spliceosome assembly. The locations of lethal single and double point mutations leads us to propose that two domains of TFIIIC contact overlapping sites on the B block element.

Alleles↗
PubMed2026

Fluoride as a Modifier of Metallome Homeostasis: A Systematic Review of Animal Studies.

Fluoride is widely used for caries prevention due to its effects on mineralized tissues, yet its potential role as a modifier of systemic metal homeostasis remains insufficiently explored. This systematic review synthesizes preclinical evidence on the association between fluoride exposure and changes in metal and semi-metal concentrations across biological matrices. A comprehensive search strategy was conducted across major databases without language or date restrictions, following SyRF, CAMARADES and PRISMA 2020 guidelines. Thirty-one animal studies were included, encompassing multiple species, exposure conditions and analytical approaches. Despite substantial methodological heterogeneity, consistent patterns emerged. Fluoride exposure was associated with element-specific redistribution of the metallome rather than uniform change. Essential elements were predominantly depleted, most consistently zinc, copper and manganese, whereas the toxic metals lead and cadmium tended to be retained. This contrast between homeostatically regulated essential elements that are lost and non-regulated toxic metals that accumulate supports the hypothesis that fluoride differentially modifies the distribution and retention of co-existing elements. The novelty of this review lies in integrating metallomic outcomes across experimental models, highlighting fluoride as a potential systemic modulator rather than a tissue-specific agent. Although variability in study design and risk of bias limits causal inference, the consistent directionality of findings across models reinforces their biological plausibility and translational relevance.

Animals↗
PubMed2024

Association of urinary levels of trace metals with type 2 diabetes and obesity in postmenopausal women in Korea: A community-based cohort study.

Several toxic metals have been associated with metabolic diseases like obesity and diabetes mellitus (DM) in humans. However, knowledge regarding the influence of many trace elements, especially in combination with essential elements is limited. This study aims to address this research gap by investigating the associations of both non-essential and essential inorganic trace elements in urine with DM and obesity, employing a group of postmenopausal women (n = 851) from the Korean Genome and Epidemiology Study (KoGES) cohort. Urine samples were collected during 2017-2018, and were analyzed for 19 trace elements using inductively coupled plasma-mass spectrometry and an automatic mercury analyzer. Outcomes of interest were metabolic diseases (DM and obesity) and DM-related traits (insulin resistance and β-cell function). After adjustment of covariates, such as age, alcohol consumption, smoking status, educational level, and daily energy intake, urinary Zn, Ni, Tl, and U levels were associated with the prevalence of DM and homeostatic model assessment (HOMA) for insulin resistance (IR) in the postmenopausal women. In the whole mixture model, however, no significant association was observed for the prevalence of DM. Urinary levels of Zn were negatively associated with HOMA of β-cell function (HOMA-β), positively correlated with HbA1c levels, HOMA-IR, and prevalent DM. In addition, urinary Zn, Co, Tl, and Cs were positively associated with obesity (body mass index ≥25 kg/m2). The present observation shows that several individual elements and their mixtures may be associated with the prevalence of DM, IR, or obesity.

Humans↗
PubMed1994

A conserved upstream element is essential for transcription of the Leishmania tarentolae mini-exon gene.

We demonstrate that the mini-exon genes of Leishmania tarentolae are individually transcribed by an enzyme pharmacologically identified as RNA polymerase II. To study transcription in these ancient eukaryotes, a stable transformation assay using an episomal mini-exon gene was developed. The introduced mini-exon gene, which had been marked with a 40 bp tag, yielded the predicted tagged transcript. An upstream cis-acting element that was essential for transcription of the mini-exon gene was identified by site-directed mutagenesis. Block substitution mutagenesis of the -1 to +9 and +10 to +19 regions of the exon results in 20- to 100-fold decreased levels of the tagged transcript in steady-state RNA. However, since these two mutations resulted in only a 2- to 3-fold decrease in nascent RNA levels, steady-state levels appear to be affected greatest by the stability of the resulting transcript. In contrast, mutation of the -67/-58 region resulted in undetectable levels of both steady-state and nascent RNA from the introduced gene. We conclude, therefore, that this upstream element, which is highly conserved in all Leishmania species, is a component of the mini-exon gene promoter.

Animals↗
PubMed1993

[Gynecologic oncology and clinical trials].

Clinical trials have been developed tremendously in oncology because of its clear endpoints. In Japan, however, a concept of clinical trial has not been so accepted for long time. Recently, Minister of Health and Welfare announced guide lines of clinical evaluation of anticancer drug and statistical analysis. Elements essential to design of clinical trials are following; the first element is a clearly stated hypothesis. The hypothesis must be testable, that is, the investigator must have a clear idea of how these differences will be determined in this study subjects. The trial must have a well documented protocol and have a well defined primary endpoint by which the anticipated effect of the new treatment will be evaluated. Although one or two secondary endpoints may also be identified in the trial, the primary endpoint is the major focus of the trial and determines trial design, size, and early stopping rules. The clinical trial must be appropriately designed so that the hypothesis can be adequately tested and evaluated. The study may compare the new therapy to a standard treatment or assess the basic characteristics of the treatment. The clinical trial must be designed so that adequate sensitivity (significance level) and power to provide a high degree of confidence that results are not spurious. The next critical aspect to the performance of a successful clinical trial is the ability to accrue adequate numbers of patients within a reasonable period of time for the study to be completed. The next essential element to the design of a clinical trial is the prospective selection of statistical tool appropriate to the data to be collected.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

A 20 nucleotide upstream element is essential for the nopaline synthase (nos) promoter activity.

The nopaline synthase (nos) promoter is expressed in a wide range of plant cell types and regulated by various developmental and environmental factors. The nos upstream control region essential for this regulation was studied by means of synthetic oligomers using transient and stable transformation systems. Insertion of a 20 nucleotide sequence containing two hexamer motifs and a spacer region into deletion mutants lacking the upstream control region was essential for promoter activity. Mutation of one or more nucleotides of either hexamer sequence significantly altered the strength of expression of the nos promoter. Point mutations within the spacer region also strongly influenced promoter strength. Insertion of multiple copies of the 20 nucleotide sequence into the nonfunctional deletion mutants proportionally increased the promoter activity. These results suggest that this twenty nucleotide sequence is essential for the nos promoter to function. Substitution of the nos element with the ocs or 35S as-1 which contain similar hexamer motifs restored not only promoter activity but also responses to wounding, auxin, methyl jasmonate, and salicylic acid.

Amino Acid Oxidoreductases↗
PubMed1983

Vigorous supplementation of a hypocaloric diet prevents cardiac arrhythmias and mineral depletion.

We have previously demonstrated that a hypocaloric, nutritionally deficient, liquid protein diet is associated with potentially life-threatening cardiac arrhythmias, which increased in frequency and complexity over the duration of the study. The present investigation was designed to evaluate the metabolic and cardiac changes associated with a hypocaloric, but otherwise nutritionally complete, diet. Six healthy, obese females from 154 to 182 percent of ideal body weight were evaluated in a metabolic ward for 48 days. The subjects ingested a weight maintenance diet during an eight-day period, which was followed by 40 days of an experimental diet containing 472 kcal of a mixture of protein (60 percent of calories), carbohydrate (25 percent), and fat (15 percent). This diet equaled or exceeded the recommended daily allowances for minerals, trace elements, vitamins, and essential fatty acids. The subjects were monitored for balances of nitrogen and minerals, as well as for the appearance of cardiac arrhythmias by 24-hour electrocardiographic recordings. Nitrogen balance was positive, and the previously demonstrated negative balances for potassium, sodium, calcium, magnesium, and phosphorus were either reversed or markedly decreased. In contrast to our previous study, no arrhythmias were observed in subjects ingesting the present experimental diet, and no significant change in cardiac rhythm was found in 13 obese, but otherwise healthy, outpatients. The data, based on a limited number of subjects, suggest that a hypocaloric diet vigorously supplemented with essential elements, micronutrients, and vitamins appears to be safer than the once popular, incomplete liquid protein preparation.

Adult↗
PubMed1989

Identification of a promoter region for 3.6-kilobase mRNA of hepatitis B virus and specific cellular binding protein.

The promoter region for transcription of the 3.6-kilobase mRNA of hepatitis B virus was identified by the chloramphenicol acetyltransferase assay by using HuH-7 hepatoma cells and was found to function directly in virus production by way of the transient expression system of HBV. The 5'-upstream sequence from nucleotides 1573 to 1657 (the transcription start site) was indispensable for promoter function, while the AT-rich sequence (from nucleotides 1581 to 1604) containing a directly repeated sequence TGTT connecting the same flanking sequence PyAAAGAC (where Py is a pyrimidine) at both sides was an essential element within this promoter region. A specific cellular factor which interacted with the essential element was detected in the HuH-7 cell extract. A similar binding factor was also observed in HepG2 and huH2-2 hepatoma cells. This factor may thus be responsible for regulating 3.6-kilobase mRNA, pregenome RNA transcription, or both.

Base Sequence↗