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Reversible tyrosine phosphorylation and cell cycle control.

In eukaryotic organisms, reversible tyrosine phosphorylation has been established as an important element in the regulation of cell growth and more recently as an essential element in the regulation of the cell division cycle. The activity of p34cdc2, a protein kinase whose activity is required for the entry of cells into mitosis, is tightly controlled by reversible phosphorylation at tyrosine 15. A complex network of interacting protein kinases and protein phosphatases regulate the state of p34cdc2 tyrosine phosphorylation and therefore the entry of cells into mitosis. In the fission yeast Schizosaccharomyces pombe, genes encoding several of these protein kinases and protein phosphatases have been obtained through genetic approaches. In this review, we will focus on the protein kinases encoded by wee1+, mik1+ and cdr1+/nim1+ and the protein phosphatases encoded by cdc25+ and pyp1+, pyp2+ and pyp3+. Homologs of many of these regulators have been identified and characterized in higher eukaryotes underscoring the importance of reversible tyrosine phosphorylation as a universal mechanism for the regulation of the cell division cycle.

CDC2 Protein Kinase↗

A methodology for supporting research and scholarship.

The Office for Nursing Research and Scholarship was established in the spring of 1999 in a school of nursing on a large health sciences campus. In the first 2 years of operation, 11 federal grants were developed and submitted; 5 are currently funded, 3 have received competitive priority scores, 2 are in revision, and 1 awaits review. Intramural and private funding and preparation of manuscripts for publication have noticeably increased during this interval. Objective and subjective evaluation data from users are encouraging and provide a means for continuous formative evaluation and improvement. Recently, we conducted a systematic assessment of our office, focusing on service use, successful aspects, and organization. Through the assessment, we identified a methodology for organization and the essential elements needed to support successful research and scholarship. This article describes the essential services and how they are interrelated and delivered and how we structure staff responsibilities to facilitate delivery.

Computer Systems↗

Premature termination of RNA polymerase II mediated transcription of a seed protein gene in Schizosaccharomyces pombe.

The poly(A) signal and downstream elements with transcriptional pausing activity play an important role in termination of RNA polymerase II transcription. We show that an intronic sequence derived from the plant seed protein gene (AmA1) specifically acts as a transcriptional terminator in the fission yeast, Schizosaccharomyces pombe. The 3'-end points of mRNA encoded by the AmA1 gene were mapped at different positions in S.pombe and in native cells of Amaranthus hypochondriacus. Deletion analyses of the AmA1 intronic sequence revealed that multiple elements essential for proper transcriptional termination in S.pombe include two site-determining elements (SDEs) and three downstream sequence elements. RT-PCR analyses detected transcripts up to the second SDE. This is the first report showing that the highly conserved mammalian poly(A) signal, AAUAAA, is also functional in S.pombe. The poly(A) site was determined as Y(A) both in native and heterologous systems but at different positions. Deletion of these cis-elements abolished 3'-end processing in S.pombe and a single point mutation in this motif reduced the activity by 70% while enhancing activity at downstream SDE. These results indicate that the bipartite sequence elements as signals for 3'-end processing in fission yeast act in tandem with other cis-acting elements. A comparison of these elements in the AmA1 intron that function as a transcriptional terminator in fission yeast with that of its native genes showed that both require an AT-rich distal and proximal upstream element. However, these sequences are not identical. Transcription run-on analysis indicates that elongating RNA polymerase II molecules accumulate over these pause signals, maximal at 611-949 nt. Furthermore, we demonstrate that the AmA1 intronic terminator sequence acts in a position-independent manner when placed within another gene.

3' Untranslated Regions↗

Bioregenerative [correction of bioregnerative] life support: not a picnic.

If humans are to live permanently in space, regenerative life support systems are an enabling technology and must replace the picnic approach of taking all supplies required for each mission. These systems are classified by technologies as either physical/chemical or bioregenerative. Both of these system-types can recycle water, remove carbon dioxide, produce oxygen, and recover essential elements from waste products. Bioregenerative can also produce food, thus, making it essential if humans are to exist in space independent of earth. A solely bioregenerative life support system includes plants as a biomass production module and microbial organisms in bioreactors as a resource recovery module. In the Advanced Life Support Program, bioregenerative life support systems are being investigated through a research and technology development project which includes large scale testing as part of the Breadboard Project and human tests conducted in the soon to be constructed BioPlex facility. Research and technology development efforts are directed toward optimizing biomass productivity in controlled chambers by developing light weight, energy efficient, and automated systems; recycling liquid and solid wastes; baselining the operation of bioreactors; determining system microbial stability; assessing chemical contamination; and building models required for long term system operations. The program will include space flight studies in the near future to determine if these life support technologies will function in microgravity. When a bioregenerative system is finally incorporated into a mission, the conversion from a picnic and resupply mentality to permanent recycling and independence from earth will be complete.

Biofilms↗

How well recommended are the recommended dietary allowances?

The Recommended Dietary Allowances serve two basic uses: As guidelines for planning diets and food supplies and as a tool for evaluating nutritional adequacy of food consumed. Establishing standards to serve these functions is not simple. Differences in individuals in different population groups dictate allowances with relatively high margins of safety to prevent deficiencies. Even so, anomalies arise. Surveys have shown that intakes of vitamin A and protein are likely to exceed their respective allowances. On the other hand, calcium and thiamin intakes of older women and iron in teenage boys and women in the reproductive years are difficult to meet in terms of nutrient density ratios. In addition, insufficient data make it impossible to set allowances for some essential trace elements--and, other essential elements may yet be discovered. Thus the allowances are not guaranteed to represent the totality of nutritional needs.

Adolescent↗

Trace elements and inflammatory response: implications for nutritional support.

The acute-phase response to injury or infection is associated with alteration in dynamics of many trace elements, particularly iron, zinc and copper. The fall in serum iron and zinc, and rise in serum copper, are brought about by changes in the concentration of specific tissue proteins controlled by cytokines, especially interleukin 1, tumor necrosis factor, and interleukin 6. These are generally believed to be beneficial aspects of the early acute phase response. One difficulty associated with these changes is that assessment of status for these elements is particularly difficult, since plasma concentration may bear little relationship to tissue status. Simultaneous assessment of the acute-phase response, for example, serum C-reactive protein, together with trace elements and monitoring changes in concentrations, may, however, permit interpretation of trace element requirements. Suggestions are made for the requirements for these and other essential elements during enteral or intravenous nutrition, together with proposed methods of interpreting laboratory tests.

Acute Disease↗

Teniasis: effect on element status of children.

The aim of this study was to investigate the changes of level of the essential elements of copper, magnesium, and zinc status in cases of teniasis in children. Copper, magnesium, and zinc levels were measured in 40 children who were positive for intestinal parasite of Taenia saginata. Scores were obtained for the positives and their 30 age- and sex-matched T. saginata-negative healthy children. The mean concentration of copper, magnesium, and zinc in blood showed no statistically difference in T. saginata-positive children than in their controls both in females (p>0.05) and males (p>0.05). However, a clear numerically decrease was observed especially in magnesium and zinc levels compared to the controls both in females and males. The average magnesium concentration in T. saginata-positive female children and male children were 20+/-1.9 and 22+/-2.2 mg/L and it was 27+/-2.1 and 27+/-2.3 mg/L in controls, respectively. The mean values of the zinc in blood were 0.76+/-0.5 and 0.72+/-0.4 mg/L in T. saginata-positive female children and male children and 0.85+/-0.3 and 0.81+/-0.5 mg/L in female and male controls, respectively. No correlation could be demonstrated between age and mean values of copper, magnesium, and zinc in T. saginata-positive females and males and controls (p>0.05). No significant correlation could be found between blood copper, magnesium and zinc levels in T. saginata-positive female and male children and controls (p>0.05). Although there was no statistical correlation observed in copper, magnesium, and zinc levels between patients and controls, there seem to be, especially in magnesium and zinc levels, a decrease, whereas no change was seen in the zinc level in children infected with T. saginata compared to controls.

Case-Control Studies↗

Therapeutic communities: diversity in treatment elements.

This study addresses the need to describe the diversity of therapeutic community (TC) programs. The Survey of Essential Elements Questionnaire (SEEQ) was used to develop a typology of TC programs based on 19 programs that identified themselves as traditional or modified TCs in the Drug Abuse Treatment Outcome Studies (DATOS). These traditional and modified TCs differed in adherence to the elements of TC treatment, on operational characteristics, and in client mix. Differences in treatment philosophy and approach included the emphasis on self-reliance, and the use of work as a therapeutic agent for traditional TCs. There were also trends for traditional TC programs to utilize community-as-method, provide educational and vocational training, and include family members as part of therapy. Modified programs showed a greater tendency to rely on counselors. Implications of the findings for program quality, health care policy, and research are discussed.

Combined Modality Therapy↗

Compilation and analysis of plant mitochondrial promoter sequences: An illustration of a divergent evolution between monocot and dicot mitochondria.

We have analyzed 67 sequences surrounding transcription initiation sites identified in higher plant mitochondria. The sequences were classified, independently for monocots and dicots, according to the presence of the CRTA core element found upstream of the first transcribed nucleotide and previously reported as an essential element of plant mitochondrial consensus promoters. This compilation provides new elements concerning the structure of consensus promoters and the relative importance of non-conserved promoters in plant mitochondria. It can be emphasized that promoter regions exhibit several differences between monocot and dicot mitochondria, presumably reflecting a divergent evolution: The sequences classified among consensus promoters as well as the distance between the first transcribed nucleotide and the core element are highly conserved in dicots while more plasticity is observed in monocots. It also appears that the proportion of promoters with neither the conserved promoter sequence nor any conserved motif is far greater in dicots than in monocots.

Base Sequence↗

Differential regulation of Streptococcus mutans gtfBCD genes in response to copper ions.

To persist in the oral cavity, bacteria must be able to tolerate environmental fluctuation, particularly in pH, nutrients, and essential elements. Glucosyltransferases B, C, and D of Streptococcus mutans synthesize glucans, and play essential roles in the sucrose-dependent adhesion of the organism to tooth surfaces. Transcriptions of gtfB, gtfC, and gtfD could be differentially regulated through independent promoters. To test the hypothesis that environmental factors frequently encountered in the dental plaque might serve as effector molecules involved in regulation, transcripts of individual gtfs were identified by reverse transcriptase-polymerase chain reaction assay and confirmed by Northern blot analysis using anti-sense RNA probes. When S. mutans was grown in different medium at low pH, differential regulation of the gtfs was observed. More specifically, the transcription and translational expression of gtfD but not gtfB and gtfC was specifically induced by copper ion (Cu(2+)). The up-regulation was independent of the Cu(2+)-transport operon copYAZ. These findings support the involvement of Cu(2+) as an effector molecule in the regulation of S. mutans gtfD. Nutrient change dominates influence of pH but not the effect of Cu(2+).

Blotting, Northern↗

Local air quality management as a risk management process: assessing, managing and remediating the risk of exceeding an air quality objective in Great Britain.

Air quality is managed in Great Britain via an effects-based, risk management process designed to provide a dynamic solution to public health issues associated with elevated concentrations of seven specified air pollutants. This paper is concerned with an examination and evaluation of the process of Local Air Quality Management (LAQM) in Great Britain from the late 1980s to date as a risk management process. The statutory basis of LAQM process is provided by the Environment Act 1995. The Act provides a framework in which national and local actions are required to identify and remediate areas of poor air quality. Within this framework, the implementation of the process at national and local levels is considered, leading to an identification and assessment of risks in the formulation and implementation of air quality management policy and practice. Local Authorities began the process of Review and Assessment in 1999 and the first round of the process concluded in 2001. Following this, some 129 Local Authorities declared one or more Air Quality Management Areas (AQMAs). The Review and Assessment elements of the framework were subjected to an evaluation in 2001 and the essential elements of it were confirmed as fit for purpose. The evaluation led to a confirmation of the process of LAQM but also a simplification based on the experience of Round 1. Now, a two step process is required comprising of an Updating and Screening Assessment and, where a risk of exceeding an Air Quality Objective (AQO) is identified, a Detailed Assessment follows. The Government has identified a time scale for Review and Assessment through to 2010 and also introduced the requirement of a regular Progress Report in order that a Local Authority is able to address routine matters of air quality management. The risks inherent in epidemiological or scientific uncertainty are factored into the LAQM process at an early stage of the process and, by identifying the risks and subjecting them to regular review, the process provides a 'level playing field' across spatial and temporal scales. Whilst the process of LAQM described in this paper has been developed for Great Britain, the generic elements of the process are applicable to other countries challenged by air pollution problems which require both national and local action to resolve them.

Air Pollution↗

Hair as a biopsy material: trace element data on one man over two decades.

BACKGROUND: Hair mineral analyses are being performed frequently both with and without medical advice. Reasons for analysis often are ill defined. OBJECTIVE: To assess variability of trace element data both within a series of samples from an individual and among mean values published from other research laboratories. DESIGN: Many samples of hair were collected carefully from a healthy man over a comparatively long period of time and were processed and analyzed under standard conditions. Extensive published data from other research laboratories also were reviewed and compared. RESULTS: Coefficients of variation for trace elements in hair of the donor ranged from 17 to 74% for the essential elements copper, selenium and zinc and from 53 to 121% for the potential intoxicants aluminum, cadmium and lead. The ratio of high mean to low mean for values published by others on hair samples from healthy people ranged from two for selenium and zinc to 18 for aluminum. CONCLUSIONS: Hair analysis should be based on a diagnostic hypothesis such as cadmium intoxication or copper deficiency rather than on the ease of analysis or attempts to explain vague symptoms because within-person variability is large and interlaboratory agreement on normal values is poor.

Aluminum↗

Chromium content in different kinds of Spanish infant formulae and estimation of dietary intake by infants fed on reconstituted powder formulae.

Chromium is well documented as an essential element for humans. Trivalent chromium, the main chemical form found in foods, is essential for maintaining normal glucose metabolism. Owing to analytical difficulties, several literature reports of chromium content of foods, especially for the lower levels, show large variability and should be interpreted with caution. Zeeman background correction, transversely heated graphite furnace atomic absorption spectrometry was used to determine the chromium content of 104 different infant formulae (cow's milk and soy protein based) marketed in Spain following an acid-digestion sample preparation procedure in a closed, pressurized and microwave digestion unit. The mean and range of chromium values, regarding types and main protein-based infant formulae are presented. Additionally, the influence of the type of container used, the impact of industrial process from different manufacturers and the physical state (powder and liquid formulae) on chromium levels is also discussed. In general, the infant formulae contain a higher chromium concentration than that found in human milk (reference range: 0.20-8.18 microg l-1), particularly in the case of hypoallergenic (18.16 +/- 7.89 microg l-1), lactose-free (11.37 +/- 3.07 microg l-1), pre-term (11.48 +/- 3.15 microg l-1) and soya (10.43 +/- 4.05 microg l-1) formulae. The maximum theoretical estimated intake of infants fed on the studied formulae was lower than the upper limit safety for trivalent chromium of 1 mg kg-1 (14 microg kg-1 b.w. day-1) recommended by the experts of Council for Responsible Nutrition (Hathcock 2004; available at: http://crnusa.org/safety.html), amounting to about 10, 15-18 and 26% of the standard (adapted and follow-up) and toddler, soya, lactose-free and pre-term, and hypoallergenic formulae, respectively. Therefore, manufacturers are called upon to make continued efforts to routinely monitor chromium levels, particularly for specialised and pre-term formulae, and at the same time, might consider the inclusion of labelling the levels of chromium at least in these complex formulations.

Animals↗

Roxithromycin antagonism with essential and trace elements.

In order to ascertain the role of various essential and trace element complexation on the antibacterial activity of various macrolide antibiotics, the synergistic or antagonistic behavior of roxithromycin metal complexes have been studied and compared with the parent drug. Metal complexes of roxithromycin with magnesium, calcium, chromium, manganese, iron, cobalt, nickel, copper, zinc and cadmium have been investigated for their antibacterial activity and compared with roxithromycin by observing the changes in minimum inhibitory concentration (MIC) and by measuring the zone of inhibition of complexes against both Gram-negative and Gram-positive microorganisms. Various microorganisms used were Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Salmonella typhi, Proteus vulgaris, Shigella dysentery, Klebsiella pneumoniae and Staphylococcus epidermidis. For MIC observation, serial dilution method was employed and zone sizes were determined by diffusion disk method. Our investigations divulge that formation of roxithromycin complexes results in antagonistic behavior against few microorganisms where in MIC is increased with respect to the parent drug, while against most of the microorganism, there was no effect on the MIC of the roxithromycin metal complexes with respect to parent roxithromycin.

Journal Article↗

Clarithromycin synergism with essential and trace elements.

In order to ascertain the role of various essential and trace element complexation on the antibacterial activity of various macrolide antibiotics, the synergistic or antagonistic behavior of clarithromycin metal complexes has been studied and compared with the parent drug. Metal complexes of clarithromycin with magnesium, calcium, chromium, manganese, iron, cobalt, nickel, copper, zinc and cadmium has been investigated for their antibacterial activity and compared with clarithromycin by observing the changes in minimum inhibitory concentration (MIC) and by measuring the zone of inhibition. of complexes against both gram negative and gram positive microorganisms. Various microorganisms used were Staphylococcus aureus, Streptococcus faecalis, Escherichia coli, Salmonella typhii, Proteus vulgaris, Shigella dysentary, Kelebcilla pneumoni and Staphylococcus epidermidis. For MIC observation, serial dilution method was employed and zone sizes were determined by diffusion disk method. Our investigations divulge that formation of clarithromycin complexes results in synergistic effect i.e., antimicrobial activity of complexes of clarithromycin increases with respect to parent clarithromycin drug and MIC of drug metal complexes decreased.

Journal Article↗

Erythromycin synergism with essential and trace elements.

In order to establish the role of various essential and trace element complexation on the antibacterial activity of various macrolide antibiotics, the synergistic or antagonistic behavior of erythromycin metal complexes have been studied and compared with the parent drug. Metal complexes of erythromycin with magnesium, calcium, chromium, manganese, iron, cobalt, nickel, copper, zinc and cadmium have been investigated for their antibacterial activity and compared with erythromycin by observing the changes in minimum inhibitory concentration (MIC) and by measuring the zone of inhibition of complexes against both Gram-negative and Gram-positive microorganisms. Various microorganisms used were Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Salmonella typhi, Proteus vulgaris, Shigella dysentery, Klebsiella pneumoniae and Staphylococcus epidermidis. For MIC observation, serial dilution method was employed and zone sizes were determined by diffusion disk method. Our investigations reveal that formation of erythromycin complexes result in synergistic effect i.e., antimicrobial activity of complexes of erythromycin increases with respect to parent erythromycin drug and MIC of drug metal complexes decreased.

Anti-Bacterial Agents↗

Fluctuation of trace elements during methylmercury toxication and chelation therapy.

The aim of the present investigation was to check the fluctuation in essential elements, such as Na, K, Mg, Mn, Cu, Zn, Cr and Ni in the brain, spinal cord, liver and kidney of mice during methylmercury chloride (MMC) toxication and therapy with monothiols (N-acetyl-DL-homocysteine thiolactone and glutathione) and vitamins (vitamin B complex and E). Mercury deposition and its elimination during chelation therapy were also screened for comparative purposes. The animals were dosed for 7 days with MMC 1 mg/kg/d and some were then kept without treatment for a further. 7 days. Other MMC-treated animals were immediately given one of the above antidotes for 7 days. All the animals were sacrificed on the 15th day. There was a decrease in all elements during MMC toxication with few exceptions, for example, copper was increased in the liver as was sodium in the kidney. Treatment with the thiols and vitamins restored the levels of these elements in certain tissues towards normal, but their concentrations remained abnormal in most instances. The fluctuations in the concentration of these elements were attributed to their association with various macromolecules.

Analysis of Variance↗

Structure and function of DnaA and the DnaA-box in eubacteria: evolutionary relationships of bacterial replication origins.

DnaA protein (a trans-acting element) and its binding sequence, DnaA-box: (a cis-acting element) are two elements essential for the initiation of chromosomal replication in Escherichia coli and other enteric bacteria. Recently these two elements have been found to be conserved in three Gram-positive bacteria (Bacillus subtilis, Micrococcus luteus and Mycoplasma capricolum) as well as in Gram-negative pseudomonads. DnaA protein was also found to be essential in the initiation of the replication of the B. subtilis chromosome, and regions containing multiple repeats of DnaA-box (DnaA-box region) are found to be active as autonomously replicating elements both in B. subtilis and pseudomonads. In this MicroReview we compare first the structures of these DnaA-box regions and their locations on the chromosome and then functional aspects of DnaA protein and DnaA-box regions in the initiation and regulation of chromosomal replication. From these observations we propose evolutionary relationships between replication origins of eubacteria.

Amino Acid Sequence↗