Minireview: physiological and pharmacological properties of vanadium

Vanadium is distributed extensively in nature. It is a trace element and is present in almost all living organisms including man. Even though vanadium was originally recognized for its ability to inhibit membrane Na+-K+-ATPase, various laboratory studies now document that this element has the capacity to affect the activity of various intracellular enzyme systems and may modify their physiological functions. Vanadium may be an essential element for normal development and may play an important role in various homeostatic mechanisms, and thus vanadium deficiency may prove to be an important concern. Abnormalities in biological disposition of vanadium may be involved in the pathogenesis of certain neurological disorders or cardiovascular diseases. While the essentiality of this element for living organisms is yet to be established with certainty, vanadium has become an increasingly important element and is used extensively in various heavy industries such as steel, oil, etc.; thus, the incidence of exposure to toxic levels of vanadium to industrial workers has been an increasing concern for toxicologists. To date, little information is available on the physiological or pharmacological actions of vanadium; hence, it is difficult to reach any definitive conclusion concerning its biological significance, essentiality and its role in pathological states. An attempt has been made in this review to broadly document what is known of various biological actions of vanadium.     

The newer trace elements

The application of the concept of a “controlled environment” led to the identification of eight trace elements with a proven or postulated biological function during this decade. Rigorous reduction of metallic contamination from air, drinking water, and diet is necessary to reduce exposure to the element under investigation below requirement levels. An essential function for a trace element is suggested when deficiency is produced, and indepently confirmed, in two or more animal species, and also when the signs of deficiency are prevented or cured by supplements. As yet, a direct role for the “new trace elements” in the human organism has not been demonstrated.     

Building the blueprint of life

With recent breakthroughs in experimental microbiology making it possible to synthesize and implant an entire genome to create a living cell, the challenge of constructing a working blueprint for the first truly minimal synthetic organism is more important than ever. Here we review the significant progress made in the design and creation of a minimal organism. We discuss how comparative genomes, gene essentiality data, naturally small genomes, and metabolic modeling are all being applied to produce a catalogue of the biological functions essential for life. We compare the minimal gene sets from three published sources with functions identified in 13 existing gene essentiality datasets. We examine how genome-scale metabolic models have been applied to design a minimal metabolism for growth in simple and complex media. Additionally, we survey the progress of efforts to construct a minimal organism, either through implementation of combinatorial deletions in Bacillus subtilis and Escherichia coli or through the synthesis and implantation of synthetic genomes.     

Metabolic function of the lungs and regulation of homeostasis

Morphological, biochemical and pathophysiological data on the significance of the metabolic (non-respiratory) function of the lungs in the regulation of homeostasis have been summarized. The key "strategic" position of the lungs in the blood circulation system, the concentration of a unique set of biochemical regulatory factors in the lung endothelium, as well the presence of a multiple system of nervous and humoral control ensure the realization of a specific mission by lungs as a regulator of the functional integrity of the organism. The lungs serve as a barrier controlling the passage of deleterious substances into arterial blood and consequently into the brain and other organs and at the same time the lungs are responsible for the controlled synthesis and elimination of physiologically active substances essential for the work of the same systems. These functions attain special significance under stress-induced situations as a result of homeostatic disruptions and as a consequence of grave extrapulmonary injuries. The author's concept on a compensatory function of the lung kallikrein-kinin system under extreme conditions of organism is given. This pathway opens up the prospects for search of ways of correcting functional disruption in organism.     

Selenium Metabolism and Biosynthesis of Selenoproteins in the Human Body

Biochemistry (Moscow) - As an essential trace element, selenium (Se) plays a tremendous role in the functioning of the human organism being used for the biosynthesis of selenoproteins (proteins...     

遗传工程食物的健康安全性问题——介绍20002001年FAO/WHO联合专家顾问委员会的结论意见与建议

本文介绍联合国专家有关遗传工程植物性食物对人体健康安全问题的结论性意见和建议。由于世界各国公众对转基因生物作为食物的安全问题日益担心,联合国世界粮农组织(FAO)和世界卫生组织(WHO)在2000年和2001年共同召集了两次FAOWHO联合专家顾问委员会会议,会后公布了两份详尽的报告。针对当前一些有争议的问题,联合专家委员会提出了合理的并具权威性的结论意见和建议,其中包括实质等同性概念、对健康的长期效应、抗菌素抗性基因问题、潜在的过敏原性及其新修订的评估策略———树型判定法。     

Identification of essential alphaproteobacterial genes reveals operational variability in conserved developmental and cell cycle systems

The cell cycle of Caulobacter crescentus is controlled by a complex signalling network that co‐ordinates events. Genome sequencing has revealed many C. crescentus cell cycle genes are conserved in other Alphaproteobacteria, but it is not clear to what extent their function is conserved. As many cell cycle regulatory genes are essential in C. crescentus, the essential genes of two Alphaproteobacteria, Agrobacterium tumefaciens (Rhizobiales) and Brevundimonas subvibrioides (Caulobacterales), were elucidated to identify changes in cell cycle protein function over different phylogenetic distances as demonstrated by changes in essentiality. The results show the majority of conserved essential genes are involved in critical cell cycle processes. Changes in component essentiality reflect major changes in lifestyle, such as divisome components in A. tumefaciens resulting from that organism's different growth pattern. Larger variability of essentiality was observed in cell cycle regulators, suggesting regulatory mechanisms are more customizable than the processes they regulate. Examples include variability in the essentiality of divJ and divK spatial cell cycle regulators, and non‐essentiality of the highly conserved and usually essential DNA methyltransferase CcrM. These results show that while essential cell functions are conserved across varying genetic distance, much of a given organism's essential gene pool is specific to that organism.     

Enzymes are enriched in bacterial essential genes

Essential genes, those indispensable for the survival of an organism, play a key role in the emerging field, synthetic biology. Characterization of functions encoded by essential genes not only has important practical implications, such as in identifying antibiotic drug targets, but can also enhance our understanding of basic biology, such as functions needed to support cellular life. Enzymes are critical for almost all cellular activities. However, essential genes have not been systematically examined from the aspect of enzymes and the chemical reactions that they catalyze. Here, by comprehensively analyzing essential genes in 14 bacterial genomes in which large-scale gene essentiality screens have been performed, we found that enzymes are enriched in essential genes. Essential enzymes have overrepresented ligases (especially those forming carbon-oxygen bonds and carbon-nitrogen bonds), nucleotidyltransferases and phosphotransferases, while have underrepresented oxidoreductases. Furthermore, essential enzymes tend to associate with more gene ontology domains. These results, from the aspect of chemical reactions, provide further insights into the understanding of functions needed to support natural cellular life, as well as synthetic cells, and provide additional parameters that can be integrated into gene essentiality prediction algorithms.     

Effect of trace elements upon the biomass production of some candida species

Trace element studies were carried out on nine species of Candida. Out of twenty-three trace elements tested, Fe, Zn, Mn and Cu were found to be essential for the growth of all the yeast species whereas the rest of the elements exhibited variable essentiality. All the species of yeasts investigated required different concentrations of trace elements for their optimum growth. Concentrations higher than the optimum have been found to be inhibitory for the growth of all the yeasts studied here.     

Physiological state control of fermentation processes

In this article a novel approach to the control of fermentation processes is introduced. A "physiological state control approach" has been developed using the concept of representing fermentation processes through the current physiological state of the cell culture. No conventional mathematical model is required for the synthesis of such a control system.The main idea is based on the fact that during batch, feed-batch, or even continuous cultivation the physiological characteristics of the cell population, jointly expressed by the term "physiological state", are not constant but rather variable, which is reflected in expected or unexpected changes in the behavior of the control plant, and which requires flexible alteration of the current control strategy. The proposed approach involves decomposition of the physiological state space into several subspaces called "physiological situations." In every physiological situation the cell population expresses stable characteristics, and therefore an invariant control strategy can be effectively applied. The on-line functions of the physiological state control system consist of the calculation of physiological state variables, determination of the current physiological situation as an element of a previously defined set of known physiological situations, switching of the relevant control strategy, and calculation of the control action. Attention is focused on the synthesis of the novel and nonstandard part of the control system - the algorithm for online recognition of the current physiological state. To this end an effective approach, based on artificial intelligence methods, particularly fuzzy sets theory and pattern recognition theory, was developed. Its practical realization is demonstrated using data from a continuous fermentation process for single cell protein production.     

Nutritional requirements for web synthesis in the tetragnathid spider Nephila clavipes

Trap-constructing organisms provide a unique opportunity for the study of resource allocation, because an observer can unambiguously determine the allocation to foraging. In species that synthesize a trap from physiologically important compounds, there is the further advantage that there may be direct trade-offs between allocation of resources to foraging and physiological functions. We examined the ability of the spider Nephila clavipes (L.; Araneae: Tetragnathidae) to synthesize resources that are known to be used for both web synthesis and non-foraging physiological functions. We found that choline, required for both web function and physiological function, is an essential nutrient: it is not synthesized by this spider. Under laboratory conditions with a diet of fruit flies, choline is limiting, and the spiders make allocation trade-offs between investing choline in foraging (the web) or in their body.     

Fine tuning the myosin motor: the role of the essential light chain in striated muscle myosin

It has long been known that the essential light chain isoform of striated muscle affects the function of the myosin motor. There are two isoforms: A1-type and A2-type that differ by the presence of an extra 40 amino acids at the N-terminus of A1-type light chains. Evidence has accumulated from a variety of experimental techniques that this extension of A1-type light chains makes a direct contact with actin, increasing the overall affinity between myosin and actin and that this interaction is responsible for the modulation of myosin motor function. Some recent work, however, has provided some contradictory data. Experiments using more physiologically relevant forms of myosin have suggested that the effect of the N-terminal region of A1-type light chains may, in some circumstances, be to weaken, rather than strengthen the actin-myosin interaction. Work with transgenic mice in which this region was mutated showed no measurable phenotypic effects on either muscle or whole organism function questioning the in vivo significance of the light chain-actin interaction. It is also possible that the essential light chain has other functions in the cell. There is evidence that the protein may interact with IQGAP, a regulator of the actin cytoskeleton. The consequences of this interaction are unknown. This review aims to summarise the biochemical data on striated muscle myosin essential light chain isoform function and to reconcile it with these recent discoveries.     

A global approach to identify novel broad-spectrum antibacterial targets among proteins of unknown function

Attempted allelic replacement of 144 Streptococcus pneumoniae open reading frames of previously uncharacterized function led to the identification of 36 genes essential for growth under laboratory conditions. Of these, 14 genes (obg, spoIIIJ2, trmU, yacA, yacM, ydiC, ydiE, yjbN, yneS, yphC, ysxC, ytaG, yloI and yxeH4) were also essential in Staphylococcus aureus and Haemophilus influenzae or Escherichia coli, 2 genes (yrrK and ydiB) were only essential in H. influenzae as well as S. pneumoniae and 8 genes were necessary for growth of S.pneumoniae and S. aureus and did not have a homolog in H. influenzae(murD2, ykqC, ylqF, yqeH, ytgP, yybQ) or were not essential in that organism (yqeL, yhcT). The proteins encoded by these genes could represent good targets for novel antibiotics covering different therapeutic profiles. The putative functions of some of these essential proteins, inferred by bioinformatic analysis, are presented. Four mutants, with deletions of loci not essential for in vitro growth, were found to be severely attenuated in a murine respiratory tract infection model, suggesting that not all targets for antibacterial therapeutics are revealed by simple in vitro essentiality testing. The results of our experiments together with those collated from previously reported studies including Bacillus subtilis, E. coli and Mycoplasma sp. demonstrate that gene conservation amongst bacteria does not necessarily indicate that essentiality in one organism can be extrapolated to others. Moreover, this study demonstrates that different experimental procedures can produce apparently contradictory results.     

Insights on zinc regulation of food intake and macronutrient selection

Zinc (Zn) is an essential trace element required for human beings and animals. This divalent cation is involved in many physiological functions, including immune and antioxidant function, growth, and reproduction. Deficiency of Zn produces several pathological disorders and abnormalities in its metabolism, such as anorexia, weight loss, poor efficiency, and growth retardation. Although it has been known for more than 50 yr that Zn deficiency regularly and consistently causes anorexia in many animal species, the mechanism that causes this phenomenon still remains an enigma. The present review describes recent research investigating the relationship between Zn deficiency and the regulation of food intake, as well as macronutrient selection.     

Selenium interactions and toxicity: a review

Selenium is an essential trace element for mammals. Through selenoproteins, this mineral participates in various biological processes such as antioxidant defence, thyroid hormone production, and immune responses. Some reports indicate that a human organism deficient in selenium may be prone to certain diseases. Adverse health effects following selenium overexposure, although very rare, have been found in animals and people. Contrary to selenium, arsenic and cadmium are regarded as toxic elements. Both are environmental and industrial pollutants, and exposure to excessive amounts of arsenic or cadmium can pose a threat to many people’s health, especially those living in polluted regions. Two other elements, vanadium and chromium(III) in trace amounts are believed to play essential physiological functions in mammals. This review summarizes recent studies on selenium interactions with arsenic and cadmium and selenium interactions with vanadium and chromium in mammals. Human studies have demonstrated that selenium may reduce arsenic accumulation in the organism and protect against arsenic-related skin lesions. Selenium was found to antagonise the prooxidant and genotoxic effects of arsenic in rodents and cell cultures. Also, studies on selenium effects against oxidative stress induced by cadmium in various animal tissues produced promising results. Reports suggest that selenium protection against toxicity of arsenic and cadmium is mediated via sequestration of these elements into biologically inert conjugates. Selenium-dependent antioxidant enzymes probably play a secondary role in arsenic and cadmium detoxification. So far, few studies have evaluated selenium effects on chromium(III) and vanadium actions in mammals. Still, they show that selenium may interact with these minerals. Taken together, the recent findings regarding selenium interaction with other elements extend our understanding of selenium biological functions and highlight selenium as a potential countermeasure against toxicity induced by arsenic and cadmium.     

Defining the role of essential genes in human disease

A greater understanding of the causes of human disease can come from identifying characteristics that are specific to disease genes. However, a full understanding of the contribution of essential genes to human disease is lacking, due to the premise that these genes tend to cause developmental abnormalities rather than adult disease. We tested the hypothesis that human orthologs of mouse essential genes are associated with a variety of human diseases, rather than only those related to miscarriage and birth defects. We segregated human disease genes according to whether the knockout phenotype of their mouse ortholog was lethal or viable, defining those with orthologs producing lethal knockouts as essential disease genes. We show that the human orthologs of mouse essential genes are associated with a wide spectrum of diseases affecting diverse physiological systems. Notably, human disease genes with essential mouse orthologs are over-represented among disease genes associated with cancer, suggesting links between adult cellular abnormalities and developmental functions. The proteins encoded by essential genes are highly connected in protein-protein interaction networks, which we find correlates with an over-representation of nuclear proteins amongst essential disease genes. Disease genes associated with essential orthologs also are more likely than those with non-essential orthologs to contribute to disease through an autosomal dominant inheritance pattern, suggesting that these diseases may actually result from semi-dominant mutant alleles. Overall, we have described attributes found in disease genes according to the essentiality status of their mouse orthologs. These findings demonstrate that disease genes do occupy highly connected positions in protein-protein interaction networks, and that due to the complexity of disease-associated alleles, essential genes cannot be ignored as candidates for causing diverse human diseases.     

An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations

Aging is an inherently complex process that is manifested within an organism at genetic, molecular, cellular, organ, and system levels. Although the fundamental mechanisms are still poorly understood, a growing body of evidence points toward reactive oxygen species (ROS) as one of the primary determinants of aging. The "oxidative stress theory" holds that a progressive and irreversible accumulation of oxidative damage caused by ROS impacts on critical aspects of the aging process and contributes to impaired physiological function, increased incidence of disease, and a reduction in life span. While compelling correlative data have been generated to support the oxidative stress theory, a direct cause-and-effect relationship between the accumulation of oxidatively mediated damage and aging has not been strongly established. The goal of this minireview is to broadly describe mechanisms of in vivo ROS generation, examine the potential impact of ROS and oxidative damage on cellular function, and evaluate how these responses change with aging in physiologically relevant situations. In addition, the mounting genetic evidence that links oxidative stress to aging is discussed, as well as the potential challenges and benefits associated with the development of anti-aging interventions and therapies.     

Zinc may play a role in the regulation of thyrotropin function

We studied the in vitro and in vivo influence of physiologically relevant zinc concentrations on the thyrotropin function both at the pituitary and hypothalamic level. Zinc gluconate (Zn Glu) concentrations from 5 to 100 microM decreased basal TSH release from anterior pituitary gland in vitro, but did not affect TSH-stimulated release by TRH, cAMP or high K+ concentrations. Zn Glu altered neither the basal nor stimulated production of TRH by hypothalami in vitro. In vivo brain third ventricle injection of Zn Glu decreased serum TSH 30-60 min after injection. The ability of physiological concentrations of zinc to influence TSH secretion both in vitro and in vivo suggest that this trace element might be involved in the regulation of thyrotropin function.     

New insights into the physiological actions of selenoproteins from genetically modified mice

Selenium (Se) is an essential trace element in mammals. Dietary Se restriction or conditions of Se malabsorption lead to deficiency syndromes or exacerbate established diseases in humans and in many animal models. It is assumed that most, if not all, physiological actions of Se are mediated by selenocysteine (Sec) containing proteins. However, the exact role of particular selenoproteins for certain molecular pathways, for the metabolism of nutrients, hormones or cellular components and for the development and adaptive responses of the organism have often remained elusive. Through the use of transgenic animals, it becomes increasingly feasible to interfere specifically with the expression of single selenoproteins in certain tissues or at certain times. While some transgenic animals exhibit phenotypes that were expected from biochemical studies, in other instances the observed effects were a surprise in view of earlier hypotheses.