In this paper, ''metallomics'' is proposed as a new scientific field in order to integrate the research fields related to biometals. Metallomics should be a scientific field in symbiosis with genomics and proteomics, because syntheses and metabolic functions of genes (DNA and RNA) and proteins cannot be performed without the aid of various metal ions and metalloenzymes. In metallomics, metalloproteins, metalloenzymes and other metal-containing biomolecules are defined as ''metallomes'', in a similar manner to genomes in genomics as well as proteomes in proteomics. Since the identification of metallomes and the elucidation of their biological or physiological functions in the biological systems is the main research target of metallomics, chemical speciation for specific identification of bioactive metallomes is one of the most important analytical technologies to establish metallomics as the integrated bio-metal science. In order to rationalize the concept of metallomics, the distributions of the elements in man, human blood serum and sea-water, a challenge to allelements analysis of one biological cell, and some other research topics are introduced with emphasis on recent development of chemical speciation of trace metals in some biological samples.
A search for the rare decay K L → π 0 νν was performed. With the data collected in 2015, corresponding to 2.2 × 10 19 protons on target, a single event sensitivity of ð1.30 AE 0.01 stat AE 0.14 syst Þ × 10 −9 was achieved and no candidate events were observed. We set an upper limit of 3.0 × 10 −9 for the branching fraction of K L → π 0 νν at the 90% confidence level (C.L.), which improved the previous limit by almost an order of magnitude. An upper limit for K L → π 0 X 0 was also set as 2.4 × 10 −9 at the 90% C.L., where X 0 is an invisible boson with a mass of 135 MeV=c 2 .
Definitions for the terms "metallome" and "metallomics" are proposed. The state of the art of analytical techniques and methods for systematic studies of metal content, speciation, localization, and use in biological systems is briefly summarized and critically evaluated.Keywords: metals; metabolomics; metallomics; proteomics; speciation.
RATIONALE AND HISTORY OF THE USE OF THE TERMS REGARDING THE METAL-RELATED -OMICSThe knowledge of the complete genetic blueprint of an increasing number of organisms has resulted in efforts aimed at the global analysis and functional study of a particular class of components of a living organism and the emergence of different "-omics". The concepts of genomics (the study of genes and their function) and proteomics (the study of the set of proteins produced by an organism, their localization, structure, stability, and interaction) have become part of the everyday language of life sciences [1,2].Metal ions are a vital component of the chemistry of life [3]. One-third of all proteins is believed to require a metal cofactor, such as copper, iron, zinc, or molybdenum [4], delivered as a simple or complex ion or a metal-containing compound (e.g., methylcobalamin). The intracellular concentration of several metals, their distribution among the various cell compartments, and their incorporation in metallo proteins are tightly controlled [5]. The understanding of mechanisms by which a metal is sensed, stored, or incorporated as a cofactor requires, in addition to the identification of metalloproteins, the characterization of the pool of non-protein molecules (products of enzymatic or biochemical reactions) interacting with metal ions or of metabolites of exogenous metallocompounds, such as metallodrugs. A systematic approach to the study of metal content, speciation, localization, and use in biological systems is becoming increasingly important [6].
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