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Estrogen, a steroid hormone, is associated with several human activities, including environmental, industrial, agricultural, pharmaceutical and medical fields. In this review paper, estrogenic activity associated with traditional Chinese medicines (TCMs) is discussed first by focusing on the assays needed to detect estrogenic activity (animal test, cell assay, ligand-binding assay, protein assay, reporter-gene assay, transcription assay and yeast two-hybrid assay), and then, their sources, the nature of activities (estrogenic or anti-estrogenic, or other types), and pathways/functions, along with the assay used to detect the activity, which is followed by a summary of effective chemicals found in or associated with TCM. Applications of estrogens in TCM are then discussed by a comprehensive search of the literature, which include basic study/pathway analysis, cell functions, diseases/symptoms and medicine/supplements. Discrepancies and conflicting cases about estrogenicity of TCM among assays or between TCM and their effective chemicals, are focused on to enlarge estrogenic potentials of TCM by referring to omic knowledge such as transcriptome, proteome, glycome, chemome, cellome, ligandome, interactome and effectome.

During the past decades the components involved in cellular signal transduction from membrane receptors to gene activation in the nucleus have been studied in detail. Based on the qualitative biochemical knowledge, signalling pathways are drawn as static graphical schemes. However, the dynamics and control of information processing through signalling cascades is not understood. Here we show that based on time resolved measurements it is possible to quantitatively model the nonlinear dynamics of signal transduction. To select an appropriate model we performed parameter estimation by maximum likelihood and statistical testing. We apply this approach to the JAK-STAT signalling pathway that was believed to represent a feed-forward cascade. We show by comparison of different models that this hypothesis is insufficient to explain the experimental data and suggest a new model including a delayed feedback.

The article is an overview of IMCB in the 21st century. It mentions the work done by the institution and the focus of the institution, which are: Cancer Biology, Cell Biology, Developmental biology, infectious diseases, structural biology and translational research.

The response of genes to cell stimuli is often measured by microarrays. However, studying the function of these genes rarely elucidate as to how the stimuli activate or suppress these genes. To understand the mechanisms of cell stimulation, we describe a computational method for analyzing mammalian promoters of early response genes to detect the transcription factors activated by cell stimulation. We first analyzed promoters of the response genes, for transcription factor binding sites conserved between human and mouse. We then applied hypergeometric statistics in conjunction with Bonferroni correction to identify the top transcription factors whose binding sites were significantly over-represented among these promoters. In five data sets with early response genes, a significantly larger than expected number of genes had binding sites in their promoters for transcription factors previously known to be involved in response to the stimulus, while data sets with measurements at longer time points (24 hours) failed to show such over-representation. Because the end points of signal transduction pathways are transcription factors, this methodology is useful for exploring signaling pathways activated by various stimuli through microarray studies.

HemAT is a signal transducer protein responsible for aerotaxis control of some bacteria and archaea, which contains a heme-containing globin domain as the sensor of its physiological effector, O₂. The interaction between the heme-bound ligand and the surrounding amino acid residue(s) plays a crucial role for selective sensing of O₂ and signal transduction by HemAT. In this work, we have elucidated by resonance Raman spectroscopy how O₂ and CO interact with HemAT-Hs and HemAT-Rr, HemAT from Halobacterium salinarum and Rhodospirillum rubrum, respectively. HemAT-Hs and HemAT-Rr showed three conformers in the O₂-bound form, as is the case of HemAT-Bs, HemAT from Bacillus subtilis. Though the hydrogen bonding patterns observed in the three conformers were the same for HemAT-Bs, HemAT-Hs, and HemAT-Rr, the involved residues for the hydrogen bonding interaction were different from one another.

Total internal reflection fluorescence correlation spectroscopy (TIR-FCS) is an appropriate method for measuring diffusion constants and the number of fluorescent molecules very close to the coverglass surface. Recently, we have reported the application of TIR-FCS to cell biology, measuring membrane-binding farnesylated green fluorescent proteins (EGFP-F) in living cells. In this research, we measured the signal transduction molecule, protein kinase C (PKC), fused with EGFP in living HeLa cells by using TIR-FCS. We observed two different diffusional mobilities of PKCβII-EGFP, three-dimensional faster diffusion near the plasma membrane and slower lateral diffusion on the plasma membrane after adinosine tri phosphate (ATP) activation. These results indicate that it is possible to use TIR-FCS in the study of molecular dynamics and interactions of signal transduction proteins on the plasma membrane of the living cell.

The zebrafish has been an increasingly popular animal model for human diseases as it offers the combined advantages compared to various animal models and cell based assays; in particular, the feasibility of high throughput studies as an economical vertebrate model. In this past decade, we and several other laboratories have developed various hepatocellular carcinoma (HCC) models using the zebrafish and demonstrated the conservation of HCC between zebrafish and human at both histopathological and molecular levels. In this review, we focus on the conservation of signal transductions during hepatocarcinogenesis between zebrafish and human. Based on existing zebrafish HCC models, indeed many alterations of signal pathways that cause human liver cancers can also result in HCC in zebrafish, such as Ras pathway, EGFR pathway, Wng/β-catenin pathway, TGF-β pathway, PI3K/AKT pathway, JAK/STAT pathway, Hippo pathway, src tyrosine kinase pathway, etc. In future, zebrafish may be used for better quantification of signaling molecules and thus to aid development of more effective therapeutic methods.

The following sections are included:

• Summary

• Introduction

• Hydrogen Peroxide Production Associated with Photosynthesis
  • Peroxisomal Hydrogen Peroxide Production Associated with Photorespiration
  • Chloroplastic Hydrogen Peroxide Production Associated with the Mehler Reaction

• Ascorbic Acid

• Glutathione
  • Regulation of Glutathione Biosynthesis

• Coupling Between Ascorbate and Glutathione Pools

• Ascorbate and Glutathione in Signal Transduction

• References

The following sections are included:

• Summary

• The Prr System
  • PrrA
  • PrrB
  • PrrC

• Electron Transport
  • cbb₃ Cytochrome Oxidase

• Redox Control

• Signal Transduction Pathway

• PpsR/AppA, Repressor/Antirepressor

• TspO

• Rdx
  • rdxBHIS
  • RdxB

• Conclusions

• Perspectives

• Acknowledgments

• References

Plants respond to abiotic stresses, such as drought, high salinity, and cold, to acquire stress tolerance. Molecular and genomic studies have shown that a number of genes with various functions are induced by abiotic stresses, and that various transcription factors are involved in the regulation of stress-inducible genes in Arabidopsis and rice. These gene products function not only in stress tolerance but also in stress response. In this review, recent progress in the analysis of complex cascades of gene expression in drought and cold stress responses is summarized. Various genes involved in stress tolerance are also discussed for their application to molecular breeding of drought, salinity, and/or cold stress tolerance.

The rice genome sequenced and annotated by the IRGSP has identified 37,544 protein-coding genes. In an effort to identify genes encoding transcription factors and signal transduction components, more than 7,000 genes belonging to 87 classes have been used to prepare a local database. Detailed analysis of genes for plant hormone response, CDPKs, C₂H₂ zinc-finger, and SET domain proteins unraveled interesting evolutionary aspects in relation to genes and the rice genome. A 51k microarray, SAGE analysis, and real-time polymerase chain reaction revealed differential expression of target genes during reproductive development and stress conditions. Several genes specific to reproductive floral organs and seed development have been identified. A large number of SAGE tags are observed from intergenic regions and antisense strands reflecting the unexplored transcription potential of the rice genome. Analysis of rice gene promoter activities has been undertaken in transgenic tobacco/Arabidopsis to demarcate regions conferring anther-/pollen-specific expression. OSISAP1, a gene coding for a stress-associated zinc-finger protein, and its promoter have been functionally validated in transgenic tobacco and rice. Genes for proteins interacting with OSISAP1 have also been found to be stress-inducible. Investigations on functional analysis of stress-responsive genes are in progress.

Neurotrophic factors were originally defined as paracrine molecules that promote the survival, differentiation, and repair of embryonic or adult neuronal cells. These factors include neurotrophins, neuropoietic cytokines, and the GDNF family of neurotrophic factors. Data recently obtained with transgenic and knockout mice revealed that neurotrophic factors and their receptors are also expressed in many organs outside the nervous system, and play an important role in embryonic development and in the maintenance of adult tissues. This review focuses on the role of neurotrophic factors in the development and maintenance of the male germ line after birth. Emphasis is given to glial cell line-derived neurotrophic factor (GDNF), some of the signaling molecules recently discovered downstream of the Ret receptor, and the cooperation between GDNF and other juxtacrine and paracrine factors.

Considering the important issues concerning food, environment, and energy that humans are facing in the 21st century, humans mostly depend on plants. Unlike animals which move from an inappropriate environment, plants do not move, but rapidly sense diverse environmental changes or invasion by other organisms such as pathogens and insects in the place they root, and adapt themselves by changing their own bodies, through which they developed adaptability. Whole genetic information corresponding to the blueprints of many biological systems has recently been analyzed, and comparative genomic studies facilitated tracing strategies of each organism in their evolutional processes. Comparison of factors involved in intracellular signal transduction between animals and plants indicated diversification of different gene sets. Reversible binding of Ca²⁺ to sensor proteins play key roles as a molecular switch both in animals and plants. Molecular mechanisms for signaling network of environmental sensing and adaptation in plants will be discussed with special reference to Ca²⁺ as a key element in information processing.