Regulatory aspects of low intensity photon emission

Photon emission from unicellular and multicellular organisms has been a subject of study for many decennia. In contrast to the well-known phenomenon of bioluminescence originating in luciferin-luciferase reactions, low intensity emission in the visible region of the electromagnetic spectrum has been found in almost every species studied so far. At present, the nomenclature of this phenomenon has not crystallized and it is referred to by a variety of names, such as mitogenetic radiation 29, dark luminescence 7, low-level chemiluminescence 20,36, and biophotons 57. Particular attention has been focussed on the relationship between photon emission and the regulation of various aspects of cellular metabolism, although in many cases quantitative data are still lacking. Throughout the history of this field of research the question of a functional biological role of the low intensity emission has been repeatedly raised; this is reflected, for instance, in the heterogeneity of the terms used to describe it. The discussion concerns the possible participation of photons of low intensity in intra- and intercellular communication. This paper reviews literature on the metabolic regulation of low intensity emission, as well as the regulation of photon emission initiated by external light. Furthermore, recent data are discussed with respect to a possible biocommunicative function of low intensity photon emission.     

Biophoton emission fromDaphnia magna: A possible factor in the self-regulation of swarming

Summary The formation of swarms by planktonic organisms was first described almost 100 years ago, but the mechanisms governing the development of patterns in population size and density are still not understood. In this study, we investigated one biophysical factor that may play an important role in swarm-formation. Spontaneous ultraweak photon emission in the visible range has been well documented for living cells, tissues and individuals in the plant and animal kingdom, including humans. We demonstrate here that the intensity of light emitted by the planktonic crustaceanDaphnia magna is a function of population density in relation to body size. The effects are discussed on the basis of the theory of Dicke^1,2, and it is suggested that biophoton emission may be a basic factor in the self-regulation of swarm density.     

Photon emission in tumor biology.

Photon emission from mammalian cells has been subject of study for many years. Growing research activity is directed on the photon emission within the field of tumor biology. These studies, applying high-sensitivity photon counting methods, have paid attention to several aspects, including photon emission from serum of tumor-bearing animals, photon emission of tumors and of isolated tumor cells. In addition, research activity is increased with respect to the photon emission induced by white light from cultured tumor cells. In this review we report on the different aspects of spontaneous and induced photon emission of tumor cells as compared to normal cells. Throughout these studies the question of a functional biological role of this spontaneous and light-induced photon emission has been raised and some different points of view will be discussed.     

Photon emission in tumor biology

Photon emission from mammalian cells has been subject of study for many years. Growing research activity is directed on the photon emission within the field of tumor biology. These studies, applying high-sensitivity photon counting methods, have paid attention to several aspects, including photon emission from serum of tumor-bearing animals, photon emission of tumors and of isolated tumor cells. In addition, research activity is increased with respect to the photon emission by white light from cultured tumor cells. In this review we report on the different aspects of spontaneous and induced photon emission of tumor cells as compared to normal cells. Throughout these studies the question of a functional biological role of this spontaneous and light-induced photon emission has been raised and some different points of view will be discussed.     

Diversity of Cl− Channels

Cl⁻ channels are widely found anion pores that are regulated by a variety of signals and that play various roles. On the basis of molecular biologic findings, ligand-gated Cl⁻ channels in synapses, cystic fibrosis transmembrane conductors (CFTRs) and ClC channel types have been established, followed by bestrophin and possibly by tweety, which encode Ca²⁺-activated Cl⁻ channels. The ClC family has been shown to possess a variety of functions, including stabilization of membrane potential, excitation, cellvolume regulation, fluid transport, protein degradation in endosomal vesicles and possibly cell growth. The molecular structure of Cl⁻ channel types varies from 1 to 12 transmembrane segments. By means of computer-based prediction, functional Cl⁻ channels have been synthesized artificially, revealing that many possible ion pores are hidden in channel, transporter or unidentified hydrophobic membrane proteins. Thus, novel Cl⁻-conducting pores may be occasionally discovered, and evidence from molecular biologic studies will clarify their physiologic and pathophysiologic roles. Received 28 July 2005; received after revision 25 August 2005; accepted 21 September 2005     

Physical aspects of delayed luminescence inAcetabularia acetabulum

Delayed photo-induced luminescence has been studied inAcetabularia acetabulum individuals. The number of photons re-emitted when the wavelength, the intensity, or the duration of the incident radiation were varied are reported for 10 individuals. Reproducibility of the measurements in the same and in different individuals was good. The association between the incident radiation and photon re-emission was found to be non-linear. The relaitonship between the quantities involved in the phenomenon is discussed and a phenomenological equation describing the relationship is presented.     

Super-high sensitivity systems for detection and spectral analysis of ultraweak photon emission from biological cell cells and tissues

Summary In this paper we summarize and discuss the modern technology and systems, studied and established by our research group, for performing the detection and special analysis incorporated with the super-high senstivity photon counting method for the study of ultraweak photon emission; for example, extra-weak bioluminescence and chemiluminescence from living cells and tissues, closely related to biochemical and biophysical processes and activities. An excellent sensitivity of the basic photon counting system, making it possible to achieve count rates in the very low range of one photoelectron per second to one per minute, allowed us to carry out in vivo as well as in vitro measurements, and analyses of ultraweak bioluminescence and chemiluminescence. Recent results concerning ultraweak photon emission from blood samples and organ homogenates of rats are presented and reviewed as one of the interesting and valuable applications of our modern technology for studying ultraweak cell and tissue radiation.     

Super-high sensitivity systems for detection and spectral analysis of ultraweak photon emission from biological cells and tissues

In this paper we summarize and discuss the modern technology and systems, studied and established by our research group, for performing the detection and special analysis incorporated with the super-high sensitivity photon counting method for the study of ultraweak photon emission; for example, extra-weak bioluminescence and chemiluminescence from living cells and tissues, closely related to biochemical and biophysical processes and activities. An excellent sensitivity of the basic photon counting system, making it possible to achieve count rates in the very low range of one photoelectron per second to one per minute, allowed us to carry out in vivo as well as in vitro measurements, and analyses of ultraweak bioluminescence and chemiluminescence. Recent results concerning ultraweak photon emission from blood samples and organ homogenates of rats are presented and reviewed as one of the interesting and valuable applications of our modern technology for studying ultraweak cell and tissue radiation.     

Recent advances in the biosynthesis of modified tetrapyrroles: the discovery of an alternative pathway for the formation of heme and heme d 1

Hemes (a, b, c, and o) and heme d ₁ belong to the group of modified tetrapyrroles, which also includes chlorophylls, cobalamins, coenzyme F₄₃₀, and siroheme. These compounds are found throughout all domains of life and are involved in a variety of essential biological processes ranging from photosynthesis to methanogenesis. The biosynthesis of heme b has been well studied in many organisms, but in sulfate-reducing bacteria and archaea, the pathway has remained a mystery, as many of the enzymes involved in these characterized steps are absent. The heme pathway in most organisms proceeds from the cyclic precursor of all modified tetrapyrroles uroporphyrinogen III, to coproporphyrinogen III, which is followed by oxidation of the ring and finally iron insertion. Sulfate-reducing bacteria and some archaea lack the genetic information necessary to convert uroporphyrinogen III to heme along the “classical” route and instead use an “alternative” pathway. Biosynthesis of the isobacteriochlorin heme d ₁, a cofactor of the dissimilatory nitrite reductase cytochrome cd ₁, has also been a subject of much research, although the biosynthetic pathway and its intermediates have evaded discovery for quite some time. This review focuses on the recent advances in the understanding of these two pathways and their surprisingly close relationship via the unlikely intermediate siroheme, which is also a cofactor of sulfite and nitrite reductases in many organisms. The evolutionary questions raised by this discovery will also be discussed along with the potential regulation required by organisms with overlapping tetrapyrrole biosynthesis pathways.     

Cytosolic free Ca2+ in insulin secreting cells and its regulation by isolated organelles

Summary The role of Ca²⁺ in secretagogue-induced insulin release is documented not only by the measurements of⁴⁵Ca fluxes in pancreatic islets, but also, by direct monitoring of cytosolic free Ca²⁺, [Ca²⁺]_i. As demonstrated, using the fluorescent indicator quin 2, glyceraldehyde, carbamylcholine and alanine raise [Ca²⁺]_i in the insulin secreting cell line RINm5F, whereas glucose has a similar effect in pancreatic islet cells. The regulation of cellular Ca²⁺ homeostasis by organelles from a rat insulinoma, was investigated with a Ca²⁺ selective electrode. The results suggest that both the endoplasmic reticulum and the mitochondria participate in this regulation, albeit at different Ca²⁺ concentrations. By contrast, the secretory granules do not appear to be involved in the short-term regulation of [Ca²⁺]_i. Evidence is presented that inositol 1,4,5-trisphosphate, which is shown to mobilize Ca²⁺ from the endoplasmic reticulum, is acting as an intracellular mediator in the stimulation of insulin release.     

Na+,K+-ATPase as a docking station: protein–protein complexes of the Na+,K+-ATPase

The Na⁺,K⁺-ATPase, or sodium pump, is well known for its role in ion transport across the plasma membrane of animal cells. It carries out the transport of Na⁺ ions out of the cell and of K⁺ ions into the cell and thus maintains electrolyte and fluid balance. In addition to the fundamental ion-pumping function of the Na⁺,K⁺-ATPase, recent work has suggested additional roles for Na⁺,K⁺-ATPase in signal transduction and biomembrane structure. Several signaling pathways have been found to involve Na⁺,K⁺-ATPase, which serves as a docking station for a fast-growing number of protein interaction partners. In this review, we focus on Na⁺,K⁺-ATPase as a signal transducer, but also briefly discuss other Na⁺,K⁺-ATPase protein–protein interactions, providing a comprehensive overview of the diverse signaling functions ascribed to this well-known enzyme.     

Photon emission from normal and tumor human tissues

Photon emission in the visible and near ultraviolet range by samples of human tissue removed during surgery has been measured by means of a low noise photomultiplier coupled to a data acquisition system. The results show that among the 25 analyzed samples the 9 from normal tissues had an emission rate of the order of some tens of photons/cm² min, while most of the 16 tumor tissue samples had a very much higher rate.     

Ras proteins in the control of the cell cycle and cell differentiation

The Ras family of small GTPases includes three closely related proteins: H-, K-, and N-Ras. Ras proteins are involved in the transduction of signals elicited by activated surface receptors, acting as key components by relaying signals downstream through diverse pathways. Mutant, constitutively activated forms of Ras proteins are frequently found in cancer. While constitutive Ras activation induces oncogenic-like transformation in immortalized fibroblasts, it causes growth arrest in primary vertebrate cells. Induction of p53 and cyclin-dependent kinase inhibitors such as p15^INK4b, p16^INK4a, p19^ARF, and p21^WAF1 accounts for this response. Interestingly, while ras has usually been regarded as a transforming oncogene, the analysis of Ras function in most of the cellular systems studied so far indicates that the promotion of differentiation is the most prominent effect of Ras. While in some cell types, particularly muscle, Ras inhibits differentiation, in others such as neuronal, adipocytic, or myeloid cells, Ras induces differentiation, in some cases accompanied by growth arrest. Several possible mechanisms for the pleiotropic effects of Ras in animal cells are discussed. Received 8 March 2000; received after revision 24 May 2000; accepted 24 May 2000     

Acetyl-coenzyme A synthetase (AMP forming)

Acetyl-coenzyme A synthetase (AMP forming; Acs) is an enzyme whose activity is central to the metabolism of prokaryotic and eukaryotic cells. The physiological role of this enzyme is to activate acetate to acetyl-coenzyme A (Ac-CoA). The importance of Acs has been recognized for decades, since it provides the cell the two-carbon metabolite used in many anabolic and energy generation processes. In the last decade researchers have learned how carefully the cell monitors the synthesis and activity of this enzyme. In eukaryotes and prokaryotes, complex regulatory systems control acs gene expression as a function carbon flux, with a second layer of regulation exerted posttranslationally by the NAD⁺/sirtuin-dependent protein acetylation/deacetylation system. Recent structural work provides snapshots of the dramatic conformational changes Acs undergoes during catalysis. Future work on the regulation of acs gene expression will expand our understanding of metabolic integration, while structure/function studies will reveal more details of the function of this splendid molecular machine.Received 4 December 2003; received after revision 2 March 2004; accepted 16 March 2004     

Role of p75 neurotrophin receptor in stem cell biology: more than just a marker

p75^NTR, the common receptor for both neurotrophins and proneurotrophins, has been widely studied because of its role in many tissues, including the nervous system. More recently, a close relationship between p75^NTR expression and pluripotency has been described. p75^NTR was shown to be expressed in various types of stem cells and has been used to prospectively isolate stem cells with different degrees of potency. Here, we give an overview of the current knowledge on p75^NTR in stem cells, ranging from embryonic to adult stem cells, and cancer stem cells. In an attempt to address its potential role in the control of stem cell biology, the molecular mechanisms underlying p75^NTR signaling in different models are also highlighted. p75^NTR-mediated functions include survival, apoptosis, migration, and differentiation, and depend on cell type, (pro)neurotrophin binding, interacting transmembrane co-receptors expression, intracellular adaptor molecule availability, and post-translational modifications, such as regulated proteolytic processing. It is therefore conceivable that p75^NTR can modulate cell-fate decisions through its highly ramified signaling pathways. Thus, elucidating the potential implications of p75^NTR activity as well as the underlying molecular mechanisms of p75^NTR will shed new light on the biology of both normal and cancer stem cells.     

Chemistry of some potent animal toxins

Conclusion I have discussed in this article only the most active toxins, with the result that many interesting substances have been omitted, e.g. the toxins from bee and wasp venoms (apamin, melittin, etc.), of many amphibians (bufotoxins, etc.), ciguatoxins, and many more. Poisons are found in every phylum except birds. Shrews exemplify venomous mammals. One gets a good illustration of the number of poisonous animals by studying the monumental and impressive work byHalstead ¹⁰⁶ which consequently excludes terrestrial animals. An interesting fact in this connection is that there are about 20,000 species of spiders, most of which are poisonous.A toxin ranking list has to be included in an article of this kind. The list is, of course, far from complete. Data on molecular weights, mouse lethal doses, etc. are lacking for many potent toxins, such as the dysentery toxin, a neurotoxin with a toxicity comparable to that of the botulinus toxins¹⁰⁷, the toxins from the jelly fishChironex fleckeri ¹⁰⁶.A comparison on molar basis gives a better notion of the toxicities. Curare has about 1/30 of the toxicity of the curarimimetic snake venom neurotoxins, clearly indicating that curare has a much lower affinity for the acetylcholine receptor.Toxic organisms have developed during millions of years more and more refined toxins, and this evolution has probably brought into existence toxins against every physiological function. Neurochemistry is to a great extent unexplored. Progress in this field will in the nearest future depend on specific toxins from various natural sources. Toxins from spiders, scorpions, snakes, frogs, and fishes are therefore not mere curiosities but valuable tools for research on the molecular mechanisms of neural function and synaptic transmission.     

Nervous tissue proteoglycans

The structure, biosynthesis, localization, and possible functional roles of nervous tissue glycosaminoglycans and proteoglycans were last reviewed several years ago^70,74. Since that time, there has been an exponential increase in publications on the neurobiology of proteoglycans. This review will therefore focus on reports which have appeared in the period after 1988, and especially on those concerning the properties of individual characterized nervous tissue proteoglycans. Related areas such as the regulation of glycosaminoglycan biosynthesis and the roles of cell surface proteoglycans in adhesion and growth control are covered in other contributions to this special topic issue.     

Involvement of Na<Superscript>+</Superscript>, K<Superscript>+</Superscript>-ATPase and its inhibitors in HuR-mediated cytokine mRNA stabilization in lung epithelial cells

Increasing evidence demonstrates that Na⁺, K⁺-ATPase plays an important role in pulmonary inflammation, but the mechanism remains largely unknown. In this study, we used cardiotonic steroids as Na⁺, K⁺-ATPase inhibitors to explore the possible involvement of Na⁺, K⁺-ATPase in pulmonary epithelial inflammation. The results demonstrated that mice after ouabain inhalation developed cyclooxygenase-2-dependent acute lung inflammation. The in vitro experiments further confirmed that Na⁺, K⁺-ATPase inhibitors significantly stimulated cyclooxygenase-2 expression in lung epithelial cells of human or murine origin, the process of which was participated by multiple cis-elements and trans-acting factors. Most importantly, we first described here that Na⁺, K⁺-ATPase inhibitors could evoke a significant Hu antigen R nuclear export in lung epithelial cells, which stabilized cyclooxygenase-2 mRNA by binding with a proximal AU-rich element within its 3′-untranslated region. In conclusion, HuR-mediated mRNA stabilization opens new avenues in understanding the importance of Na⁺, K⁺-ATPase, as well as its inhibitors in inflammation.     

Plants as a direct source of fuel

Summary Euphorbia lathyris, a plant which has been proposed as an energy farm candidate yields a total of 35% of its dry weight as simple organic extractables. Chemical analyses of the extracts show that 5% of the dry weight is a mixture of reduced terpenoids, in the form of triterpenoids, and 20% of the dry weight is simple sugars in the form of hexoses. The terpenoids can be converted to a gasoline-like substance and the sugars can be fermented to alcohol. Based on a biomass yield of about 25 dry tons ha^–1 year^–1, the total energy that can be obtained from this plant in the form of liquid fuels is 48 MJ ha^–1 year^–1, 26 MJ in the form of hydrocarbons and 22 MJ in the form of ethanol. A conceptual process study for the large scale recovery ofEuphorbia lathyris products indicates that this crop is a net energy producer. Several lines of investigation have been started to increase the hydrocarbon yield of this plant. Tissue cultures ofE. lathyris have been established and will be used for selection, with the aim of regenerating a superior plant. Biochemical studies have been initiated to elucidate regulation of terpenoid metabolism. Future plans include eventual genetic engineering to select the most desirable plant for hydrocarbon production.This work was supported by the Assistant Secretary for Conservation and Solar Energy, Office of Solar Energy, Solar Applications for Industry Division of the US Department of Energy under Contract No. W-7405-ENG-48.