Calcium Signals Driven by Single Channel Noise

Usually, the occurrence of random cell behavior is appointed to small copy numbers of molecules involved in the stochastic process. Recently, we demonstrated for a variety of cell types that intracellular Ca2+ oscillations are sequences of random spikes despite the involvement of many molecules in spike generation. This randomness arises from the stochastic state transitions of individual Ca2+ release channels and does not average out due to the existence of steep concentration gradients. The system is hierarchical due to the structural levels channel - channel cluster - cell and a corresponding strength of coupling. Concentration gradients introduce microdomains which couple channels of a cluster strongly. But they couple clusters only weakly; too weak to establish deterministic behavior on cell level. Here, we present a multi-scale modelling concept for stochastic hierarchical systems. It simulates active molecules individually as Markov chains and their coupling by deterministic diffusion. Thus, we are able to follow the consequences of random single molecule state changes up to the signal on cell level. To demonstrate the potential of the method, we simulate a variety of experiments. Comparisons of simulated and experimental data of spontaneous oscillations in astrocytes emphasize the role of spatial concentration gradients in Ca2+ signalling. Analysis of extensive simulations indicates that frequency encoding described by the relation between average and standard deviation of interspike intervals is surprisingly robust. This robustness is a property of the random spiking mechanism and not a result of control

Bootstrapping the energy flow in the beginning of life.

This paper suggests that the energy flow on which all living structures depend only started up slowly, the low-energy, initial phase starting up a second, slightly more energetic phase, and so on. In this way, the build up of the energy flow follows a bootstrapping process similar to that found in the development of computers, the first generation making possible the calculations necessary for constructing the second one, etc. In the biogenetic upstart of an energy flow, non-metals in the lower periods of the Periodic Table of Elements would have constituted the most primitive systems, their operation being enhanced and later supplanted by elements in the higher periods that demand more energy. This bootstrapping process would put the development of the metabolisms based on the second period elements carbon, nitrogen and oxygen at the end of the evolutionary process rather than at, or even before, the biogenetic even

Two approaches to the study of the origin of life.

This paper compares two approaches that attempt to explain the origin of life, or biogenesis. The more established approach is one based on chemical principles, whereas a new, yet not widely known approach begins from a physical perspective. According to the first approach, life would have begun with - often organic - compounds. After having developed to a certain level of complexity and mutual dependence within a non-compartmentalised organic soup, they would have assembled into a functioning cell. In contrast, the second, physical type of approach has life developing within tiny compartments from the beginning. It emphasises the importance of redox reactions between inorganic elements and compounds found on two sides of a compartmental boundary. Without this boundary, ¿life¿ would not have begun, nor have been maintained; this boundary - and the complex cell membrane that evolved from it - forms the essence of life

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

Extrachromosomal elements as possible agents of adaptation and development.

Despite the increasing credence accorded the concept, the ecology of extrachromosomal elements is still poorly documented, theories concerning their phylogeny and interrelationships are speculative, and the terminology applied to such agents remains confused. In many instances, extrachromosomal elements are regarded as bizarre curiosities that are something of an epiphenomenon in general evolutionary biology. The present review attempts to construct a balanced theory of evolution in which proper emphasis is given to possible roles for plasmids and viruses in the processes of growth, adaptation, and speciation

A study of some facultatively thermophilic soil viruses

1) Results of some pilot studies on the ecology of thermophilic phage in soil are reported. 2) The possible use of phage as a monitor for the activity of spore-forming bacteria in soil has been assessed. 3) It has been shown that the optimal temperature for the growth of "thermophilic" phage in soil is 45°C (or 37°) and not 55°. This fact, in conjunction with other data, suggests that most phage parasitic upon B. stearothermophilus are biochemically adapted to mesophily in soil rather than thermophily. It is suggested that all thermophilic viruses isolated for soil bacteria represent merely a mutant minority of a population of particles widely distributed with respect to heat tolerance. 4) 4 facultatively thermophilic viruses have been isolated for B. stearothermophilus T16. 5) The biological properties of 2 of these phages, D-S and D-6, have been determined. 6) The growth and lytic ability of phages D-S and D-6 have been compared at a mesophilic and thermophilic temperature. 7) The thermostability of phage D-S in broth and in dilute and strong salt solution has been determined. From this data some inferences concerning the nature of thermo-phily can be drawn. 8) The morphology of phage D-5 has been elucidated from an electron microscopic study 9) The problem of the origin of the genetic code is discussed in the light of known data. 10) It is postulated that ancient codes contained only 2 bases and coded for only a few amino acids. 11) It is suggested that the 2 primordial bases may have been U and I. Features of the code and its evolution are examined in terms of this theory. 12) Evidence for amino acid - polynucleotide interaction is reviewed. 13) Some selective advantages of circular DNA are described in terms of selected contemporary genomes. 14) It is postulated that DNA circularity played an obligatory role in the extension of gene data throughout evolution. The significance of repeat base sequences in eucaryote DNA is assessed in terms of this theory. 15) The role of viruses as gene vectors is discussed. It is postulated that the genomes of viruses and cellular species are in constant interaction and that this exchange of gene data has been not merely advantageous but necessary for the evolutionary process

Translocatable resistance to mercuric and phenylmercuric ions in soil bacteria.

Of a sample of 42 gram-negative Hg-resistant bacteria, three (a Pseudomonas fluorescens, a Klebsiella sp. and a Citrobacter sp.) contained translocatable elements conferring resistance to Hg2+ (all three) and to Hg2+ and phenylmercuric acetate (P. fluorescens). The discovery of transposable phenylmercuric acetate resistance extends the range of known resistance "transposons" from heavy metals and antibiotics to organometallic compounds