Quantum entanglement in photoactive prebiotic systems

This paper contains the review of quantum entanglement investigations in living systems, and in the quantum mechanically modelled photoactive prebiotic kernel systems. We define our modelled self-assembled supramolecular photoactive centres, composed of one or more sensitizer molecules, precursors of fatty acids and a number of water molecules, as a photoactive prebiotic kernel systems. We propose that life first emerged in the form of such minimal photoactive prebiotic kernel systems and later in the process of evolution these photoactive prebiotic kernel systems would have produced fatty acids and covered themselves with fatty acid envelopes to become the minimal cells of the Fatty Acid World. Specifically, we model self-assembling of photoactive prebiotic systems with observed quantum entanglement phenomena. We address the idea that quantum entanglement was important in the first stages of origins of life and evolution of the biospheres because simultaneously excite two prebiotic kernels in the system by appearance of two additional quantum entangled excited states, leading to faster growth and self-replication of minimal living cells. The quantum mechanically modelled possibility of synthesizing artificial self-reproducing quantum entangled prebiotic kernel systems and minimal cells also impacts the possibility of the most probable path of emergence of protocells on the Earth or elsewhere. We also examine the quantum entangled logic gates discovered in the modelled systems composed of two prebiotic kernels. Such logic gates may have application in the destruction of cancer cells or becoming building blocks of new forms of artificial cells including magnetically active ones.     

A possible role of fluctuating clay-water systems in the production of ordered prebiotic oligomers

Summary A model is proposed for the intermediate stages of prebiotic evolution, based on the characteristics of the adsorption and condensation of amino acids and nucleotides on the surface area of clay minerals in a fluctuating environment. Template replication and translation of adsorbed oligonucleotides and catalytic effects by peptide products on further condensation are proposed, due to specific properties of hypohydrous clay surfaces as well as the biomolecules themselves. Experimental evidence supports some of the proposed interactions, and all of them can be tested experimentally.on leave from the Faculty of Agriculture, The Hebrew University of Jerusalem, Rehovot, Israel, 1975–76     

From prebiotic chemistry to cellular metabolism--the chemical evolution of metabolism before Darwinian natural selection

It is generally assumed that the complex map of metabolism is a result of natural selection working at the molecular level. However, natural selection can only work on entities that have three basic features: information, metabolism and membrane. Metabolism must include the capability of producing all cellular structures, as well as energy (ATP), from external sources; information must be established on a material that allows its perpetuity, in order to safeguard the goals achieved; and membranes must be able to preserve the internal material, determining a selective exchange with external material in order to ensure that both metabolism and information can be individualized. It is not difficult to understand that protocellular entities that boast these three qualities can evolve through natural selection. The problem is rather to explain the origin of such features under conditions where natural selection could not work. In the present work we propose that these protocells could be built by chemical evolution, starting from the prebiotic primordial soup, by means of chemical selection. This consists of selective increases of the rates of certain specific reactions because of the kinetic or thermodynamic features of the process, such as stoichiometric catalysis or autocatalysis, cooperativity and others, thereby promoting their prevalence among the whole set of chemical possibilities. Our results show that all chemical processes necessary for yielding the basic materials that natural selection needs to work may be achieved through chemical selection, thus suggesting a way for life to begin.     

Model for prebiotic pyrophosphate formation: Condensation of precipitated orthophosphate at low temperature in the absence of condensing or phosphorylating agents

Summary The formation of pyrophosphate (PPi) by condensation of orthophosphate (Pi) at low temperature (37°C) in the absence of condensing or phosphorylating agents could have been an ancient process in chemical evolution. In the present investigation the synthesis of³²PPi from³²Pi was carried out at pH 8.0 and PPi was found in larger amounts in the presence of insoluble Pi (with calcium or manganese ions) than in its absence (with magnesium ions, or with no divalent cations present). After 10 days of incubation in the presence of precipitated calcium phosphate, about 1.6 nmol/ml of PPi was formed (0.057% yield relative to insoluble Pi). The hypothesis that the reaction is dependent on precipitated Pi was reinforced by the effect of adding dimethyl sulfoxide (2.1–9.9 M) in the presence of magnesium ions: the amount of magnesium phosphate precipitated in the presence of the organic solvent was proportional to the amount of PPi formed. The large and negative activation entropies found in aqueous media with calcium ions and in a medium containing 11.3 M dimethyl sulfoxide with magnesium ions suggest that the reaction was favored by a hydrophobic phenomenon at the surface of solid Pi. This reaction could serve as a model for prebiotic formation of PPi.     

Hyphal fusion during initial stages of trap formation in Arthrobotrys oligospora

Hyphal fusion during initial stages of trap formation by Arthrobotrys oligospora was studied by video-enhanced contrast and electron microscopy. Trap initials grew perpendicularly to the parent hypha, then curved around and anastomosed with a peg that developed on the hypha. Trap initials usually developed 40–140 m apart while the anastomosis occurred 20–25 m from the initial. Vigorous cytoplasmic movements in trap initials and developed traps corresponded to intense staining with fluorescein diacetate (FDA) of these cells. In addition, bundles of microfilaments were seen in developing loops of traps. On fusion organelle migration took place from the tip cell of the trap into the peg. Later on a septum was formed at the site of fusion.     

Dynamics of pattern formation in biomimetic systems

This paper is an attempt to conceptualize pattern formation in self-organizing systems and, in particular, to understand how structures, oscillations or waves arise in a steady and homogenous environment, a phenomenon called symmetry breaking. The route followed to develop these ideas was to couple chemical oscillations produced by Belousov-Zhabotinsky reaction with confined reaction environments, the latter being an essential requirement for any process of Life. Special focus was placed on systems showing organic or lipidic compartments, which represent more reliable biomimetic matrices.     

On modeling and complexity of developing systems

We consider the general properties of developing systems, the approaches to their modeling, and the question of their complexity. The notion “complex system” is vague; somewhat more distinct is the complexity of the model describing a phenomenon. We propose to discuss two pertinent issues. (i) The complexity of basic models is minimal; in other words, complicated basic models are needless. (ii) Living systems are simpler than inanimate ones. Though developing systems are seen in abiotic as well as in biotic nature, the fundamental difference is that living beings are capable of goal-setting and purposeful development; hence they can be described with simpler basic models.     

Metabolic modeling of endosymbiont genome reduction on a temporal scale

A fundamental challenge in Systems Biology is whether a cell‐scale metabolic model can predict patterns of genome evolution by realistically accounting for associated biochemical constraints. Here, we study the order in which genes are lost in an in silico evolutionary process, leading from the metabolic network of Eschericia coli to that of the endosymbiont Buchnera aphidicola. We examine how this order correlates with the order by which the genes were actually lost, as estimated from a phylogenetic reconstruction. By optimizing this correlation across the space of potential growth and biomass conditions, we compute an upper bound estimate on the model's prediction accuracy (R=0.54). The model's network‐based predictive ability outperforms predictions obtained using genomic features of individual genes, reflecting the effect of selection imposed by metabolic stoichiometric constraints. Thus, while the timing of gene loss might be expected to be a completely stochastic evolutionary process, remarkably, we find that metabolic considerations, on their own, make a marked 40% contribution to determining when such losses occur.     

Comparative survival of probiotic lactobacilli spray-dried in the presence of prebiotic substances

AIMS: Probiotic milk-based formulations were spray-dried with various combinations of prebiotic substances in an effort to generate synbiotic powder products. METHODS AND RESULTS: To examine the effect of growth phase and inclusion of a prebiotic substance in the feed media on probiotic viability during spray-drying, Lactobacillus rhamnosus GG was spray-dried in lag, early log and stationary phases of growth in reconstituted skim milk (RSM) (20% w/v) or RSM (10% w/v), polydextrose (PD) (10% w/v) mixture at an outlet temperature of 85-90 degrees C. Stationary phase cultures survived best (31-50%) in both feed media and were the most stable during powder storage at 4-37 degrees C over 8 weeks, with 30-140-fold reductions in cell viability at 37 degrees C in RSM and PD/RSM powders, respectively. Stationary phase Lact. rhamnosus GG was subsequently spray-dried in the presence of the prebiotic inulin in the feed media, composed of RSM (10% w/v) and inulin (10% w/v), and survival following spray-drying was of the order 7.1-43%, while viability losses of 20,000-90,000-fold occurred in these powders after 8 weeks' storage at 37 degrees C. Survival of the Lactobacillus culture after spray-drying in powders produced using PD (20% w/v) or inulin (20% w/v) as the feed media was only 0.011-0.45%. To compare different probiotic lactobacilli during spray-drying, stationary phase Lact. rhamnosus E800 and Lact. salivarius UCC 500 were spray-dried using the same parameters as for Lact. rhamnosus GG in either RSM (20% w/v) or RSM (10% w/v) and PD (10% w/v). Lact. rhamnosus E800 experienced approx. 25-41% survival, yielding powders containing approximately 10(9) CFU g(-1), while Lact. salivarius UCC 500 performed poorly, experiencing over 99% loss in viability during spray-drying in both feed media. In addition to the superior survival of Lact. rhamnosus GG after spray-drying, both strains experienced higher viability losses (570-700-fold) during storage at 37 degrees C over 8 weeks compared with Lact. rhamnosus GG. CONCLUSIONS: Stationary phase cultures were most suitable for the spray-drying process, while lag phase was most susceptible. The presence of the prebiotics PD and inulin did not enhance viability during spray-drying or powder storage. SIGNIFICANCE AND IMPACT OF THE STUDY: High viability (approximately 10(9) CFU g(-1)) powders containing probiotic lactobacilli in combination with prebiotics were developed, which may be useful as functional food ingredients for the manufacture of probiotic foods.     

Stereoselective decarboxylation of amino acids in the solid state,with special reference to chiral discrimination in prebiotic evolution

Summary The decarboxylations of sublimated solidd- andl-leucine by nonpolarized -rays give quite different quantum yields, indicating significant selection. The G(CO₂) value for thed-isomer is higher than that for thel-isomer by a factor of 2 within a dose range of 10³–10⁵ rads. The G value for thedl-racemate is close to that of thed-isomer. The effect vanishes if instead of sublimation, crystallization from aqueous solution is the last preparation step. Our results on sublimated leucine agree well with those reported for -induced decarboxylation of solid -phenylalanine prepared similarly by sublimation. The asymmetry increases with longer cooling periods after irradiation. An intrinsic energy difference due to parity nonconservation between enantiomers is discussed as a possible stereoselective mechanism, with special reference to the prebiotic origin of asymmetry in living matter. Other possible sources of the observed effects are also discussed.     

An application of the theoretical group methods to modeling of complex systems

The applicability of theoretical group methods to studying complex physical and biological systems with the potential of self-organization was demonstrated. The problem of calculating climate sensitivity parameters taking into account the cyclone-anticyclone structure of the atmosphere optically dense in the infrared region is considered as an example.     

Dynamic heterogeneous spatio-temporal pattern formation in host-parasitoid systems with synchronised generations

In this paper we develop a general mathematical model describing the spatio-temporal dynamics of host-parasitoid systems with forced generational synchronisation, for example seasonally induced diapause. The model itself may be described as an individual-based stochastic model with the individual movement rules derived from an underlying continuum PDE model. This approach permits direct comparison between the discrete model and the continuum model. The model includes both within-generation and between-generation mechanisms for population regulation and focuses on the interactions between immobile juvenile hosts, adult hosts and adult parasitoids in a two-dimensional domain. These interactions are mediated, as they are in many such host-parasitoid systems, by the presence of a volatile semio-chemical (kairomone) emitted by the hosts or the hosts food plant. The model investigates the effects on population dynamics for different host versus parasitoid movement strategies as well as the transient dynamics leading to steady states. Despite some agreement between the individual and continuum models for certain motility parameter ranges, the model dynamics diverge when host and parasitoid motilities are unequal. The individual-based model maintains spatially heterogeneous oscillatory dynamics when the continuum model predicts a homogeneous steady state. We discuss the implications of these results for mechanistic models of phenotype evolution.P. Schofield gratefully acknowledges the financial support of the BBSRC and The Wellcome Trust.     

Dissecting the energy metabolism in Mycoplasma pneumoniae through genome‐scale metabolic modeling

Mycoplasma pneumoniae, a threatening pathogen with a minimal genome, is a model organism for bacterial systems biology for which substantial experimental information is available. With the goal of understanding the complex interactions underlying its metabolism, we analyzed and characterized the metabolic network of M. pneumoniae in great detail, integrating data from different omics analyses under a range of conditions into a constraint‐based model backbone. Iterating model predictions, hypothesis generation, experimental testing, and model refinement, we accurately curated the network and quantitatively explored the energy metabolism. In contrast to other bacteria, M. pneumoniae uses most of its energy for maintenance tasks instead of growth. We show that in highly linear networks the prediction of flux distributions for different growth times allows analysis of time‐dependent changes, albeit using a static model. By performing an in silico knock‐out study as well as analyzing flux distributions in single and double mutant phenotypes, we demonstrated that the model accurately represents the metabolism of M. pneumoniae. The experimentally validated model provides a solid basis for understanding its metabolic regulatory mechanisms.     

The formation of mixed disulphides in rat lung following paraquat administration Correlation with changes in intermediary metabolism

We have investigated the hypothesis that the formation of mixed disulphides between protein sulphydryl and glutathione may be responsible for controlling the activity of the pentose phosphate pathway and fatty acid synthesis in rat lung. Using lung slices, taken from rats 2 h after dosing with a range of concentrations (5–80 mg/kg) of the pulmonary toxin paraquat, the pentose phosphate pathway was found to be stimulated in direct proportion to a reduction in fatty acid synthesis. These effects were also linearly related to an increase in mixed (total) disulphide levels in the lung. This was quantitatively similar to an increase in mixed (glutathione) disulphides, although non-protein sulphydryl and oxidised levels remained normal. Thus, an early biochemical event in the mechanism of paraquat toxicity in the lung involves an increased formation of mixed (glutathione) disulphides and simulatneous regulation of pentose phosphate pathway activity and fatty acid synthesis. These data support the concept that the formation of mixed disulphides of protein and glutathione is a mechanism for maintaining NADPH levels despite the ‘redox’ stress caused by the cyclical and NADPH dependent reduction and reoxidation of paraquat.     

In vitro evaluation of the fermentation properties and potential prebiotic activity of Agave fructans

Aims: This study was carried out to evaluate in vitro the fermentation properties and the potential prebiotic activity of Agave‐fructans extracted from Agave tequilana (Predilife). Methods and Results: Five different commercial prebiotics were compared using 24‐h pH‐controlled anaerobic batch cultures inoculated with human faecal slurries. Measurement of prebiotic efficacy was obtained by comparing bacterial changes, and the production of short‐chain fatty acids (SCFA) was also determined. Effects upon major groups of the microbiota were monitored over 24 h incubations by fluorescence in situ hybridization. SCFA were measured by HPLC. Fermentation of the Agave fructans (Predilife) resulted in a large increase in numbers of bifidobacteria and lactobacilli. Conclusions: Under the in vitro conditions used, this study has shown the differential impact of Predilife on the microbial ecology of the human gut. Significance and Impact of the Study: This is the first study reporting of a potential prebiotic mode of activity for Agave fructans investigated which significantly increased populations of bifidobacteria and lactobacilli compared to cellulose used as a control.     

Dynamic modeling of complex biological systems: a link between metabolic and macroscopic description

In this study, a class of dynamic models based on metabolic reaction pathways is analyzed, showing that systems with complex intracellular reaction networks can be represented by macroscopic reactions relating extracellular components only. Based on rigorous assumptions, the model reduction procedure is systematic and allows an equivalent 'input-output' representation of the system to be derived. The procedure is illustrated with a few examples.     

Comparison of prebiotic effects of arabinoxylan oligosaccharides and inulin in a simulator of the human intestinal microbial ecosystem

In this study, the prebiotic potential of arabinoxylan oligosaccharides (AXOS) was compared with inulin in two simulators of the human intestinal microbial ecosystem. Microbial breakdown of both oligosaccharides and short-chain fatty acid production was colon compartment specific, with ascending and transverse colon being the predominant site of inulin and AXOS degradation, respectively. Lactate levels (+5.5 mM) increased in the ascending colon during AXOS supplementation, while propionate levels (+5.1 mM) increased in the transverse colon. The concomitant decrease in lactate in the transverse colon suggests that propionate was partially formed over the acrylate pathway. Furthermore, AXOS supplementation strongly decreased butyrate in the ascending colon, this in parallel with a decrease in Roseburia spp. and Bacteroides / Prevotella / Porphyromonas (−1.4 and −2.0 log CFU) levels. Inulin treatment had moderate effects on lactate, propionate and butyrate levels. Denaturing gradient gel electrophoresis analysis revealed that inulin changed microbial metabolism by modulating the microbial community composition. In contrast, AXOS primarily affected microbial metabolism by 'switching on' AXOS-degrading enzymes (xylanase, arabinofuranosidase and xylosidase), without significantly affecting microbial community composition. Our results demonstrate that AXOS has a higher potency than inulin to shift part of the sugar fermentation toward the distal colon parts. Furthermore, due to its stronger propionate-stimulating effect, AXOS is a candidate prebiotic capable of lowering cholesterol and beneficially affecting fat metabolism of the host.     

Application of theoretical group methods in the modeling of complex systems

It has been shown that theoretical group methods can be applied in studies of complex physical and biological systems in which the phenomenon of self-organization takes place. The problem of calculating the parameters of climatic sensitivity with allowance for the cyclone-anticyclone structure of the atmosphere optically dense in the infrared region is considered as an example.     

Pharmacological analysis of the participation of ethanol-oxidizing enzyme systems in ethanol metabolism at different stages of experimental alcoholism

Using head space chromatography, the pharmacological analysis of changes in the activity of ethanol-oxidizing enzymatic systems: alcohol dehydrogenase, catalase, microsomal ethanol-oxidizing system under the effect of pyrazole and aminotriazole, has been performed on the model of experimental alcoholism in rats. It was shown that the rate of ethanol elimination from the rats' blood at all stages of experimental alcoholism was determined by alcohol dehydrogenase, while catalase and microsomal ethanol-oxidizing system activities did not play an important role.     

Toward convergence of experimental studies and theoretical modeling of the chromatin fiber

Understanding the structural organization of eukaryotic chromatin and its control of gene expression represents one of the most fundamental and open challenges in modern biology. Recent experimental advances have revealed important characteristics of chromatin in response to changes in external conditions and histone composition, such as the conformational complexity of linker DNA and histone tail domains upon compact folding of the fiber. In addition, modeling studies based on high-resolution nucleosome models have helped explain the conformational features of chromatin structural elements and their interactions in terms of chromatin fiber models. This minireview discusses recent progress and evidence supporting structural heterogeneity in chromatin fibers, reconciling apparently contradictory fiber models.