Question 9: Prospects for the Construction of Artificial Cells or Protocells

The construction of artificial cells or protocells that are a simplified version of contemporary cells will have implications for both the understanding of the origins of cellular Life and the design of “cell-like” chemical factories. In this short communication, we discuss the progress and remaining issues related to the construction of protocells from metabolic products. We further outline the de novo design of a simple chemical system that mimics the functional properties of a living cell without being composed of molecules of biological origin, thereby addressing issues related to Life’s origins. Presented at: International School of Complexity—4th Course: Basic Questions on the Origins of Life; “Ettore Majorana” Foundation and Centre for Scientific Culture, Erice, Italy, 1–6 October 2006.     

Astrocatalysis—Abiogenic synthesis and chemical evolution at pregeological stages of the Earth’s formation

The Earth’s biosphere appeared in a self-organization process along with the appearance of the Solar System. It is shown, based on the methods of self-organization examination and existing knowledge, that major stages of the chemical evolution in the early development of the biosphere include the “cold prehistory of life” in dense molecular nebulae, “pre-planetary chemocoenosis,” “RNA-world” in a circumsolar nebula, and primary biocoenoses of protocells (life) on the planetary bodies. Estimates for carbon in the primordial biosphere on the young Earth’s surface give 2.4 × 10¹⁹ kg. The decay of the primordial Earth’s biomass and biogeochemical cycles in 2.5 Myr led to the “planet of bacteria” with 2.0 × 10¹⁵ kg of biota in the Proterozoic (at the time of an oxygenated atmosphere). The main parameters (pressure, temperature, and state of catalytic solid phase) are estimated for these stages of the early evolution of life. It is shown that the abiogenic synthesis of the primordial matter was preformed in the Solar System on a grand scale with practically every atom in nanoparticles-catalysts participating. Selection among catalytically active nanoparticles worked towards the ability to synthesize high molecular compounds in a protoplanetary disk. Autocatalysts participated in the preplanetary chemical evolution, beginning from such simple substances as ethylene or glycolaldehyde. Primary synthesis of autocatalysts depended on external sources of energy, e.g., on ultraviolet radiation.     

Question 7: Construction of a Semi-Synthetic Minimal Cell: A Model for Early Living Cells

Using a Synthetic Biology approach we are building a semi-synthetic minimal cell. This represents an exercise to shape a minimal-cell model system recalling the simplicity of early living cells in early evolution. We have recently introduced into liposome compartments a minimal set of enzymes named “Puresystem” (PS) synthesizing EGFP proteins. To establish reproduction of the shell compartment with a minimal set of genes we have cloned the genes for the Fatty Acid Synthase (FAS) type I enzymes. These FAS genes introduced into liposomes, translated into FAS enzymes by PS and in the presence of precursors produce fatty acids. The resulting release of fatty acid molecules within liposome vesicles should promote vesicle growth and reproduction. The core reproduction of a minimal cell corresponding to the replication of the minimal genome will require a few genes for the DNA replication and the PS, and a minimum set of genes for the synthesis of t-RNAs. In future the reconstruction of a minimal ribosome will bring the number of genes for ribosomal proteins from 54 of an existing minimal genome down to 30–20 genes. A Synthetic Biology approach could bring the number of essential genes for a minimal cell down to 100 or less. International School of Complexity–4th Course: Basic Questions on the Origins of Life; “Ettore Majorana” Foundation and Centre for Scientific Culture, Erice, Italy, 1–6 October 2006.     

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.     

Do we live in a largely top-down regulated world?

Based on a review of mostly recent literature for a public lecture, the question is discussed whether we live in a largely “top-down” regulated world rather than one formed “bottom-up” by the resources for plant and animal growth. Of course, the top-down mechanism is predicated by bottom-up production, especially by the plants. Examples for the effects of grazing and predation for the land and the open sea, but including coral reefs, are discussed. The answer to the question posed by the title is affirmative. Ecosystems altered by man and urgent needs for marine conservation are briefly treated.     

“Bottom-up” approach for implementing nano/microstructure using biological and chemical interactions

The “Bottom-up” approach for implementing nano/microstructure using biological self-assembled systems has been investigated with tremendous interest by many researchers in the field of medical diagnostics, material synthesis, and nano/microelectronics. As a result, the techniques for achieving these systems have been extensively explored in recent years. The developed or developing techniques are based on many interdisciplinary areas such as biology, chemistry, physics, electrical engineering, mechanical engineering, and so on. In this paper, we review the fundamentals behind the self-assembly concepts and describe the state of art in the biological and chemical self-assembled systems for the implementation of nano/microstructures. These structures described in the paper can be applied to the implementation of hybrid biosensors, biochip, novel bio-mimetic materials, and nano/microelectronic devices.     

The cancer cell’s “power plants” as promising therapeutic targets: An overview

This introductory article to the review series entitled “The Cancer Cell’s Power Plants as Promising Therapeutic Targets” is written while more than 20 million people suffer from cancer. It summarizes strategies to destroy or prevent cancers by targeting their energy production factories, i.e., “power plants.” All nucleated animal/human cells have two types of power plants, i.e., systems that make the “high energy” compound ATP from ADP and P _i . One type is “glycolysis,” the other the “mitochondria.” In contrast to most normal cells where the mitochondria are the major ATP producers (>90%) in fueling growth, human cancers detected via Positron Emission Tomography (PET) rely on both types of power plants. In such cancers, glycolysis may contribute nearly half the ATP even in the presence of oxygen (“Warburg effect”). Based solely on cell energetics, this presents a challenge to identify curative agents that destroy only cancer cells as they must destroy both of their power plants causing “necrotic cell death” and leave normal cells alone. One such agent, 3-bromopyruvate (3-BrPA), a lactic acid analog, has been shown to inhibit both glycolytic and mitochondrial ATP production in rapidly growing cancers (Ko et al., Cancer Letts., 173, 83–91, 2001), leave normal cells alone, and eradicate advanced cancers (19 of 19) in a rodent model (Ko et al., Biochem. Biophys. Res. Commun., 324, 269–275, 2004). A second approach is to induce only cancer cells to undergo “apoptotic cell death.” Here, mitochondria release cell death inducing factors (e.g., cytochrome c). In a third approach, cancer cells are induced to die by both apoptotic and necrotic events. In summary, much effort is being focused on identifying agents that induce “necrotic,” “apoptotic” or apoptotic plus necrotic cell death only in cancer cells. Regardless how death is inflicted, every cancer cell must die, be it fast or slow.     

Between classical and ideal: enhancing wildland fire prediction using cluster computing

One of the challenges still open to wildland fire simulators is the capacity of working under real-time constrains with the aim of providing fire spread predictions that could be useful in fire mitigation interventions. We propose going one step beyond the classical wildland fire prediction by linking evolutionary optimization strategies to the traditional scheme with the aim of emulating an “ideal” fire propagation model as much as possible. In order to accelerate the fire prediction, this enhanced prediction scheme has been developed in a fashion on a Linux cluster using MPI. Furthermore, a sensitivity analysis has been carried out to determine the input parameters that we can fix to their typical values in order to reduce the search-space involved in the optimization process and, therefore, accelerates the whole prediction strategy. Baker Abdalhaq received the BSc. Computer Science from Princess Sumaya University College, Royal JordanianSocieaty, Amman Jordania in 1993. In 2001 and 2004, he got the MSc and PhD in Computer Science from Universitat Autónoma de Barcelona (UAB), respectively. His main research interest is focused on parallel fire simulation and, in particular, how to take advantage of the computational power provided for massively distributed systems to enhance wildland fire prediction. Ana Cortés received both her first degree and her PhD in Computer Science from the Universitat Autonoma de Barcelona (UAB), Spain, in 1990 and 2000, respectively. She is currently assistant professor of Computer Science at the UAB, where she is a member of the Computer Architecture and Operating Systems Group at the Computer Science Department. Her current research interests concern software support for parallel and distributed computing including algorithms and software tools for the load-balancing of parallel programs. She has also been working on enhancing wildland fire prediction by exploiting parallel/distributed systems. Tomàs Margalef got a BS degree in physics in 1988 from Universitat Autónoma de Barcelona (UAB). In 1990 he obtained the MSc in Computer Science and in 1993 the PhD in Computer Science from UAB. Since 1988 he has been working in several aspects related to parallel and distributed computing. Currently, his research interests focuses on development of high performance applications, automatic performance analysis and dynamic performance tuning. Since 1997 he has been working on exploiting parallel/distributed processing to accelerate and improve the prediction of forest fire propagation. He is an ACM member. Germán Bianchini received the BSc. Computer Science from Universidad Nacional Del Comahue, Argentina, in 2002. In 2004 and 2006, he got the MSc and PhD in Computer Science from Universitat Autónoma de Barcelona (UAB), respectively. His main research interest is focused on parallel fire simulation and, in particular, how to take advantage of the computational power provided for massively distributed systems to enhance wildland fire prediction. Emilio Luque received the Licenciate in physics and PhD degrees from the University Complutense of Madrid (UCM) in 1968 and 1973 respectively. Between 1973 and 1976 he was an associate professor at the UCM. Since 1976 he is a professor of “Computer Architecture and Technology” at the University Autonoma of Barcelona (UAB), where he is leading the Computer Architecture and Operating System (CAOS) Group at the Computer Science Department. Professor Luque has been the Computer Science Department chairman for more than 10 years. He has been invited lecturer/researcher in Universities of USA, Argentina, Brazil, Poland, Ireland, Cuba, Italy, Germany and PR of China. He has published more than 35 papers in technical journals and more than 100 papers at international conferences and his current/major research areas are: computer architecture, interconnection networks, task scheduling in parallel systems, parallel and distributed simulation environments, environment and programming tools for automatic performance tuning in parallel systems, cluster and Grid computing, parallel computing for environmental applications (forest fire simulation, forest monitoring) and distributed video on demand (VoD) systems.     

An integrated modelling approach to forecast the impact of human pressure in the Seine estuary

Within the framework of the European Water Framework Directive, the Seine-Normandie Water Agency has defined prospective scenarios describing possible trends of evolution of the pressures on water resources. In order to evaluate the resulting water quality improvement or degradation of water bodies in the Seine river basin, an integrated modelling was proposed. The approach consisted in coupling three models, the seneque model for upstream sub-basins, the ProSe model for the Seine river and main tributaries and finally the s i am1d model for the downstream estuary. After consistency verification, the integrated model was applied to scenarios proposed by the Seine-Normandie Water Agency. As a result of improvement in the nitrogen treatment by waste water treatment plants, the annual load of ammonia at the basin scale will be reduced by 65%. The oxygen and ammonia criteria in the estuary will improve from “bad” to “good”. However the nitrate criteria will remain “poor”, given the strong influence of non-point sources. Despite a 70–75% drop of the point orthophosphate loads, the criteria for this variable will also remain “poor”. The nutrient levels will be high enough to maintain eutrophication in the system; a general trend to a shift from N-limitation to P-limitation will be accentuated.     

Comprehensive evaluation of multiple cropping systems on upland red soil

According to the principles and methods of ecology and system engineering, we set up an evaluation indicator system for multi-component and multiple cropping systems, evaluated the comprehensive benefits of multi-component and multiple cropping systems using grey relation clustering analysis and screened out the optimized model based on research done in the upland red soil in Jiangxi Agricultural University from 1984 to 2004. The results show that the grey relation degree of “cabbage/potato/maize — sesame” was the highest among 23 multi-component and multiple cropping systems and was clustered into the optimized system. This indicates that “cabbage/potato/maize — sesame” can bring the best social, economic and ecological benefits, increase product yield and farmers’ income and promote sustainable development of agricultural production. Therefore, it is suitable for promotion on upland red soil. The grey relation degree of “canola/Chinese milk vetch/maize/mung bean/maize” was second, which is suitable for implementation at the city outskirts. In conclusion, these two planting patterns are expected to play important roles in the reconstruction of the planting structure and optimization of the planting patterns on upland red soil. __________ Translated from Acta Ecologica Sinica, 2006, 26(8): 2532–2539 [译自: 生态学报]     

Physics,biology and sociology: II. Suggestion for a synthesis

In continuation of previous studies (Bull. Math. Biophysics,28, 283–308; 655–661, 1966;29, 139–152, 1967) it is shown that the difference between the “metric” aspects of physics and the “relational” aspects of biological and social sciences disappear by accepting the broader definition of “relation”, such as that given in mathematics and logic. A conceptual superstructure then becomes possible from which all three branches of knowledge may be derived, though none of them can be derived from the others.     

Physiological bases of oligotrophy of microorganisms and the concept of microbial community

Three groups of physiological processes in microorganisms are considered the physiological basis of oligotrophy: the greater substrate affinity of the oligotrophs' transport systems, efficient or “economical” metabolism, and existence of a “master reaction” or “rate-determining steps” controlling the rate of metabolism. Heterotrophic microorganisms are divided into three unequal groups according to “reaction norma.” Two groups representing the extremes are small groups with the “narrow” reaction norma, regarding the concentrations and structure of the assimilated organic compounds and variability limits of the physiological characteristics mentioned above. The third, intermediate group includes the majority of microorganisms with the “wide” reaction norma.     

From “Lists of Traits” to “Open-Mindedness”: Emerging Issues in Cultural Competence Education

The incorporation of “culture” into U.S. biomedicine has been increasing at a rapid pace over the last several decades. Advocates for “cultural competence” point to changing patient demographics and growing health disparities as they call for improved educational efforts that train health providers to care for patients from a variety of backgrounds. Medical anthropologists have long been critical of the approach to “culture” that emerges in cultural competence efforts, identifying an essentialized, static notion of culture that is conflated with racial and ethnic categories and seen to exist primarily among exotic “Others.” With this approach, culture can become a “list of traits” associated with various racial and ethnic groups that must be mastered by health providers and applied to patients as necessary. This article uses an ethnographic examination of cultural competence training to highlight recent efforts to develop more nuanced approaches to teaching culture. I argue that much of contemporary cultural competence education has rejected the “list of traits” approach and instead aims to produce a new kind of health provider who is “open-minded,” willing to learn about difference, and treats each patient as an individual. This shift, however, can ultimately reinforce behavioral understandings of culture and draw attention away from the social conditions and power differentials that underlie health inequalities.     

Interpreting co-variation in species richness and productivity in terrestrial vegetation: Making sense of causations and correlations at multiple scales

This commentary examines conventional and recent ideas regarding the interpretation of species richness-productivity relationships (SRPR) in terrestrial vegetation. A new conceptual modelling approach — cascading graph diagrams — is used to search for maximum parsimony by distilling and clarifying synthetic linkages between several potential causes of variation and co-variation in these two vegetation attributes at three distinctly different spatial scales: global/continental scale (variation between climatic/geographic regions within a continent, or across latitudes); regional scale (variation between local communities representing different habitat (soil) fertility types or different habitat disturbance levels within a climatic/geographic region); and local community scale (variation between neighbourhood plots within a particular plant community/habitat). In contrast with a number of interpretations in recent literature, the approach developed here emphases that SRPR at each scale in terrestrial vegetation involve a “cascade” of several intermediary causational variables that have not been generally accounted for in previous studies of SRPR. Accordingly, SRPR are expected usually to be correlational, sometimes indirectly causational, but never directly causational, at any scale. Rather than suggesting that causational mechanisms “scale up”, the analysis here illustrates that several mechanistic features may be shared across scales and that in some cases, mechanisms may “scale down”. This has crucial implications for identifying testable and un-confounded hypotheses for future research and for selecting effective experimental designs and appropriate methods of data analyses for the interpretation of SRPR in natural vegetation.     

The meaning of character combination for the separation of EEG-data

Summary Standard EEG risk evaluation works on scoring systems that use different types of questionnaires. Here, an alternative for SIDS (Sudden Infant Death Syndrome) risk detection is presented that is based exclusively on EEG data which possibly could substitute the procedure of questioning the parents and allow a direct qualification of the physiological disposition of the individual neonate: Using EEG-characters an approved SIDS-case could be discriminated as well against the group of “healthy” infants as against the “high-risk-group”. The results of this study may confirm the evidence that the EEG analysis can be a promising approach to predict an increased SIDS risk.     

Exploration type-specific standard values of extramatrical mycelium – a step towards quantifying ectomycorrhizal space occupation and biomass in natural soil

The present study aims at providing standard values for the exploration type (ET)-specific quantification of extramatrical mycelium (EMM) of ectomycorrhizal fungi applicable to ecological field studies. These values were established from mycelial systems of ectomycorrhizae (ECM) synthesized in rhizotrons with near-to-natural peat substrate. Based on image analysis, the “Specific Potential Mycelial Space Occupation” (sPMSO), i.e. the ET-specific complete area that is covered by the EMM systems (mm² cm⁻¹ ECM⁻¹), and the “Specific Actual Mycelial Space Occupation” (sAMSO), i.e. the projection area of mycelial systems (mm² cm⁻¹ ECM⁻¹), were analyzed as an extension of a previously described approach. The “Specific Extramatrical Mycelial Length” (sEML) [m cm⁻¹ ECM⁻¹] and the “Specific Extramatrical Mycelial Biomass” (sEMB) (μg cm⁻¹ ECM⁻¹) were calculated for each of the ET via the proportion of hyphal projected area, hyphal length and biomass, the latter two being derived from previous measurements on Piloderma croceum, a “Medium-Distance” (MD)-ET. Both sPMSO and sAMSO were highest for the “Long-Distance” (LD)-ET, whereas those of the “Short-Distance” (SD)-ET and MD-ET were similar, although showing high variation. In contrast, mycelial density per occupied area of the MD-ET was twice as high as that of the LD-ET. Proportional to the sAMSO, the EMM length and biomass differed considerably between the three ET with values of the MD-ET being 1.9 times higher than those of SD-ET, and those of the LD-ET being 15 times higher than those of the SD-ET. These standards in relation to ECM length may ease quantification of mycelial space occupation and biomass in a relatively simple way. Thereby, the ET-specific contribution of EMM can be distinguished—also of non-cultivable species—and up-scaling to large-scale estimation of cost/benefit relations is possible.     

Logic in a Dynamic Brain

The ability of the human brain to carry out logical reasoning can be interpreted, in general, as a by-product of adaptive capacities of complex neural networks. Thus, we seek to base abstract logical operations in the general properties of neural networks designed as learning modules. We show that logical operations executable by McCulloch–Pitts binary networks can also be programmed in analog neural networks built with associative memory modules that process inputs as logical gates. These modules can interact among themselves to generate dynamical systems that extend the repertoire of logical operations. We demonstrate how the operations of the exclusive-OR or the implication appear as outputs of these interacting modules. In particular, we provide a model of the exclusive-OR that succeeds in evaluating an odd number of options (the exclusive-OR of classical logic fails in his case), thus paving the way for a more reasonable biological model of this important logical operator. We propose that a brain trained to compute can associate a complex logical operation to an orderly structured but temporary contingent episode by establishing a codified association among memory modules. This explanation offers an interpretation of complex logical processes (eventually learned) as associations of contingent events in memorized episodes. We suggest, as an example, a cognitive model that describes these “logical episodes”.     

A mathematical study of non-equimolar ternary gas diffusion

In view of the increasing evidence that multicomponent diffusion effects could be significant in biological gas exchange systems, a non-equimolar film model of multicomponent diffusion was derived. “Osmotic” ternary diffusion was studied for the gas systems He−N₂−O₂, He−SF₆−O₂, and N₂−SF₆−O₂. Diffusional fluxes and concentration profiles were calculated under both the “square-root” and the “product” flux conditions. Results were also compared with those obtained using the equimolar flux condition. It was found that the greater the difference of the diffusibilities between the two active components in a system, the greater the osmotic fluxes, and also the more alinear the concentration profiles. These results support the suggestion that the “product” condition applies to molecular diffusion in free space, the “square-root” condition to molecular diffusion in pores, and the equimolar flux condition to closed diffusion systems.     

Research Needs for Understanding and Predicting the Behavior of Managed Ecosystems: Lessons from the Study of Agroecosystems

Managed ecosystems are complex, dynamic systems with spatially varying inputs and outputs that are the result of interrelated physical, biological, and human decision-making processes. To gain an adequate understanding of these systems and predict their behavior, we believe that it is necessary to move beyond stylized theoretical models and loosely coupled disciplinary simulation models to what we describe as “fully integrated models.” Herein we present a conceptual framework for a more integrated approach to the study of managed ecosystems using the example of agricultural ecosystems. We then propose the implementation of a research agenda that fosters coordinated disciplinary research aimed at a better understanding and quantification of linkages across disciplinary models. Key research issues include the effects of spatial scale, the assessment of uncertainty in coupled models, and methods for collecting and analyzing spatially referenced data. Received 6 October 2000; accepted 10 April 2001.     

A logic for biological systems

This paper proposes a specification language, hybrid projection temporal logic of modelling, analyzing and verifying biological systems which can be considered, in general, to be hybrid systems consisting of a non-trivial mixture of discrete and continuous components. The syntax and semantics of the logic are presented, and some examples of hybrid systems are modelled to illustrate the formalism.