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1.  Global analysis of river systems: from Earth system controls to Anthropocene syndromes. 
Continental aquatic systems from rivers to the coastal zone are considered within two perspectives: (i) as a major link between the atmosphere, pedosphere, biosphere and oceans within the Earth system with its Holocene dynamics, and (ii) as water and aquatic biota resources progressively used and transformed by humans. Human pressures have now reached a state where the continental aquatic systems can no longer be considered as being controlled by only Earth system processes, thus defining a new era, the Anthropocene. Riverine changes, now observed at the global scale, are described through a first set of syndromes (flood regulation, fragmentation, sediment imbalance, neo-arheism, salinization, chemical contamination, acidification, eutrophication and microbial contamination) with their related causes and symptoms. These syndromes have direct influences on water uses, either positive or negative. They also modify some Earth system key functions such as sediment, water, nutrient and carbon balances, greenhouse gas emissions and aquatic biodiversity. Evolution of river syndromes over the past 2000 years is complex: it depends upon the stages of regional human development and on natural conditions, as illustrated here for the chemical contamination syndrome. River damming, eutrophication and generalized decrease of river flow due to irrigation are some of the other global features of river changes. Future management of river systems should also consider these long-term impacts on the Earth system.
PMCID: PMC1693284  PMID: 14728790
2.  Welcome to Journal of Ethnobiology and Ethnomedicine 
Ethnobiology is a multidisciplinary field of study that draws on approaches and methods from both the social and biological sciences. Ethnobiology aims at investigating culturally based biological and environmental knowledge, cultural perception and cognition of the natural world, and associated behaviours and practices. Ethnomedicine is concerned with the cultural interpretations of health, disease and illness and also addresses the health care seeking process and healing practices. Research interest and activities in the areas of ethnobiology and ethnomedicine have increased tremendously in the last decade. Since the inception of the disciplines, scientific research in ethnobiology and ethnomedicine has made important contributions to understanding traditional subsistence and medical knowledge and practice. The Journal of Ethnobiology and Ethnomedicine (JEE) invites manuscripts and reviews based on original interdisciplinary research from around the world on the inextricable relationships between human cultures and nature, on Traditional Environmental Knowledge (TEK), folk and traditional medical knowledge, as well as on the relevance of the above for Primary Health Care (PHC) policies in developing countries.
PMCID: PMC1266047
3.  Welcome to the Journal of Neuroinflammation! 
Welcome to the Journal of Neuroinflammation, an open-access, peer-reviewed, online journal that focuses on innate immunological responses of the central nervous system, involving microglia, astrocytes, cytokines, chemokines, and related molecular processes. 'Neuroinflammation' is an encapsulization of the idea that microglial and astrocytic responses and actions in the central nervous system have a fundamentally inflammation-like character, and that these responses are central to the pathogenesis and progression of a wide variety of neurological disorders. This concept has its roots in the discoveries of inflammatory cytokines and proteins in the plaques of Alzheimer disease, and these ideas have been extended to other neurodegenerative diseases, to ischemic/toxic diseases, to tumor biology and even to normal brain development. The Journal of Neuroinflammation, published by BioMed Central, will bring together work focusing on microglia, astrocytes, cytokines, chemokines, and related molecular processes in the central nervous system. All articles published in the Journal of Neuroinflammation will be immediately listed in PubMed, and access to published articles will be universal and free through the internet.
PMCID: PMC483051  PMID: 15285806
4.  Welcome to Automated Experimentation: a new open access journal 
Modern experimental science provides more opportunities for yet larger series of experiments. Demand for experimental results also has become more diverse, requiring results that have direct connections to systems outside the laboratory. With this has come an ability to automate many areas of experimental science, not only the experiments themselves but also the larger processes that contribute to experimentation and analysis more broadly. As automated experimentation becomes more widely used and understood, we launch this journal to provide a proper publication channel for this new breed of interdisciplinary research as well as a bridge to all significant groundwork research that would facilitate possible automated experimentation. With this in mind, we are interested in publishing all kinds of research into scientific experimentation, including research where the potential for automation is at proof or concept or early deployment stage.
PMCID: PMC2809325  PMID: 20098588
5.  Secondary Ultraweak Luminescence from Humic Acids Induced by γ-Radiation 
Humic substances (HSs) are products of biochemical transformations of plant and animal residues that make up a major fraction of the organic carbon of soil and aquatic systems in the environment. Because radioisotopes occur in the Earth’s crust and because the entire biosphere is continuously exposed to cosmic radiation, ionizing radiation continually interacts with HSs. This chronic irradiation could have a significant ecological impact. However, very few publications are available that address possible consequences of chronic exposure of HSs to ionizing radiation from terrestrial and cosmic sources. This study was conducted to investigate possible impacts of exposure of HSs to ionizing radiation.
Dried humic acid (HA) or its associated aqueous solution (in 0.1 M Na2CO3) were exposed to absorbed γ-radiation in high doses of 1–90 kGy using a 60Co source. Following the γ-ray exposures, a secondary, ultraweak radiation emanation with wavelengths in the spectral range λ= 340–650 nm was recorded as a long-lived chemiluminescence (CL) from the aqueous solutions; however, the CL was not observed after irradiating dry HA.
Absorption spectra (for λ=240–800 nm) of irradiated solutions indicated that polymerization/degradation processes were operating on the HA macromolecules. The effect of specific CL enhancers (luminol and lucigenin) on the intensity and kinetics of the CL implicated the participation of reactive oxygen species and free radicals in the CL and polymerization/degradation processes. For the range of absorbed doses used (1–10 kGy), the intensity of the induced CL was nonlinearly related to dose, suggesting that complex radical formation mechanisms were involved.
PMCID: PMC2657483  PMID: 19330147
humic acid; luminescence; γ-irradiation
6.  New insights into the evolutionary history of biological nitrogen fixation 
Nitrogenase, which catalyzes the ATP-dependent reduction of dinitrogen (N2) to ammonia (NH3), accounts for roughly half of the bioavailable nitrogen supporting extant life. The fundamental requirement for fixed forms of nitrogen for life on Earth, both at present and in the past, has led to broad and significant interest in the origin and evolution of biological N2 fixation. One key question is whether the limited availability of fixed nitrogen was a factor in life's origin or whether there were ample sources of fixed nitrogen produced by abiotic processes or delivered through the weathering of bolide impact materials to support this early life. If the latter, the key questions become what were the characteristics of the environment that precipitated the evolution of this oxygen sensitive process, when did this occur, and how was its subsequent evolutionary history impacted by the advent of oxygenic photosynthesis and the rise of oxygen in the Earth's biosphere. Since the availability of fixed sources of nitrogen capable of supporting early life is difficult to glean from the geologic record, there are limited means to get direct insights into these questions. Indirect insights, however, can be gained through phylogenetic studies of nitrogenase structural gene products and additional gene products involved in the biosynthesis of the complex metal-containing prosthetic groups associated with this enzyme complex. Insights gained from such studies, as reviewed herein, challenge traditional models for the evolution of biological nitrogen fixation and provide the basis for the development of new conceptual models that explain the stepwise evolution of this highly complex life sustaining process.
PMCID: PMC3733012  PMID: 23935594
nitrogen fixation; great oxidation event; NIf; methanogens
7.  The carbon cycle on early Earth—and on Mars? 
One of the goals of the present Martian exploration is to search for evidence of extinct (or even extant) life. This could be redefined as a search for carbon. The carbon cycle (or, more properly, cycles) on Earth is a complex interaction among three reservoirs: the atmosphere; the hydrosphere; and the lithosphere. Superimposed on this is the biosphere, and its presence influences the fixing and release of carbon in these reservoirs over different time-scales. The overall carbon balance is kept at equilibrium on the surface by a combination of tectonic processes (which bury carbon), volcanism (which releases it) and biology (which mediates it). In contrast to Earth, Mars presently has no active tectonic system; neither does it possess a significant biosphere. However, these observations might not necessarily have held in the past. By looking at how Earth's carbon cycles have changed with time, as both the Earth's tectonic structure and a more sophisticated biology have evolved, and also by constructing a carbon cycle for Mars based on the carbon chemistry of Martian meteorites, we investigate whether or not there is evidence for a Martian biosphere.
PMCID: PMC1664679  PMID: 17008211
Earth; Mars; carbon; cycle; life
8.  Earthing: Health Implications of Reconnecting the Human Body to the Earth's Surface Electrons 
Environmental medicine generally addresses environmental factors with a negative impact on human health. However, emerging scientific research has revealed a surprisingly positive and overlooked environmental factor on health: direct physical contact with the vast supply of electrons on the surface of the Earth. Modern lifestyle separates humans from such contact. The research suggests that this disconnect may be a major contributor to physiological dysfunction and unwellness. Reconnection with the Earth's electrons has been found to promote intriguing physiological changes and subjective reports of well-being. Earthing (or grounding) refers to the discovery of benefits—including better sleep and reduced pain—from walking barefoot outside or sitting, working, or sleeping indoors connected to conductive systems that transfer the Earth's electrons from the ground into the body. This paper reviews the earthing research and the potential of earthing as a simple and easily accessed global modality of significant clinical importance.
PMCID: PMC3265077  PMID: 22291721
9.  Differential Geometry Based Multiscale Models 
Bulletin of mathematical biology  2010;72(6):1562-1622.
Large chemical and biological systems such as fuel cells, ion channels, molecular motors, and viruses are of great importance to the scientific community and public health. Typically, these complex systems in conjunction with their aquatic environment pose a fabulous challenge to theoretical description, simulation, and prediction. In this work, we propose a differential geometry based multiscale paradigm to model complex macromolecular systems, and to put macroscopic and microscopic descriptions on an equal footing. In our approach, the differential geometry theory of surfaces and geometric measure theory are employed as a natural means to couple the macroscopic continuum mechanical description of the aquatic environment with the microscopic discrete atom-istic description of the macromolecule. Multiscale free energy functionals, or multiscale action functionals are constructed as a unified framework to derive the governing equations for the dynamics of different scales and different descriptions. Two types of aqueous macromolecular complexes, ones that are near equilibrium and others that are far from equilibrium, are considered in our formulations. We show that generalized Navier–Stokes equations for the fluid dynamics, generalized Poisson equations or generalized Poisson–Boltzmann equations for electrostatic interactions, and Newton's equation for the molecular dynamics can be derived by the least action principle. These equations are coupled through the continuum-discrete interface whose dynamics is governed by potential driven geometric flows. Comparison is given to classical descriptions of the fluid and electrostatic interactions without geometric flow based micro-macro interfaces. The detailed balance of forces is emphasized in the present work. We further extend the proposed multiscale paradigm to micro-macro analysis of electrohydrodynamics, electrophoresis, fuel cells, and ion channels. We derive generalized Poisson–Nernst–Planck equations that are coupled to generalized Navier–Stokes equations for fluid dynamics, Newton's equation for molecular dynamics, and potential and surface driving geometric flows for the micro-macro interface. For excessively large aqueous macromolecular complexes in chemistry and biology, we further develop differential geometry based multiscale fluid-electro-elastic models to replace the expensive molecular dynamics description with an alternative elasticity formulation.
PMCID: PMC2914853  PMID: 20169418
Variational principle; Multiscale; Geometric flows; Solvation analysis; Electrostatic analysis; Implicit solvent models; Molecular dynamics; Elasticity; Navier–Stokes equation; Poisson–Boltzmann equation; Nernst–Planck equation
10.  Welcome to Journal of Foot and Ankle Research: a new open access journal for foot health professionals 
Journal of Foot and Ankle Research (JFAR) is a new, open access, peer-reviewed online journal that encompasses all aspects of policy, organisation, delivery and clinical practice related to the assessment, diagnosis, prevention and management of foot and ankle disorders. JFAR will cover a wide range of clinical subject areas, including diabetology, paediatrics, sports medicine, gerontology and geriatrics, foot surgery, physical therapy, dermatology, wound management, radiology, biomechanics and bioengineering, orthotics and prosthetics, as well the broad areas of epidemiology, policy, organisation and delivery of services related to foot and ankle care. The journal encourages submission from all health professionals who manage lower limb conditions, including podiatrists, nurses, physical therapists and physiotherapists, orthopaedists, manual therapists, medical specialists and general medical practitioners, as well as health service researchers concerned with foot and ankle care. All manuscripts will undergo open peer review, and all accepted manuscripts will be freely available on-line using the open access platform of BioMed Central.
PMCID: PMC2547890  PMID: 18822156
11.  Warming will affect phytoplankton differently: evidence through a mechanistic approach 
Although the consequences of global warming in aquatic ecosystems are only beginning to be revealed, a key to forecasting the impact on aquatic communities is an understanding of individual species' vulnerability to increased temperature. Despite their microscopic size, phytoplankton support about half of the global primary production, drive essential biogeochemical cycles and represent the basis of the aquatic food web. At present, it is known that phytoplankton are important targets and, consequently, harbingers of climate change in aquatic systems. Therefore, investigating the capacity of phytoplankton to adapt to the predicted warming has become a relevant issue. However, considering the polyphyletic complexity of the phytoplankton community, different responses to increased temperature are expected. We experimentally tested the effects of warming on 12 species of phytoplankton isolated from a variety of environments by using a mechanistic approach able to assess evolutionary adaptation (the so-called ratchet technique). We found different degrees of tolerance to temperature rises and an interspecific capacity for genetic adaptation. The thermal resistance level reached by each species is discussed in relation to their respective original habitats. Our study additionally provides evidence on the most resistant phytoplankton groups in a future warming scenario.
PMCID: PMC3189365  PMID: 21508031
phytoplankton; climate change; warming; genetic adaptation; ratchet technique
12.  Pollutant Dehalogenation Capability May Depend on the Trophic Evolutionary History of the Organism: PBDEs in Freshwater Food Webs 
PLoS ONE  2012;7(7):e41829.
Organohalogen compounds are some of the most notorious persistent pollutants disturbing the Earth biosphere. Although human-made, these chemicals are not completely alien to living systems. A large number of natural organohalogens, part of the secondary metabolism, are involved in chemical trophic interactions. Surprisingly, the relationship between organisms’ trophic position and synthetic organohalogen biotransformation capability has not been investigated. We studied the case for polybromodiphenyl ethers (PBDE), a group of flame-retardants of widespread use in the recent years, in aquatic food webs from remote mountain lakes. These relatively simple ecosystems only receive pollution by atmospheric transport. A large predominance of the PBDE congener currently in use in Europe, BDE-209, largely dominated the PBDE composition of the basal resources of the food web. In contrast, primary consumers (herbivores and detritivores) showed a low proportion of BDE-209, and dominance of several less brominated congeners (e.g. BDE-100, BDE47). Secondary consumers (predators) showed large biomagnification of BDE-209 compare to other congeners. Finally, top predator fish characterized by low total PBDE concentrations. Examination of the bromine stable isotopic composition indicates that primary consumers showed higher PBDE biotransformation capability than secondary consumers. We suggest that the evolutionary response of primary consumers to feeding deterrents would have pre-adapted them for PBDE biotransformation. The observed few exceptions, some insect taxa, can be interpreted in the light of the trophic history of the evolutionary lineage of the organisms. Bromine isotopic composition in fish indicates that low PBDE values are due to not only biotransformation but also to some other process likely related to transport. Our finding illustrates that organohalogen compounds may strongly disturb ecosystems even at low concentrations, since the species lacking or having scarce biotransformation capability may be selectively more exposed to these halogenated hydrophobic semi-volatile organic pollutants due to their high bioaccumulation potential.
PMCID: PMC3407054  PMID: 22848624
13.  Reconnecting to the Biosphere 
Ambio  2011;40(7):719-738.
Humanity has emerged as a major force in the operation of the biosphere, with a significant imprint on the Earth System, challenging social–ecological resilience. This new situation calls for a fundamental shift in perspectives, world views, and institutions. Human development and progress must be reconnected to the capacity of the biosphere and essential ecosystem services to be sustained. Governance challenges include a highly interconnected and faster world, cascading social–ecological interactions and planetary boundaries that create vulnerabilities but also opportunities for social–ecological change and transformation. Tipping points and thresholds highlight the importance of understanding and managing resilience. New modes of flexible governance are emerging. A central challenge is to reconnect these efforts to the changing preconditions for societal development as active stewards of the Earth System. We suggest that the Millennium Development Goals need to be reframed in such a planetary stewardship context combined with a call for a new social contract on global sustainability. The ongoing mind shift in human relations with Earth and its boundaries provides exciting opportunities for societal development in collaboration with the biosphere—a global sustainability agenda for humanity.
PMCID: PMC3357749  PMID: 22338712
Social–ecological systems; Resilience; Ecosystem services; Natural capital; Adaptive governance; Planetary stewardship
14.  The Emergence and Early Evolution of Biological Carbon-Fixation 
PLoS Computational Biology  2012;8(4):e1002455.
The fixation of into living matter sustains all life on Earth, and embeds the biosphere within geochemistry. The six known chemical pathways used by extant organisms for this function are recognized to have overlaps, but their evolution is incompletely understood. Here we reconstruct the complete early evolutionary history of biological carbon-fixation, relating all modern pathways to a single ancestral form. We find that innovations in carbon-fixation were the foundation for most major early divergences in the tree of life. These findings are based on a novel method that fully integrates metabolic and phylogenetic constraints. Comparing gene-profiles across the metabolic cores of deep-branching organisms and requiring that they are capable of synthesizing all their biomass components leads to the surprising conclusion that the most common form for deep-branching autotrophic carbon-fixation combines two disconnected sub-networks, each supplying carbon to distinct biomass components. One of these is a linear folate-based pathway of reduction previously only recognized as a fixation route in the complete Wood-Ljungdahl pathway, but which more generally may exclude the final step of synthesizing acetyl-CoA. Using metabolic constraints we then reconstruct a “phylometabolic” tree with a high degree of parsimony that traces the evolution of complete carbon-fixation pathways, and has a clear structure down to the root. This tree requires few instances of lateral gene transfer or convergence, and instead suggests a simple evolutionary dynamic in which all divergences have primary environmental causes. Energy optimization and oxygen toxicity are the two strongest forces of selection. The root of this tree combines the reductive citric acid cycle and the Wood-Ljungdahl pathway into a single connected network. This linked network lacks the selective optimization of modern fixation pathways but its redundancy leads to a more robust topology, making it more plausible than any modern pathway as a primitive universal ancestral form.
Author Summary
The existence of the biosphere today depends on its capacity to fix inorganic into living matter. A wide range of evidence also suggests that the earliest life forms on Earth likewise derived their carbon from . From these two observations one can assume that the global biological carbon cycle has always been based on , and we show here that this assumption can be used as a powerful constraint to help organize and explain the deep evolution of life on Earth. Using a novel method that fully integrates aspects of metabolic and phylogenetic analysis, we are able to reconstruct the complete early evolutionary history of biological carbon-fixation, relating all ways in which life today performs this function to a single ancestral form. The diversification in carbon-fixation appears to underpin most of the deepest branches in the tree of life, and this early metabolic diversification – reaching back to the first cells – appears to have been driven not by the contingencies of history, but by direct links to the physical-chemical environment. The ancestral carbon-fixation pathway that we identify is different from any modern form, but better suited to the capabilities of the earliest primitive cells.
PMCID: PMC3334880  PMID: 22536150
15.  Immunomodulation by Different Types of N-Oxides in the Hemocytes of the Marine Bivalve Mytilus galloprovincialis 
PLoS ONE  2012;7(5):e36937.
The potential toxicity of engineered nanoparticles (NPs) for humans and the environment represents an emerging issue. Since the aquatic environment represents the ultimate sink for NP deposition, the development of suitable assays is needed to evaluate the potential impact of NPs on aquatic biota. The immune system is a sensitive target for NPs, and conservation of innate immunity represents an useful basis for studying common biological responses to NPs. Suspension-feeding invertebrates, such as bivalves, are particularly at risk to NP exposure, since they have extremely developed systems for uptake of nano and microscale particles integral to intracellular digestion and cellular immunity. Evaluation of the effects of NPs on functional parameters of bivalve immunocytes, the hemocytes, may help understanding the major toxic mechanisms and modes of actions that could be relevant for different NP types in aquatic organisms.In this work, a battery of assays was applied to the hemocytes of the marine bivalve Mytilus galloprovincialis to compare the in vitro effects of different n-oxides (n-TiO2, n-SiO2, n-ZnO, n-CeO2) chosen on the basis of their commercial and environmental relevance. Physico-chemical characterization of both primary particles and NP suspensions in artificial sea water-ASW was performed. Hemocyte lysosomal and mitochondrial parameters, oxyradical and nitric oxide production, phagocytic activity, as well as NP uptake, were evaluated. The results show that different n-oxides rapidly elicited differential responses hemocytes in relation to their chemical properties, concentration, behavior in sea water, and interactions with subcellular compartments. These represent the most extensive data so far available on the effects of NPs in the cells of aquatic organisms. The results indicate that Mytilus hemocytes can be utilized as a suitable model for screening the potential effects of NPs in the cells of aquatic invertebrates, and may provide a basis for future experimental work for designing environmentally safer nanomaterials.
PMCID: PMC3350491  PMID: 22606310
16.  Electronic Submission of Academic Works: A Survey of Current Editorial Practices of Radiologic Journals  
Journal of Digital Imaging  2001;14(2):107-110.
Computers are nearly ubiquitous in academic medicine, and authors create and compile much of their work in the electronic environment, yet the process of manuscript submission often fails to utilize the advantages of electronic communication. The purpose of this report is to review the submission policies of major academic journals in the field of radiology and assess current editorial practices relating to electronic submission of academic works. The authors surveyed 16 radiologic journals that are indexed in the Index Medicus and available in our medical center library. They compared the manuscript submission policies of these journals as outlined in recent issues of the journals and the corresponding worldwide web sites. The authors compared the journals on the following criteria: web site access to instructions; electronic submission of text, both with regard to initial submission and final submission of the approved document; text hardcopy requirements; word processing software restrictions; electronic submission of figures, figure hardcopy requirements; figure file format restrictions; and electronic submission media. Although the trend seems to be toward electronic submission, there currently is no clear-cut standard of practice. Because all of the journals that accept electronic documents also require a hardcopy, many of the advantages gained through electronic submission are nullified. In addition, many publishers only utilize electronic documents after a manuscript has been accepted, thus utilizing the benefits of digital information in the printing process but not in the actual submission and peer-review process.
PMCID: PMC3452756  PMID: 11440253
17.  Adaptive evolution and functional constraint at TLR4 during the secondary aquatic adaptation and diversification of cetaceans 
Cetaceans (whales, dolphins and porpoises) are a group of adapted marine mammals with an enigmatic history of transition from terrestrial to full aquatic habitat and rapid radiation in waters around the world. Throughout this evolution, the pathogen stress-response proteins must have faced challenges from the dramatic change of environmental pathogens in the completely different ecological niches cetaceans occupied. For this reason, cetaceans could be one of the most ideal candidate taxa for studying evolutionary process and associated driving mechanism of vertebrate innate immune systems such as Toll-like receptors (TLRs), which are located at the direct interface between the host and the microbial environment, act at the first line in recognizing specific conserved components of microorganisms, and translate them rapidly into a defense reaction.
We used TLR4 as an example to test whether this traditionally regarded pattern recognition receptor molecule was driven by positive selection across cetacean evolutionary history. Overall, the lineage-specific selection test showed that the dN/dS (ω) values along most (30 out of 33) examined cetartiodactylan lineages were less than 1, suggesting a common effect of functional constraint. However, some specific codons made radical changes, fell adjacent to the residues interacting with lipopolysaccharides (LPS), and showed parallel evolution between independent lineages, suggesting that TLR4 was under positive selection. Especially, strong signatures of adaptive evolution on TLR4 were identified in two periods, one corresponding to the early evolutionary transition of the terrestrial ancestors of cetaceans from land to semi-aquatic (represented by the branch leading to whale + hippo) and from semi-aquatic to full aquatic (represented by the ancestral branch leading to cetaceans) habitat, and the other to the rapid diversification and radiation of oceanic dolphins.
This is the first study thus far to characterize the TLR gene in cetaceans. Our data present evidences that cetacean TLR4 has undergone adaptive evolution against the background of purifying selection in response to the secondary aquatic adaptation and rapid diversification in the sea. It is suggested that microbial pathogens in different environments are important factors that promote adaptive changes at cetacean TLR4 and new functions of some amino acid sites specialized for recognizing pathogens in dramatically contrasted environments to enhance the fitness for the adaptation and survival of cetaceans.
PMCID: PMC3384459  PMID: 22443485
18.  The Emergence of Environmental Homeostasis in Complex Ecosystems 
PLoS Computational Biology  2013;9(5):e1003050.
The Earth, with its core-driven magnetic field, convective mantle, mobile lid tectonics, oceans of liquid water, dynamic climate and abundant life is arguably the most complex system in the known universe. This system has exhibited stability in the sense of, bar a number of notable exceptions, surface temperature remaining within the bounds required for liquid water and so a significant biosphere. Explanations for this range from anthropic principles in which the Earth was essentially lucky, to homeostatic Gaia in which the abiotic and biotic components of the Earth system self-organise into homeostatic states that are robust to a wide range of external perturbations. Here we present results from a conceptual model that demonstrates the emergence of homeostasis as a consequence of the feedback loop operating between life and its environment. Formulating the model in terms of Gaussian processes allows the development of novel computational methods in order to provide solutions. We find that the stability of this system will typically increase then remain constant with an increase in biological diversity and that the number of attractors within the phase space exponentially increases with the number of environmental variables while the probability of the system being in an attractor that lies within prescribed boundaries decreases approximately linearly. We argue that the cybernetic concept of rein control provides insights into how this model system, and potentially any system that is comprised of biological to environmental feedback loops, self-organises into homeostatic states.
Author Summary
Life on Earth is perhaps greater than three and a half billion years old and it would appear that once it started it never stopped. During this period a number of dramatic shocks and drivers have affected the Earth. These include the impacts of massive asteroids, runaway climate change and increases in brightness of the Sun. Has life on Earth simply been lucky in withstanding such perturbations? Are there any self-regulating or homeostatic processes operating in the Earth system that would reduce the severity of such perturbations? If such planetary processes exist, to what extent are they the result of the actions of life? In this study, we show how the regulation of environmental conditions can emerge as a consequence of life's effects. If life is both affected by and affects it environment, then this coupled system can self-organise into a robust control system that was first described during the early cybernetics movement around the middle of the twentieth century. Our findings are in principle applicable to a wide range of real world systems - from microbial mats to aquatic ecosystems up to and including the entire biosphere.
PMCID: PMC3656095  PMID: 23696719
19.  Phylodynamics and movement of Phycodnaviruses among aquatic environments 
The ISME Journal  2011;6(2):237-247.
Phycodnaviruses have a significant role in modulating the dynamics of phytoplankton, thereby influencing community structure and succession, nutrient cycles and potentially atmospheric composition because phytoplankton fix about half the carbon dioxide (CO2) on the planet, and some algae release dimethylsulphoniopropionate when lysed by viruses. Despite their ecological importance and widespread distribution, relatively little is known about the evolutionary history, phylogenetic relationships and phylodynamics of the Phycodnaviruses from freshwater environments. Herein we provide novel data on Phycodnaviruses from the largest river system on earth—the Amazon Basin—that were compared with samples from different aquatic systems from several places around the world. Based on phylogenetic inference using DNA polymerase (pol) sequences we show the presence of distinct populations of Phycodnaviridae. Preliminary coarse-grained phylodynamics and phylogeographic inferences revealed a complex dynamics characterized by long-term fluctuations in viral population sizes, with a remarkable worldwide reduction of the effective population around 400 thousand years before the present (KYBP), followed by a recovery near to the present time. Moreover, we present evidence for significant viral gene flow between freshwater environments, but crucially almost none between freshwater and marine environments.
PMCID: PMC3260511  PMID: 21796218
Amazon; Phycodnaviridae; phylodinamics; phylogeny
20.  GMFilter and SXTestPlate: software tools for improving the SNPlex™ genotyping system 
BMC Bioinformatics  2009;10:81.
Genotyping of single-nucleotide polymorphisms (SNPs) is a fundamental technology in modern genetics. The SNPlex™ mid-throughput genotyping system (Applied Biosystems, Foster City, CA, USA) enables the multiplexed genotyping of up to 48 SNPs simultaneously in a single DNA sample. The high level of automation and the large amount of data produced in a high-throughput laboratory require advanced software tools for quality control and workflow management.
We have developed two programs, which address two main aspects of quality control in a SNPlex™ genotyping environment: GMFilter improves the analysis of SNPlex™ plates by removing wells with a low overall signal intensity. It enables scientists to automatically process the raw data in a standardized way before analyzing a plate with the proprietary GeneMapper software from Applied Biosystems. SXTestPlate examines the genotype concordance of a SNPlex™ test plate, which was typed with a control SNP set. This program allows for regular quality control checks of a SNPlex™ genotyping platform. It is compatible to other genotyping methods as well.
GMFilter and SXTestPlate provide a valuable tool set for laboratories engaged in genotyping based on the SNPlex™ system. The programs enhance the analysis of SNPlex™ plates with the GeneMapper software and enable scientists to evaluate the performance of their genotyping platform.
PMCID: PMC2661053  PMID: 19267942
21.  Prebiotic replicase evolution in a surface-bound metabolic system: parasites as a source of adaptive evolution 
The remarkable potential of recent forms of life for reliably passing on genetic information through many generations now depends on the coordinated action of thousands of specialized biochemical "machines" (enzymes) that were obviously absent in prebiotic times. Thus the question how a complicated system like the living cell could have assembled on Earth seems puzzling. In seeking for a scientific explanation one has to search for step-by-step evolutionary changes from prebiotic chemistry to the emergence of the first proto-cell.
We try to sketch a plausible scenario for the first steps of prebiotic evolution by exploring the ecological feasibility of a mineral surface-bound replicator system that facilitates a primitive metabolism. Metabolism is a hypothetical network of simple chemical reactions producing monomers for the template-copying of RNA-like replicators, which in turn catalyse metabolic reactions. Using stochastic cellular automata (SCA) simulations we show that the surface-bound metabolic replicator system is viable despite internal competition among the genes and that it also maintains a set of mild "parasitic" sequences which occasionally evolve functions such as that of a replicase.
Replicase activity is shown to increase even at the expense of slowing down the replication of the evolving ribozyme itself, due to indirect mutualistic benefits in a diffuse form of group selection among neighbouring replicators. We suggest possible paths for further evolutionary changes in the metabolic replicator system leading to increased metabolic efficiency, improved replicase functionality, and membrane production.
PMCID: PMC2575217  PMID: 18826645
22.  Coevolution of amino acid residues in the key photosynthetic enzyme Rubisco 
One of the key forces shaping proteins is coevolution of amino acid residues. Knowing which residues coevolve in a particular protein may facilitate our understanding of protein evolution, structure and function, and help to identify substitutions that may lead to desired changes in enzyme kinetics. Rubisco, the most abundant enzyme in biosphere, plays an essential role in the process of carbon fixation through photosynthesis, thus facilitating life on Earth. This makes Rubisco an important model system for studying the dynamics of protein fitness optimization on the evolutionary landscape. In this study we investigated the selective and coevolutionary forces acting on large subunit of land plants Rubisco using Markov models of codon substitution and clustering approaches applied to amino acid substitution histories.
We found that both selection and coevolution shape Rubisco, and that positively selected and coevolving residues have their specifically favored amino acid composition and pairing preference. The mapping of these residues on the known Rubisco tertiary structures showed that the coevolving residues tend to be in closer proximity with each other compared to the background, while positively selected residues tend to be further away from each other. This study also reveals that the residues under positive selection or coevolutionary force are located within functionally important regions and that some residues are targets of both positive selection and coevolution at the same time.
Our results demonstrate that coevolution of residues is common in Rubisco of land plants and that there is an overlap between coevolving and positively selected residues. Knowledge of which Rubisco residues are coevolving and positively selected could be used for further work on structural modeling and identification of substitutions that may be changed in order to improve efficiency of this important enzyme in crops.
PMCID: PMC3190394  PMID: 21942934
Rubisco; coevolution; phylogeny; positive selection
23.  Genomic approaches in the identification of hypoxia biomarkers in model fish species 
Eutrophication leading to hypoxic water conditions has become a major problem in aquatic systems worldwide. Monitoring the levels and biological effects of lowered oxygen levels in aquatic systems may provide data useful in management of natural aquatic environments. Fishes represent an economically important resource that is subject to hypoxia exposure effects. Due to the extreme diversity of fish species and their habitats, fishes in general have evolved unique capabilities to modulate gene expression patterns in response to hypoxic stress. Recent studies have attempted to document quantitative changes in gene expression patterns induced in various fish species in response to reduced dissolved oxygen levels. From a management perspective, the goal of these studies is to provide a more complete characterization of hypoxia responsive genes in fish, as molecular indicators (biomarkers) of ecosystem hypoxic stress.
The molecular genetic response to hypoxia is highly complex and overlaps with other stress responses making it difficult to identify hypoxia specific responses using traditional single gene or low throughput approaches. Therefore, recent approaches have been aimed at developing functional genomic (e.g. high density microarray and real-time PCR) and proteomic (two-dimensional fluorescence difference in gel electrophoresis coupled with mass spectrometry based peptide identification) technologies that employ fish species. Many of the fish species utilized in these studies do not have the advantages of underlying genome resources (i.e., genome or transcriptome sequences). Efforts have attempted to establish correlations between discreet molecular responses elicited by fish in response to hypoxia and changes in the genetic profiles of stressed organs or tissues. Notable progress in these areas has been made using several different versions of either cDNA or oligonucleotide based microarrays to profile changes in gene expression patterns in response to hypoxic stress.
Due to these efforts, hundreds of hypoxia responsive genes have been identified both from laboratory reared aquaria fish and from feral fish derived from both fresh and saltwater habitats. Herein, we review these reports and the emergence of hypoxia biomarker development in aquatic species. We also include some of our own recent results using the medaka (Oryzias latipes) as a model to define genetic profiles of hypoxia exposure.
PMCID: PMC2782826  PMID: 20161383
Aquatic; Biomarker; Fish; Genomics; Hypoxia; Microarray
24.  Convergence and divergence in the evolution of aquatic birds. 
Aquatic birds exceed other terrestrial vertebrates in the diversity of their adaptations to aquatic niches. For many species this has created difficulty in understanding their evolutionary origin and, in particular, for the flamingos, hamerkop, shoebill and pelecaniforms. Here, new evidence from nuclear and mitochondrial DNA sequences and DNA-DNA hybridization data indicates extensive morphological convergence and divergence in aquatic birds. Among the unexpected findings is a grouping of flamingos and grebes, species which otherwise show no resemblance. These results suggest that the traditional characters used to unite certain aquatic groups, such as totipalmate feet, foot-propelled diving and long legs, evolved more than once and that organismal change in aquatic birds has proceeded at a faster pace than previously recognized.
PMCID: PMC1088747  PMID: 11429133
25.  Differences in Gene Expression between First and Third Trimester Human Placenta: A Microarray Study 
PLoS ONE  2012;7(3):e33294.
The human placenta is a rapidly developing organ that undergoes structural and functional changes throughout the pregnancy. Our objectives were to investigate the differences in global gene expression profile, the expression of imprinted genes and the effect of smoking in first and third trimester normal human placentas.
Materials and Methods
Placental samples were collected from 21 women with uncomplicated pregnancies delivered at term and 16 healthy women undergoing termination of pregnancy at 9–12 weeks gestation. Placental gene expression profile was evaluated by Human Genome Survey Microarray v.2.0 (Applied Biosystems) and real-time polymerase chain reaction.
Almost 25% of the genes spotted on the array (n = 7519) were differentially expressed between first and third trimester placentas. Genes regulating biological processes involved in cell proliferation, cell differentiation and angiogenesis were up-regulated in the first trimester; whereas cell surface receptor mediated signal transduction, G-protein mediated signalling, ion transport, neuronal activities and chemosensory perception were up-regulated in the third trimester. Pathway analysis showed that brain and placenta might share common developmental routes. Principal component analysis based on the expression of 17 imprinted genes showed a clear separation of first and third trimester placentas, indicating that epigenetic modifications occur throughout pregnancy. In smokers, a set of genes encoding oxidoreductases were differentially expressed in both trimesters.
Differences in global gene expression profile between first and third trimester human placenta reflect temporal changes in placental structure and function. Epigenetic rearrangements in the human placenta seem to occur across gestation, indicating the importance of environmental influence in the developing feto-placental unit.
PMCID: PMC3307733  PMID: 22442682

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