A robust, agnostic molecular biosignature based on machine learning.

The search for definitive biosignatures-unambiguous markers of past or present life-is a central goal of paleobiology and astrobiology. We used pyrolysis-gas chromatography coupled to mass spectrometry to analyze chemically disparate samples, including living cells, geologically processed fossil organic material, carbon-rich meteorites, and laboratory-synthesized organic compounds and mixtures. Data from each sample were employed as training and test subsets for machine-learning methods, which resulted in a model that can identify the biogenicity of both contemporary and ancient geologically processed samples with ~90% accuracy. These machine-learning methods do not rely on precise compound identification: Rather, the relational aspects of chromatographic and mass peaks provide the needed information, which underscores this method's utility for detecting alien biology.

On the roles of function and selection in evolving systems.

Physical laws-such as the laws of motion, gravity, electromagnetism, and thermodynamics-codify the general behavior of varied macroscopic natural systems across space and time. We propose that an additional, hitherto-unarticulated law is required to characterize familiar macroscopic phenomena of our complex, evolving universe. An important feature of the classical laws of physics is the conceptual equivalence of specific characteristics shared by an extensive, seemingly diverse body of natural phenomena. Identifying potential equivalencies among disparate phenomena-for example, falling apples and orbiting moons or hot objects and compressed springs-has been instrumental in advancing the scientific understanding of our world through the articulation of laws of nature. A pervasive wonder of the natural world is the evolution of varied systems, including stars, minerals, atmospheres, and life. These evolving systems appear to be conceptually equivalent in that they display three notable attributes: 1) They form from numerous components that have the potential to adopt combinatorially vast numbers of different configurations; 2) processes exist that generate numerous different configurations; and 3) configurations are preferentially selected based on function. We identify universal concepts of selection-static persistence, dynamic persistence, and novelty generation-that underpin function and drive systems to evolve through the exchange of information between the environment and the system. Accordingly, we propose a "law of increasing functional information": The functional information of a system will increase (i.e., the system will evolve) if many different configurations of the system undergo selection for one or more functions.

Quantifying the Potential for Nitrate-Dependent Iron Oxidation on Early Mars: Implications for the Interpretation of Gale Crater Organics.

Geological evidence and atmospheric and climate models suggest habitable conditions occurred on early Mars, including in a lake in Gale crater. Instruments aboard the Curiosity rover measured organic compounds of unknown provenance in sedimentary mudstones at Gale crater. Additionally, Curiosity measured nitrates in Gale crater sediments, which suggests that nitrate-dependent Fe2+ oxidation (NDFO) may have been a viable metabolism for putative martian life. Here, we perform the first quantitative assessment of an NDFO community that could have existed in an ancient Gale crater lake and quantify the long-term preservation of biological necromass in lakebed mudstones. We find that an NDFO community would have the capacity to produce cell concentrations of up to 106 cells mL-1, which is comparable to microbes in Earth's oceans. However, only a concentration of <104 cells mL-1, due to organisms that inefficiently consume less than 10% of precipitating nitrate, would be consistent with the abundance of organics found at Gale. We also find that meteoritic sources of organics would likely be insufficient as a sole source for the Gale crater organics, which would require a separate source, such as abiotic hydrothermal or atmospheric production or possibly biological production from a slowly turning over chemotrophic community.

Open-ended versus bounded evolution: Mineral evolution as a case study.

To what extent are naturally evolving systems limited in their potential diversity (i.e. "bounded") versus unrestricted ("open-ended")? Minerals provide a quantitative model evolving system, with well-documented increases in mineral diversity through multiple stages of planetary evolution over billions of years. A recent framework that unifies behaviors of both biotic and abiotic evolving systems posits that all such systems are characterized by combinatorial richness subject to selection. In the case of minerals, combinatorial richness derives from the possible combinations of chemical elements coupled with permutations of their formulas' coefficients. Observed mineral species, which are selected for persistence through deep time, represent a miniscule fraction of all possible element configurations. Furthermore, this model predicts that as planetary systems evolve, stable minerals become an ever-smaller fraction of the "possibility space." A postulate is that "functional information," defined as the negative log2 of that fraction, must increase as a system evolves. We have tested this hypothesis for minerals by estimating the fraction of all possible chemical formulas observed from one stage of mineral evolution to the next, based on numbers of different essential elements and the maximum chemical formula complexity at each of nine chronological stages of mineral evolution. We find a monotonic increase in mineral functional information through these nine stages-a result consistent with the hypothesis. Furthermore, analysis of the chemical formulas of minerals demonstrates that the modern Earth may be approaching the maximum limit of functional information for natural mineral systems-a result demonstrating that mineral evolution is not open-ended.

New Estimates of Nitrogen Fixation on Early Earth.

Fixed nitrogen species generated by the early Earth's atmosphere are thought to be critical to the emergence of life and the sustenance of early metabolisms. A previous study estimated nitrogen fixation in the Hadean Earth's N2/CO2-dominated atmosphere; however, that previous study only considered a limited chemical network that produces NOx species (i.e., no HCN formation) via the thermochemical dissociation of N2 and CO2 in lightning flashes, followed by photochemistry. Here, we present an updated model of nitrogen fixation on Hadean Earth. We use the Chemical Equilibrium with Applications (CEA) thermochemical model to estimate lightning-induced NO and HCN formation and an updated version of KINETICS, the 1-D Caltech/JPL photochemical model, to assess the photochemical production of fixed nitrogen species that rain out into the Earth's early ocean. Our updated photochemical model contains hydrocarbon and nitrile chemistry, and we use a Geant4 simulation platform to consider nitrogen fixation stimulated by solar energetic particle deposition throughout the atmosphere. We study the impact of a novel reaction pathway for generating HCN via HCN2, inspired by the experimental results which suggest that reactions with CH radicals (from CH4 photolysis) may facilitate the incorporation of N into the molecular structure of aerosols. When the HCN2 reactions are added, we find that the HCN rainout rate rises by a factor of five in our 1-bar case and is about the same in our 2- and 12-bar cases. Finally, we estimate the equilibrium concentration of fixed nitrogen species under a kinetic steady state in the Hadean ocean, considering loss by hydrothermal vent circulation, photoreduction, and hydrolysis. These results inform our understanding of environments that may have been relevant to the formation of life on Earth, as well as processes that could lead to the emergence of life elsewhere in the universe.

Molecular assembly indices of mineral heteropolyanions: some abiotic molecules are as complex as large biomolecules.

Molecular assembly indices, which measure the number of unique sequential steps theoretically required to construct a three-dimensional molecule from its constituent atomic bonds, have been proposed as potential biosignatures. A central hypothesis of assembly theory is that any molecule with an assembly index ≥15 found in significant local concentrations represents an unambiguous sign of life. We show that abiotic molecule-like heteropolyanions, which assemble in aqueous solution as precursors to some mineral crystals, range in molecular assembly indices from 2 for H2CO3 or Si(OH)4 groups to as large as 21 for the most complex known molecule-like subunits in the rare minerals ewingite and ilmajokite. Therefore, values of molecular assembly indices ≥15 do not represent unambiguous biosignatures.

Superionic to superionic phase change in water: consequences for the interiors of uranus and neptune.

Using density functional molecular dynamics free energy calculations, we show that the body centered cubic (bcc) phase of superionic ice previously believed to be the only phase is, in fact, thermodynamically unstable compared to a novel phase with oxygen positions in face centered cubic lattice sites. The novel phase has a lower proton mobility than the bcc phase and may exhibit a higher melting temperature. We predict a transition between the two phases at a pressure of 1±0.5 Mbar, with potential consequences for the interiors of ice giants such as Uranus and Neptune.

Cells as the first data scientists.

The concepts that we generally associate with the field of data science are strikingly descriptive of the way that life, in general, processes information about its environment. The 'information life cycle', which enumerates the stages of information treatment in data science endeavours, also captures the steps of data collection and handling in biological systems. Similarly, the 'data-information-knowledge ecosystem', developed to illuminate the role of informatics in translating raw data into knowledge, can be a framework for understanding how information is constantly being transferred between life and the environment. By placing the principles of data science in a broader biological context, we see the activities of data scientists as the latest development in life's ongoing journey to better understand and predict its environment. Finally, we propose that informatics frameworks can be used to understand the similarities and differences between abiotic complex evolving systems and life.

Virtual blood banking in Hong Kong.

OBJECTIVE. To review our experience in virtual blood banking for intra-operative transfusion in Hong Kong. DESIGN. Retrospective study. SETTING. Three major acute hospitals and a specialised centre for joint replacement surgery with installation of an Operating Theatre Blood Transaction System. PATIENTS. Patients undergoing surgery under anaesthesia and requiring intra-operative transfusion for the period from the implementation of the system in individual institutes (Queen Elizabeth Hospital: June 1997; Princess Margaret Hospital: May 2001; Queen Mary Hospital: October 2009; and Hong Kong Buddhist Hospital: December 2010) till September 2011. RESULTS. Under the system, 58 923 units of red cells were released intra-operatively for 18 264 patients (11% of the total number of blood units issued by the blood banks in these institutes during the study period). About 1% of them (613 units) entailed unmatched red cells given to 183 patients for emergency transfusions during surgery. The mean time required for the issue of the first unit of red cells was less than 1 minute. A total of 1231 units of red cells were returned unused after being released. Among them, 95 units were deemed unfit for re-issue because they had left the temperature-monitored blood storage refrigerators in the operating theatres for more than 30 minutes. There was no delay in transfusion or postponement of surgery due to problems or downtime of the Operating Theatre Blood Transaction System. CONCLUSION. Our experience has shown that our virtual blood banking system was efficient and effective, and helped ensure that the right patient received the right amount of the right blood at the right time. The system can be implemented either locally in the same hospital with a central blood bank, or in a more remote and networked site without a nearby supporting blood bank.

Asymptotic burnout and homeostatic awakening: a possible solution to the Fermi paradox?

Previous studies show that city metrics having to do with growth, productivity and overall energy consumption scale superlinearly, attributing this to the social nature of cities. Superlinear scaling results in crises called 'singularities', where population and energy demand tend to infinity in a finite amount of time, which must be avoided by ever more frequent 'resets' or innovations that postpone the system's collapse. Here, we place the emergence of cities and planetary civilizations in the context of major evolutionary transitions. With this perspective, we hypothesize that once a planetary civilization transitions into a state that can be described as one virtually connected global city, it will face an 'asymptotic burnout', an ultimate crisis where the singularity-interval time scale becomes smaller than the time scale of innovation. If a civilization develops the capability to understand its own trajectory, it will have a window of time to affect a fundamental change to prioritize long-term homeostasis and well-being over unyielding growth-a consciously induced trajectory change or 'homeostatic awakening'. We propose a new resolution to the Fermi paradox: civilizations either collapse from burnout or redirect themselves to prioritizing homeostasis, a state where cosmic expansion is no longer a goal, making them difficult to detect remotely.

Searching for Life, Mindful of Lyfe's Possibilities.

We are embarking on a new age of astrobiology, one in which numerous interplanetary missions and telescopes will be designed, built, and launched with the explicit goal of finding evidence for life beyond Earth. Such a profound aim warrants caution and responsibility when interpreting and disseminating results. Scientists must take care not to overstate (or over-imply) confidence in life detection when evidence is lacking, or only incremental advances have been made. Recently, there has been a call for the community to create standards of evidence for the detection and reporting of biosignatures. In this perspective, we wish to highlight a critical but often understated element to the discussion of biosignatures: Life detection studies are deeply entwined with and rely upon our (often preconceived) notions of what life is, the origins of life, and habitability. Where biosignatures are concerned, these three highly related questions are frequently relegated to a low priority, assumed to be already solved or irrelevant to the question of life detection. Therefore, our aim is to bring to the fore how these other major astrobiological frontiers are central to searching for life elsewhere and encourage astrobiologists to embrace the reality that all of these science questions are interrelated and must be furthered together rather than separately. Finally, in an effort to be more inclusive of life as we do not know it, we propose tentative criteria for a more general and expansive characterization of habitability that we call genesity.

Modeling Virus and Bacteria Populations in Europa's Subsurface Ocean.

The search for life in the universe is often informed by the study of "extreme" environments on Earth, which provide analogs for habitable locations in the Solar System, and whose microbial inhabitants may therefore also serve as analogs for potential life forms in extraterrestrial milieus. Recent work has highlighted the ubiquity and importance of viral entities in terrestrial ecosystems, which calls for a greater understanding of the roles that viruses might play in hypothetical extraterrestrial biomes. While some studies have modeled the dynamics of viral and bacterial populations in icy ocean environments on Earth, previous work has yet to apply these findings to icy ocean worlds such as Jupiter's moon Europa. It is commonly theorized that hydrothermal vents on Europa could produce the necessary reductants for chemosynthesis to take place on the ocean bottom. In the case that Europa's ocean is a reductant-limited environment, how might reductants and organic matter reach the sub-ice region to power a more easily accessible ecosystem? Here, we propose a 'viral elevator,' a mechanism that functions similarly to the 'viral shunt' in Earth's oceans, which could create and shuttle dissolved organic matter (DOM) to a hypothetical sub-ice biosphere through viral carriers. Current models of Europa's ocean currents and stratification support the movement of DOM to the sub-ice biosphere. We adapt an existing model for bacterial and viral population dynamics in Earth's Arctic sea ice to Europa and use parameters from various Arctic-based studies as proxies for Europa's environment. We find that viral burst size has the most significant effect on the virus-to-bacteria ratio (VBR) and system longevity in closed systems (such as brine pockets within Europa's icy crust), with higher burst sizes clearly increasing both. When applying our model to an open system with an influx of DOM from the viral elevator, we found that a steady-state system is attainable, with resulting sub-ice biofilms on the order of 0.1 mm thick (global equivalent layer). This has implications for future searches for life on Europa, given that life directly under the ice will be easier to detect and observe than life near the ocean bottom.

Nitrogen Fixation at Early Mars.

The Mars Science Laboratory (MSL) recently discovered nitrates in Gale Crater (e.g., Stern et al., 2015; Sutter et al., 2017). One possible mechanism for ancient nitrate deposition on Mars is through HNOx formation and rain out in the atmosphere, for which lightning-induced NO is likely the fundamental source. This study investigates nitrogen (N2) fixation in early Mars' atmosphere, with implications for early Mars' habitability. We consider a 1 bar atmosphere of background CO2, with abundance of N2, hydrogen, and methane varied from 1% to 10% to explore a swath of potential early Mars climates. We derive lightning-induced thermochemical equilibrium fluxes of NO and HCN by coupling the lightning-rate parametrization from the study of Romps et al. (2014) with chemical equilibrium with applications, and we use a Geant4 simulation platform to estimate the effect of solar energetic particle events. These fluxes are used as input into KINETICS, the Caltech/JPL coupled photochemistry and transport code, which models the chemistry of 50 species linked by 495 reactions to derive rain-out fluxes of HNOx and HCN. We compute equilibrium concentrations of cyanide and nitrate in a putative northern ocean at early Mars, assuming hydrothermal vent circulation and photoreduction act as the dominant loss mechanisms. We find average oceanic concentrations of ∼0.1-2 nM nitrate and ∼0.01-2 mM cyanide. HCN is critical for protein synthesis at concentrations >0.01 M (e.g., Holm and Neubeck, 2009), and our result is astrobiologically significant if secondary local concentration mechanisms occurred. Nitrates may act as high-potential electron acceptors for early metabolisms, although the minimum concentration required is unknown. Our study derives concentrations that will be useful for future laboratory studies to investigate the habitability at early Mars. The aqueous nitrate concentrations correspond to surface nitrate precipitates of ∼1-8 × 10-4 wt % that may have formed after the evaporation of surface waters, and these values roughly agree with recent MSL measurements.

Defining Lyfe in the Universe: From Three Privileged Functions to Four Pillars.

Motivated by the need to paint a more general picture of what life is-and could be-with respect to the rest of the phenomena of the universe, we propose a new vocabulary for astrobiological research. Lyfe is defined as any system that fulfills all four processes of the living state, namely: dissipation, autocatalysis, homeostasis, and learning. Life is defined as the instance of lyfe that we are familiar with on Earth, one that uses a specific organometallic molecular toolbox to record information about its environment and achieve dynamical order by dissipating certain planetary disequilibria. This new classification system allows the astrobiological community to more clearly define the questions that propel their research-e.g., whether they are developing a historical narrative to explain the origin of life (on Earth), or a universal narrative for the emergence of lyfe, or whether they are seeking signs of life specifically, or lyfe at large across the universe. While the concept of "life as we don't know it" is not new, the four pillars of lyfe offer a novel perspective on the living state that is indifferent to the particular components that might produce it.

Tumour angiogenesis: its mechanism and therapeutic implications in malignant gliomas.

Angiogenesis is a key event in the progression of malignant gliomas. The presence of microvascular proliferation leads to the histological diagnosis of glioblastoma multiforme. Tumour angiogenesis involves multiple cellular processes including endothelial cell proliferation, migration, reorganisation of extracellular matrix and tube formation. These processes are regulated by numerous pro-angiogenic and anti-angiogenic growth factors. Angiogenesis inhibitors have been developed to interrupt the angiogenic process at the growth factor, receptor tyrosine kinase and intracellular kinase levels. Other anti-angiogenic therapies alter the immune response and endogeneous angiogenesis inhibitor levels. Most anti-angiogenic therapies for malignant gliomas are in Phase I/II trials and only modest efficacies are reported for monotherapies. The greatest potential for angiogenesis inhibitors may lie in their ability to combine safely with chemotherapy and radiotherapy.

Living at the Extremes: Extremophiles and the Limits of Life in a Planetary Context.

Prokaryotic life has dominated most of the evolutionary history of our planet, evolving to occupy virtually all available environmental niches. Extremophiles, especially those thriving under multiple extremes, represent a key area of research for multiple disciplines, spanning from the study of adaptations to harsh conditions, to the biogeochemical cycling of elements. Extremophile research also has implications for origin of life studies and the search for life on other planetary and celestial bodies. In this article, we will review the current state of knowledge for the biospace in which life operates on Earth and will discuss it in a planetary context, highlighting knowledge gaps and areas of opportunity.

Corrigendum: Living at the Extremes: Extremophiles and the Limits of Life in a Planetary Context.

[This corrects the article DOI: 10.3389/fmicb.2019.00780.].