NoRCEL's Engagement in Africa: The AstroScience Exploration Network (ASEN).

Abstract The AstroScience Exploration Network (ASEN) is the latest innovative initiative from the Network of Researchers on the Chemical Emergence of Life (NoRCEL). Materializing on the vibrancy of the African continent, recognizing its people as a key asset, and building on specific strategic advantages, ASEN will funnel the appetite for scientific knowledge through an educational hub that paves the way for the Global South to come to the fore in new global endeavors and will eventually help build a variety of career paths in a diversifying economy.

Feeding Our Microbiota: Stimulation of the Immune/Semiochemical System and the Potential Amelioration of Non-Communicable Diseases.

Non-communicable diseases are those conditions to which causative infectious agents cannot readily be assigned. It is increasingly likely that at least some of these conditions are due to the breakdown of the previously mutualistic intestinal microbiota under the influence of a polluted, biocide-rich, environment. Following the mid-20th century African studies of Denis Burkitt, the environmental cause of conditions such as obesity has been ascribed to the absence of sufficient fibre in the modern diet, however in itself that is insufficient to explain the parallel rise of problems with both the immune system and of mental health. Conversely, Burkitt himself noted that the Maasai, a cattle herding people, remained healthy even with their relatively low intake of dietary fibre. Interestingly, however, Burkitt also emphasised that levels of non-communicable disease within a population rose as faecal weight decreased significantly, to about one third of the levels found in healthy populations. Accordingly, a more cogent explanation for all the available facts is that the fully functioning, adequately diverse microbiome, communicating through what has been termed the microbiota-gut-brain axis, helps to control the passage of food through the digestive tract to provide itself with the nutrition it needs. The method of communication is via the production of semiochemicals, interkingdom signalling molecules, potentially including dopamine. In turn, the microbiome aids the immune system of both adult and, most importantly, the neonate. In this article we consider the role of probiotics and prebiotics, including fermented foods and dietary fibre, in the stimulation of the immune system and of semiochemical production in the gut lumen. Finally, we reprise our suggestion of an ingestible sensor, calibrated to the detection of such semiochemicals, to assess both the effectiveness of individual microbiomes and methods of amelioration of the associated non-communicable diseases.

The Enclosed Intestinal Microbiome: Semiochemical Signals from the Precambrian and Their Disruption by Heavy Metal Pollution.

It is increasingly likely that many non-communicable diseases of humans and associated animals are due to the degradation of their intestinal microbiomes, a situation often referred to as dysbiosis. An analysis of the resultant diseases offers an opportunity to probe the function of these microbial partners of multicellular animals. In our view, it now seems likely that vertebrate animals and their microbiomes have coevolved throughout the Ediacaran-Cambrian transition and beyond, operating by semiochemical messaging between the multicellular host and its microbial community guest. A consideration of the overall role of the mutualistic intestinal microbiome as an enclosed bioreactor throws up a variety of challenging concepts. In particular: the significance of the microbiome with respect to the immune system suggests that microeukaryotes could act as microbial sentinel cells; the ubiquity of bacteriophage viruses implies the rapid turnover of microbial composition by a viral-shunt mechanism; and high microbial diversity is needed to ensure that horizontal gene transfer allows valuable genetic functions to be expressed. We have previously postulated that microbes of sufficient diversity must be transferred from mother to infant by seemingly accidental contamination during the process of natural birth. We termed this maternal microbial inheritance and suggested that it operates alongside parental genetic inheritance to modify gene expression. In this way, the adjustment of the neonate immune system by the microbiome may represent one of the ways in which the genome of a vertebrate animal interacts with its microbial environment. The absence of such critical functions in the neonate may help to explain the observation of persistent immune-system problems in affected adults. Equally, granted that the survival of the guest microbiome depends on the viability of its host, one function of microbiome-generated semiochemicals could be to facilitate the movement of food through the digestive tract, effectively partitioning nutrition between host and guest. In the event of famine, downregulation of microbial growth and therefore of semiochemical production would allow all available food to be consumed by the host. Although it is often thought that non-communicable diseases, such as type 2 diabetes, are caused by consumption of food containing insufficient dietary fibre, our hypothesis suggests that poor-quality food is not the prime cause but that the tendency for disease follows the degradation of the intestinal microbiome, when fat build-up occurs because the relevant semiochemicals can no longer be produced. It is the purpose of this paper to highlight the possibility that the origins of the microbiome lie in the Precambrian and that the disconnection of body and microbiome gives rise to non-communicable disease through the loss of semiochemical signalling. We further surmise that this disconnect has been largely brought about by heavy metal poisoning, potentially illuminating a facet of the exposome, the sum total of environmental insults that influence the expression of the genetic inheritance of an animal.

The Way forward for the Origin of Life: Prions and Prion-Like Molecules First Hypothesis.

In this paper the hypothesis that prions and prion-like molecules could have initiated the chemical evolutionary process which led to the eventual emergence of life is reappraised. The prions first hypothesis is a specific application of the protein-first hypothesis which asserts that protein-based chemical evolution preceded the evolution of genetic encoding processes. This genetics-first hypothesis asserts that an "RNA-world era" came before protein-based chemical evolution and rests on a singular premise that molecules such as RNA, acetyl-CoA, and NAD are relics of a long line of chemical evolutionary processes preceding the Last Universal Common Ancestor (LUCA). Nevertheless, we assert that prions and prion-like molecules may also be relics of chemical evolutionary processes preceding LUCA. To support this assertion is the observation that prions and prion-like molecules are involved in a plethora of activities in contemporary biology in both complex (eukaryotes) and primitive life forms. Furthermore, a literature survey reveals that small RNA virus genomes harbor information about prions (and amyloids). If, as has been presumed by proponents of the genetics-first hypotheses, small viruses were present during an RNA world era and were involved in some of the earliest evolutionary processes, this places prions and prion-like molecules potentially at the heart of the chemical evolutionary process whose eventual outcome was life. We deliberate on the case for prions and prion-like molecules as the frontier molecules at the dawn of evolution of living systems.

De Novo Nucleic Acids: A Review of Synthetic Alternatives to DNA and RNA That Could Act as Bio-Information Storage Molecules.

Modern terran life uses several essential biopolymers like nucleic acids, proteins and polysaccharides. The nucleic acids, DNA and RNA are arguably life's most important, acting as the stores and translators of genetic information contained in their base sequences, which ultimately manifest themselves in the amino acid sequences of proteins. But just what is it about their structures; an aromatic heterocyclic base appended to a (five-atom ring) sugar-phosphate backbone that enables them to carry out these functions with such high fidelity? In the past three decades, leading chemists have created in their laboratories synthetic analogues of nucleic acids which differ from their natural counterparts in three key areas as follows: (a) replacement of the phosphate moiety with an uncharged analogue, (b) replacement of the pentose sugars ribose and deoxyribose with alternative acyclic, pentose and hexose derivatives and, finally, (c) replacement of the two heterocyclic base pairs adenine/thymine and guanine/cytosine with non-standard analogues that obey the Watson-Crick pairing rules. This manuscript will examine in detail the physical and chemical properties of these synthetic nucleic acid analogues, in particular on their abilities to serve as conveyors of genetic information. If life exists elsewhere in the universe, will it also use DNA and RNA?

Viruses as a survival strategy in the armory of life.

Viruses have generally been thought of as infectious agents. New data on mimivirus, however, suggests a reinterpretation of this thought. Earth's biosphere seems to contain many more viruses than previously thought and they are relevant in the maintenance of ecosystems and biodiversity. Viruses are not considered to be alive because they are not free-living entities and do not have cellular units. Current hypotheses indicate that some viruses may have been the result of genomic reduction of cellular life forms. However, new studies relating to the origins of biological systems suggest that viruses could also have originated during the transition from First to the Last Universal Common Ancestor (from FUCA to LUCA). Within this setting, life has been established as chemical informational system and could be interpreted as a macrocode of multiple layers. The first entity to acquire these features was the First Universal Common Ancestor (FUCA) that evolved to an intermediate ancestral that could be named T-LUCA (Transitional-LUCA) and be equated to Woese's concept of progenotes. T-LUCA may have remained as undifferentiated subsystems with viruses-like structures. The net result is that both cellular life forms and viruses shared protein synthesis apparatuses. In short, virus is a strategy of life reached by two paths: T-LUCAs like entities and the reduction of cellular life forms.

Synthesis of Nucleic Acid Bases by Metal Ferrite Nanoparticles from a Single Carbon Atom Precursor Molecule: Formamide.

The synthesis of prebiotic molecules from simple precursors is believed to be a crucial scheme in order to study the origin of life processes. The present study describes the one-pot synthesis of purine and pyrimidine nucleic acid bases in the presence of pre-biologically significant binary metal oxide nanoparticles, metal ferrites, namely NiFe2O4, CoFe2O4, CuFe2O4, ZnFe2O4 and MnFe2O4. The products identified are cytosine, isocytosine, 4(3H)-pyrimidinone, adenine, hypoxanthine and purine. The ability of isocytosine (a constitutional isomer of cytosine) to recognize cytosine and guanine through normal and reversed Watson-Crick pairing respectively, demonstrates an important storyline for the genesis of ancient nucleic acids. The relevance of other synthesized nucleic acid bases with respect to the origin of life is also discussed. The divalent metal ions in iron oxide make it an appropriate catalytic system because it demonstrates excellent catalytic performance for the nucleic acid bases synthesis with significantly high yield, as compared to pure iron oxide and some other minerals like silica, alumina, manganese oxides and double metal cyanide complexes.

Seeing the wood for the trees: A new way to view the human intestinal microbiome and its connection with non-communicable disease.

Our paper briefly reviews the connection of the intestinal microbiome to the rise in non-communicable conditions related to atopic disease, obesity and mental health. We consider that the microbiome is best treated as if it were a single entity and have borrowed the terms semiochemical, allomone and kairomone (5) to describe interspecies relationship between the microbiome and ourselves (Fig. 1). We use the term dysbiosis to describe the breakdown of these relationships leading to disease (Fig. 2). As a result of this analysis we tentatively suggest that components of the microbiome assess microbial antigens in our food and pass this information back to our immune system via as yet undescribed chemical messengers: kairomones. We call these hypothetical microbial agents Sentinel Cells. Our suggestion is that atopic disease arises partly as a result of consuming processed food that has insufficient antigens to activate this kairomone feedback mechanism, which atrophies as a result. We note that this is potentially similar to the Old Friends concept of Rook and his co-workers (16). We suggest that obesity is a consequence of dysbiosis-induced waning of the output of allomone-like psychotropic compounds (including the known microbial metabolites dopamine and serotonin) leading to the weakening of the gut-brain axis and a negative effect on mental health. Although dysbiosis can occur in other ways, including antibiotic use and sterile caesarian section, we believe that all these problems can be overcome to provide a future free of these non-communicable diseases.

Conceptual challenges for the emergence of the biological system: Cell theory and self-replication.

We re-evaluate research relating to the current theories of the emergence of biological systems. The challenge being that research programmes concerning the emergence of these systems are viewed as the same as those relating to the origin of cells. Cells are strikingly important biological entities, hard wired into the entire field of biology. The development of biological systems took place much earlier than the origin of cells and even before the existence of the Last Universal Common Ancestor (LUCA); a period which could be construed as being preLUCA and which would have taken place during in a ribonucleoprotein world. This latter entity was named FUCA (First Universal Common Ancestor) and could be viewed as a "great-grandmother" to LUCA, from which the three domains of life, namely Archaea, Bacteria, and Eukarya (emerging as a chimera of the two) evolved. RNA-world theories are the focus of mainstream research programmes for the origin of life stricto sensu. In the RNA-world view, self-replication of nucleic acids is seen as one of the most relevant events in the pre-biotic world. Without denying the relevance of self-replication, we argue here that the most germane event which occurred in the pre-biotic world was the crosstalk between nucleic acids and peptides. When these two macromolecules started to interact, the singularity that aggregated the complexity required to produce life began to emerge. Thus, comprehension of the early origins of the translation machinery and the assembly of the genetic code is key. Therefore, the relevance of cell theory and self-replication should be re-evaluated as well as the concept of life itself.

The Landscape of the Emergence of Life.

This paper reports on the various nuances of the origins of life on Earth and highlights the latest findings in that arena as reported at the Network of Researchers on Horizontal Gene Transfer and the Last Universal Common Ancestor (NoR HGT and LUCA) which was held from the 3-4th November 2016 at the Open University, UK. Although the answers to the question of the origin of life on Earth will not be fathomable anytime soon, a wide variety of subject matter was able to be covered, ranging from examining what constitutes a LUCA, looking at viral connections and "from RNA to DNA", i.e., could DNA have been formed simultaneously with RNA, rather than RNA first and then describing the emergence of DNA from RNA. Also discussed are proteins and the origins of genomes as well as various ideas that purport to explain the origin of life here on Earth and potentially further afield elsewhere on other planets.

Thermal Condensation of Glycine and Alanine on Metal Ferrite Surface: Primitive Peptide Bond Formation Scenario.

The amino acid condensation reaction on a heterogeneous mineral surface has been regarded as one of the important pathways for peptide bond formation. Keeping this in view, we have studied the oligomerization of the simple amino acids, glycine and alanine, on nickel ferrite (NiFe2O4), cobalt ferrite (CoFe2O4), copper ferrite (CuFe2O4), zinc ferrite (ZnFe2O4), and manganese ferrite (MnFe2O4) nanoparticles surfaces, in the temperature range from 50-120 °C for 1-35 days, without applying any wetting/drying cycles. Among the metal ferrites tested for their catalytic activity, NiFe2O4 produced the highest yield of products by oligomerizing glycine to the trimer level and alanine to the dimer level, whereas MnFe2O4 was the least efficient catalyst, producing the lowest yield of products, as well as shorter oligomers of amino acids under the same set of experimental conditions. It produced primarily diketopiperazine (Ala) with a trace amount of alanine dimer from alanine condensation, while glycine was oligomerized to the dimer level. The trend in product formation is in accordance with the surface area of the minerals used. A temperature as low as 50 °C can even favor peptide bond formation in the present study, which is important in the sense that the condensation process is highly feasible without any sort of localized heat that may originate from volcanoes or hydrothermal vents. However, at a high temperature of 120 °C, anhydrides of glycine and alanine formation are favored, while the optimum temperature for the highest yield of product formation was found to be 90 °C.

The Landscape of the Emergence of Life.

Is it unrealistic to presuppose that all of the steps that could lead to the formation of life could occur in one setting?[...].

The Routes of Emergence of Life from LUCA during the RNA and Viral World: A Conspectus.

How did life emerge on Earth? The aim of the Network of Researchers on Horizontal Gene Transfer and the Last Universal Cellular Ancestor (NoR HGT & LUCA) is to understand how the genetics of LUCAs were reorganised prior to the advent of the three domains of life. This paper reports the research of eminent scientists who have come together within the network and are making significant contributions to the wider knowledge base surrounding this, one of science's remaining mysteries. I also report on their relevance in relation to LUCAs and life's origins, as well as ask a question: what next?

Prebiotic RNA synthesis by montmorillonite catalysis.

This review summarizes our recent findings on the role of mineral salts in prebiotic RNA synthesis, which is catalyzed by montmorillonite clay minerals. The clay minerals not only catalyze the synthesis of RNA but also facilitate homochiral selection. Preliminary data of these findings have been presented at the "Horizontal Gene Transfer and the Last Universal Common Ancestor (LUCA)" conference at the Open University, Milton Keynes, UK, 5-6 September 2013. The objective of this meeting was to recognize the significance of RNA in LUCA. We believe that the prebiotic RNA synthesis from its monomers must have been a simple process. As a first step, it may have required activation of the 5'-end of the mononucleotide with a leaving group, e.g., imidazole in our model reaction (Figure 1). Wide ranges of activating groups are produced from HCN under plausible prebiotic Earth conditions. The final step is clay mineral catalysis in the presence of mineral salts to facilitate selective production of functional RNA. Both the clay minerals and mineral salts would have been abundant on early Earth. We have demonstrated that while montmorillonite (pH 7) produced only dimers from its monomers in water, addition of sodium chloride (1 M) enhanced the chain length multifold, as detected by HPLC. The effect of monovalent cations on RNA synthesis was of the following order: Li+ > Na+ > K+. A similar effect was observed with the anions, enhancing catalysis in the following order: Cl- > Br- > I-. The montmorillonite-catalyzed RNA synthesis was not affected by hydrophobic or hydrophilic interactions. We thus show that prebiotic synthesis of RNA from its monomers was a simple process requiring only clay minerals and a small amount of salt.

Electron induced chemistry: a new frontier in astrochemistry.

The commissioning of the ALMA array and the next generation of space telescopes heralds the dawn of a new age of Astronomy, in which the role of chemistry in the interstellar medium and in star and planet formation may be quantified. A vital part of these studies will be to determine the molecular complexity in these seemingly hostile regions and explore how molecules are synthesised and survive. The current hypothesis is that many of these species are formed within the ice mantles on interstellar dust grains with irradiation by UV light or cosmic rays stimulating chemical reactions. However, such irradiation releases many secondary electrons which may themselves induce chemistry. In this article we discuss the potential role of such electron induced chemistry and demonstrate, through some simple experiments, the rich molecular synthesis that this may lead to.

Horizontal Gene Transfer and Its Part in the Reorganisation of Genetics during the LUCA Epoch.

Currently there are five known mechanisms of horizontal gene transfer (HGT): transduction, conjugation, transformation, gene transfer agents and membrane vesicle transfer. The question here is: what part did HGT play in the reorganisation of genetics during the last universal common ancestor (LUCA) epoch? LUCA is a construct to explain the origin of the three domains of life; namely Archaea, Bacteria and Eukarya. This editorial offers a general introduction to the relevance and ultimate significance of HGT in relation to the LUCA. [...].