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Enceladus, an icy moon of Saturn, is a compelling destination for a probe seeking biosignatures of extraterrestrial life because its subsurface ocean exhibits significant organic chemistry that is directly accessible by sampling cryovolcanic plumes. State-of-the-art organic chemical analysis instruments can perform valuable science measurements at Enceladus provided they receive sufficient plume material in a fly-by or orbiter plume transit. To explore the feasibility of plume sampling, we performed light gas gun experiments impacting micrometer-sized ice particles containing a fluorescent dye biosignature simulant into a variety of soft metal capture surfaces at velocities from 800 m ⋅ s-1 up to 3 km ⋅ s-1 Quantitative fluorescence microscopy of the capture surfaces demonstrates organic capture efficiencies of up to 80 to 90% for isolated impact craters and of at least 17% on average on indium and aluminum capture surfaces at velocities up to 2.2 km ⋅ s-1 Our results reveal the relationships between impact velocity, particle size, capture surface, and capture efficiency for a variety of possible plume transit scenarios. Combined with sensitive microfluidic chemical analysis instruments, we predict that our capture system can be used to detect organic molecules in Enceladus plume ice at the 1 nM level-a sensitivity thought to be meaningful and informative for probing habitability and biosignatures.

In this work, we consider the potential of cometary impacts to deliver complex organic molecules and the prebiotic building blocks required for life to rocky exoplanets. Numerical experiments have demonstrated that for these molecules to survive, impacts at very low velocities are required. This work shows that for comets scattered from beyond the snow-line into the habitable zone, the minimum impact velocity is always lower for planets orbiting Solar-type stars than M-dwarfs. Using both an analytical model and numerical N-body simulations, we show that the lowest velocity impacts occur onto planets in tightly packed planetary systems around high-mass (i.e. Solar-mass) stars, enabling the intact delivery of complex organic molecules. Impacts onto planets around low-mass stars are found to be very sensitive to the planetary architecture, with the survival of complex prebiotic molecules potentially impossible in loosely packed systems. Rocky planets around M-dwarfs also suffer significantly more high velocity impacts, potentially posing unique challenges for life on these planets. In the scenario that cometary delivery is important for the origins of life, this study predicts the presence of biosignatures will be correlated with (i) decreasing planetary mass (i.e. escape velocity), (ii) increasing stellar-mass and (iii) decreasing planetary separation (i.e. exoplanets in tightly-packed systems). [ABSTRACT FROM AUTHOR]

Artificial cells are synthetic constructs that emulate natural cells, with potential applications in areas of energy science, environmental treatment, and the study of life's origins. Nevertheless, the construction of artificial cells is a formidable undertaking, given the intricate nature of natural cells in structures, functions, and working mechanisms. With precise control, high automation, and excellent uniformity, microfluidics has emerged as a promising approach for the construction of artificial cells. This review summarizes the latest microfluidic techniques utilized to construct artificial cells, ranging from simple droplets to sophisticated cell‐inspired systems. These include the generation of droplets, the production of vesicles (lipid‐based and polymer‐based vesicles), the fabrication of polymeric microparticles with various compartments, shapes, and microstructures, as well as the manufacture of sophisticated cell‐inspired systems. The characteristics of different methods for the construction of artificial cells are discussed in detail. Furthermore, the wide‐ranging applications of artificial cells are also showcased. Finally, contemporary obstacles and forthcoming advancements are discussed in the field of microfluidic‐based artificial cells. This review is supposed to stimulate research in the construction of more functional and natural‐like artificial cells, as well as works in the fields of material, biology, environment, medicine, and energy. [ABSTRACT FROM AUTHOR]

Anangu, Pitjantjatjara and Yankunytjatjara people living in the north‐western areas of South Australia, conceptualize changes in the surface of land as evincing the presence of Ancestral power. Rain is one such catalyst of change, though it is by no means a certainty on the Pitjantjatjara Yankunytjatjara Lands. When it does appear, water does not stay long on the surface: it is shimmering and unstable. This chapter examines the nature of various water sources in contemporary indigenous life, the spatial relationships between earth and sky and the dialectic between life and death that they mediate. [ABSTRACT FROM AUTHOR]

COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate the potential of small molecules from natural products to offer neuroprotection in models of neurodegenerative diseases. Through our analysis, we discovered that flavonoids, alkaloids, terpenoids, and other natural compounds exhibit neuroprotective effects by modulating signaling pathways known to be impacted by COVID-19. Some of these compounds also directly target SARS-CoV-2 viral replication. Therefore, molecules of natural origin show promise as potential agents to prevent or mitigate nervous system damage in COVID-19 patients. Further research and the evaluation of different stages of the disease are warranted to explore their potential benefits. [ABSTRACT FROM AUTHOR]

The Moon‐forming impact vaporized part of Earth's mantle, and turned the rest into a magma ocean, from which carbon dioxide degassed into the atmosphere, where it stayed until water rained out to form the oceans. The rain dissolved CO2 and made it available to react with transition metal catalysts in the Earth's crust so as to ultimately generate the organic compounds that form the backbone of microbial metabolism. The Moon‐forming impact was key in building a planet with the capacity to generate life in that it converted carbon on Earth into a homogeneous and accessible substrate for organic synthesis. Today all ecosystems, without exception, depend upon primary producers, organisms that fix CO2. According to theories of autotrophic origin, it has always been that way, because autotrophic theories posit that the first forms of life generated all the molecules needed to build a cell from CO2, forging a direct line of continuity between Earth's initial CO2‐rich atmosphere and the first microorganisms. By modern accounts these were chemolithoautotrophic archaea and bacteria that initially colonized the crust and still inhabit that environment today. [ABSTRACT FROM AUTHOR]

The origin of life and the detection of alien life have historically been treated as separate scientific research problems. However, they are not strictly independent. Here, we discuss the need for a better integration of the sciences of life detection and origins of life. Framing these dual problems within the formalism of Bayesian hypothesis testing, we demonstrate via simple examples how high confidence in life detection claims require either (1) a strong prior hypothesis about the existence of life in a particular alien environment, or conversely, (2) signatures of life that are not susceptible to false positives. As a case study, we discuss the role of priors and hypothesis testing in recent results reporting potential detection of life in the venusian atmosphere and in the icy plumes of Enceladus. While many current leading biosignature candidates are subject to false positives because they are not definitive of life, our analyses demonstrate why it is necessary to shift focus to candidate signatures that are definitive. This indicates a necessity to develop methods that lack substantial false positives, by using observables for life that rely on prior hypotheses with strong theoretical and empirical support in identifying defining features of life. Abstract theories developed in pursuit of understanding universal features of life are more likely to be definitive and to apply to life-as-we-don't-know-it. We discuss Molecular Assembly theory as an example of such an observable which is applicable to life detection within the solar system. In the absence of alien examples these are best validated in origin of life experiments, substantiating the need for better integration between origins of life and biosignature science research communities. This leads to a conclusion that extraordinary claims in astrobiology (e.g., definitive detection of alien life) require extraordinary explanations, whereas the evidence itself could be quite ordinary. [ABSTRACT FROM AUTHOR]

There are no theorems (proven theories) in the biological sciences. We propose that the 3 31 nt minihelix tRNA evolution theorem be universally accepted as one. The 3 31 nt minihelix theorem completely describes the evolution of type I and type II tRNAs from ordered precursors (RNA repeats and inverted repeats). Despite the diversification of tRNAome sequences, statistical tests overwhelmingly support the theorem. Furthermore, the theorem relates the dominant pathway for the origin of life on Earth, specifically, how tRNAomes and the genetic code may have coevolved. Alternate models for tRNA evolution (i.e., 2 minihelix, convergent and accretion models) are falsified. In the context of the pre-life world, tRNA was a molecule that, via mutation, could modify anticodon sequences and teach itself to code. Based on the tRNA sequence, we relate the clearest history to date of the chemical evolution of life. From analysis of tRNA evolution, ribozyme-mediated RNA ligation was a primary driving force in the evolution of complexity during the pre-life-to-life transition. TRNA formed the core for the evolution of living systems on Earth. [ABSTRACT FROM AUTHOR]

Miller and Urey applied electric sparks to a reducive mixture of CH4, NH3, and water to obtain a complex organic mixture including biomolecules. In this study, we examined the impact of temperature, initial pressure, ammonia concentration, and the spark generator on the chemical profile of a Miller–Urey-type prebiotic broth. We analyzed the broth composition using Gas Chromatography combined with Mass Spectroscopy (GC/MS). The results point towards strong compositional changes with the nature of the spark. Ammonia exhibited catalytic properties even with non-nitrogen-containing compounds. A more elevated temperature led to a higher variety of substances. We conclude that to reproduce such a broth as well as possible, all the studied parameters need to be tightly controlled, the most difficult and important being spark generation. [ABSTRACT FROM AUTHOR]

Most contemporary theories for the chemical origins of life include the prebiotic synthesis of informational polymers, including strong interpretations of the RNA World hypothesis. Existing challenges to the prebiotic emergence of RNA have encouraged exploration of the possibility that RNA was preceded by an ancestral informational polymer, or proto-RNA, that formed more easily on the early Earth. We have proposed that the proto-nucleobases of proto-RNA would have readily formed glycosides with ribose and that these proto-nucleosides would have formed base pairs as monomers in aqueous solution, two properties not exhibited by the extant nucleosides or nucleotides. Here we demonstrate that putative proto-nucleotides of the model proto-nucleobases barbituric acid and melamine can be formed in the same one-pot reaction with ribose-5-phosphate. Additionally, the proto-nucleotides formed in these reactions spontaneously form assemblies that are consistent with the presence of Watson–Crick-like base pairs. Together, these results provide further support for the possibility that heterocycles closely related to the extant bases of RNA facilitated the prebiotic emergence of RNA-like molecules, which were eventually replaced by RNA over the course of chemical and biological evolution. [ABSTRACT FROM AUTHOR]

This work addresses the kinetic requirements for compensating the entropic cost of self-organization and natural selection, thereby revealing a fundamental principle in biology. Metabolic and evolutionary features of life cannot therefore be separated from an origin of life perspective. Growth, self-organization, evolution and dissipation processes need to be metabolically coupled and fueled by low-entropy energy harvested from the environment. The evolutionary process requires a reproduction cycle involving out-of-equilibrium intermediates and kinetic barriers that prevent the reproductive cycle from proceeding in reverse. Model analysis leads to the unexpectedly simple relationship that the system should be fed energy with a potential exceeding a value related to the ratio of the generation time to the transition state lifetime, thereby enabling a process mimicking natural selection to take place. Reproducing life's main features, in particular its Darwinian behavior, therefore requires satisfying constraints that relate to time and energy. Irreversible reaction cycles made only of unstable entities reproduce some of these essential features, thereby offering a physical/chemical basis for the possible emergence of autonomy. Such Emerging Autonomous Systems (EASs) are found to be capable of maintaining and reproducing their kind through the transmission of a stable kinetic state, thereby offering a physical/chemical basis for what could be deemed an epigenetic process. [ABSTRACT FROM AUTHOR]

Reduced-oxidation-state phosphorus (reduced P, hereafter) compounds were likely available on the early Earth via meteorites or through various geologic processes. Due to their reactivity and high solubility, these compounds could have played a significant role in the origin of various organophosphorus compounds of biochemical significance. In the present work, we study the reactions between reduced P compounds and their oxidation products, with the three nucleosides (uridine, adenosine, and cytidine), with organic alcohols (glycerol and ethanolamine), and with the tertiary ammonium organic compound, choline chloride. These reactions were studied in the non-aqueous solvent formamide and in a semi-aqueous solvent comprised of urea: ammonium formate: water (UAFW, hereafter) at temperatures of 55–68 °C. The inorganic P compounds generated through Fenton chemistry readily dissolve in the non-aqueous and semi-aqueous solvents and react with organics to form organophosphites and organophosphates, including those which are identified as phosphate diesters. This dual approach (1) use of non-aqueous and semi-aqueous solvents and (2) use of a reactive inorganic P source to promote phosphorylation and phosphonylation reactions of organics readily promoted anhydrous chemistry and condensation reactions, without requiring any additive, catalyst, or other promoting agent under mild heating conditions. We also present a comparative study of the release of P from various prebiotically relevant phosphate minerals and phosphite salts (e.g., vivianite, apatite, and phosphites of iron and calcium) into formamide and UAFW. These results have direct implications for the origin of biological P compounds from non-aqueous solvents of prebiotic provenance. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most deadly brain tumor, effective treatment options for which still remain elusive. The current treatment procedure of maximal resection followed by chemotherapy has proved to be grossly insufficient to prevent disease progression and death. Despite best efforts, the maximum survival post-diagnosis is a mere 1.5 years. Therefore, there is a huge unmet clinical need to find effective therapeutic procedures to prevent the pathogenesis and relapse of GBM. Small-molecule inhibitors of signaling pathways are an attractive option to prevent various types of tumors. However, no effective small-molecule inhibitors have been successful against GBM in clinical trials. Various signaling pathways are altered and an array of signaling molecules, transcription factors (TFs), and epigenetic modifying factors have been implicated in the pathogenesis of GBM. JAK-STAT pathway alteration is an important contributor to GBM pathogenesis and relapse. Many small-molecule inhibitors of JAKs, or STAT TFs, especially JAK2 and STAT3, have been assessed for their anti-tumor activity in GBM. However, no definitive success so far has been achieved. Herein, by using two small-molecule inhibitors of JAK3, we show that they are quite effective in inhibiting GBM cell proliferation and neurosphere formation, downregulating their stemness character, and inducing differentiation into neuronal origin cells. The effect of a single treatment with the drugs, both in a serum-containing differentiation medium and in a proliferation medium containing EGF and FGF, was really strong in limiting GBM cell growth, suggesting a potential therapeutic application for these JAK inhibitors in GBM therapy. [ABSTRACT FROM AUTHOR]

The origin of life entails a continuum from simple prebiotic chemistry to cells with genes and molecular machines. Using life as a guide to this continuum, we consider how selection could promote increased complexity before the emergence of genes. Structured, far-from-equilibrium environments such as hydrothermal systems drive the reaction between CO2 and H2 to form organics that self-organize into protocells. CO2 fixation within protocells generates a reaction network with a topology that prefigures the universal core of metabolism. Positive feedback loops amplify flux through this network, giving a metabolic heredity that promotes growth. Patterns in the genetic code show that genes and proteins arose through direct biophysical interactions between amino acids and nucleotides in this protometabolic network. Random genetic sequences template nonrandom peptides, producing selectable function in growing protocells. This context-dependent emergence of information gives rise seamlessly to an autotrophic last universal common ancestor. [ABSTRACT FROM AUTHOR]

Liquid–liquid phase separation (LLPS) is a process that often occurs due to binding between oppositely charged biopolymers, and has gained increasing attention recently due to their ubiquity in biological systems and ability to direct essential cellular processes. However, while these discoveries in biology are recent, the field of origins of life has been investigating LLPS for nearly 100 years, ever since the first suggestions by Oparin and Haldane that primitive LLPS could have been precursors to the first cells on Earth. Since then, a significant amount of work has been done to elucidate different primitive LLPS systems that could have been relevant as protocellular models. Given the structural similarities between primitive LLPS and modern membraneless organelles, there may even be an evolutionary link between the two, although this remains a question to be answered. Nevertheless, in order to answer this, a source that compares compositional aspects of modern biological condensates and primitive LLPS is necessary. Here, we first focus on membraneless organelles composed of intrinsically disordered proteins (IDPs) and nucleic acids. Then, as a parallel, we explore primitive membraneless compartments composed of simple biopolymers such as short peptides and nucleic acids. This is followed by a discussion of how the first biomolecules on Earth may have originated, analyzing the environmental and chemical conditions that could have favored primitive LLPS processes. Finally, we directly compare composition of modern biological condensates and primitive phase‐separated compartments, further discussing the potential of primitive IDPs on early Earth, but also the evolution from membraneless to membrane‐bound cells. This review aims to provide a compositional comparison of modern and primitive phase‐separated structures in order to help researchers in both fields understand the current state of knowledge, how this knowledge evolved, and the current gaps that need to be further addressed. [ABSTRACT FROM AUTHOR]

In the 1787 Transcendental Deduction of the Categories Kant indicates the only possible ways by which one can account for a necessary agreement of experience with the concepts of its objects (B166), using analogies between modes of explanation and biological theories about the origin of life. He endorses epigenesis as a model for his system of pure reason (B167). This paper examines various interpretive claims about the meaning of this theory of generation and its significance for Kant's philosophy (Section 1), showing that, after his Critical shift in perspective, in 1775/77 Kant already combined preformed elements and their purposively oriented formation by natural forces (Section 2). Contrary to the standard view, Kant's theory of race appears to constitute the background to assess Blumenbach's later (1799/1781) shift to epigenesis after supporting Haller's preformism (Section 3). In Section 4, I argue that the ground of affinity between epigenesis and formal idealism rests in tracing the first origin of these conformities: external a posteriori climate conditions and predisposed germs and dispositions within the generative power of the human body; and external a posteriori experience and spontaneous a priori concepts of its objects, within pure sensory intuiting and pure thinking. In both cases the external empirical conditions would function as occasioning propelling factors affecting internal pre-established forms of generation. [ABSTRACT FROM AUTHOR]

Here I pursue a deconstructive reading of astrobiology, the emerging science dedicated to a double quest: solving the mystery of life's origin and discovering life beyond Earth. Astrobiology, I argue, is organized as a response to the aporetic formulation assumed by the origin of life in modern molecular biology, where (as Derrida's argues in Life Death) it becomes the origin of textuality. Because all Earth life shares a single genetic code, astrobiologists are seeking a second; hoping that a sort of multi-planetary comparative genomics may reveal the secret to life's origin. But the aporia repeats in the figure of the biosignature, the trace of life. [ABSTRACT FROM AUTHOR]

The emergence of functional oligonucleotides on early Earth required a molecular selection mechanism to screen for specific sequences with prebiotic functions. Cyclic processes such as daily temperature oscillations were ubiquitous in this environment and could trigger oligonucleotide phase separation. Here, we propose sequence selection based on phase separation cycles realized through sedimentation in a system subjected to the feeding of oligonucleotides. Using theory and experiments with DNA, we show sequence-specific enrichment in the sedimented dense phase, in particular of short 22-mer DNA sequences. The underlying mechanism selects for complementarity, as it enriches sequences that tightly interact in the dense phase through base-pairing. Our mechanism also enables initially weakly biased pools to enhance their sequence bias or to replace the previously most abundant sequences as the cycles progress. Our findings provide an example of a selection mechanism that may have eased screening for auto-catalytic self-replicating oligonucleotides. [ABSTRACT FROM AUTHOR]

Thermophily is an ancient trait among microorganisms. The molecular principles to sustain high temperatures, however, are often described as adaptations, somewhat implying that they evolved from a non-thermophilic background and that thermophiles, i.e., organisms with growth temperature optima (TOPT) above 45°C, evolved from mesophilic organisms (TOPT 25-45°C). On the contrary, it has also been argued that LUCA, the last universal common ancestor of Bacteria and Archaea, may have been a thermophile, and mesophily is the derived trait. In this study, we took an experimental approach toward the evolution of a mesophile from a thermophile. We selected the acetogenic bacterium T. kivui (TOPT 66°C) since acetogenesis is considered ancient physiology and cultivated it at suboptimal low temperatures. We found that the lowest possible growth temperature (TMIN) under the chosen conditions was 39°C. The bacterium was subsequently subjected to adaptive laboratory evolution (ALE) by serial transfer at 45°C. Interestingly, after 67 transfers (approximately 180 generations), the adapted strain Adpt45_67 did not grow better at 45°C, but a shift in the TOPT to 60°C was observed. Growth at 45°C was accompanied by a change in the morphology as shorter, thicker cells were observed that partially occurred in chains. While the proportion of short-chain fatty acids increased at 50°C vs. 66°C in both strains, Adpt45_67 also showed a significantly increased proportion of plasmalogens. The genome analysis revealed 67 SNPs compared to the type strain, among these mutations in transcriptional regulators and in the cAMP binding protein. Ultimately, the molecular basis of the adaptation of T. kivui to a lower TOPT remains to be elucidated. The observed change in phenotype is the first experimental step toward the evolution of thermophiles growing at colder temperatures and toward a better understanding of the cold adaptation of thermophiles on early Earth. [ABSTRACT FROM AUTHOR]

Glycolaldehyde (CH2OHCHO) is the simplest monosaccharide sugar in the interstellar medium, and it is directly involved in the origin of life via the 'RNA world' hypothesis. We present the first detection of CH2OHCHO towards the hot molecular core G358.93–0.03 MM1 using the Atacama Large Millimetre/Submillimetre Array (ALMA). The calculated column density of CH2OHCHO towards G358.93–0.03 MM1 is (1.52 ± 0.9) × 1016 cm−2 with an excitation temperature of 300 ± 68.5 K. The derived fractional abundance of CH2OHCHO with respect to H2 is (4.90 ± 2.92) × 10−9, which is consistent with that estimated by existing two-phase warm-up chemical models. We discuss the possible formation pathways of CH2OHCHO within the context of hot molecular cores and hot corinos and find that CH2OHCHO is likely formed via the reactions of radical HCO and radical CH2OH on the grain-surface of G358.93–0.03 MM1. [ABSTRACT FROM AUTHOR]

Serpentinization in hydrothermal vents is central to some autotrophic theories for the origin of life because it generates compartments, reductants, catalysts and gradients. During the process of serpentinization, water circulates through hydrothermal systems in the crust where it oxidizes Fe (II) in ultramafic minerals to generate Fe (III) minerals and H2. Molecular hydrogen can, in turn, serve as a freely diffusible source of electrons for the reduction of CO2 to organic compounds, provided that suitable catalysts are present. Using catalysts that are naturally synthesized in hydrothermal vents during serpentinization H2 reduces CO2 to formate, acetate, pyruvate, and methane. These compounds represent the backbone of microbial carbon and energy metabolism in acetogens and methanogens, strictly anaerobic chemolithoautotrophs that use the acetyl-CoA pathway of CO2 fixation and that inhabit serpentinizing environments today. Serpentinization generates reduced carbon, nitrogen and — as newer findings suggest — reduced phosphorous compounds that were likely conducive to the origins process. In addition, it gives rise to inorganic microcompartments and proton gradients of the right polarity and of sufficient magnitude to support chemiosmotic ATP synthesis by the rotor-stator ATP synthase. This would help to explain why the principle of chemiosmotic energy harnessing is more conserved (older) than the machinery to generate ion gradients via pumping coupled to exergonic chemical reactions, which in the case of acetogens and methanogens involve H2-dependent CO2 reduction. Serpentinizing systems exist in terrestrial and deep ocean environments. On the early Earth they were probably more abundant than today. There is evidence that serpentinization once occurred on Mars and is likely still occurring on Saturn’s icy moon Enceladus, providing a perspective on serpentinization as a source of reductants, catalysts and chemical disequilibrium for life on other worlds. [ABSTRACT FROM AUTHOR]

Chemical complexity is vital not only for the origin of life but also for biological evolution. The chemical evolution of a complex prebiotic mixture containing acetylene, carbon monoxide (CO), and nickel sulfide (NiS) has been analyzed with mass spectrometry as an untargeted approach to reaction monitoring. Here we show through isotopic 13C-labelling, multiple reaction products, encompassing diverse CHO and CHOS compounds within the complex reaction mixture. Molecules within the same chemical spaces displayed varying degrees of 13C-labelling, enabling more robust functional group characterization based on targeted investigations and differences in saturation levels among the described classes. A characteristic C2-addition pattern was detected in all compound classes in conjunction with a high diversity of thio acids, reminiscent of extant microbial C2-metabolism. The analysis involved a time-resolved molecular network, which unveiled the behavior of sulfur in the system. At the onset of the reaction, early formed compounds contain more sulfur atoms compared to later emerging compounds. These results give an essential insight into the still elusive role of sulfur dynamics in the origin of life. Moreover, our results provide temporally resolved evidence of the progressively increasing molecular complexity arising from a limited number of compounds. Various fatty acids and aldehydes can be synthesized from acetylene and carbon monoxide by nickel sulfide catalysts under volcanic hydrothermal conditions compatible with aqueous early earth conditions, however, their chemical complexity remains underexplored. Here, the authors use 13C-labelling together with untargeted ultrahigh-resolution mass spectrometry to categorize carboxylic acid functional groups, revealing C2-addition driven compound diversity as well as new sulfur containing classes. [ABSTRACT FROM AUTHOR]

An increasing amount of evidence suggests that early ocean hydrothermal systems were sustained sources of ammonia, an essential nitrogen species for prebiotic synthesis of life’s building blocks. However, it remains a riddle how the abiotically generated ammonia was retained at the vent–ocean interface for the subsequent chemical evolution. Here, we demonstrate that, under simulated geoelectrochemical conditions in early ocean hydrothermal systems (≤ − 0.6 V versus the standard hydrogen electrode), mackinawite gradually reduces to zero-valent iron (Fe0), generating interlayer Fe0 sites. This reductive conversion leads to an up to 55-fold increase in the solid/liquid partition coefficient for ammonia, enabling over 90% adsorption of 1 mM ammonia in 1 M NaCl at neutral pH. A coordinative binding of ammonia on the interlayer Fe0 sites was computed to be the major mechanism of selective ammonia adsorption. Mackinawite is a ubiquitous sulfide precipitate in submarine hydrothermal systems. Given its reported catalytic function in amination, the extreme accumulation of ammonia on electroreduced mackinawite should have been a crucial initial step for prebiotic nitrogen assimilation, paving the way to the origin of life. [ABSTRACT FROM AUTHOR]

We review the initiation of palisade enclosed village communities in central southwestern Ontario, using data from a series of related early Late Woodland sites that we interpret as showing an east to west settlement sequence. New AMS dates based on samples of carbonized maize provide a revised chronology for the origin of village life, which began in the twelfth century. We show how villages developed alongside community pattern and ceramic attribute trends into the fourteenth-century middle Late Woodland period. A suite of dates from the most westerly site in the sequence on the Norfolk sand plain document the timing of an abrupt change in community pattern during the late fourteenth century. [ABSTRACT FROM AUTHOR]

Genetics and molecular biology research have progressed for over a century; however, no laws of biology resembling those of physics have been identified, despite the expectations of some physicists. It may be that it is not the properties of matter alone but evolved properties of matter in combination with atomic physics and chemistry that gave rise to the origin and complexity of life. It is proposed that any law of biology must also be a product of evolution that co-evolved with the origin and progression of life. It was suggested that molecular complexity and redundancy exponentially increase over time and have the following relationship: DNA sequence complexity (Cd) < molecular complexity (Cm) < phenotypic complexity (Cp). This study presents a law of redundancy, which together with the law of complexity, is proposed as an evolutionary law of biology. Molecular complexity and redundancy are inseparable aspects of biochemical pathways, and molecular redundancy provides the first line of defense against environmental challenges, including those of deleterious mutations. Redundancy can create problems for precision medicine because in addition to the issues arising from the involvement of multiple genes, redundancy arising from alternate pathways between genotypes and phenotypes can complicate gene detection for complex diseases and mental disorders. This study uses cancer as an example to show how cellular complexity, molecular redundancy, and hidden variation affect the ability of cancer cells to evolve and evade detection and elimination. Characterization of alternate biochemical pathways or "escape routes" can provide a step in the fight against cancer. [ABSTRACT FROM AUTHOR]

The Aryl hydrocarbon receptor is an ancient transcriptional factor originally discovered as a sensor of dioxin. In addition to its function as a receptor of environmental toxicants, it plays an important role in development. Although a significant amount of research has been carried out to understand the AHR signal transduction pathway and its involvement in species' susceptibility to environmental toxicants, none of them to date has comprehensively studied its evolutionary origins. Studying the evolutionary origins of molecules can inform ancestral relationships of genes. The vertebrate genome has been shaped by two rounds of whole-genome duplications (WGD) at the base of vertebrate evolution approximately 600 million years ago, followed by lineage-specific gene losses, which often complicate the assignment of orthology. It is crucial to understand the evolutionary origins of this transcription factor and its partners, to distinguish orthologs from ancient non-orthologous homologs. In this study, we have investigated the evolutionary origins of proteins involved in the AHR pathway. Our results provide evidence of gene loss and duplications, crucial for understanding the functional connectivity of humans and model species. Multiple studies have shown that 2R-ohnologs (genes and proteins that have survived from the 2R-WGD) are enriched in signaling components relevant to developmental disorders and cancer. Our findings provide a link between the AHR pathway's evolutionary trajectory and its potential mechanistic involvement in pathogenesis. [ABSTRACT FROM AUTHOR]

Ancient Egypt plays a crucial role in the history of infectious disease. An intersection for communication and commerce, Egypt linked disparate civilizations and ecologies, allowing the spread of local epidemics and Mediterranean-wide pandemics. The region south of Egypt developed a pestilential reputation, due in part to Thucydides' account of the Plague of Athens, which traced the disease's origins to that area. Later records are modeled on Thucydides' account, muddling the true origins and scope of later outbreaks. Critical reading of ancient literature and documents—particularly papyri—supplemented with archeological and palaeoscientific evidence, significantly improves our understanding of how Egypt facilitated the circulation of pathogens between the western Indian Ocean and the Mediterranean. [ABSTRACT FROM AUTHOR]

A new chiral amplification mechanism based on a stochastic approach is proposed. The mechanism includes five different chemical species, an achiral substrate (A), two chiral forms (L, D), and two intermediary species (LA, DA). The process occurs within a small, semipermeable compartment that can be diffusively coupled with the outside environment. The study considers two alternative primary sources for chiral species within the compartment, one chemical and the other diffusive. As a remarkable fact, the chiral amplification process occurs due to stochastic fluctuations of an intermediary catalytic species (LA, DA) produced in situ, given the interaction of the chiral species with the achiral substrate. The net process includes two different steps: the synthesis of the catalyst (LA and DA) and the catalytic production of new chiral species from the substrate. Stochastic simulations show that proper parameterization can induce a robust chiral state within the compartment regardless of whether the system is open or closed. We also show how an increase in the non-catalytic production of chiral species tends to negatively impact the homochirality degree of the system. By its conception, the proposed mechanism suggests a deeper connection with how most biochemical processes occur in living beings, a fact that could open new avenues for studying this fascinating phenomenon. [ABSTRACT FROM AUTHOR]

Growing evidence of the potential habitability of Ocean Worlds across our solar system is motivating the advancement of technologies capable of detecting life as we know it—sharing a common ancestry or physicochemical origin with life on Earth—or don't know it, representing a distinct emergence of life different than our one known example. Here, we propose the Electronic Life-detection Instrument for Enceladus/Europa (ELIE), a solid-state single-molecule instrument payload that aims to search for life based on the detection of amino acids and informational polymers (IPs) at the parts per billion to trillion level. As a first proof-of-principle in a laboratory environment, we demonstrate the single-molecule detection of the amino acid L-proline at a 10 μM concentration in a compact system. Based on ELIE's solid-state quantum electronic tunneling sensing mechanism, we further propose the quantum property of the HOMO–LUMO gap (energy difference between a molecule's highest energy-occupied molecular orbital and lowest energy-unoccupied molecular orbital) as a novel metric to assess amino acid complexity. Finally, we assess the potential of ELIE to discriminate between abiotically and biotically derived α-amino acid abundance distributions to reduce the false positive risk for life detection. Nanogap technology can also be applied to the detection of nucleobases and short sequences of IPs such as, but not limited to, RNA and DNA. Future missions may utilize ELIE to target preserved biosignatures on the surface of Mars, extant life in its deep subsurface, or life or its biosignatures in a plume, surface, or subsurface of ice moons such as Enceladus or Europa. One-Sentence Summary: A solid-state nanogap can determine the abundance distribution of amino acids, detect nucleic acids, and shows potential for detecting life as we know it and life as we don't know it. [ABSTRACT FROM AUTHOR]

Several methods used for the quantification of DNA are based on UV absorbance or the fluorescence of complexes with intercalator dyes. Most of these intercalators are used in gels to visualize DNA and its structural integrity. Due to many extraterrestrial samples, such as meteorites or comets, which are likely to contain very small amounts of biological material, and because the ability to detect this material is crucial for understanding the origin and evolution of life in the universe, the development of assays that can detect DNA at low limits and withstand the rigors of space exploration is a pressing need in the field of astrobiology. In this study, we present a comparison of optimized protocols used for the fast and accurate quantification of DNA using common intercalator dyes. The sensitivity of assays exceeded that generated by any commercial kit and allowed for the accurate quantification of minimum concentrations of DNA. The methods were successful when applied to the detection and measurement of DNA spiked on soil samples. Furthermore, the impact of UV radiation as a harsh condition on the surface of Mars was assessed by DNA degradation and this was also confirmed by gel electrophoresis. Overall, the methods described provide economical, simple-step, and efficient approaches for the detection of DNA and can be used in future planetary exploration missions as tests used for the extraction of nucleic acid biosignatures. [ABSTRACT FROM AUTHOR]

Between the 1870s and 1914, millions of Eastern Europeans moved to the United States. Little is known about the actual journeys of Polish, Jewish, and other migrants. A closer look at the experiences of transmigrants reveals a sophisticated system that was managed by Germany's two largest steamship lines, the Hamburg-America Line and the Bremen-based North German Lloyd. In the early 1880s, the United States shifted to a more thorough screening of arriving migrants, refusing admission to a growing number of "undesirables." In 1885, Germany's largest state, Prussia, implemented a restrictive immigration policy, much earlier than other states in and beyond Europe. The steamship lines convinced the Prussian state not to prevent migrants from Eastern Europe from crossing its territory. Before 1914, migrant aid associations also established a good accord with different state agencies in Europe and North America. They intervened on behalf of migrants who had been detained, often successfully. State officials embraced non-state actors because they solved protracted problems and relieved states of a financial burden. The article examines the origins of the privately handled transmigration system in Imperial Germany and raises the question whether it was beneficial for average migrants. [ABSTRACT FROM AUTHOR]

The existence of an object, non-superimposable on its mirror image, constitutes the phenomenon of chirality. This phenomenon is often treated as a curiosity without broader practical consequences. This paper aims to show the significant implications of chirality for chemistry and biology. Chirality is inherent to all living organisms and is essential for their functioning. For instance, biomolecules are composed of chiral building blocks (amino acids, monosaccharides), which are chiral and occur predominantly with one sense of handedness (homochirality of life). The explanation of the evolution of the homochirality of life is therefore one of the important questions connected with the origin of life. The paper also shows why asymmetry with respect to mirror reflection is a general attribute of our world. Historical milestones in the scientific reflection on chirality are also presented, starting with the French crystallographers of the late 18th century, through the work of Pasteur, the fundamentals of organic stereochemistry postulated by van 't Hoff and Le Bel, the elucidation of a structure of monosaccharides by Fischer, and ending with the discovery of the absolute configuration of a molecule and the confirmation of parity violation of weak interaction. [ABSTRACT FROM AUTHOR]

Planetary explorations have revealed that complex organics are widely present in the solar system. Astronomical infrared spectroscopic observations have discovered that complex organics are synthesized in large quantities in planetary nebulae and distributed throughout the galaxy. Signatures of organics have been found in distant galaxies, as early as 1.5 billion years after the Big Bang. A number of unsolved spectral phenomena such as diffuse interstellar bands, extended red emissions, 220 nm feature, and unidentified infrared emission bands are likely to originate from organics. In this paper, we discuss the possible chemical structures of the carriers of these unexplained phenomena, and how these organics are synthesized abiotically in the universe. We raise the possibility that the primordial solar system was enriched by complex organics synthesized and ejected by evolved stars. The implications of possible stellar organics in primordial Earth are also discussed. [ABSTRACT FROM AUTHOR]

The construction of hypothetical environments to produce organic molecules such as metabolic intermediates or amino acids is the subject of ongoing research into the emergence of life. Experiments specifically focused on an anabolic approach typically rely on a mineral catalyst to facilitate the supply of organics that may have produced prebiotic building blocks for life. Alternatively to a true catalytic system, a mineral could be sacrificially oxidized in the production of organics, necessitating the emergent 'life' to turn to virgin materials for each iteration of metabolic processes. The aim of this perspective is to view the current 'metabolism‐first' literature through the lens of materials chemistry to evaluate the need for higher catalytic activity and materials analyses. While many elegant studies have detailed the production of chemical building blocks under geologically plausible and biologically relevant conditions, few appear to do so with sub‐stoichiometric amounts of metals or minerals. Moving toward sub‐stoichiometric metals with rigorous materials analyses is necessary to demonstrate the viability of an elusive cornerstone of the 'metabolism‐first' hypotheses: catalysis. We emphasize that future work should aim to demonstrate decreased catalyst loading, increased productivity, and/or rigorous materials analyses for evidence of true catalysis. [ABSTRACT FROM AUTHOR]

The article focuses on the role of modified nucleosides in Ribonucleic Acid (RNA) folding studies inside peptide-rich droplets, shedding light on potential contributions to metabolic processes. Topics include the importance of compartmentalization of RNA in membraneless organelles, the influence of covalent RNA modifications on its structure in these compartments, and the use of next-generation sequencing.

The need to reduce data center operational costs has necessitated siting cloud computing platforms in cold locations such as the stratosphere. The stratosphere has also been found to play an important role in understanding life origins as it hosts life forms. The use of stratosphere based computing platforms however requires the hosting of multiple server payloads (requiring high energy consumption) at a higher altitude. In addition, smaller server payloads lead to smaller sized stratospheric computing platforms (SCPs) which limit interaction with stratospheric organisms. However, these challenges are not considered when designing SCPs. Hence, there is a risk of wrongly evaluating the power usage effectiveness (PUE) associated with SCPs. In addition, there is a risk of installing and deploying large sized SCPs thereby leading to contamination and limiting research potential on studying life forms. The research being presented proposes an intelligent architecture enabling the identification, selection and use of only light weight servers aboard SCPs. The incorporation of the intelligent architecture is observed to enhance the PUE by 43.9%. In addition, the use of the intelligent architecture is noted to enhance the overall PUE by 59.6% for hosting altitudes spanning the low to mid stratosphere regions. In addition, the reduction in server weight by an amount exceeding 92% is noted by simulations to enable the realization of a PUE that is close to the ideal value of unity. [ABSTRACT FROM AUTHOR]

The spontaneous emergence of function from diverse RNA sequence pools is widely considered an important transition in the origin of life. Here we show that diverse sequence pools are not a prerequisite for the emergence of function. Starting five independent selection experiments each from a single RNA seed sequence - comprising a central homopolymeric poly-A (or poly-U) segment flanked by different conserved primer binding sites - we observe transformation (continuous drift) of the seeds into low diversity sequence pools by mutation, truncation and recombination without ever reaching that of a random pool even after 24 rounds. Upon continuous error prone replication and selection for ATP binding we isolate specific ATP- or GTPbinding aptamers with low micromolar affinities. Our results have implications for early RNA evolution in the light of the high mutation rates associated with both non-enzymatic and enzymatic prebiotic RNA replication. [ABSTRACT FROM AUTHOR]

As a prominent theologian of Dutch Reformed orthodoxy, Samuel Maresius wrote De abusu philosophiae cartesianae (1670) to denounce the dangers of Cartesian theology. Despite its importance in the history of early modern Cartesianism, a crucial question about the work remains to be answered: which aspects of Cartesian theology did Maresius condemn as the most dangerous for Reformed orthodoxy? The present paper answers this question by selecting and analyzing four topics from De abusu: (1) freedom and grace, (2) the Trinity, (3) the world system, and (4) the origins of things. It shows that Maresius identified the danger of Cartesian theology as propagating heresies under the guise of benefitting the Reformed Church. He thus feared that Cartesian theology would destroy orthodoxy from within. [ABSTRACT FROM AUTHOR]

We introduce an exploratory computational chemistry experiment for senior undergraduate students. By studying the reaction mechanisms of intra- and intermolecular ethanol dehydration, students can understand the role of acid catalysts in alcohol dehydration reactions and the energy pathways at the molecular level. Through this experiment, students can develop expertise in Gaussian and GaussView, which are the general computing software of computational chemistry. Moreover, students can independently conduct structural optimization, frequency calculations, transition state searches, and other basic calculation operations. This experiment enables students to apply quantum chemical calculation methods when studying the general processes of different chemical reactions, thereby laying an important foundation for their future research. [ABSTRACT FROM AUTHOR]

Chemistry is engaged with a subject that is not static but evolving in time, in chemical space, namely, the collection of all substances and reactions reported over time. If we accept that premise, we can identify the path dependencies and self-reinforcing mechanisms that determined its current space and selected it across historical alternatives. In particular, data analysis allows us to identify two crucial turning points. One was the introduction of structural theory in 1860, the other a technological shift around 1980. [ABSTRACT FROM AUTHOR]

Simple Summary: Although life on earth is quite diverse, some biological molecules are common across all life forms, both extant and extinct, and thus are thought to have been present as life emerged. Identifying how such compounds could have formed prior to life is therefore a critical step in understanding the origin of life and the potential for life elsewhere in the solar system and beyond. One class of biomolecule crucial to modern life are nucleic acids, which carry the genetic code and are integral to cellular replication and function. In modern biology, cellular machinery synthesizes these molecules; however, prior to life's beginning, it is possible that naturally occurring minerals played a role in the synthesis and polymerization of these molecules. Only a few minerals have been tested thus far; here, we investigate a variety of minerals for their ability to promote elongation of ribonucleic acid in water. In doing so, both the minerals and their environments of formation are tested for their potential to promote elongation. We show that several newly tested minerals can promote synthesis, suggesting that a broader set of environments may have been able to host chemical reactions relevant to the origin of life than previously assumed. The origin of life on earth requires the synthesis of protobiopolymers in realistic geologic environments along strictly abiotic pathways that rely on inorganic phases (such as minerals) instead of cellular machinery to promote condensation. One such class of polymer central to biochemistry is the polynucleotides, and oligomerization of activated ribonucleotides has been widely studied. Nonetheless, the range of laboratory conditions tested to date is limited and the impact of realistic early Earth conditions on condensation reactions remains unexplored. Here, we investigate the potential for a variety of minerals to enhance oligomerization using ribonucleotide monomers as one example to model condensation under plausible planetary conditions. The results show that several minerals differing in both structure and composition enhance oligomerization. Sulfide minerals yielded oligomers of comparable lengths to those formed in the presence of clays, with galena being the most effective, yielding oligonucleotides up to six bases long. Montmorillonite continues to excel beyond other clays. Chemical pretreatment of the clay was not required, though maximum oligomer lengths decreased from ~11 to 6 bases. These results demonstrate the diversity of mineral phases that can impact condensation reactions and highlight the need for greater consideration of environmental context when assessing prebiotic synthesis and the origin of life. [ABSTRACT FROM AUTHOR]

Before the late 1980s, ideas around how the lipophilic phytocannabinoids might be working involved membranes and bioenergetics as these disciplines were "in vogue". However, as interest in genetics and pharmacology grew, interest in mitochondria (and membranes) waned. The discovery of the cognate receptor for tetrahydrocannabinol (THC) led to the classification of the endocannabinoid system (ECS) and the conjecture that phytocannabinoids might be "working" through this system. However, the how and the "why" they might be beneficial, especially for compounds like CBD, remains unclear. Given the centrality of membranes and mitochondria in complex organisms, and their evolutionary heritage from the beginnings of life, revisiting phytocannabinoid action in this light could be enlightening. For example, life can be described as a self-organising and replicating far from equilibrium dissipating system, which is defined by the movement of charge across a membrane. Hence the building evidence, at least in animals, that THC and CBD modulate mitochondrial function could be highly informative. In this paper, we offer a unique perspective to the question, why and how do compounds like CBD potentially work as medicines in so many different conditions? The answer, we suggest, is that they can modulate membrane fluidity in a number of ways and thus dissipation and engender homeostasis, particularly under stress. To understand this, we need to embrace origins of life theories, the role of mitochondria in plants and explanations of disease and ageing from an adaptive thermodynamic perspective, as well as quantum mechanics. [ABSTRACT FROM AUTHOR]

The applicability of the law of homologous series of N.I. Vavilov to constructing a system is shown using international data on one of the most ancient groups of invertebrates, that is, archeocyats. It is proved that the laws of evolutionary morphology are special cases of the law of homological series. Analysis of the features of the development of our galaxy before the formation of the Earth raises the idea that the law of homological series is the final part of a more general law of autocombinatorics. [ABSTRACT FROM AUTHOR]

The aim of this paper is to explain why, while Charles Darwin was well recognized as a scientific leader of his time, Claude Bernard never really regarded Darwinism as a scientific theory. The lukewarm reception of Darwin at the Académie des Sciences of Paris and his nomination to a chair only after 8 years contrasts with his prominence, and Bernard's attitude towards Darwin's theory of species evolution belongs to this French context. Yet we argue that Bernard rejects the scientific value of Darwinian principles mainly for epistemological reasons. Like Darwin, Bernard was interested in hereditary processes, and planned to conduct experiments on these processes that could lead to species transformation. But the potential creation of new forms of life would not vindicate Darwinism since biologists can only explain the origin of morphotypes and morphological laws by the means of untestable analogies. Because it can be the object neither of experiments nor of any empirical observation, phylogeny remains out of science's scope. Around 1878 Bernard foresaw a new general physiology based on the study of protoplasm, which he saw as the agent of all basic living phenomena. We will analyze why Bernard regarded Darwinism as part of metaphysics, yet still referred to Darwinians in his latter works in 1878. Basically, the absence of a scientific reception of Darwinism in Bernard's work should not obscure its philosophical reception, which highlights the main principles of Bernard's epistemology. [ABSTRACT FROM AUTHOR]