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How did specific useful protein sequences arise from simpler molecules at the origin of life? This seemingly needle-in-a-haystack problem has remarkably close resemblance to the old Protein Folding Problem, for which the solution is now known from statistical physics. Based on the logic that Origins must have come only after there was an operative evolution mechanism-which selects on phenotype, not genotype-we give a perspective that proteins and their folding processes are likely to have been the primary driver of the early stages of the origin of life.

The origin of life must have been preceded by Darwin-like evolutionary dynamics that could propagate it. How did that adaptive dynamics arise? And from what prebiotic molecules? Using evolutionary invasion analysis, we develop a universal framework for describing any origin story for evolutionary dynamics. We find that cooperative autocatalysts, i.e. autocatalysts whose per-unit reproductive rate grows as their population increases, have the special property of being able to cross a barrier that separates their initial degradation-dominated state from a growth-dominated state with evolutionary dynamics. For some model parameters, this leap to persistent propagation is likely, not rare. We apply this analysis to the Foldcat Mechanism, wherein peptides fold and help catalyse the elongation of each other. Foldcats are found to have cooperative autocatalysis and be capable of emergent evolutionary dynamics.

We report simulation studies of 33 single intrinsically disordered proteins (IDPs) using coarse-grained bead-spring models where interactions among different amino acids are introduced through a hydropathy matrix and additional screened Coulomb interaction for the charged amino acid beads. Our simulation studies of two different hydropathy scales (HPS1, HPS2) [Dignon et al., PLoS Comput. Biol. 14, e1005941 (2018); Tesei et al. Proc. Natl. Acad. Sci. U. S. A. 118, e2111696118 (2021)] and the comparison with the existing experimental data indicate an optimal interaction parameter ϵ = 0.1 and 0.2 kcal/mol for the HPS1 and HPS2 hydropathy scales. We use these best-fit parameters to investigate both the universal aspects as well as the fine structures of the individual IDPs by introducing additional characteristics. (i) First, we investigate the polymer-specific scaling relations of the IDPs in comparison to the universal scaling relations [Bair et al., J. Chem. Phys. 158, 204902 (2023)] for the homopolymers. By studying the scaled end-to-end distances ⟨ R N 2 ⟩ / (2 L ℓ p ) and the scaled transverse fluctuations l ̃ ⊥ 2 = ⟨ l ⊥ 2 ⟩ / L , we demonstrate that IDPs are broadly characterized with a Flory exponent of ν ≃ 0.56 with the conclusion that conformations of the IDPs interpolate between Gaussian and self-avoiding random walk chains. Then, we introduce (ii) Wilson charge index (W) that captures the essential features of charge interactions and distribution in the sequence space and (iii) a skewness index (S) that captures the finer shape variation of the gyration radii distributions as a function of the net charge per residue and charge asymmetry parameter. Finally, our study of the (iv) variation of ⟨Rg⟩ as a function of salt concentration provides another important metric to bring out finer characteristics of the IDPs, which may carry relevant information for the origin of life. [ABSTRACT FROM AUTHOR]

The path from lifes origin to the emergence of the eukaryotic cell was long and complex, and as such it is rarely treated in one publication. Here, we offer a sketch of this path, recognizing that there are points of disagreement and that many transitions are still shrouded in mystery. We assume life developed within microchambers of an alkaline hydrothermal vent system. Initial simple reactions were built into more sophisticated reflexively autocatalytic food-generated networks (RAFs), laying the foundation for lifes anastomosing metabolism, and eventually for the origin of RNA, which functioned as a genetic repository and as a catalyst (ribozymes). Eventually, protein synthesis developed, leading to lifes biology becoming dominated by enzymes and not ribozymes. Subsequent enzymatic innovation included ATP synthase, which generates ATP, fueled by the proton gradient between the alkaline vent flux and the acidic sea. This gradient was later internalized via the evolution of the electron transport chain, a preadaptation for the subsequent emergence of the vent creatures from their microchamber cradles. Differences between bacteria and archaea suggests cellularization evolved at least twice. Later, the bacterial development of oxidative phosphorylation and the archaeal development of proteins to stabilize its DNA laid the foundation for the merger that led to the formation of eukaryotic cells.

The definition, origin and recreation of life remain elusive. As others have suggested, only once we put life into reductionist physical terms will we be able to solve those questions. To that end, this work proposes the phenomenon of life to be the product of two dissipative mechanisms. From them, one characterises extant biological life and deduces a testable scenario for its origin. The proposed theory of life allows its replication, reinterprets ecological evolution and creates new constraints on the search for life. [ABSTRACT FROM AUTHOR]

The ability of living organisms to persist, grow, evolve and invade environments seemingly challenges physical laws. Emerging Autonomous Systems representing autocatalytic cycles constituted of energized components in a state of Dynamic Kinetic Stability feature some of these properties. These simple theoretical models can grow, can be transferred but need an initiation to emerge and can collapse. Moreover, they can undergo kinetic selection in a way consistent with Darwinian behaviour, though they lack the ability to undergo change. The mere existence of these systems and their open‐ended growth potential are proposed to constitute a transmissible factor of a non‐coded kind. The onset and selection of epigenetic factors may therefore have preceded that of genetic polymers. Here is addressed the question of how these systems may arise from the diversity exhibited by abiotic organic matter, sometimes associated with intractable mixtures, which may actually be useful in providing initiators. The Darwinian description of evolution may therefore be merged without critical discontinuity within an origin scenario. Accordingly, such a theory would rests solely on physicochemical laws beginning with the potential of emerging autonomous systems to compete and invade the space dimension, and to further develop along other available dimensions including variability and, possibly, cognition. [ABSTRACT FROM AUTHOR]

Background: Carbon monoxide (CO), hypothetically linked to prebiotic biosynthesis and possibly the origin of the life, emerges as a substantive growth substrate for numerous microorganisms. In anoxic environments, the coupling of CO oxidation with hydrogen (H2) production is an essential source of electrons, which can subsequently be utilized by hydrogenotrophic bacteria (e.g., organohalide-respring bacteria). While Dehalococcoides strains assume pivotal roles in the natural turnover of halogenated organics and the bioremediation of chlorinated ethenes, relying on external H2 as their electron donor and acetate as their carbon source, the synergistic dynamics within the anaerobic microbiome have received comparatively less scrutiny. This study delves into the intriguing prospect of CO serving as both the exclusive carbon source and electron donor, thereby supporting the reductive dechlorination of trichloroethene (TCE). Results: The metabolic pathway involved anaerobic CO oxidation, specifically the Wood-Ljungdahl pathway, which produced H2 and acetate as primary metabolic products. In an intricate microbial interplay, these H2 and acetate were subsequently utilized by Dehalococcoides, facilitating the dechlorination of TCE. Notably, Acetobacterium emerged as one of the pivotal collaborators for Dehalococcoides, furnishing not only a crucial carbon source essential for its growth and proliferation but also providing a defense against CO inhibition. Conclusions: This research expands our understanding of CO's versatility as a microbial energy and carbon source and unveils the intricate syntrophic dynamics underlying reductive dechlorination. 3ez2V3iuLHAKAp3AxS5o4q Video Abstract [ABSTRACT FROM AUTHOR]

To test the hypothesis that an abiotic Earth and its inert atmosphere could form chemically reactive carbon-and nitrogen-containing compounds, we designed a plasma electrochemical setup to mimic lightning-induced electrochemistry under steady-state conditions of the early Earth. Air-gap electrochemical reactions at air-water-ground interfaces lead to remarkable yields, with up to 40 moles of carbon dioxide being reduced into carbon monoxide and formic acid, and 3 moles of gaseous nitrogen being fixed into nitrate, nitrite, and ammonium ions, per mole of transmitted electrons. Interfaces enable reactants (e.g., minerals) that may have been on land, in lakes, and in oceans to participate in radical and redox reactions, leading to higher yields compared to gas-phase-only reactions. Cloud-to-ground lightning strikes could have generated high concentrations of reactive molecules locally, establishing diverse feedstocks for early life to emerge and survive globally. [ABSTRACT FROM AUTHOR]

Thioamide bonds are important intermediates in prebiotic chemistry. In cyanosulfidic prebiotic chemistry, they serve as crucial intermediates in the pathways that lead to the formation of many important biomolecules (e.g., amino acids). They can also serve as purine and pyrimidine precursors, the two classes of heterocycle employed in genetic molecules. Despite their importance, the formation of thioamide bonds from nitriles under prebiotic conditions has required large excesses of sulfide or compounds with unknown prebiotic sources. Here, we describe the thiol-catalyzed formation of thioamide bonds from nitriles. We show that the formation of the simplest of these compounds, thioformamide, forms readily in spark-discharge experiments from hydrogen cyanide, sulfide, and a methanethiol catalyst, suggesting potential accumulation on early Earth. Lastly, we demonstrate that thioformamide has a Gibbs energy of hydrolysis ( Δ G r ∘ ) comparable to other energy-currencies on early Earth such as pyrophosphate and thioester bonds. Overall, our findings imply that thioamides might have been abundant on early Earth and served a variety of functions during chemical evolution. [ABSTRACT FROM AUTHOR]

Amino acids are essential for Earth-like life and are hypothesised to have originated in interstellar space, potentially being transported to Earth via meteorite impacts. Detecting amino acids in interstellar environments and understanding their formation mechanisms through laboratory experiments are crucial for supporting this hypothesis and unravelling the origins of life. In this study, the formation of serine ( $ {\rm NH}_2{\rm CH}({\rm CH}_2{\rm OH}){\rm COOH}) $ NH 2 CH (CH 2 OH) COOH) from α-glycyl ( $ {\rm NH}_2{\rm C}{\cdot }{\rm HCOOH} $ NH 2 C ⋅ HCOOH ) and hydroxymethyl ( $ {\cdot } {\rm CH}_2{\rm OH} $ ⋅ CH 2 OH ) radicals was investigated using quantum chemical computations. It was found that the anticipated recombination reaction, along with analogous formation pathways of other natural amino acids, is accompanied by competing reactions yielding alternative products, potentially diminishing serine formation. Alternative interstellar formation pathways for serine are proposed, which could be experimentally tested by future laboratory studies. [ABSTRACT FROM AUTHOR]

The emergence of life from nonlife, or abiogenesis, remains a fundamental question in scientific inquiry. In this article, we investigate the probability of the origin of life (per conducive site) by leveraging insights from Earth's environments. If life originated endogenously on Earth, its existence is indeed endowed with informative value, although the interpretation of the attendant significance hinges critically upon prior assumptions. By adopting a Bayesian framework, for an agnostic prior, we establish a direct connection between the number of potential locations for abiogenesis on Earth and the probability of life's emergence per site. Our findings suggest that constraints on the availability of suitable environments for the origin(s) of life on Earth may offer valuable insights into the probability of abiogenesis and the frequency of life in the universe. [ABSTRACT FROM AUTHOR]

The core autocatalytic cycle of the formose reaction may be enhanced or eroded by the presence of simple molecules at life's origin. Utilizing quantum chemistry, we calculate the thermodynamics and kinetics of reactions both within the core cycle and those that deplete the reactants and intermediates, such as the Cannizzaro reaction. We find that via disproportionation of aldehydes into carboxylic acids and alcohols, the Cannizzaro reaction furnishes simple catalysts for a variety of reactions. We also find that ammonia can catalyze both in-cycle and Cannizzaro reactions while hydrogen sulfide does not; both, however, play a role in sequestering reactants and intermediates in the web of potential reactions. [ABSTRACT FROM AUTHOR]

Detecting biosignatures of life in extraterrestrial environments remains one of the primary objectives of scientific inquiry. Currently, both remote and direct detection methods are primarily aimed at identifying key molecular classes fundamental to terrestrial biology. However, a more universally applicable spectroscopic approach could involve searching for homochiral molecules. Thus, this perspective delves into the significance of homochirality as a critical factor in the origin of life. Without homochirality, the formation of self‐recognizing and self‐replicating complex molecules would be hindered. The various hypotheses concerning the origin of homochiral molecules have been explored and analyzed within this context. This perspective emphasizes the potential for discovering extraterrestrial microscopic life through the detection of homochiral molecules using chirodetecting methods such as chromatography and chiroptical spectroscopy or circular polarimetry as a promising remote technique. This discussion highlights the importance of homochirality in the broader search for life beyond Earth and underscores the need for innovative methodologies and instrumentation in astrobiological research. These techniques can be an effective method for detecting homochirality on future planetary missions. [ABSTRACT FROM AUTHOR]

Low-energy cosmic rays (LECRs) play a crucial role in the formation of planetary systems, and detecting and reconstructing the properties of early LECRs is essential for understanding the mechanisms of planetary system formation. Given that LECRs interact with the surrounding medium to produce nuclear de-excitation line emissions, which are gamma-ray emissions with energy mainly within 0.1–10 MeV and are unaffected by stellar wind modulation, these emissions can accurately reflect the properties of LECRs. This study introduces an innovative method for using gamma-ray emissions to infer LECR properties. We employed the Parker transport equation to simulate the propagation and spectral evolution of LECRs in a protoplanetary disk and calculated the characteristic gamma-ray emissions resulting from interactions between LECRs and disk material. These gamma-ray emissions encapsulate the spectral information of LECRs, providing a powerful tool to reconstruct the cosmic ray environment at that time. This method, supported by further theoretical developments and observations, will fundamentally enhance our understanding of the impact of CRs on the origin and evolution of planetary systems and address significant scientific questions regarding the cosmic ray environment at the origin of life. [ABSTRACT FROM AUTHOR]

Natural selection has a formal definition as the natural process that results in the survival and reproductive success of individuals or groups best adjusted to their environment, leading to the perpetuation of those genetic qualities best suited to that organism's environmental niche. Within conventional Neo-Darwinism, the largest source of those variations that can be selected is presumed to be secondary to random genetic mutations. As these arise, natural selection sustains adaptive traits in the context of a 'struggle for existence'. Consequently, in the 20th century, natural selection was generally portrayed as the primary evolutionary driver. The 21st century offers a comprehensive alternative to Neo-Darwinian dogma within Cognition-Based Evolution. The substantial differences between these respective evolutionary frameworks have been most recently articulated in a revision of Crick's Central Dogma, a former centerpiece of Neo-Darwinism. The argument is now advanced that the concept of natural selection should also be comprehensively reappraised. Cognitive selection is presented as a more precise term better suited to 21st century biology. Since cognition began with life's origin, natural selection represents cognitive selection. [ABSTRACT FROM AUTHOR]

The origin of life (OoL) has always been a mysterious and challenging topic that puzzles human beings. Clay minerals have unique properties and wide distribution in early Earth environments. They can not only adsorb biological small molecules to catalyze their polymerization, but play an active role in the formation and evolution of protocells. In this review, the research progress on the interactions of clay minerals with biomolecules and protocells complex structures in the field of the OoL based on chemical evolution theory is summarized. The types, structures and properties of clay minerals, biological molecules and protocell models related to the OoL are introduced in detail. The mechanism of interaction between clay minerals and biological molecules, the construction of protocells and the role of clay minerals in the formation, structure and stability of protocells are systematically described. Finally, the future research priorities and challenges in the field of OoL based on clay minerals, biomolecules and protocells are discussed. It is aspired that this review can further advance the exploration of the OoL from a new perspective, and can also bring some interesting findings and ideas to the interdisciplinary research of materials, biology, chemistry and other related disciplines.Clay minerals have a variety of interactions with small biomolecules, which can be used as structural and functional templates to promote the organic synthesis of biomolecules and the formation and evolution of protocells, playing a non‐negligible role in the field of the OoL. [ABSTRACT FROM AUTHOR]

We hypothesize that the first ancestral "protocell" molecular structures, i.e., the first RNAs and peptides that gradually transformed into real cells once the Earth had cooled sufficiently for organic molecules to appear, have left traces in the RNAs and the genes in present cells. We propose a circular RNA that could have been one of these ancestral structures whose vestigial pentameric subsequences would mark the evolution from this key moment when the protocells began to join with living organisms. In particular, we propose that, in present RNAs (ribosomal or messenger), which play an important role in the metabolism of current cells, we look for traces of the proposed primitive structure in the form of pentamers (or longer fragments) that belong to their nucleotide sequence. The result obtained can be summarized in the existence of a gradient of occurrence of such pentamers, with a high frequency for the most vital functions (protein synthesis, nucleic synthesis, cell respiration, etc.). This gradient is also visible between organisms, from the oldest (Archaea) to the most recent (Eukaryotes) in the evolution of species. [ABSTRACT FROM AUTHOR]

Urea is believed to have been essential to the synthesis of prebiotic nucleotides and thereby the RNA or DNA of the first lifeforms. Models suggesting that life began in wet‐dry cycles around shallow aquatic ponds imply that reactants such as urea were exposed to deep ultraviolet irradiation from the young sun. Detrimental photodissociation of urea induced by deep UV excitation potentially challenges these models. We here follow the primary deep ultraviolet photochemistry of aqueous urea. The data show that urea is barely excited at 200 nm due to weak ultraviolet absorption. The likelihood of photodissociation is further reduced by strong intra‐molecular coupling of the CN and CO stretch vibrations accompanied by an efficient dissipation of the excitation energy to the surrounding water molecules mitigated by urea‐water hydrogen bonds. We find that 54±5 % of the excited urea molecules dissociate. Reactions between the photoproducts and surrounding solvent molecules form carbamic acid or the carbamate anions within 0.6 ps. The molecules that do not dissociate return to the electronic ground state in 2 ps. Interestingly, the photodissociation processes of urea in the aqueous phase is different from earlier reported reactions observed following the VUV photolysis of urea in noble gas matrices and highlight the potential influence of water on the prebiotic photochemistry. [ABSTRACT FROM AUTHOR]

Resolving a robust phylogeny of an organismal group is often hindered by the limited availability of samples suitable for genomic or transcriptomic sequencing. Even for lineages of notable importance in evolutionary ecology, our phylogenetic comprehension remains largely unsatisfactory due to the challenges of acquiring samples across the clade. The long‐horned beetle genus Anoplophora Hope exemplifies such a group, globally renowned for two invasive pests—the Asian long‐horned beetle and citrus long‐horned beetle—which have inflicted significant damage to deciduous hardwood forest in North America and Europe. In contrast to the two temperate pests, the remaining 50 species in the genus inhabit subtropical forests of Southeast Asia, where most species are only infrequently encountered. Here, we present the first comprehensive phylogeny of Anoplophora using a PCR‐based target enrichment museomics approach. As a case study of employing PCR‐generated custom probes, we demonstrate the robustness and cost‐effectiveness of this in‐house method in successfully acquiring sequence data from historical specimens. Through extensive sampling of Anoplophora using museum specimens, we reveal a non‐sister relationship between the two temperate species and provide evidence for addressing taxonomic conundrums. Our biogeographical analyses indicate that the adaptation of the two temperate species occurred independently during the late Pliocene and Pleistocene after the establishment of temperate forests in East Asia in the late Miocene. Our findings highlight the importance of comprehensive phylogenetic inference in understanding the patterns and processes of these beetles' adaptation to temperate forests and lay the groundwork for investigating the genetic mechanism underlying life in the cold. [ABSTRACT FROM AUTHOR]

At the origin, the emergence of proteins was based on crucial prebiotic stages in which simple amino acids‐based building blocks spontaneously evolved from the prebiotic soup into random proto‐polymers called protoproteins. Despite advances in modern peptide synthesis, these prebiotic chemical routes to protoproteins remain puzzling. We discuss in this perspective how polymer science and systems chemistry are reaching a point of convergence in which simple monomers called N‐carboxyanhydrides would be able to form such protoproteins via the emergence of a protometabolic cycle involving aqueous polymerization and featuring macromolecular Darwinism behavior. [ABSTRACT FROM AUTHOR]

Livestock farming is considered one relevant cause of global warming. The aim of this article is to show that the environmental footprint of broilers and laying hens is small among farmed animal species. Author examines the increase in the production of broilers and laying hens over the past decades as a result of genetic selection, and as a consequence their greenhouse gas emissions, land, water and energy use have decreased. It was evidenced that with the increase of production the environmental footprint per unit of product decreases. On the other hand, in alternative housing systems, especially in free-range and organic production, all indicators deteriorate. Supplying the Earth's ever-growing population with a sufficient amount of high-quality food of animal origin, in such a way that the environmental footprint of poultry farming is reduced, can be achieved with intensive production taking into account animal welfare. New tools and methods such as genomic selection, gene editing or precision poultry breeding will help in this. [ABSTRACT FROM AUTHOR]

Many of the fundamental molecules of life share extraordinary pigment-like optical properties in the long-wavelength UV-C spectral region. These include strong photon absorption and rapid (sub-pico-second) dissipation of the induced electronic excitation energy into heat through peaked conical intersections. These properties have been attributed to a "natural selection" of molecules resistant to the dangerous UV-C light incident on Earth's surface during the Archean. In contrast, the "thermodynamic dissipation theory for the origin of life" argues that, far from being detrimental, UV-C light was, in fact, the thermodynamic potential driving the dissipative structuring of life at its origin. The optical properties were thus the thermodynamic "design goals" of microscopic dissipative structuring of organic UV-C pigments, today known as the "fundamental molecules of life", from common precursors under this light. This "UV-C Pigment World" evolved towards greater solar photon dissipation through more complex dissipative structuring pathways, eventually producing visible pigments to dissipate less energetic, but higher intensity, visible photons up to wavelengths of the "red edge". The propagation and dispersal of organic pigments, catalyzed by animals, and their coupling with abiotic dissipative processes, such as the water cycle, culminated in the apex photon dissipative structure, today's biosphere. [ABSTRACT FROM AUTHOR]

The abiotic formation of nucleotides from small, simple molecules is of large interest in the context of elucidating the origin of life scenario. In what follows, it is shown that nucleosides and nucleotides can be formed from formamide in a one-pot reaction utilizing the mineral cerium phosphate (CePO4) as a photocatalyst, a catalyst and a reactant that supplies the necessary phosphate groups. While the most abundant RNA/DNA building blocks were thymidine and thymidine monophosphate, considerable yields of other building blocks such as cytidine, cytidine monophosphate, and adenosine cyclic monophosphate were found. Comparing the yield of nucleosides and nucleotides under light conditions to that in the dark suggests that in the presence of cerium phosphate, light promotes the formation of nucleobases, whereas the formation of nucleotides from nucleosides take place even in the absence of light. The scenario described herein is considerably simpler than other scenarios involving several steps and several reactants. Therefore, by virtue of the principle of Occam's razor, it should be of large interest for the community. [ABSTRACT FROM AUTHOR]

The osmotic rupture of a cell, its osmotic lysis or cytolysis, is a phenomenon that active biological cell volume regulation mechanisms have evolved in the cell membrane to avoid. How then, at the origin of life, did the first protocells survive prior to such active processes? The pores of alkaline hydrothermal vents in the oceans form natural nanoreactors in which osmosis across a mineral membrane plays a fundamental role. Here, we discuss the dynamics of lysis and its avoidance in an abiotic system without any active mechanisms, reliant upon self‐organized behaviour, similar to the first self‐organized mineral membranes within which complex chemistry may have begun to evolve into metabolism. We show that such mineral nanoreactors could function as protocells without exploding because their self‐organized dynamics have a large regime in parameter space where osmotic lysis does not occur and homeostasis is possible. The beginnings of Darwinian evolution in proto‐biochemistry must have involved the survival of protocells that remained within such a safe regime. [ABSTRACT FROM AUTHOR]

The Game of Life (GoL) cellular automaton is modified to inject order during execution of the state transition algorithm by making selected stable structures permanently active while interacting with normal active sites to create novel structures. A survey of the modified automaton's phenomenology and an analysis of its dynamics are presented in the context of the physics of the self-organization of matter by viewing the GoL as an artificial chemistry. These new structures become seeds for additional phases of structure building, analogous to nature's gravitational and thermodynamic churning of the geosphere that created material structures in phases, beginning the transition from geochemistry to prebiotic chemistry and laying foundational substrates for life-enabling organizational processes in an emerging biosphere. Evidence of selective self-assembly during phase transitions is reported where several GoL still life structures, configured as permanently active seeds evolving with random collections of active sites, resulted in geometrically identical structures as the GoL reached an equilibrium state of static density. [ABSTRACT FROM AUTHOR]

Hypervelocity impacts can generate hydrothermal systems, which have been suggested as candidate environments for prebiotic chemistry on the early Earth. The Haughton impact structure (a 23 km diameter crater located on Devon Island, Nunavut, Arctic Canada) displays evidence of water‐rock alteration indicative of a hydrothermal system generated from a cosmic impact. To model the formation of this crater and subsequent hydrothermal alteration, we have successfully developed a new two‐code methodology that utilizes a shock physics code and a hydrothermal code (HYDROTHERM). We can best reproduce the Haughton crater with a ∼700 m diameter projectile with an impact velocity of 14 km/s. With our approach, we were able to match all the major geological constraints observed at the Haughton impact structure. Our models show that the Haughton crater interior could have sustained temperatures ideal for thermophilic and hyperthermophilic life (50–120°C) for more than 50,000 years, indicating that these systems can sustain prebiotic chemistry and life for longer than previously estimated. Plain Language Summary: Impacts of cosmic objects moving at hypervelocity can create high‐temperature hydrothermal systems. These environments have been suggested as possible sites for the formation of prebiotic chemistry on early Earth. The Haughton impact structure on Devon Island, Nunavut, Arctic Canada, has a well‐studied impact‐generated hydrothermal system and offers a unique analog to similar systems on early Earth or Mars. Here, we present a two‐code modeling technique to model the full evolution of the impact‐generated hydrothermal system at Haughton. We were able to match the major geological constraints observed at the Haughton structure. Our models suggest that the Haughton crater interior should have sustained temperatures ideal for early life (50–120°C) for >50,000 years, indicating that these systems can sustain life for longer than previously estimated. Key Points: The Haughton impact structure can be better modeled utilizing a smaller impactor (∼700 m in diameter) than previously estimatedWe successfully match a multitude of observed fluid alterations observed at Haughton with our novel two‐code methodologyOur models show that the Haughton crater interior sustained temperatures ideal for thermophilic and hyperthermophilic life for >50,000 years [ABSTRACT FROM AUTHOR]

Abstract Thioamide bonds are important intermediates in prebiotic chemistry. In cyanosulfidic prebiotic chemistry, they serve as crucial intermediates in the pathways that lead to the formation of many important biomolecules (e.g., amino acids). They can also serve as purine and pyrimidine precursors, the two classes of heterocycle employed in genetic molecules. Despite their importance, the formation of thioamide bonds from nitriles under prebiotic conditions has required large excesses of sulfide or compounds with unknown prebiotic sources. Here, we describe the thiol-catalyzed formation of thioamide bonds from nitriles. We show that the formation of the simplest of these compounds, thioformamide, forms readily in spark-discharge experiments from hydrogen cyanide, sulfide, and a methanethiol catalyst, suggesting potential accumulation on early Earth. Lastly, we demonstrate that thioformamide has a Gibbs energy of hydrolysis ( $$\Delta G^{\circ }_r$$ Δ G r ∘ ) comparable to other energy-currencies on early Earth such as pyrophosphate and thioester bonds. Overall, our findings imply that thioamides might have been abundant on early Earth and served a variety of functions during chemical evolution.

External flows of energy, entropy, and matter can cause sudden transitions in the stability of biological and industrial systems, fundamentally altering their dynamical function. How might we control and design these transitions in chemical reaction networks? Here, we analyze transitions giving rise to complex behavior in random reaction networks subject to external driving forces. In the absence of driving, we characterize the uniqueness of the steady state and identify the percolation of a giant connected component in these networks as the number of reactions increases. When subject to chemical driving (influx and outflux of chemical species), the steady state can undergo bifurcations, leading to multistability or oscillatory dynamics. By quantifying the prevalence of these bifurcations, we show how chemical driving and network sparsity tend to promote the emergence of these complex dynamics and increased rates of entropy production. We show that catalysis also plays an important role in the emergence of complexity, strongly correlating with the prevalence of bifurcations. Our results suggest that coupling a minimal number of chemical signatures with external driving can lead to features present in biochemical processes and abiogenesis. [ABSTRACT FROM AUTHOR]

ABSTRACTThe RNA world hypothesis confers a central role to RNA molecules in information encoding and catalysis. Even though evidence in support of this hypothesis has accumulated from both experiments and computational modelling, the transition from an RNA world to a world where heritable genetic information is encoded in DNA remains an open question. Recent experiments show that both RNA and DNA templates can extend complementary primers using free RNA/DNA nucleotides, either non-enzymatically or in the presence of a replicase ribozyme. Guided by these experiments, we analyse protocellular evolution with an expanded set of reaction pathways made possible through the presence of DNA nucleotides. By encapsulating these reactions inside three different types of protocellular compartments, each subject to distinct modes of selection, we show how protocells containing DNA-encoded replicases in low copy numbers and replicases in high copy numbers can dominate the population. This is facilitated by a reaction that leads to auto-catalytic synthesis of replicase ribozymes from DNA templates encoding the replicase after the chance emergence of a replicase through non-enzymatic reactions. Our work unveils a pathway for the transition from an RNA world to a mixed RNA-DNA world characterized by Darwinian evolution, where DNA sequences encode heritable phenotypes.

In the boundless landscape of scientific exploration, there exists a hidden, yet easily accessible, dimension that has often not only intrigued and puzzled researchers but also provided the key. This dimension is chirality, the property that describes the handedness of objects. The influence of chirality extends across diverse fields of study from the parity violation in electroweak interactions to the extremely large macroscopic systems such as galaxies. In this opinion piece, we will delve into the power of chirality in scientific exploration by examining some examples that, at different scales, demonstrate its role as a key to a better understanding of our world. Our goal is to incite researchers from all fields to seek, implement and utilize chirality in their research. Going this extra mile might be more rewarding than it seems at first glance, in particular with regard to the increasing demand for new functional materials in response to the contemporary scientific and technological challenges we are facing. This article is part of the theme issue 'Celebrating the 15th anniversary of the Royal Society Newton International Fellowship'. [ABSTRACT FROM AUTHOR]

Cells are the fundamental units of life, and like all life forms, they change over time. Changes in cell state are driven by molecular processes; of these many are initiated when molecule numbers reach and exceed specific thresholds, a characteristic that can be described as "digital cellular logic". Here we show how molecular and cellular noise profoundly influence the time to cross a critical threshold—the first-passage time—and map out scenarios in which stochastic dynamics result in shorter or longer average first-passage times compared to noise-less dynamics. We illustrate the dependence of the mean first-passage time on noise for a set of exemplar models of gene expression, auto-regulatory feedback control, and enzyme-mediated catalysis. Our theory provides intuitive insight into the origin of these effects and underscores two important insights: (i) deterministic predictions for cellular event timing can be highly inaccurate when molecule numbers are within the range known for many cells; (ii) molecular noise can significantly shift mean first-passage times, particularly within auto-regulatory genetic feedback circuits. Cells exhibit remarkable temporal precision in regulating their internal states. Here, by solving stochastic first passage time problems for key molecular processes Ham, Coomer et al. shed light on how cells achieve this precision. [ABSTRACT FROM AUTHOR]

Salt stress seriously affects crop growth, leading to a decline in crop quality and yield. Application of exogenous substances to improve the salt tolerance of crops and promote their growth under salt stress has become a widespread and effective means. Eugenol is a small molecule of plant origin with medicinal properties such as antibacterial, antiviral, and antioxidant properties. In this study, tobacco seedlings were placed in Hoagland's solution containing NaCl in the presence or absence of eugenol, and physiological indices related to stress tolerance were measured along with transcriptome sequencing. The results showed that eugenol improved the growth of tobacco seedlings under salt stress. It promoted carbon and nitrogen metabolism, increased the activities of nitrate reductase (NR), sucrose synthase (SS), and glutamine synthetase (GS) by 31.03, 5.80, and 51.06%. It also activated the enzymatic and non-enzymatic antioxidant systems, reduced the accumulation of reactive oxygen species in the tobacco seedlings, and increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) by 24.38%, 18.22%, 21.60%, and 28.8%, respectively. The content of glutathione (GSH) was increased by 29.49%, and the content of superoxide anion (O2−) and malondialdehyde (MDA) were reduced by 29.83 and 33.86%, respectively. Promoted osmoregulation, the content of Na+ decreased by 34.34, K+ increased by 41.25%, and starch and soluble sugar increased by 7.72% and 25.42%, respectively. It coordinated hormone signaling in seedlings; the content of abscisic acid (ABA) and gibberellic acid 3 (GA3) increased by 51.93% and 266.28%, respectively. The transcriptome data indicated that the differentially expressed genes were mainly enriched in phenylpropanoid biosynthesis, the MAPK signaling pathway, and phytohormone signal transduction pathways. The results of this study revealed the novel role of eugenol in regulating plant resistance and provided a reference for the use of exogenous substances to alleviate salt stress. [ABSTRACT FROM AUTHOR]

There is a "popular" belief that a fat-free diet is beneficial, supported by the scientific dogma indicating that high levels of fatty acids promote many pathological metabolic, cardiovascular, and neurodegenerative conditions. This dogma pressured scientists not to recognize the essential role of fatty acids in cellular metabolism and focus on the detrimental effects of fatty acids. In this work, we critically review several decades of studies and recent publications supporting the critical role of mitochondrial fatty acid metabolism in cellular homeostasis and many pathological conditions. Fatty acids are the primary fuel source and essential cell membrane building blocks from the origin of life. The essential cell membranes phospholipids were evolutionarily preserved from the earlier bacteria in human subjects. In the past century, the discovery of fatty acid metabolism was superseded by the epidemic growth of metabolic conditions and cardiovascular diseases. The association of fatty acids and pathological conditions is not due to their "harmful" effects but rather the result of impaired fatty acid metabolism and abnormal lifestyle. Mitochondrial dysfunction is linked to impaired metabolism and drives multiple pathological conditions. Despite metabolic flexibility, the loss of mitochondrial fatty acid oxidation cannot be fully compensated for by other sources of mitochondrial substrates, such as carbohydrates and amino acids, resulting in a pathogenic accumulation of long-chain fatty acids and a deficiency of medium-chain fatty acids. Despite popular belief, mitochondrial fatty acid oxidation is essential not only for energy-demanding organs such as the heart, skeletal muscle, and kidneys but also for metabolically "inactive" organs such as endothelial and epithelial cells. Recent studies indicate that the accumulation of long-chain fatty acids in specific organs and tissues support the impaired fatty acid oxidation in cell- and tissue-specific fashion. This work, therefore, provides a basis to challenge these established dogmas and articulate the need for a paradigm shift from the "pathogenic" role of fatty acids to the critical role of fatty acid oxidation. This is important to define the causative role of impaired mitochondrial fatty acid oxidation in specific pathological conditions and develop novel therapeutic approaches targeting mitochondrial fatty acid metabolism. [ABSTRACT FROM AUTHOR]

Why are some life outcomes difficult to predict? We investigated this question through in-depth qualitative interviews with 40 families sampled from a multidecade longitudinal study. Our sampling and interviewing process was informed by the earlier efforts of hundreds of researchers to predict life outcomes for participants in this study. The qualitative evidence we uncovered in these interviews combined with a mathematical decomposition of prediction error led us to create a conceptual framework. Our specific evidence and our more general framework suggest that unpredictability should be expected in many life outcome prediction tasks, even in the presence of complex algorithms and large datasets. Our work provides a foundation for future empirical and theoretical work on unpredictability in human lives. [ABSTRACT FROM AUTHOR]

Ice has been suggested to have played a significant role in the origin of life partly owing to its ability to concentrate organic molecules and promote reaction efficiency. However, the techniques for studying organic molecules in ice are absorption‐based, which limits the sensitivity of measurements. Here we introduce an emission‐based method to study organic molecules in water ice: the phosphorescence displays high sensitivity depending on the hydration state of an organic salt probe, acridinium iodide (ADI). The designed ADI aqueous system exhibits phosphorescence that can be severely perturbed when the temperature is higher than 110 K at a concentration of the order of 10−5 M, indicating changes in hydration for ADI. Using the ADI phosphorescent probe, it is found that the microstructures of water ice, i.e., crystalline vs. glassy, can be strongly dictated by a trace amount (as low as 10−5 M) of water‐soluble organic molecules. Consistent with cryoSEM images and temperature‐dependent Raman spectral data, the ADI is dehydrated in more crystalline ice and hydrated in more glassy ice. The current investigation serves as a starting point for using more sensitive spectroscopic techniques for studying water‐organics interactions at a much lower concentration and wider temperature range. [ABSTRACT FROM AUTHOR]

While RNA appears as a good candidate for the first autocatalytic systems preceding the emergence of modern life, the synthesis of RNA oligonucleotides without enzymes remains challenging. Because the uncatalyzed reaction is extremely slow, experimental studies bring limited and indirect information on the reaction mechanism, the nature of which remains debated. Here, we develop neural network potentials (NNPs) to study the phosphoester bond formation in water. While NNPs are becoming routinely applied to nonreactive systems or simple reactions, we demonstrate how they can systematically be trained to explore the reaction phase space for complex reactions involving several proton transfers and exchanges of heavy atoms. We then propagate at moderate computational cost hundreds of nanoseconds of a variety of enhanced sampling simulations with quantum accuracy in explicit solvent conditions. The thermodynamically preferred reaction pathway is a concerted, dissociative mechanism, with the transient formation of a metaphosphate transition state and direct participation of water solvent molecules that facilitate the exchange of protons through the nonbridging phosphate oxygens. Associative-dissociative pathways, characterized by a much tighter pentacoordinated phosphate, are higher in free energy. Our simulations also suggest that diprotonated phosphate, whose reactivity is never directly assessed in the experiments, is significantly less reactive than the monoprotonated species, suggesting that it is probably never the reactive species in normalpHconditions. These observations rationalize unexplained experimental results and the temperature dependence of the reaction rate, and they pave the way for the design of more efficient abiotic catalysts and activating groups. [ABSTRACT FROM AUTHOR]

The obcell hypothesis is a proposed route for the RNA world to develop into a primitive cellular one. It posits that this transition began with the emergence of the proto-ribosome which enabled RNA to colonise the external surface of lipids by the synthesis of amphipathic peptidyl-RNAs. The obcell hypothesis also posits that the emergence of a predation-based ecosystem provided a selection mechanism for continued sophistication amongst early life forms. Here, I argue for this hypothesis owing to its significant explanatory power; it offers a rationale why a ribosome which initially was capable only of producing short non-coded peptides was advantageous and it forgoes issues related to maintaining a replicating RNA inside a lipid enclosure. I develop this model by proposing that the evolutionary selection for improved membrane anchors resulted in the emergence of primitive membrane pores which enabled obcells to gradually evolve into a cellular morphology. Moreover, I introduce a model of obcell production which advances that tRNAs developed from primers of the RNA world. [ABSTRACT FROM AUTHOR]

Over 160 years after Darwin and 70 years after the discovery of DNA, two fundamental questions of biology remain unanswered: What differentiates the living from the nonliving? How can mechanistic and finalistic or holistic biology be unified? Niels Bohr introduced a concept of complementarity in quantum physics and based on the paradox of light as a simultaneous wave and particle, conjectured that a similar concept might exist in biology that would solve the paradox of life originating from the nonliving. Bohr proposed that two mutually exclusive-independent observations may be necessary to explain a phenomenon and provided support to Immanuel Kant's idea that the "purposive" behaviour of organisms could only be explained in teleological terms and that mechanical and teleological approaches were necessary and complementary to explain biology. We present a concept of complementarity whereby biochemical pathways or cellular channels for the flow of information are simultaneously complex and redundant and complexity and redundancy complement each other. The postulates of biological complementarity are that (1) it was an essential condition in the origin of life; (2) it provided physiological flexibility that allowed organisms to mount self-protection response and complexity to evolve in the face of deleterious mutations before the evolution of bi-parental sex; (3) it laid the foundation for the evolution of a choice of response when confronted with threat; and (4) it applies to all levels of biological organizations and, thus, can serve as a basis for the unification of mechanistic and holistic biology. It is proposed that teleology is simultaneously constitutive and heuristic: constitutive because organisms' "purposive" behaviours are adaptive and are grounded in mechanism (complexity and redundancy), and heuristic because with our finite cognition and our goal-oriented (humans alone are aware of "tomorrow") and anthropomorphic pre-disposition, teleology will remain useful as a guide to our making sense of the world, even how to ask a meaningful question. [ABSTRACT FROM AUTHOR]

Cell fate is a congregate readout of intrinsic competence and extrinsic signals rather than being dominantly dictated by any single cue. Precursor cells with proper chromatin states and complete signal transduction components are competent to interpret external inductive signals. Cell-intrinsic competence dictates distinct responses to the same signals, enabling the cells to differentiate towards different fates. Precursor cells with comparable competence and located in close proximity need to resist incorrect inductive signals for proper fate determination. Through blocking signal transduction components or antagonizing signal ligands, cells can establish resistance to incorrect inductive signals. During embryonic development, the inductive molecules produced by local origins normally arrive at their target tissues in a nondirectional, diffusion manner. The target organ precursor cells must correctly interpret these inductive signals to ensure proper specification/differentiation, which is dependent on two prerequisites: (i) obtaining cell-intrinsic competence; and (ii) receiving correct inductive signals while resisting incorrect ones. Gain of intrinsic competence could avoid a large number of misinductions because the incompetent cells are nonresponsive to inductive signals. However, in cases of different precursor cells with similar competence and located in close proximity, resistance to incorrect inductive signals is essential for accurate determination of cell fate. Here we outline the mechanisms of how organ precursors respond to correct and incorrect inductive signals. [ABSTRACT FROM AUTHOR]

Amino acids are one of the most important building blocks of life. During the biochemical process of translation, cells sequentially connect amino acids via amide bonds to synthesize proteins, using the genetic information in messenger RNA (mRNA) as a template. From a prebiotic perspective (i.e., without enzymatic catalysis), joining amino acids to peptides via amide bonds is difficult due to the highly endergonic nature of the condensation reaction. We show here that amides can be formed in reactions catalyzed by the transition metal sulfides from acetylene, carbon monoxide and ammonia under aqueous conditions. Some α- and β-amino acids were also formed under the same conditions, demonstrating an alternative cyanide-free path for the formation of amino acids in prebiotic environments. Experiments performed with stable isotope labeled precursors, like 15NH4Cl and 13C-acetylene, enabled the accurate mass spectroscopic identification of the products formed from the starting materials and their composition. Reactions catalyzed using the transition metal sulfides seem to offer a promising alternative pathway for the formation of amides and amino acids in prebiotic environments, bypassing the challenges posed by the highly endergonic condensation reaction. These findings shed light on the potential mechanisms by which the building blocks of life could have originated on early Earth. [ABSTRACT FROM AUTHOR]

Having evolved from a prokaryotic origin, mitochondria retain pathways required for the catabolism of energy‐rich molecules and for the biosynthesis of molecules that aid catabolism and/or participate in other cellular processes essential for life of the cell. Reviewed here are details of the mitochondrial fatty acid biosynthetic pathway (FAS II) and its role in building both the octanoic acid precursor for lipoic acid biosynthesis (LAS) and longer‐chain fatty acids functioning in chaperoning the assembly of mitochondrial multisubunit complexes. Also covered are the details of mitochondrial lipoic acid biosynthesis, which is distinct from that of prokaryotes, and the attachment of lipoic acid to subunits of pyruvate dehydrogenase, α‐ketoglutarate dehydrogenase, and glycine cleavage system complexes. Special emphasis has been placed on presenting what is currently known about the interconnected paths and loops linking the FAS II–LAS pathway and two other mitochondrial realms, the organellar translation machinery and Fe‐S cluster biosynthesis and function. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the pharmacokinetic properties and inhibitory binding interaction between naturally occurring phytochemicals and a mutated human estrogen receptor (hERa) using an in silico approach. Methods: Naturally occurring small molecules, viz, myricetin, catechin, pinobanksin, pinocembrin, gelagin and pinostrobin, were investigated for their drug-likeness and pharmacokinetic properties. After that, molecular docking was used to study their binding affinities to Y537S (Tyr537Ser: a mutated estrogen receptor alpha, prominent in metastatic breast cancers). The structure of the ligand-binding domain (LBD) of human estrogen receptor was retrieved from Protein Data Bank while the structures of the studied compounds were collected from PubChem database. Using Schrodinger docking studio, the binding interactions of each phytochemical were investigated with the mutated estrogen receptor. Results: All studied compounds were observed to be drug-like with good physicochemical properties. Myricetin, catechin, pinobanksin, pinocembrin, gelagin and pinostrobin showed good solubilities in human oral absorption and good intestinal permeability, which are the rate-limiting barriers for oral drug absorption. The distribution of the studied ligands and their plasma protein binding parameters were better than those of tamoxifen, which has previously been reported with high potential binding to albumin. None of the studied compounds showed central nervous system toxicity. The binding studies revealed good inhibition of the LBD of Y537S-hERa. This is a targeted approach to selectively inhibit this receptor which has been reported to confer ligand-independent functions to ERa. This inhibition prevents downstream signaling and metastasis, rendering breast cancer cells harboring such mutations susceptible to apoptosis upon treatment with endocrine therapies. Conclusion: The compounds have the potential to mitigate de novo resistance in breast cancer cells harboring mutated estrogen receptors and should be further investigated as they are promising for oral delivery. [ABSTRACT FROM AUTHOR]

Protocell models play a pivotal role in the exploration of the origin of life. Vesicles are one type of protocell model that have attracted much attention. Simple single-chain amphiphiles (SACs) and organic small molecules (OSMs) possess primitive relevance and were most likely the building blocks of protocells on the early Earth. OSM@SAC vesicles have been considered to be plausible protocell models. Pyrite (FeS2), a mineral with primitive relevance, is ubiquitous in nature and plays a crucial role in the exploration of the origin of life in the mineral–water interface scenario. "How do protocell models based on OSM@SAC vesicles interact with a mineral–water interface scenario that simulates a primitive Earth environment" remains an unresolved question. Hence, we select primitive relevant sodium monododecyl phosphate (SDP), isopentenol (IPN) and pyrite (FeS2) mineral particles to build a protocell model. The model investigates the basic physical and chemical properties of FeS2 particles and reveals the effects of the size, content and duration of interaction of FeS2 particles on IPN@SDP vesicles. This deepens the understanding of protocell growth mechanisms in scenarios of mineral–water interfaces in primitive Earth environments and provides new information for the exploration of the origin of life. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) cells are devoid of estrogen receptors (ERs), progesterone receptor (PRs), and human epidermal growth factor receptor 2 (HER2), and it (TNBC) counts for about 10–15% of all breast cancers. TNBC is highly invasive, having a faster growth rate and a higher risk of metastasis and recurrence. Still, chemotherapy is one of the widely used options for treating TNBC. This study reviewed the histological and molecular characterization of TNBC subtypes, signaling pathways that are aberrantly expressed, and small molecules targeting these pathways, as either single agents or in combination with other therapeutic agents like chemotherapeutics, immunotherapeutics, and antibody–drug conjugates; their mechanisms of action, challenges, and future perspectives were also reviewed. A detailed analytical review was carried out using the literature collected from the SciFinder, PubMed, ScienceDirect, Google Scholar, ACS, Springer, and Wiley databases. Several small molecule inhibitors were found to be therapeutics for treating TNBC. The mechanism of action and the different signaling pathways through which the small molecules exert their effects were studied, including clinical trials, if reported. These small molecule inhibitors include buparlisib, everolimus, vandetanib, apatinib, olaparib, salidroside, etc. Some of the signaling pathways involved in TNBC, including the VEGF, PARP, STAT3, MAPK, EGFR, P13K, and SRC pathways, were discussed. Due to the absence of these biomarkers, drug development for treating TNBC is challenging, with chemotherapy being the main therapeutic agent. However, chemotherapy is associated with chemoresistance and a high toxicity to healthy cells as side effects. Hence, there is a continuous demand for small-molecule inhibitors that specifically target several signaling pathways that are abnormally expressed in TNBC. We attempted to include all the recent developments in this field. Any omission is truly unintentional. [ABSTRACT FROM AUTHOR]

This study proposes a landscape-based scenario for the origin of viruses and cells, focusing on the adaptability of preexisting replicons from the RNP (ribonucleoprotein) world. The scenario postulates that life emerged in a subterranean "warm little pond" where organic matter accumulated, resulting in a prebiotic soup rich in nucleotides, amino acids, and lipids, which served as nutrients for the first self-replicating entities. Over time, the RNA world, followed by the RNP world, came into existence. Replicators/replicons, along with the nutritious soup from the pond, were washed out into the river and diluted. Lipid bubbles, enclosing organic matter, provided the last suitable environment for replicons to replicate. Two survival strategies emerged under these conditions: cell-like structures that obtained nutrients by merging with new bubbles, and virus-like entities that developed various techniques to transmit themselves to fresh bubbles. The presented hypothesis provides the possibility for the common origin of cells and viruses on rocky worlds hosting liquid water, like Earth. [ABSTRACT FROM AUTHOR]