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Symbolic systems (SSs) are uniquely products of living systems, such that symbolism and life may be inextricably intertwined phenomena. Within a given SS, there is a range of symbol complexity over which signaling is functionally optimized. This range exists relative to a complex and potentially infinitely large background of latent, unused symbol space. Understanding how symbol sets sample this latent space is relevant to diverse fields including biochemistry and linguistics. We quantitatively explored the graphic complexity of two biosemiotic systems: genetically encoded amino acids (GEAAs) and written language. Molecular and graphical notions of complexity are highly correlated for GEAAs and written language. Symbol sets are generally neither minimally nor maximally complex relative to their latent spaces, but exist across an objectively definable distribution, with the GEAAs having especially low complexity. The selection pressures guiding these disparate systems are explicable by symbol production and disambiguation efficiency. These selection pressures may be universal, offer a quantifiable metric for comparison, and suggest that all life in the Universe may discover optimal symbol set complexity distributions with respect to their latent spaces. If so, the "complexity" of individual components of SSs may not be as strong a biomarker as symbol set complexity distribution.

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Information concepts from physics, mathematics and computer science support many areas of research in biology. Their focus is on objective information, which provides correlations and patterns related to objects, processes, marks and signals. In these approaches only the quantitative aspects of the meaning of the information is relevant. In other areas of biology, 'meaningful information', which is subjective in nature, relies on the physiology of the organism's sensory organs and on the interpretation of the perceived signals, which is then translated into action, even if this is only mental (in brained animals). Information is involved, in terms of both amount and quality. Here we contextualize and review the main theories that deal with 'meaningful-information' at a molecular level from different areas of natural language research, namely biosemiotics, code-biology, biocommunication and biohermeneutics. As this information mediates between the organism and its environment, we emphasize how such theories compare with the neo-Darwinian treatment of genetic information, and how they project onto the rapid evolution of RNA viruses.

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Evidence of cognition in aneural cells is well-establish in the literature. This paper extends the exploration of the mechanisms of cognition by considering whether or not aneural cells may be capable of irrational cognition, making associations based on coincidental similarities and circumstantial factors. If aneural cells do harness such semiosic qualities, as with higher-level creativity, this might be how they are able to overcome old algorithms and invent tools for new situations. I will look at three examples of irrational learning in aneural systems in terms of semiotics: (1) generalisation in the immune system, based on viral molecular mimicry, whereby immune cells attack the self, which seems to be an overgeneralisation of an icon sign based on mere similarity, not identity, (2) the classical conditioning of pea plants to trope toward wind as a sign of light, which seems to be an association of an index sign based on mere temporal proximity, and (3) a pharmaceutical intervention to prevent pregnancy, using a conjugate to encrypt self with non-self, which seems to be an example of symbol use. We identify irrational cognition easily when it leads to 'wrong' outcomes, but, if it occurs, it may also lead to favourable outcomes and 'creative' solutions.

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The entry of a virus into the host cell always implies the alteration of certain intracellular molecular relationships, some of which may involve the recovery of ancient cellular activities. In this sense, viruses are archaeological tools for identifying unexpressed activities in noninfected cells. Among these, activities that hinder virus propagation may represent cellular defense mechanisms, for example, activities that mutagenize the viral genome such as ADAR-1 or APOBEC activities. Instead, those that facilitate virus propagation can be interpreted as the result of viral adaptation to-or mimicking-cellular structures, enabling the virus to perform anthropomorphic activities, including hijacking, manipulating, and reorganizing cellular factors for their own benefit. The alternative we consider here is that some of these second set of cellular activities were already in the uninfected cell but silenced, under the negative control of the cell or lineage, and that they represent a necessary precondition for viral infection. For example, specifically loading an amino acid at the 3'-end of the mRNA of some plant viruses by aminoacyl-tRNA synthetases has proved essential for virus infection despite this reaction not occurring with cellular mRNAs. Other activities of this type are discussed here, together with the biological context in which they acquire a coherent meaning, that is, genetic latency and molecular conflict.

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A biosemiotic approach to the interpretation of morphological data is apt to highlight morphological traits that have hitherto gone unnoticed for their crucial roles in intraspecific sign interpretation and communication processes. Examples of such traits include specific genital structures found in the haplogyne spiders Dysdera erythrina (Walckenaer 1802) and Dysdera crocata (Koch 1838). In both D. erythrina and D. crocata, the distal sclerite of the male bulb and the anterior diverticulum of the female endogyne exhibit a striking, previously unreported correspondence in size and shape, allowing for a precise match between these structures during copulation. In D. erythrina, the sclerite at the tip of the bulb and the anterior diverticulum are semi-circular in shape, whereas in D. crocata they are rectangular. From the perspective of biosemiotics, which studies the production and interpretation of signs and codes in living systems, these structures are considered the morphological zones of an intraspecific sign interpretation process. This process constitutes one of the necessary prerequisites for sperm transfer and the achievement of fertilization. Therefore, these morphological elements deserve particular attention as they hold higher taxonomic value compared to morphological traits of the bulb for which a relevant role in mating and fertilization has not been proven. Thus, an approach to species delimitation based on biosemiotics, with its specific evaluation of morphological structures, provides new insights for the multidisciplinary endeavour of modern integrative taxonomy.

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The theory of organic evolution is incomplete until it can explain life's meaningmaking capacity and its role in the evolutionary processes, i.e. until semiosis is included. The extended synthesis theory of evolution has made a decisive step towards such an integrative theory, yet the explicit inclusion of semiotics of life is still to come. Here, we describe the steps made towards the semiotics-based theory of evolution, as the next stage after evo-devo and eco-evo-devo approaches. This includes demonstration of independent roles that natural selection, plastic adjustment, and interpretative choice have in adaptive evolution, and the distinction between adaptive and neutral modifications in genetic, plastic and interpretative mechanisms. Real meaning-making takes place only due to organism's interpretative processes. It should be complemented with a description of the ways by which knowledge (defined as products of semiotic learning), or rather the constraints of semiosis, can be inherited. This will complete the inclusion of semiosis into the extended mechanism of evolution.

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An enduring problem concerning the evolution of RNA viruses stems from the fact that their long-term rates of evolution (substitutions/ site/year) are lower than those calculated by comparing sequences of isolates collected over short time periods or within a single host (shortterm or intra-host evolution). This inconsistency has been attributed to several reasons, including deviations from the assumption of a molecularclock (constancy of mutational inputs as a function of time) and variations in viral multiplication rates, among others. We previously proposed a non-phylogenetic method for extracting information contained in mRNAs, that cannot be identified from examination of primary sequences alone, and that we called «archaeological¼ information. In this new approach, mRNAs are of interest as molecules, not for their primary sequence or encoded proteins but for encrypted information established in a remote past. In the present article, we propose that an archaeological approach may also contribute to explain higher short-term than long-term evolution rates in RNA viruses, in this case, by using the archaeological concept of palimpsest. The palimpsest is a record of historical changes, but it is not a successively ordered or a complete record, rather it is the product of two opposing activities, one of writing and rewriting and the other of erasing. In RNA virus quasispecies, the gain or loss of mutations is reflected in changes in the submolar frequency of myriads of variants in the population. The fact that mutation elimination is not always complete, turns viral quasispecies into complex palimpsests of viral variants or sub-populations thereof. Here we relate two main different temporalities of the quasispecies palimpsest (short- and long-term) to the stability of mutations in response to changes related to three components of the virus: the virions, the infected cell and the host cell lineage. Host cell lineage-related viral memory would be mostly irre versible as they are adaptive products to host cell changes. In contrast, memories related to the environment of the virion or responsive to the environment of the infected cell, which is shortterm mutational input, is less constrained provided the alteration in the ancestral information carried by the RNA is only transient. The two intermixed memory components result in two differently contributing mutation rates whose influence in the final result depends on whether the timescales used to take the sequences for comparison are short or long term.

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This is a digest of how various researchers in biology and astrobiology have explored questions of what defines living organisms-definitions based on functions or structures observed in organisms, or on systems terms, or on mathematical conceptions like closure, chirality, quantum mechanics and thermodynamics, or on biosemiotics, or on Darwinian evolution-to clarify the field and make it easier for endeavors in artificial intelligence to make progress. Current ideas are described to promote work between astrobiologists and computer scientists, each concerned with living organisms. A four-parameter framework is presented as a scaffold that is later developed into what machines lack to be considered alive: systems, evolution, energy and consciousness, and includes Jagers operators and the idea of dual closure. A novel definition of consciousness is developed which describes mental objects both with and without communicable properties, and this helps to clarify how consciousness in machines may be studied as an emergent process related to choice functions in systems. A perspective on how quantization, acting on nucleic acids, sets up natural limits to system behavior is offered as a partial address to the problem of biogenesis.

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We review the organization and contents of the 20th Gatherings in Biosemiotics. As the organizers, we share our insights from organizing a community research project in the year where the Covid-19 pandemic halted international travel. We try to describe the challenges of putting together the yearly conference on Biosemiotics and the main content that was presented by the research community.

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Prions or PrPSc (prion protein, Scrapie isoform) are proteins with an aberrant three-dimensional conformation that present the ability to alter the three-dimensional structure of natively folded PrPC (prion protein, cellular isoform) inducing its abnormal folding, giving raise to neurological diseases known as Transmissible spongiforms encephalopathies (TSEs) or prion diseases. In this work, through a biosemiotic study, we will analyze the molecular code of meanings that are known in the molecular pathway of PrPC and how it is altered in prion diseases. This biosemiotic code presents a socio-semiotic correlate in organisms that could be unraveled with the ultimate goal of understanding the code of signs that mediates the process. Finally, we will study recent works that indicate possible relationships in the code between prion proteins and other proteins such as the tau protein and alpha-synuclein to evaluate if it is possible that there is a semiotic expansion of the PrP code and prion diseases in the meaning recently expounded by Prusiner, winner of the Nobel Prize for describing these unusual pathological processes.

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RNAs can do many things. They can store information, act in the world, and respond to the world. Because of these capabilities biologists have proposed a primordial 'RNA world' in which RNA, rather than DNA, performed the central role of replicator and repository of adaptive information. Deacon dismisses this hypothesis because replication is not about anything and because the structure of replicating molecules cannot contain information about the environment. I dispute both claims. An RNA and its opposite-sense complement represent each other and, by two rounds of complementation, represent themselves. Although (with some exceptions) nucleic acid sequences do not change in response to their present environment, these sequences embody information about ancestral environments via the selective filtering of alternative sequences in those environments. Nucleic acid sequences are the textual record of what has worked in the past.

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Since early cybernetics studies by Wiener, Pask, and Ashby, the properties of living systems are subject to deep investigations. The goals of this endeavour are both understanding and building: abstract models and general principles are sought for describing organisms, their dynamics and their ability to produce adaptive behavior. This research has achieved prominent results in fields such as artificial intelligence and artificial life. For example, today we have robots capable of exploring hostile environments with high level of self-sufficiency, planning capabilities and able to learn. Nevertheless, the discrepancy between the emergence and evolution of life and artificial systems is still huge. In this paper, we identify the fundamental elements that characterize the evolution of the biosphere and open-ended evolution, and we illustrate their implications for the evolution of artificial systems. Subsequently, we discuss the most relevant issues and questions that this viewpoint poses both for biological and artificial systems.

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La medicina contemporánea se caracteriza por una creciente subespecialización, así como por la adquisición de un mayor conocimiento respecto de la interacción entre las distintas estructuras del organismo (biosemiótica) tanto en estado de salud como de enfermedad. Se propone, en este artículo, una nueva conceptualización del organismo basada en la perspectiva de considerarlo conformado por un espacio biológico (células, tejidos y órganos) y un espacio biosemiótico (intercambio de señales entre ellos). Su desarrollo daría lugar a una nueva subespecialidad dedicada al estudio e interferencia de la biosemiótica de la enfermedad (medicina biosemiótica), lo que propiciaría el desarrollo de una medicina de procesos, tendiente al diagnóstico y tratamiento temprano de las enfermedades

Contemporary medicine is characterized by an increasing subspecialization and the acquisition of a greater knowledge about the interaction among the different body structures (biosemiotics), both in health and disease. This article proposes a new conceptualization of the body based on considering it as a biological space (cells, tissues, and organs) and a biosemiotic space (exchange of signs among them). Its development would lead to a new subspecialty focused on the study and interference of disease biosemiotics (biosemiotic medicine), which would trigger a process-based medicine centered on early diagnosis and management of disease.

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Contemporary medicine is characterized by an increasing subspecialization and the acquisition of a greater knowledge about the interaction among the different body structures (biosemiotics), both in health and disease. This article proposes a new conceptualization of the body based on considering it as a biological space (cells, tissues, and organs) and a biosemiotic space (exchange of signs among them). Its development would lead to a new subspecialty focused on the study and interference of disease biosemiotics (biosemiotic medicine), which would trigger a processbased medicine centered on early diagnosis and management of disease.

La medicina contemporánea se caracteriza por una creciente subespecialización, así como por la adquisición de un mayor conocimiento respecto de la interacción entre las distintas estructuras del organismo (biosemiótica) tanto en estado de salud como de enfermedad. Se propone, en este artículo, una nueva conceptualización del organismo basada en la perspectiva de considerarlo conformado por un espacio biológico (células, tejidos y órganos) y un espacio biosemiótico (intercambio de señales entre ellos). Su desarrollo daría lugar a una nueva subespecialidad dedicada al estudio e interferencia de la biosemiótica de la enfermedad (medicina biosemiótica), lo que propiciaría el desarrollo de una medicina de procesos, tendiente al diagnóstico y tratamiento temprano de las enfermedades.

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The symbol grounding problem raises its head in the fields of the philosophy of AI, philosophy of psychology and philosophy of cognitive sciences. The solution to the symbol grounding problem must account for the genesis of mental representations in the world. It has to offer a strategy for grounding mental representations in the objective domain. Orthodox representationalist theories do not provide a satisfactory reply to the symbol grounding problem. On the other hand, there are embodied-enactivist approaches that dissolve the problem but only at the cost of representations and internal phenomenal states. The code model of biosemiotics provides a biologically viable (i.e., mechanistic) venue for developing a new solution to the problem. For the same reason, it could reconcile representationalism to the embodied approach.

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Different theories concerning the origin of RNA (and, in particular, mRNA) point to the concatenation and expansion of proto-tRNA-like structures. Different biochemical and biophysical tools have been used to search for ancient-like RNA elements with a specific structure in genomic viral RNAs, including that of the hepatitis C virus, as well as in cellular mRNA populations, in particular those of human hepatocytes. We define this method as "archaeological," and it has been designed to discover evolutionary patterns through a nonphylogenetic and nonrepresentational strategy. tRNA-like elements were found in structurally or functionally relevant positions both in viral RNA and in one of the liver mRNAs examined, the antagonist interferon-alpha subtype 5 (IFNA5) mRNA. Additionally, tRNA-like elements are highly represented within the hepatic mRNA population, which suggests that they could have participated in the formation of coding RNAs in the distant past. Expanding on this finding, we have observed a recurring dsRNA-like motif next to the tRNA-like elements in both viral RNAs and IFNA5 mRNA. This suggested that the concatenation of these RNA motifs was an activity present in the RNA pools that might have been relevant in the RNA world. The extensive alteration of sequences that likely triggered the transition from the predecessors of coding RNAs to the first fully functional mRNAs (which was not the case in the stepwise construction of noncoding rRNAs) hinders the phylogeny-based identification of RNA elements (both sequences and structures) that might have been active before the advent of protein synthesis. Therefore, our RNA archaeological method is presented as a way to better understand the structural/functional versatility of a variety of RNA elements, which might represent "the losers" in the process of RNA evolution as they had to adapt to the selective pressures favoring the coding capacity of the progressively longer mRNAs.

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More is not automatically better. Generation and accumulation of information reflecting the complexity of zoonotic diseases as ecological systems do not necessarily lead to improved interpretation of the obtained information and understanding of these complex systems. The traditional conceptual framework for analysis of diseases ecology is neither designed for, nor adaptable enough, to absorb the mass of diverse sources of relevant information. The multidirectional and multidimensional approaches to analyses form an inevitable part in defining a role of zoonotic pathogens and animal hosts considering the complexity of their inter-relations. And the more data we have, the more involved the interpretation needs to be. The keyword for defining the roles of microbes as pathogens, animals as hosts, and environmental parameters as infection drivers is "functional importance." Microbes can act as pathogens toward their host only if/when they recognize the animal organism as the target. The same is true when the host recognizes the microbe as a pathogen rather than harmless symbiont based on the context of its occurrence in that host. Here, we propose conceptual tools developed in the realm of the interdisciplinary sciences of complexity and biosemiotics for extending beyond the currently dominant mindset in ecology and evolution of infectious diseases. We also consider four distinct hierarchical levels of perception guiding how investigators can approach zoonotic agents, as a subject of their research, representing differences in emphasizing particular elements and their relations versus more unified systemic approaches.

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The organic code concept and its operationalization by molecular codes have been introduced to study the semiotic nature of living systems. This contribution develops further the idea that the semantic capacity of a physical medium can be measured by assessing its ability to implement a code as a contingent mapping. For demonstration and evaluation, the approach is applied to a formal medium: elementary cellular automata (ECA). The semantic capacity is measured by counting the number of ways codes can be implemented. Additionally, a link to information theory is established by taking multivariate mutual information for quantifying contingency. It is shown how ECAs differ in their semantic capacities, how this is related to various ECA classifications, and how this depends on how a meaning is defined. Interestingly, if the meaning should persist for a certain while, the highest semantic capacity is found in CAs with apparently simple behavior, i.e., the fixed-point and two-cycle class. Synergy as a predictor for a CA's ability to implement codes can only be used if context implementing codes are common. For large context spaces with sparse coding contexts synergy is a weak predictor. Concluding, the approach presented here can distinguish CA-like systems with respect to their ability to implement contingent mappings. Applying this to physical systems appears straight forward and might lead to a novel physical property indicating how suitable a physical medium is to implement a semiotic system.

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RNA viruses have very small genomes which limits the functions they can encode. One of the strategies employed by these viruses is to mimic key factors of the host cell so they can take advantage of the interactions and activities these factors typically participate in. The viral RNA genome itself was first observed to mimic cellular tRNA over 40 years ago. Since then researchers have confirmed that distinct families of RNA viruses are accessible to a battery of cellular factors involved in tRNA-related activities. Recently, potential tRNA-like structures have been detected within the sequences of a 100 mRNAs taken from human cells, one of these being the host defense interferon-alpha mRNA; these are then additional to the examples found in bacterial and yeast mRNAs. The mimetic relationship between tRNA, cellular mRNA, and viral RNA is the central focus of two considerations described below. These are subsequently used as a preface for a final hypothesis drawing on concepts relating to mimicry from the social sciences and humanities, such as power relations and creativity. Firstly, the presence of tRNA-like structures in mRNAs indicates that the viral tRNA-like signal could be mimicking tRNA-like elements that are contextualized by the specific carrier mRNAs, rather than, or in addition to, the tRNA itself, which would significantly increase the number of potential semiotic relations mediated by the viral signals. Secondly, and in particular, mimicking a host defense mRNA could be considered a potential new viral strategy for survival. Finally, we propose that mRNA's mimicry of tRNA could be indicative of an ancestral intracellular conflict in which species of mRNAs invaded the cell, but from within. As the meaning of the mimetic signal depends on the context, in this case, the conflict that arises when the viral signal enters the cell can change the meaning of the mRNAs' internal tRNA-like signals, from their current significance to that they had in the distant past.