The concept of scaffolding has wide resonance in several scientific fields. Here we attempt to adopt it for the study of development. In this perspective, the embryo is conceived as an integral whole, comprised of several hierarchical modules as in a recurrent circularity of emerging patterns. Within the developmental hierarchy, each module yields an inter-level relationship that makes it possible for the scaffolding to mediate the production of selectable variations. A wide range of genetic, cellular and morphological mechanisms allows the (...) scaffolding to integrate these modular variations into a functionally coordinate unit. A genetic scaffolding accounts for the inherited invariance of pattern formation during the embryo’s growth. At higher level, cells behave as agents endowed with the capacity to interpret any scaffolding variation as signs. The full hierarchy of a multi-level scaffolding is eventually attained when the embryo acquires the capacity to impose a number of developmental constraints on its constituting parts in a top-down direction. The acquisition of this capacity allows a semiotic threshold to emerge between the living cellular world and the underlying non-living molecular world. As this boundary is gradually defined during development, cells enter into new functional relationships, while, at the same time, are relieved from their physical determinism. The resulting constraints can thus become the driving forces that upgrade embryonic scaffolding from the simple molecular signalling to the complexity of sign recognition proper of a cellular community. In this semiotic perspective, the apparent goal directness of any developmental strategy should no longer be accounted for by a predetermined genetic program, but by the gradual definition of the relationships selected amongst the ones historically explored. (shrink)

In this introductory article to the special issue on Multi-level semiosis we attempt to stage the background for qualifying the notion of “multi-levelness” when considering communication processes and semiosis in all life forms, i.e. from the cellular to the organismic level. While structures are organized hierarchically, communication processes require a kind of processual organization that may be better described as being heterarchical. Theoretically, the challenge arises in the temporal domain, that is, in the developmental and evolutionary dimension of dynamic semiotic (...) processes. We discuss the importance of this fundamental difference in order to explain how levels, domains and orders of magnitude, on the one hand, and synchronic and diachronic processes, on the other, contribute to the overall organization of every living being. To account for such multi-level organization, semiotic freedom is assumed to be a scalar property that endows living systems at different levels and domains with the capacity to ponder selectively the overall structural coherence and functional compatibility of their heterarchical processing, which is increasingly less conditioned by the underlying molecular determinism. (shrink)

The majority of G protein-coupled receptors (GPCRs) self-assemble in the form dimeric/oligomeric complexes along the plasma membrane. Due to the molecular interactions they participate, GPCRs can potentially provide the framework for discriminating a wide variety of intercellular signals, as based on some kind of combinatorial receptor codes. GPCRs can in fact transduce signals from the external milieu by modifying the activity of such intracellular proteins as adenylyl cyclases, phospholipases and ion channels via interactions with specific G-proteins. However, in spite of (...) the number of cell functions they can actually control, both GPCRs and their associated signal transduction pathways are extremely well conserved, for only a few alleles with null or minor functional alterations have so far been found. This would seem to suggest that, beside a mechanism for DNA repairing, there must be another level of quality control that may help maintaining GPCRs rather stable throughout evolution. We propose here receptor oligomerization to be a basic molecular mechanism controlling GPCRs redundancy in many different cell types, and the plasma membrane as the first hierarchical cell structure at which selective categorical sensing may occur. Categorical sensing can be seen as the cellular capacity for identifying and ordering complex patterns of mixed signals out of a contextual matrix, i.e., the recognition of meaningful patterns out of ubiquitous signals. In this context, redundancy and degeneracy may appear as the required feature to integrate the cell system into functional units of progressively higher hierarchical levels. (shrink)

Any living organism interacts with and responds specifically to environmental molecules by expressing specific olfactory receptors. In this paper, this specificity will be first examined in causal terms with particular emphasis on the mechanisms controlling olfactory gene expression, cell-to-cell interactions and odor-decoding processes. However, this type of explanation does not entirely justify the role olfactory receptors have played during evolution, since they are also expressed ectopically in different organs and/or tissues. Homologous olfactory genes have in fact been found in such (...) diverse cells and/or organs as spermatozoa, testis and kidney where they are assumed to act as chemotactic sensors or renin modulators. To justify their functional diversity, homologous olfactory receptors are assumed to share the same basic role: that of conferring a self-identity to cells or tissues under varying environmental conditions. By adopting this standpoint, the functional attribution as olfactory or chemotactic sensors to these receptors should not be seen either as a cause conditioning receptor gene expression, or as a final effect resulting from genetically predetermined programs, but as a direct consequence of the environmental conditions olfactory receptor genes have explored during evolution. The association of odorant patterns with specific environmental or contextual situations makes their relationship semiotically triadic, due to the emergence of an interpretant capable of perceiving odorants as meaningful signs out of a noisy background. This perspective highlights the importance of odorant-receptor relationships as respect to the properties of the interacting partners. It is our contention that only when taken together can these different explanatory strategies provide a realistic account of how olfactory receptor genes have been structurally and functionally modified during evolution. (shrink)

Cell communication plays a key role in multicellular organisms. In developing embryos as in adult organisms, cells communicate by coordinating their differentiation through the establishment and/or renewal of a variety of cell communication channels. Under both these conditions, cells interact by either receptor signalling, surface recognition of specific cell adhesion molecules or transfer of cytoplasmic components through junctional coupling. In recent years, it has become apparent that cells may also communicate through the extracellular release of microvesicles. They may originate as (...) either exosomes from the endosomal compartment upon fusion of multivesicular bodies with the plasma membrane or be shed directly from the plasma membrane via extensions of the cell surface. Microvesicles may disperse over long distances through body fluids and deliver their molecular cargo onto a variety of target cells. As a general rule, the metabolic fate of these cells is determined by the molecular nature of the vesicular cargo, while targeting itself depends on the affinity of the molecules expressed on the enclosing membrane. In this paper, we will be arguing that intercellular vesicular transfer is substantially different from other types of cell communication, allowing cells and molecules to interact on varying levels. Cells interacting via ligand signalling owe their specificity to the steric coupling with cognate receptor molecules. As such, it is a pure molecular process that affects target cells only upon integration into their responding repertoire. In this relationship, coupled cells are reciprocally adapted to each other through the selection of their respective signalling capacities, following exploration of their receptor specificity. Interaction by intercellular vesicles realizes a substantially different type of cell communication. Vesicular traffic allows donor cells to carry out a horizontal type of gene transfer and target this information over long distances via independently controlled mechanisms. Because of this independence, cells interacting via vesicular traffic are not expected to adapt their signalling correspondences, but to control instead the efficiency of their cargo delivery irrespective of the receptor repertoire expressed by the target tissue. In this paper, the multifaceted functions of the intercellular vesicular traffic will be discussed in a multilevel biosemiotic perspective with the aim of unravelling the cellular mechanisms devised by nature to accomplish communication. (shrink)

Receptor oligomerization plays a key role in maintaining genome stability and restricting protein mutagenesis. When properly folded, protein monomers assemble as oligomeric receptors and interact with environmental ligands. In a gene-centered view, the ligand specificity expressed by these receptors is assumed to be causally predetermined by the cell genome. However, this mechanism does not fully explain how differentiated cells have come to express specific receptor repertoires and which combinatorial codes have been explored to activate their associated signaling pathways. It is (...) our contention that the plasma membrane acts as the locus where several contextual cues may be integrated. As such it allows the semiotic selection of those receptor configurations that provide cells with the minimum essential requirements for agency. The occurrence of protein misfolding makes it impossible for receptor monomers to assemble along the membrane and to sustain meaningful relationships with environmental ligands. How could a cell lineage deal with these loss-of-function mutations during evolution and restrain gene redundancy accordingly? In this paper, we will be arguing that the easiest way for bacteria clones to accomplish this goal is by getting rid of cells expressing mutated receptor proteins. The mechanism sustaining this cell selection is also occurring in many somatic tissues and its function is currently believed to counteract in vivo protein mutagenesis. Our discussion will be mainly focused on the significance and semiotic nature of the interplay between membrane receptors and the epigenetic control of gene expression, as mediated by the control of mismatched repairing and protein folding mechanisms. (shrink)

Thick description was originally proposed to overcome the limitations of quantitative research and ground anthropological observations in concrete people’s expectations, rather than in normative theories. The ultimate objective was to account for the emotional aspects of worldviews and value-orientations that would otherwise be left tacit or implicit by quantitative investigations. The present paper aimed at reviewing the _conceptual framework_ that has characterized this relational turn and has made possible a deeper understanding of the subjective experience. The primary objective is thus (...) to make explicit the assumptions upon which thick description relies and discuss how these renewed conditions allow meaning to emerge in interpersonal relationships. We argue that both these objectives would be theoretically attainable if primarily centered on the exploration of the _possibility space_ and on the patient’s experience as driven by the power of _counterfactual thinking_. Under these conditions, human subjects may be led to recognize the contextual and semiotic dimension of _boundaries_ and, in so doing, become aware of the beneficial effects of weaving past and new experiences in meaningful relationships. (shrink)

The biopsychosocial model was initially proposed to overcome the normative assumption that human diseases are exclusively due to disordered biochemical and/or neurophysiological processes. The model attempts to explain how expectations, thoughts and feelings modify the patient’s motivations to deal with illness and recovery. By considering the physical health in this perspective, healthcare professionals may test the importance of socially and culturally shared principles in alleviating illness experience. The entire biopsychosocial hierarchy may thus appear as a complex network of relationships between (...) the strict logic of scientific explanations and the emotional sustainability with which beliefs may either be defended, changed or even refused. In this paper, we aim at reviewing some of the evidence-based biomedical and psychological findings that provide a unified framework for the biopsychosocial model as a multilevel integrative process. To tackle this objective, we propose to approach the model in biosemiotic terms. It is our contention that the entire biopsychosocial hierarchy could be better understood if approached biosemiotically and the multilevel interconnection of this hierarchy re-examined in the light of a collaborative meaning-making process. (shrink)

Established at the annual meeting of the International Society for Biosemiotic Studies on July 3rd 2014, in conjunction with Springer Publishing, publishers of the Society’s official journal, Biosemiotics, the Annual Biosemiotic Achievement Award seeks to recognize those papers published in the journal that present novel and potentially important contributions to the ongoing project of biosemiotic research, its scientific impact, and its future prospects. Here the winner of the Biosemiotics Achievement Award for 2019 is announced: the award goes to Y.H. Hendlin (...) for the article ‘I Am a Fake Loop: the Effects of Advertising-Based Artificial Selection’. (shrink)

Germ cells are cross-roads of development and evolution. They define the origin of every new generation and, at the same time, represent the biological end-product of any mature organism. Germ cells are endowed with the following capacities: to store a self-descriptive program, to accumulate a protein-synthesizing machinery, and to incorporate enough nourishment to sustain embryonic development. To accomplish this goal, germ cells do not simply unfold a pre-determined program or realize a sole instructive role. On the contrary, due to the (...) complexity of their cytoarchitecture and the nature of the soma-to-germ interactions, they are heavily involved in processes of sign recognition and meaningful tissue exploration. At each stage of their inward migration, germ plasma membranes act as semiotic interfaces allowing cells to interact with the surrounding extracellular milieu and experience the compatibility of selected developmental sequences. The question of which signaling pathways are activated at each developmental stage does not result from a strictly predetermined program instructing germ cell stemness. Rather, each developmental sequence is an open-ended semiotic relationship explored and gradually defined during evolution by the context-dependency of specific cell-to-cell interactions. In this way, any structural and functional novelty that has emerged in the course of germ cell interactions may be interpreted as an exaptation fixed in the species genome in response to specific environmental constraints. (shrink)

The egg behaves as a prospective cell sustaining the developmental processes of the future embryo. In biosemiotic terms, this apparent teleonomic behaviour can be accounted for without referring to the exclusive causal role played by its genetic makeup. We envision two different processes that are uniquely found in the oocyte: (1) the first involves the mechanisms by which large amounts of mRNA accumulate in the ooplasm to establish the embryo axes prior to fertilization; (2) the second involves transfer of an (...) excess of maternally supplied ribosomes to the oocyte to provide the future embryo with newly synthesized proteins. In this paper, we argue that the information required to sustain embryonic development is not due to any physical properties of the zygotic DNA and the maternal mRNAs, but to their spatially and temporally ordered relationship in the zygote’s internal space. (shrink)