From Molecular Recognition to the "Vehicles" of Evolutionary Complexity: An Informational Approach.

Countless informational proposals and models have explored the singular characteristics of biological systems: from the initial choice of information terms in the early days of molecular biology to the current bioinformatic avalanche in this "omic" era. However, this was conducted, most often, within partial, specialized scopes or just metaphorically. In this paper, we attempt a consistent informational discourse, initially based on the molecular recognition paradigm, which addresses the main stages of biological organization in a new way. It considers the interconnection between signaling systems and information flows, between informational architectures and biomolecular codes, between controlled cell cycles and multicellular complexity. It also addresses, in a new way, a central issue: how new evolutionary paths are opened by the cumulated action of multiple variation engines or mutational 'vehicles' evolved for the genomic exploration of DNA sequence space. Rather than discussing the possible replacement, extension, or maintenance of traditional neo-Darwinian tenets, a genuine informational approach to evolutionary phenomena is advocated, in which systemic variation in the informational architectures may induce differential survival (self-construction, self-maintenance, and reproduction) of biological agents within their open ended environment.

The psychosocial burden of hand eczema: Data from a European dermatological multicentre study.

BACKGROUND: The essential physical role, visibility and social importance of the hands place a major psychological burden on patients with hand eczema. OBJECTIVES: The aim of this study was to identify the psychological, social and clinical characteristics of patients with hand eczema, in particular the prevalences of depression, anxiety, suicidal ideation, and comorbidities. MATERIALS AND METHODS: Data on patients with hand eczema were analysed from a large European multicentre study conducted with dermatology outpatients from 13 countries. Groups of patients and controls were compared to analyse the psychological burden of hand eczema. RESULTS: Female patients with hand eczema had higher Hospital Anxiety and Depression Scale (HADS) scores for anxiety (n = 86, median = 7.0) than controls (n = 900, median = 5.0, P = .02), and for depression (median = 4.0) than controls (3.0, P < .001). Patients with high suicidal ideation, with low socioeconomic status and who were widowed or divorced were more likely to fulfil the HADS criteria for anxiety [odds ratio (OR) > 1, P = .038, P < .001, and P < .001, respectively]. The median Dermatology Life Quality Index score was 7.0 (n = 68). DISCUSSION: This study identifies a specific psychological burden experienced by hand eczema patients, highlighting the need for focused psychosocial interventions. Physicians in particular should be aware of the need to identify anxiety and depression in female patients.

Natural intelligence and the 'economy' of social emotions: A connection with AI sentiment analysis.

By approaching the concept of Natural Intelligence a new path may be open in a variety of theoretical and applied problems on social emotions. There is no doubt that intelligence emerges as a biological/informational phenomenon, although paradoxically a consistent elaboration of that concept has been missing. Regarding emotions, they have been keeping an unclear status, being often restricted to the anthropological or to ethological approaches closer to the behaviorist paradigm. Herein we propose a different track, centered in the life cycle advancement. The life cycle in its integrity becomes the nucleus of natural intelligence's informational processes, including the consistent expression of emotions along the maximization of fitness occasions. In human societies, the overall 'economy' of social emotions is manifest, showing up in the conspicuous interplay between bonding processes and different classes of social emotions. The essential link between natural intelligence, emotions, and the life cycle of individuals may harmonize with current progresses - and blind spots - of artificial intelligence fields such as 'sentiment analysis.'

The biological information flow: From cell theory to a new evolutionary synthesis.

Traditionally ignored in comparison with the energy flow, the interest on the information flow and in general on the informational perspective is nowadays manifest in biological fields. Herein we will revisit classical ideas on biomolecular information processing, basically from Efim Liberman and Michael Conrad, weaving them together with new views on the information flow as captured by cellular signaling systems and with the development of biological complexity. A consistent new explanatory framework looms-potentially contributing to a new cell theory. It would incorporate fundamental conceptualizations on the mechanisms of molecular recognition and informational architectures, the life cycle and the characterization of meaning, and finally the emergence of biological complexity. Concerning the evolutionary process, this informational approach depicts an indefinite series of recursion processes performed in the open-ended environment of the real world, potentially affected by multiple contingencies modifying the informational architectures involved in recursion. Consequently, a large variety of molecular tools and systems would have been incorporated speeding up the variability of genomes and facilitating their displacement in sequence space. To the extent to which the comparison with human mobility in physical space may hold, a power law could be hypothesized interconnecting the variability outcomes of the different evolutionary 'vehicles' or variation modes. Contributing to a renewed discussion on the evolutionary process is another essential goal of the present work.

The Cost of Loneliness: Assessing the Social Relationships of the Elderly via an Abbreviated Sociotype Questionnaire for inside and outside the Clinic.

Gauging the social relationships of the elderly is a significant sociometric research subject and a deep biomedical concern-particularly after the COVID-19 pandemic. It is imperative for facultatives in primary care, for geriatric clinics, and for social care services. In this respect, this article explores the validity of an abbreviated version of the Sociotype Questionnaire (SOCQ), a tool previously developed by the authors for assessing the social relationships of the general population, now specifically addressed to the elderly population. The aim is to construct a 4-item dichotomous scale (SOCG-4) out of the 12 items of the original scale of the SOCQ, so that it can serve to discriminate among the patients in primary care and the geriatric clinic, helping the facultative to find those in need of social care or of psychosocial intervention. The population data have been obtained from a series of previous studies on social relationships in different segments of the elderly population (Ntotal = 915). The resulting abbreviated version of SOCG-4 was extracted by means of confirmatory factor analysis, with the congruence, validity, and relationship with the determinants as close to optimal. The significant correlations with SOCQ (0.82), UCLA (-0.55), Barthel (0.40), and other relevant tests are obtained. The test was also put to trial in a pilot study, being applied to 150 subjects via phone surveys, home visiting, and geriatric clinic-it becomes particularly useful for assessing the social relationships in geriatric clinic use. The 4-item Geriatric Sociotype scale (SOCG-4) appears as a valid measurement instrument for use in the clinic and in other social care instances.

Use of Laughter for the Detection of Parkinson's Disease: Feasibility Study for Clinical Decision Support Systems, Based on Speech Recognition and Automatic Classification Techniques.

Parkinson's disease (PD) is an incurable neurodegenerative disorder which affects over 10 million people worldwide. Early detection and correct evaluation of the disease is critical for appropriate medication and to slow the advance of the symptoms. In this scenario, it is critical to develop clinical decision support systems contributing to an early, efficient, and reliable diagnosis of this illness. In this paper we present a feasibility study for a clinical decision support system for the diagnosis of PD based on the acoustic characteristics of laughter. Our decision support system is based on laugh analysis with speech recognition methods and automatic classification techniques. We evaluated different cepstral coefficients to identify laugh characteristics of healthy and ill subjects combined with machine learning classification models. The decision support system reached 83% accuracy rate with an AUC value of 0.86 for PD-healthy laughs classification in a database of 20,000 samples randomly generated from a pool of 120 laughs from healthy and PD subjects. Laughter could be employed for the efficient and reliable detection of PD; such a detection system can be achieved using speech recognition and automatic classification techniques; a clinical decision support system can be built using the above techniques. Significance: PD clinical decision support systems for the early detection of the disease will help to improve the efficiency of available and upcoming therapeutic treatments which, in turn, would improve life conditions of the affected people and would decrease costs and efforts in public and private healthcare systems.

Sociotype and cultural evolution the acceleration of cultural change alongside industrial revolutions.

The present work explores, from the vantage point of the sociotype, the dramatic acceleration of cultural change alongside the successive industrial revolutions, particularly in the ongoing information era. Developed within the genotype-phenotype-sociotype conceptual triad, the sociotype means the average social environment that is adaptively demanded by the "social brain" of each individual. For there is a regularity of social interaction, centered on social bonding and talking time, which has been developed as an adaptive trait, evolutionarily rooted, related to the substantial size increase of human groups. A quantitative approach to the sociotype basic traits shows fundamental competitive interrelationships taking place within an overall "attention economy." Approaching these figures via the Planckian Distribution Equation, they can be connected with many other competitive processes taking place in the biological, economic, and cultural realms. Concerning culture, the cognitive limits of the individual, which we consider commensurate with the sociotype general limitations, impose by themselves a strict boundary on the cultural items effectively handled by each individual, fostering the overall competition and decay. Further, the emergence of differentiated generations with ample discrepancy in styles of life, social aspirations, and dominant technologies would represent a systematic bias in the competition and replacement of cultural items. Intriguingly, the cultural acceleration detected in modern societies alongside the successive industrial revolutions, with an ostensible climax in the ongoing fourth industrial revolution -the information era- might be itself a paradoxical consequence of the sociotype's dynamic constancy.

Plausibility of a Neural Network Classifier-Based Neuroprosthesis for Depression Detection via Laughter Records.

The present work explores the diagnostic performance for depression of neural network classifiers analyzing the sound structures of laughter as registered from clinical patients and healthy controls. The main methodological novelty of this work is that simple sound variables of laughter are used as inputs, instead of electrophysiological signals or local field potentials (LFPs) or spoken language utterances, which are the usual protocols up-to-date. In the present study, involving 934 laughs from 30 patients and 20 controls, four different neural networks models were tested for sensitivity analysis, and were additionally trained for depression detection. Some elementary sound variables were extracted from the records: timing, fundamental frequency mean, first three formants, average power, and the Shannon-Wiener entropy. In the results obtained, two of the neural networks show a diagnostic discrimination capability of 93.02 and 91.15% respectively, while the third and fourth ones have an 87.96 and 82.40% percentage of success. Remarkably, entropy turns out to be a fundamental variable to distinguish between patients and controls, and this is a significant factor which becomes essential to understand the deep neurocognitive relationships between laughter and depression. In biomedical terms, our neural network classifier-based neuroprosthesis opens up the possibility of applying the same methodology to other mental-health and neuropsychiatric pathologies. Indeed, exploring the application of laughter in the early detection and prognosis of Alzheimer and Parkinson would represent an enticing possibility, both from the biomedical and the computational points of view.

Fundamental, Quantitative Traits of the "Sociotype".

In whatever domain of life, from cells to organisms to societies, communicative exchanges underlie the formation and maintenance, and decay, of the emerging collective structures. It can be clearly seen in the human social world. The different classes of social bonds in a complex society revolve around, and are intimately related with, the communicative relationships that every individual entertains-essentially via face-to-face conversation. In the present work we have investigated the fundamental metrics of both social bonds and communicative exchanges along the development of the "sociotype" construct. It is a new approach developed by the authors within the genotype-phenotype-sociotype conceptual triad. The sociotype means the relative constancy, or better the similar fabric, of the social world in which each individual life is developed. In order to ascertain the metrics of the fundamental quantitative traits inherent in the sociotype, a fieldwork involving a total of 1475 individuals (68.59% female, and 49.79 mean age, SD = 21.47) was carried out. The four relational realms of family, friends, work/study, and acquaintances were investigated. The overall results about conversation time (an average of 220 min/day), and about the number of social bonds (an average of 98), differ from previous assumptions, such as Dunbar's number or Killworth's number. Other results about gender, age, and use of social media and Internet contribute to highlight significant differences among the different social segments, and particularly the diminished "sociotype" of the elderly. Finally, it is curious that a non-Gaussian distribution has been obtained for the specific population allotment of these metrics, and intriguingly the Planckian distribution equation (PDE) appears to be a most cogent fit.

How prokaryotes 'encode' their environment: Systemic tools for organizing the information flow.

An important issue related to code biology concerns the cell's informational relationships with the environment. As an open self-producing system, a great variety of inputs and outputs are necessary for the living cell, not only consisting of matter and energy but also involving information flows. The analysis here of the simplest cells will involve two basic aspects. On the one side, the molecular apparatuses of the prokaryotic signaling system, with all its variety of environmental signals and component pathways (which have been called 1-2-3 Component Systems), including the role of a few second messengers which have been pointed out in bacteria too. And in the other side, the gene transcription system as depending not only on signaling inputs but also on a diversity of factors. Amidst the continuum of energy, matter, and information flows, there seems to be evidence for signaling codes, mostly established around the arrangement of life-cycle stages, in large metabolic changes, or in the relationships with conspecifics (quorum sensing) and within microbial ecosystems. Additionally, and considering the complexity growth of signaling systems from prokaryotes to eukaryotes, four avenues or "roots" for the advancement of such complexity would come out. A comparative will be established in between the signaling strategies and organization of both kinds of cellular systems. Finally, a new characterization of "informational architectures" will be proposed in order to explain the coding spectrum of both prokaryotic and eukaryotic signaling systems. Among other evolutionary aspects, cellular strategies for the construction of novel functional codes via the intermixing of informational architectures could be related to the persistence of retro-elements with obvious viral ancestry.

Cellular Gauge Symmetry and the Li Organization Principle: A Mathematical Addendum. Quantifying energetic dynamics in physical and biological systems through a simple geometric tool and geodetic curves.

The present Addendum complements the accompanying paper "Cellular Gauge Symmetry and the Li Organization Principle"; it illustrates a recently-developed geometrical physical model able to assess electronic movements and energetic paths in atomic shells. The model describes a multi-level system of circular, wavy and zigzag paths which can be projected onto a horizontal tape. This model ushers in a visual interpretation of the distribution of atomic electrons' energy levels and the corresponding quantum numbers through rather simple tools, such as compasses, rulers and straightforward calculations. Here we show how this geometrical model, with the due corrections, among them the use of geodetic curves, might be able to describe and quantify the structure and the temporal development of countless physical and biological systems, from Langevin equations for random paths, to symmetry breaks occurring ubiquitously in physical and biological phenomena, to the relationships among different frequencies of EEG electric spikes. Therefore, in our work we explore the possible association of binomial distribution and geodetic curves configuring a uniform approach for the research of natural phenomena, in biology, medicine or the neurosciences.

Topodynamics of metastable brains.

The brain displays both the anatomical features of a vast amount of interconnected topological mappings as well as the functional features of a nonlinear, metastable system at the edge of chaos, equipped with a phase space where mental random walks tend towards lower energetic basins. Nevertheless, with the exception of some advanced neuro-anatomic descriptions and present-day connectomic research, very few studies have been addressing the topological path of a brain embedded or embodied in its external and internal environment. Herein, by using new formal tools derived from algebraic topology, we provide an account of the metastable brain, based on the neuro-scientific model of Operational Architectonics of brain-mind functioning. We introduce a "topodynamic" description that shows how the relationships among the countless intertwined spatio-temporal levels of brain functioning can be assessed in terms of projections and mappings that take place on abstract structures, equipped with different dimensions, curvatures and energetic constraints. Such a topodynamical approach, apart from providing a biologically plausible model of brain function that can be operationalized, is also able to tackle the issue of a long-standing dichotomy: it throws indeed a bridge between the subjective, immediate datum of the naïve complex of sensations and mentations and the objective, quantitative, data extracted from experimental neuro-scientific procedures. Importantly, it opens the door to a series of new predictions and future directions of advancement for neuroscientific research.

The "sociotype" construct: Gauging the structure and dynamics of human sociality.

Exploring the pertinence of a "sociotype" construct, established along the conceptual chain genotype-phenotype-sociotype, is the essential purpose of the present paper. Further, by following the sociotype's conceptual guidelines, a new psychometric indicator has been developed in order to gauge the level of social interaction around each individual-the sociotype questionnaire (SOCQ). A first version of this questionnaire has been elaborated by gathering data about the different classes of social bonds (family, friends, acquaintances, and work/study colleagues) in general population and about the dynamic update of these bonds via face-to-face conversation and other modes of interaction. A specific fieldwork was undertaken, involving 1,075 participants, all of them Spanish adults (with diverse social and regional backgrounds). The data obtained were analyzed by means of the correlational method with an analytical cross-sectional design: the number of factors and the consistency and reliability of the resulting scales were evaluated and correlated. The new sociotype indicator resulting from that fieldwork, in spite of its limitations, seems to be valid and reliable, as well as closely associated with widely used metrics of loneliness and psychological distress. It is interesting that the construct noticeably varies throughout the life course and circumstances of individuals, based on their gender and age, and adjusting to the different situations of social networking. This is the first study, to the best of our knowledge, which has tried to reach both a theoretical and an operational formulation of the sociotype construct, by establishing an ad hoc psychometric questionnaire. We think that the information provided by this operational definition opens a new direction of work that could be useful to guide the development and evaluation of programs aimed at improving and strengthening social networking in people at risk, especially for the elderly.

Cellular gauge symmetry and the Li organization principle: General considerations.

Based on novel topological considerations, we postulate a gauge symmetry for living cells and proceed to interpret it from a consistent Eastern perspective: the li organization principle. In our framework, the reference system is the living cell, equipped with general symmetries and energetic constraints standing for the intertwined biochemical, metabolic and signaling pathways that allow the global homeostasis of the system. Environmental stimuli stand for forces able to locally break the symmetry of metabolic/signaling pathways, while the species-specific DNA is the gauge field that restores the global homeostasis after external perturbations. We apply the Borsuk-Ulam Theorem (BUT) to operationalize a methodology in terms of topology/gauge fields and subsequently inquire about the evolution from inorganic to organic structures and to the prokaryotic and eukaryotic modes of organization. We converge on the strategic role that second messengers have played regarding the emergence of a unitary gauge field with profound evolutionary implications. A new avenue for a deeper investigation of biological complexity looms. Philosophically, we might be reminded of the duality between two essential concepts proposed by the great Chinese synthesizer Zhu Xi (in the XIII Century). On the one side the li organization principle, equivalent to the dynamic interplay between symmetry and information; and on the other side the qi principle, equivalent to the energy participating in the process-both always interlinked with each other. In contemporary terms, it would mean the required interconnection between information and energy, and the necessity to revise essential principles of information philosophy.

How the living is in the world: An inquiry into the informational choreographies of life.

Understanding the nature of life has always been a fundamental objective of human knowledge. It is no wonder that biology, as the science of life, together with physics, has traditionally been the discipline that has generated the deepest philosophical and social repercussions. In our time, the major achievements in bioinformatics, systems biology, and "omic" fields (genomics, proteomics, metabolomics, etc.) have not only spurred a new biotechnological and biomedical 'postindustrial revolution', but they have also disclosed an intriguing molecular panorama of biological organization that invites us to reinterpret central themes of philosophy in the light of the new knowledge. Essential tenets of phenomenology may take an intriguing new turn when contemplated from these new biological perspectives: Does the living cell instantiate a unique biomolecular way of being in the world? How is life self-produced in continuous communication with the surrounding world? How can the incessant flows of mass, energy and information inherent of embodiment be coherently harnessed across billions of cellular individuals? In this paper, based on the latest developments in cellular signaling, we will discuss the dynamic intertwining between self-production and communication that characterizes life at the prokaryotic, eukaryotic, organismic, and social levels of organization. An in-depth analysis of the particular transcriptional responses of a bacterium (Escherichia coli K-12 strain), taking as a model system, will follow. It is the creation, transmission and reception of signals which, in all instances, provides guidance and orientation to the inner self-production activities of the living agent and connects it with the world. Transitions to new levels of organization are marked by the emergence of new forms of communication, embedded in the correspondingly augmented life-cycles of the more complex entities. As will be argued here, the ascending complexity of life is always information-based and recapitulates level after level, a successful "informational formula" for being in the world. The phenomenological basis for the naturalization of cognition has moved from the biological to a new scientific arena: informational. The philosophical notion of being-in-the-world (Dasein; Heidegger) is shown to be completely compatible with the latest advances in biology and information science.

Bionformation: untangling the networks of life.

The growth of numerous subdisciplines at the interface between biology and computer science paves the way for reconsidering the special relationship between information and life. In this sense, the term 'bioinformation' appears as an integrative notion that is useful to promote a new understanding of the heterogeneous networkings that characterize life. Two conceptual avenues are explored here: representation and symmetry. It is argued that the special organization of the living cell, based on the overlapping of both sequential and 'amorphous' architectures, endlessly strives to fill in the occurring 'functional voids' or symmetry breakings; and it endlessly produces physiological networkings and evolutionary novelties as a byproduct. Characterizing the special dynamics inherent in the living cell may be a precondition for understanding the information-production processes on which other emergent informational entities are based, particularly, nervous systems and societies.

Emergence of power laws from partitional dynamics.

This work explores the possibility of producing some specific power laws (with exponential cut-off) out from a partitional dynamics. The data obtained from the partitions of integers in the interval 1-60 have been used to find the coefficients of a power law and its exponential cut-off, and also of a single hyperbolic form after renormalization. There is also the speculation that this type of power law, so easily derived from arithmetic minimalist operations, may underlie the communication exchanges of living cells and the structural games of self-constructing agents endowed with relative structural freedom.

Learning and evolution in bacterial taxis: an operational amplifier circuit modeling the computational dynamics of the prokaryotic 'two component system' protein network.

Adaptive behavior in unicellular organisms (i.e., bacteria) depends on highly organized networks of proteins governing purposefully the myriad of molecular processes occurring within the cellular system. For instance, bacteria are able to explore the environment within which they develop by utilizing the motility of their flagellar system as well as a sophisticated biochemical navigation system that samples the environmental conditions surrounding the cell, searching for nutrients or moving away from toxic substances or dangerous physical conditions. In this paper we discuss how proteins of the intervening signal transduction network could be modeled as artificial neurons, simulating the dynamical aspects of the bacterial taxis. The model is based on the assumption that, in some important aspects, proteins can be considered as processing elements or McCulloch-Pitts artificial neurons that transfer and process information from the bacterium's membrane surface to the flagellar motor. This simulation of bacterial taxis has been carried out on a hardware realization of a McCulloch-Pitts artificial neuron using an operational amplifier. Based on the behavior of the operational amplifier we produce a model of the interaction between CheY and FliM, elements of the prokaryotic two component system controlling chemotaxis, as well as a simulation of learning and evolution processes in bacterial taxis. On the one side, our simulation results indicate that, computationally, these protein 'switches' are similar to McCulloch-Pitts artificial neurons, suggesting a bridge between evolution and learning in dynamical systems at cellular and molecular levels and the evolutive hardware approach. On the other side, important protein 'tactilizing' properties are not tapped by the model, and this suggests further complexity steps to explore in the approach to biological molecular computing.