In addition to biochemical gradients and transcriptional networks, cell behavior is regulated by endogenous bioelectrical cues originating in the activity of ion channels and pumps, operating in a ...wide variety of cell types. Instructive signals mediated by changes in resting potential control proliferation, differentiation, cell shape, and apoptosis of stem, progenitor, and somatic cells. Of importance, however, cells are regulated not only by their own Vmem but also by the Vmem of their neighbors, forming networks via electrical synapses known as gap junctions. Spatiotemporal changes in Vmem distribution among nonneural somatic tissues regulate pattern formation and serve as signals that trigger limb regeneration, induce eye formation, set polarity of whole-body anatomical axes, and orchestrate craniofacial patterning. New tools for tracking and functionally altering Vmem gradients in vivo have identified novel roles for bioelectrical signaling and revealed the molecular pathways by which Vmem changes are transduced into cascades of downstream gene expression. Because channels and gap junctions are gated posttranslationally, bioelectrical networks have their own characteristic dynamics that do not reduce to molecular profiling of channel expression (although they couple functionally to transcriptional networks). The recent data provide an exciting opportunity to crack the bioelectric code, and learn to program cellular activity at the level of organs, not only cell types. The understanding of how patterning information is encoded in bioelectrical networks, which may require concepts from computational neuroscience, will have transformative implications for embryogenesis, regeneration, cancer, and synthetic bioengineering.
All epistemic agents physically consist of parts that must somehow comprise an integrated cognitive self. Biological individuals consist of subunits (organs, cells, and molecular networks) that are ...themselves complex and competent in their own native contexts. How do coherent biological Individuals result from the activity of smaller sub-agents? To understand the evolution and function of metazoan creatures' bodies and minds, it is essential to conceptually explore the origin of multicellularity and the scaling of the basal cognition of individual cells into a coherent larger organism. In this article, I synthesize ideas in cognitive science, evolutionary biology, and developmental physiology toward a hypothesis about the origin of Individuality: "Scale-Free Cognition." I propose a fundamental definition of an Individual based on the ability to pursue goals at an appropriate level of scale and organization and suggest a formalism for defining and comparing the cognitive capacities of highly diverse types of agents. Any Self is demarcated by a computational surface - the spatio-temporal boundary of events that it can measure, model, and try to affect. This surface sets a functional boundary - a cognitive "light cone" which defines the scale and limits of its cognition. I hypothesize that higher level goal-directed activity and agency, resulting in larger cognitive boundaries, evolve from the primal homeostatic drive of living things to reduce stress - the difference between current conditions and life-optimal conditions. The mechanisms of developmental bioelectricity - the ability of all cells to form electrical networks that process information - suggest a plausible set of gradual evolutionary steps that naturally lead from physiological homeostasis in single cells to memory, prediction, and ultimately complex cognitive agents,
scale-up of the basic drive of infotaxis. Recent data on the molecular mechanisms of pre-neural bioelectricity suggest a model of how increasingly sophisticated cognitive functions emerge smoothly from cell-cell communication used to guide embryogenesis and regeneration. This set of hypotheses provides a novel perspective on numerous phenomena, such as cancer, and makes several unique, testable predictions for interdisciplinary research that have implications not only for evolutionary developmental biology but also for biomedicine and perhaps artificial intelligence and exobiology.
Pattern formation, as occurs during embryogenesis or regeneration, is the crucial link between genotype and the functions upon which selection operates. Even cancer and aging can be seen as ...challenges to the continuous physiological processes that orchestrate individual cell activities toward the anatomical needs of an organism. Thus, the origin and maintenance of complex biological shape is a fundamental question for cell, developmental, and evolutionary biology, as well as for biomedicine. It has long been recognized that slow bioelectrical gradients can control cell behaviors and morphogenesis. Here, I review recent molecular data that implicate endogenous spatio‐temporal patterns of resting potentials among non‐excitable cells as instructive cues in embryogenesis, regeneration, and cancer. Functional data have implicated gradients of resting potential in processes such as limb regeneration, eye induction, craniofacial patterning, and head‐tail polarity, as well as in metastatic transformation and tumorigenesis. The genome is tightly linked to bioelectric signaling, via ion channel proteins that shape the gradients, downstream genes whose transcription is regulated by voltage, and transduction machinery that converts changes in bioelectric state to second‐messenger cascades. However, the data clearly indicate that bioelectric signaling is an autonomous layer of control not reducible to a biochemical or genetic account of cell state. The real‐time dynamics of bioelectric communication among cells are not fully captured by transcriptomic or proteomic analyses, and the necessary‐and‐sufficient triggers for specific changes in growth and form can be physiological states, while the underlying gene loci are free to diverge. The next steps in this exciting new field include the development of novel conceptual tools for understanding the anatomical semantics encoded in non‐neural bioelectrical networks, and of improved biophysical tools for reading and writing electrical state information into somatic tissues. Cracking the bioelectric code will have transformative implications for developmental biology, regenerative medicine, and synthetic bioengineering.
We discuss the question of when a gapped two-dimensional electron system without any symmetry has a protected gapless edge mode. While it is well known that systems with a nonzero thermal Hall ...conductance, KH≠0 , support such modes, here we show that robust modes can also occur when KH=0 —if the system has quasiparticles with fractional statistics. We show that some types of fractional statistics are compatible with a gapped edge, while others are fundamentally incompatible. More generally, we give a criterion for when an electron system with Abelian statistics and KH=0 can support a gapped edge: We show that a gapped edge is possible if and only if there exists a subset of quasiparticle types M such that (1) all the quasiparticles in M have trivial mutual statistics, and (2) every quasiparticle that is not in M has nontrivial mutual statistics with at least one quasiparticle in M . We derive this criterion using three different approaches: a microscopic analysis of the edge, a general argument based on braiding statistics, and finally a conformal field theory approach that uses constraints from modular invariance. We also discuss the analogous result for two-dimensional boson systems.
Synthetic biology and bioengineering provide the opportunity to create novel embodied cognitive systems (otherwise known as minds) in a very wide variety of chimeric architectures combining evolved ...and designed material and software. These advances are disrupting familiar concepts in the philosophy of mind, and require new ways of thinking about and comparing truly diverse intelligences, whose composition and origin are not like any of the available natural model species. In this Perspective, I introduce TAME-Technological Approach to Mind Everywhere-a framework for understanding and manipulating cognition in unconventional substrates. TAME formalizes a non-binary (continuous), empirically-based approach to strongly embodied agency. TAME provides a natural way to think about animal sentience as an instance of collective intelligence of cell groups, arising from dynamics that manifest in similar ways in numerous other substrates. When applied to regenerating/developmental systems, TAME suggests a perspective on morphogenesis as an example of basal cognition. The deep symmetry between problem-solving in anatomical, physiological, transcriptional, and 3D (traditional behavioral) spaces drives specific hypotheses by which cognitive capacities can increase during evolution. An important medium exploited by evolution for joining active subunits into greater agents is developmental bioelectricity, implemented by pre-neural use of ion channels and gap junctions to scale up cell-level feedback loops into anatomical homeostasis. This architecture of multi-scale competency of biological systems has important implications for plasticity of bodies and minds, greatly potentiating evolvability. Considering classical and recent data from the perspectives of computational science, evolutionary biology, and basal cognition, reveals a rich research program with many implications for cognitive science, evolutionary biology, regenerative medicine, and artificial intelligence.
Significant progress in the molecular investigation of endogenous bioelectric signals during pattern formation in growing tissues has been enabled by recently developed techniques. Ion flows and ...voltage gradients produced by ion channels and pumps are key regulators of cell proliferation, migration, and differentiation. Now, instructive roles for bioelectrical gradients in embryogenesis, regeneration, and neoplasm are being revealed through the use of fluorescent voltage reporters and functional experiments using well‐characterized channel mutants. Transmembrane voltage gradients (Vmem) determine anatomical polarity and function as master regulators during appendage regeneration and embryonic left‐right patterning. A state‐of‐the‐art recent study reveals that they can also serve as prepatterns for gene expression domains during craniofacial patterning. Continued development of novel tools and better ways to think about physical controls of cell‐cell interactions will lead to mastery of the morphogenetic information stored in physiological networks. This will enable fundamental advances in basic understanding of growth and form, as well as transformative biomedical applications in regenerative medicine.
Regenerative biology has focused largely on chemical factors and transcriptional networks. However, endogenous ion flows serve as key epigenetic regulators of cell behavior. Bioelectric signaling ...involves feedback loops, long-range communication, polarity, and information transfer over multiple size scales. Understanding the roles of endogenous voltage gradients, ion flows, and electric fields will contribute to the basic understanding of numerous morphogenetic processes and the means by which they can robustly restore pattern after perturbation. By learning to modulate the bioelectrical signals that control cell proliferation, migration, and differentiation, we gain a powerful set of new techniques with which to manipulate growth and patterning in biomedical contexts. This chapter reviews the unique properties of bioelectric signaling, surveys molecular strategies and reagents for its investigation, and discusses the opportunities made available for regenerative medicine.
Many studies on memory emphasize the material substrate and mechanisms by which data can be stored and reliably read out. Here, I focus on complementary aspects: the need for agents to dynamically ...reinterpret and modify memories to suit their ever-changing selves and environment. Using examples from developmental biology, evolution, and synthetic bioengineering, in addition to neuroscience, I propose that a perspective on memory as preserving salience, not fidelity, is applicable to many phenomena on scales from cells to societies. Continuous commitment to creative, adaptive confabulation, from the molecular to the behavioral levels, is the answer to the persistence paradox as it applies to individuals and whole lineages. I also speculate that a substrate-independent, processual view of life and mind suggests that memories, as patterns in the excitable medium of cognitive systems, could be seen as active agents in the sense-making process. I explore a view of life as a diverse set of embodied perspectives—nested agents who interpret each other’s and their own past messages and actions as best as they can (polycomputation). This synthesis suggests unifying symmetries across scales and disciplines, which is of relevance to research programs in Diverse Intelligence and the engineering of novel embodied minds.
•Linear program of routing and passenger matching for shared autonomous vehicles considering congestion.•System optimal traffic assignment formulation with the link transmission model.•Formulation ...may be useful for congestion-aware, real-time routing heuristics.•Shared autonomous vehicle scenarios are compared with a system optimal dynamic traffic assignment benchmark.•Peak hour travel patterns significantly increase congestion and vehicle miles traveled as compared with off-peak scenarios.
We study the shared autonomous vehicle (SAV) routing problem while considering congestion. SAVs essentially provide a dial-a-ride service to travelers, but the large number of vehicles involved (tens of thousands of SAVs to replace personal vehicles) results in SAV routing causing significant congestion. We combine the dial-a-ride service constraints with the linear program for system optimal dynamic traffic assignment, resulting in a congestion-aware formulation of the SAV routing problem. Traffic flow is modeled through the link transmission model, an approximate solution to the kinematic wave theory of traffic flow. SAVs interact with travelers at origins and destinations. Due to the large number of vehicles involved, we use a continuous approximation of flow to formulate a linear program. Optimal solutions demonstrate that peak hour demand is likely to have greater waiting and in-vehicle travel times than off-peak demand due to congestion. SAV travel times were only slightly greater than system optimal personal vehicle route choice. In addition, solutions can determine the optimal fleet size to minimize congestion or maximize service.
While it is well known that three dimensional quantum many-body systems can support nontrivial braiding statistics between particlelike and looplike excitations, or between two looplike excitations, ...we argue that a more fundamental quantity is the statistical phase associated with braiding one loop α around another loop β, while both are linked to a third loop γ. We study this three-loop braiding in the context of (Z(N))(K) gauge theories which are obtained by gauging a gapped, short-range entangled lattice boson model with (Z(N))(K) symmetry. We find that different short-range entangled bosonic states with the same (Z(N))(K) symmetry (i.e., different symmetry-protected topological phases) can be distinguished by their three-loop braiding statistics.
PDF
