Physiological regulation is extremely complex and cannot be described by homeostasis, the mathematical model generally used in medical science. Homeostasis is based on assumptions which have never been tested or substantiated and when simulated appears not to be consistent with the real behavior of physiological regulation. As a consequence, drugs and drug treatments are developed on a trial and error basis, without a functional model guiding the process. This paper evaluates a mathematical model published previously which much better corresponds to the complex behavior of regulated physiological processes. The compensatory response - the reaction of the body's defense mechanism to disturbances - is shown to be a major factor in the effects of drugs. Its magnitude at any moment is argued not to be determined by the actual drug dose, but by the dose the organism expects. Model simulations show the compensatory response to be the primary factor in curing diseases while it can be isolated from the drug effect to cure without the side effects characteristic of drugs. If instead of homeostasis a better functioning model had enabled a real understanding of the body's defense mechanism, the compensatory response could have been a powerful tool of modern medicine.
Nervous and neurodegenerative diseases are considered one of the most common groups among humanity, and the number of these diseases in the population is constantly increasing. At the same time, the prevalence of gastrointestinal and digestive system pathologies is also steadily growing. The literature contains numerous data on the relationship between the nervous system and the digestive system through a bidirectional microbiota-gut-brain axis, as well as connections via the circulatory and immune systems, among others. This work attempts to compile existing literature on this topic, summarize it, identify common patterns, and assess how strongly the gut can influence the course of various CNS disorders. It also aims to identify specific strains that may impact certain disorders and pathologies. Additionally, an effort was made to understand the mechanisms by which the microbiota affects the brain.
Quantum mechanics has revolutionized computational drug discovery by addressing fundamental limitations of classical approaches. Its significance lies in accurately modeling electronic phenomena crucial for drug-target interactions, including polarization, charge transfer, and covalent reactivity, which classical force fields inadequately represent. This comprehensive review examines quantum mechanical methods in pharmaceutical applications from 2020 to 2025. The literature search methodology employed PubMed, Web of Science, and arXiv databases (January 2020-January 2025), focusing on improvements in density functional theory, QM/MM implementations, machine-learned force fields, and alchemical free energy protocols. We critically evaluate 156 primary research articles and 42 review papers, analyzing performance metrics from community benchmarking studies, including SAMPL, GMTKN55, and pharmaceutical consortia datasets. The review encompasses methodological advances, practical applications, and regulatory considerations for quantum-enhanced drug discovery. Quantum mechanical enhancements provide substantial benefits for specific challenging cases rather than universal improvements across all drug discovery applications. Current methodological innovations have significantly improved computational tractability while maintaining chemical accuracy. A critical evaluation of cost-benefit trade-offs reveals that targeted applications to metal-containing systems, covalent modifications, and polarization-dominated interactions yield the highest return on computational investment. Best practices for reproducible implementation and practical method selection guidelines are crucial for the successful integration of a pharmaceutical pipeline.
Behavioral ecology of fungi is an emerging field investigating how fungi respond to environmental stimuli through morphological and physiological changes. Progress requires methodologies suited to fungal biology. Here, we developed an experimental approach to test for memory in the ectomycorrhizal fungus Laccaria bicolor. We hypothesized that mycelium exposed to pea cotyledons would retain directional information about the nutrient source. To test this, a portion of the mycelium was transferred to fresh medium, where memory would be assessed by asymmetrical growth toward the former nutrient position. The hypothesis was not supported, but the methods offer a framework for exploring fungal behavior in both ectomycorrhizal and saprotrophic species. Although no evidence of memory was found, this study highlights the value of publishing both positive and negative results and provides tools to advance research on fungal cognition and behavior.
Microtubules are nanoscale spintronic oscillators with memristive properties. Spintronic and memristive effects, together with some unique conditions found in the axon initial segment (AIS), allow quantum coherence to emerge spontaneously in a population of microtubules located within the AIS. According to the QBIT theory, the spontaneous emergence of coherence in a population of microtubules is the necessary and sufficient condition for the generation of a micro-consciousness (a quale) by the brain. Simultaneous generation of multiple qualia by synchronized activity in different parts of the cerebral cortex gives rise to the appearance of a macro-consciousness: a seemingly unified subjective experience.
Understanding how populations of cells collectively coordinate activity to produce the complex structures and behaviors that characterize multicellular organisms, and which coordinated activities, if any, survive processes that reshape cells and tissues into organoids, are fundamental issues in modern biology. Here, we show how techniques from complex systems and multivariate information theory provide a framework for inferring the structure of collective organization in non-neural tissue. Many of these techniques were developed in the context of theoretical neuroscience, where these statistics have been found to be altered during different cognitive, clinical, or behavioral states, and are generally thought to be informative about the underlying dynamics linking biology to cognition. Here, we show that these same patterns of coordinated activity are also present in the aneural tissues of evolutionarily distant biological systems: preparations of embryonic Xenopus laevis tissue (known as “basal Xenobots”). These similarities suggest that such patterns of activity either arose independently in these two systems (epithelial constructs and brains); are epiphenomenological byproducts of other dynamics conserved across vastly different configurations of life; or somehow directly support adaptive behavior across diverse living systems. Finally, these results provide unambiguous support for the hypothesis that, despite their apparent simplicity as collections of non-neural epithelial cells, Xenobots are in fact integrated, complex systems in their own right, with sophisticated internal information structures.
Plant cognition has progressed from anecdote to rigor, yet the field still lacks a quantitative test for when distributed plant activity crosses into unified - perhaps conscious - processing. I introduce Pattern-Temporal Synergy (PTS), a substrate-agnostic metric rooted in Dynergeia, a relation-first ontology in which consciousness is reflexive coherence among five universal patterns - self-reference, division-creation, information integration, responsiveness, and flux - phase-locked inside a system's binding window (τ). Each pattern is operationalized with established signal-processing measures; their median strength is multiplied by their mean synergy and released only if a τ-specific coherence gate is met. Three preregistered hypotheses anchor the study: H1 baseline PTS > 0 in intact plants; H2 4% diethyl-ether collapses PTS below threshold ϕ; H3 PTS rebounds on wash-out. A multispecies protocol - Mimosa pudica, Arabidopsis thaliana, Picea abies - combines 64-channel surface electrodes, glutamate-sensitive Ca2+ imaging and micro-optode O2/heat-flux probes. Sliding 3 ×τ windows with phase-shuffled surrogates yield z-scored PTS trajectories, adjudicated by preregistered effect-size criteria. By turning decades of qualitative insight into falsifiable numbers, PTS offers plant biology a litmus test for conscious-level processing, directly challenges Integrated Information Theory and supplies a road-map for cross-kingdom comparisons - including neuromorphic silicon. Confirmatory results would shift debates on plant sentience from speculation to data; null results would equally refine what consciousness requires.
According to Information Vortex Theory, the spatially distributed wave energy associated with the constituent molecules of an incepting cell interacts with the surrounding space to generate a rotating bioinformation field, forming a vortex. This vortex, characterized as a local maximum of energy density, constitutes both inbound and outbound energy fluxes, corresponding to signal reception and dispersal, respectively. The vortex represents a foundational step in the emergence of life, facilitating both the storage of information and, through successive wave superpositions, the basic processing of information. This mechanism is posited to underpin the self-organizing principles that are essential to life’s origin. This study delineates the sequence of events within the information vortex that are causative to the emergence of plant life, emphasizing the role of a central information processing means, which determines evolutionary steps. An environmental context that resists cytoplasmic motion leads to signals favoring pinocytosis, which progressively intensify within the emerging information vortex while concurrently diminishing the expression of phagocytic wave forms. Furthermore, asexual reproductive events, represented by self-division waveforms, propagate this encoded information across successive generations. To elucidate these mechanisms, system-level modeling incorporating feedback loops and adaptive interventions is developed, illustrating the iterative nature of learning and pattern reinforcement. In parallel, a wave-theory-based mathematical framework is introduced to characterize the information vortex energy fluxes and the encoding of the arriving signals epigenetically in the genome.
Seed germination is a strictly regulated, multistage, and complex process in which a seed matures into a plant through a series of processes. Dormancy is defined as the inability of a viable seed to reach maturity. A seed can enter dormancy at any point in its development if it is still in the mother plant (primary dormancy) or if it is released because of environmental conditions (secondary dormancy). Germination is determined by a myriad of factors, such as agronomic (type of mother plant and growing conditions), chemical (nutrients), environmental (biotic and abiotic, including extreme conditions), molecular (genes), and physiological (hormones) factors. The authors propose the involvement of ‘X-factors,’ which are currently unknown, in shaping seed fate. Despite many efforts in plant neurobiology, studies on consciousness remain elusive. This article aims to put forth constructive suggestions and instigate future work on seed (or plant) cognition and consciousness, emphasizing the involvement of X-factors rather than arguing about the topic. The authors propose the involvement of ‘X-factors, ’ which are currently unknown, in shaping seed fate. This review article addresses the factors that influence germination and highlights the consciousness and X-factors of seeds and plants.
Creativity, which is the leverage of imagination to attain valued goals, is one of the defining features of humans. It is the trait that gives an advantage to humans in solving problems, enhancing their survival. Creativity is a critical evolved trait, hard-wired in the human genome and linked with many benefits, including mating success, psychological well-being, and human thriving. Evidence suggests creativity is a critical source of meaning. Many features of the modern world promote the interrelated factors of low trust, fear, and acute stress which make people vulnerable to meaninglessness or meaning crisis and these same factors negatively impact creativity. This suggests a relationship between meaning in life and creativity in which meaninglessness may negatively impact creativity and vice versa. In this paper, the role of creativity in providing meaning in human life, as the essence of human existence to repay our evolutionary or existential debt, and the intricate relationship between psychological well being, creativity and meaning in life are discussed. The need and ways to prioritize creativity in society to improve psychological well-being and make people live meaningfully are also discussed.
The individualistic and collectivistic intelligent behaviors observed in mammals, birds, and fishes have been appreciated by many scientists in recent years and supported by the Cambridge Declaration on Consciousness in 2012. Behavioral studies in lower organisms like arthropods and cephalopods showed the presence of multisensory integration, decision-making, and goal-directed behavior in these non-vertebrate animals. The presence of intelligent and history-dependent behaviors has been studied in microorganisms, and recent studies propose the possibility of cognition in single cellular organisms. The Cellular Basis of Consciousness (CBC), proposed by Arthur Reber in 2016 and elaborated by Baluška and Reber in 2019, suggests the possibility of consciousness in single cellular organisms. However, the critics of the Cellular Basis of Consciousness theory state that the individual bacterial cell does not make choices, and the decision-making is the result of stochastic differences in protein levels. Here, we want to address the criticism of decision-making in bacteria. An attempt is made to give a new perspective to the existing model to explain the flexibility in bacterial behavior in an ever-changing environment. The authors would like to consider an alternative perspective on flexibility in decision-making as the result of multiple pathways that have convergence and divergence as observed in the brain. Flexibility provides the possibility to have individualistic behavior, and the existence of such pathways can be considered as the molecular mechanism underlying individualistic decision-making in bacteria as well as in humans.
Polyamines play crucial roles in various biological processes, including cell proliferation and differentiation, immune response modulation, and signal transduction. Ornithine decarboxylase (ODC) initiates polyamine biosynthesis by catalyzing the conversion of ornithine to putrescine in a pyridoxal phosphate (PLP)-dependent manner. While the structures of mammalian and protozoan ODCs have been elucidated, fungal ODCs remain uncharacterized. In this study, AlphaFold2 was employed to simulate the structures of ODCs from four fungi: Kluyveromyces lactis, Candida albicans, Debaryomyces hansenii, and Schizosaccharomyces pombe. The results indicated that, although these ODCs share α/β-barrel and β-sheet domains, their active site conformations exhibit subtle differences. Additionally, substrate selectivity among ODCs and related decarboxylases varied depending on the distance between the Cα of aspartate or glutamate residues within the specificity helix and the C4α of PLP. Notably, the bacterial Campylobacter jejuni decarboxylase (CjCANSDC), which binds the largest substrate, exhibits the longest distance, whereas fungal ODC, which binds the smallest substrate, displays the shortest distance. Furthermore, significant differences in the composition of amino acid residues within the active sites were also observed. This study provides insights into the structural diversity and catalytic activity of ODCs across a broad range of organisms, advancing the understanding of structure-dependent evolutionary processes.
We argue here that the Origin of Life (OOL) problem is not just a chemistry problem but is also, and primarily, a cognitive science problem. When interpreted through the lens of the Conway-Kochen theorem and the Free Energy Principle, contemporary physics characterizes all complex dynamical systems that persist through time as Bayesian agents. If all persistent systems are to some - perhaps only minimal - extent cognitive, are all persistent systems to some extent alive, or are living systems only a subset of cognitive systems? We argue that no bright line can be drawn, and we re-assess, from this perspective, the Fermi paradox and the Drake equation. We conclude that improving our abilities to recognize and communicate with diverse intelligences in diverse embodiments, whether based on familiar biochemistry or not, will either resolve or obviate the OOL problem.
Emerging research has highlighted the significant role of microbiota-gut-brain communication in child psychiatric disorders, including autism spectrum disorder (ASD) and anxiety disorders. Despite this, mainstream psychiatric interventions for children continue to focus predominantly on neurological and psychological therapies, neglecting the critical influence of gut microbiota on brain development and behavior. This commentary underscores the need for greater integration of microbiota-targeted therapies, such as dietary interventions, prebiotics, and probiotics, into early psychiatric intervention strategies. By addressing the gut-brain axis as a key component of neurodevelopmental and psychiatric outcomes, clinicians can adopt a more holistic and biologically informed approach to treatment. We propose that future research and clinical practice should prioritize interdisciplinary collaboration to explore how microbiota-based treatments can be incorporated into existing child psychiatry frameworks, offering new avenues for improving long-term mental health outcomes.
Using Lotus creticus-rhizobia-A. salicina interaction networks, we address first the soil invasion success of A. salicina, and second, we report either A. salicina-rhizobia partnership should form an isolated module within the symbiosis interaction network. Different indexes were used to determine A. salicina model invasion success and the network topology. Our results indicated that A. salicina invasion decreased soil microbial biomass, basal respiration, and enzymatic activities. Housekeeping gene-based phylogeny showed that the invasive A. salicina is exclusively associated with a novel putative nodulating Paraburkholderia sp. not considered, up to now, as a natural symbiont of this species, and the native legume L. creticus nodulating strains, belonged to three new putative undescribed distinct chromosomal lineages within the Rhizobium, Allomesorhizobium, and Mesorhizobium genera. Analysis using nodC gene identified one symbiovar for A. salicina Paraburkholderia symbiont (sv. tropicalis) and three symbiovars for L. creticus endosynbionts (sv. viciae, sv hedysari and sv. loti). Moreover, L. creticus-rhizobia-A. salicina interaction networks are significantly modular with high levels of specialization. Network topology remained consistent over the invasion gradient, whereas native legume-associated rhizobia underwent significant change as acacias took over more the landscape. The absence of mutual overlapping networks emphasizes the importance of the simultaneous invasion of rhizobia–acacia species complexes in successful acacia invasion, suggesting unique interactions that often arise and evolve.
We isolated endophytic Fusarium strains from the healthy roots, stems, and leaves of Dendrobium moschatum to investigate their plant growth-promoting activities in vitro. Subsequently, Indole acetic acid (IAA) was quantified and the IaaM gene (responsible for IAA synthesis in fungi) was amplified and sequenced. Finally, a germination assay was performed with seeds of D. moschatum and a plant growth assay with protocorms of Dendrobium longicornu to test their plant growth-promoting activities. Five Fusarium isolates (CDS11, PDL1, PDL3, PDR6, PDR7) were identified in this study. The highest amount (60µgml-1) of indole acetic acid was recorded in the PDR7 extract, whereas it was not detected in PDR6 and CDS11. The fungal extracts of isolates PDR6 and PDR7 were highly effective for seed germination by approximately 80% and 90% (respectively) of the host plant. The fungal extract of PDR7 showed a high IAA content and promoted in vitro seed germination of the host (D. moschatum) and protocorm development of the non-host (D. longicornu). In contrast, IAA content in the fungal extract of PDR6 remained undetected but was effective in both seed germination and protocorm development. Our results demonstrated the potential beneficial application of endophytic Fusarium in orchid mass propagation.
Quorum sensing (QS) is a critical bacterial communication system regulating behaviors like biofilm formation, virulence, and antibiotic resistance. This review highlights QS’s role in polymicrobial infections, where bacterial species interactions enhance antibiotic resistance. We examine QS mechanisms, such as acyl-homoserine lactones (AHLs) in Gram-negative bacteria and autoinducing peptides (AIPs) in Gram-positive bacteria, and their impact on biofilm-associated antibiotic resistance. The challenges uniquely associated with polymicrobial infections, such as those found in cystic fibrosis lung infections, chronic wound infections, and medical device infections, are also summarized. Furthermore, we explore various laboratory models, including flow cells and dual-species culture models, used to study QS interactions in polymicrobial environments. The review also discusses promising quorum sensing inhibitors (QSIs), such as furanones and AHL analogs, which have demonstrated efficacy in reducing biofilm formation and virulence in laboratory and clinical studies. By addressing the interplay between QS and antibiotic resistance, this paper aims to advance therapeutic strategies that disrupt bacterial communication and improve antibiotic efficacy, ultimately mitigating the global challenge of antibiotic resistance in polymicrobial infections.
The bird of paradise plant is a clumping tropical species native to South Africa. It is a dramatic plant with distinctive iridescent orange and midnight blue flowers that resemble an exotic bird peeking out from the broad leaves in autumn, winter and spring. An experiment was conducted during the two seasons of 2021 and 2022 at a private farm in Damanhour, Beheira Governorate, Egypt (31“°” 04 ”°“N, 30“°” 47’ °E) to study the effect different concentrations of nano-potassium and chitosan and their combinations on the bird of Paradise (Sterlitiza reginae). The experiment was conducted in a randomized complete block in a split-plot design with five replicates; nano-potassium was used at 0, 100, 150, and 200 mg/l and assigned to the main plots, whereas the sub-plots involved 0, 0.25, 0.50 and 0.75 g/l of chitosan. An increase in plant height and leaf length was recorded when the plants were treated with 200 mg/l nano-potassium and 0.75 g/l chitosan. Spraying plants with concentrations of 150 mg/l nano-potassium and 0.75 g/l chitosan is associated with the superiority of S. reginae plants in other traits, such as leaves wide, number of leaves/plant, days to flowering, number of inflorescence/plant, number of florets/inflorescence, stalk length and diameter, inflorescence weight, longevity of inflorescence, and flowering period, compared to the other treatments. We conclude that adding nano-potassium and/or chitosan to the bird of paradise plant leads to an improvement in terms of vegetative and yield characteristics under newly reclaimed lands.
There is increasing evidence that exposure to weak electromagnetic fields (EMFs) generated by modern telecommunications or household appliances has physiological consequences, including reports of electromagnetic field hypersensitivity (EHS) leading to adverse health effects. Although symptoms can be serious, no underlying mechanism for EHS is known and there is no general cure or effective therapy. Here, we present the case study of a self-reported EHS patient whose symptoms include severe headaches, generalized fatigue, cardiac arrhythmia, attention and memory deficit, and generalized systemic pain within minutes of exposure to telecommunications (Wifi, cellular phones), high tension lines and electronic devices. Tests for cerebral, cardiovascular, and other physiological anomalies proved negative, as did serological tests for inflammation, allergies, infections, auto-immune conditions, and hormonal imbalance. However, further investigation revealed deficits in cellular anti-oxidants and increased radical scavenging enzymes, indicative of systemic oxidative stress. Significantly, there was a large increase in circulating antibodies for oxidized Low-Density Lipoprotein (LDLox), byproducts of oxidative stress accumulating in membranes of vascular cells. Because a known primary effect of EMF exposure is to increase the concentration of cellular oxidants, we propose that pathology in this patient may be causally related to a resulting increase in LDLox synthesis. This in turn could trigger an exaggerated auto-immune response consistent with EHS symptoms. This case report thereby provides a testable mechanistic framework for EHS pathology with therapeutic implications for this debilitating and poorly understood condition.
As every life form is composed of cells, elements of consciousness, namely memory and sentience, must be grounded in mechanisms that are integral to unicellular organisms. Earlier studies indicated that cellular cytoskeletal structures consisting of excitable, flexible, and oscillating polymers such as microtubules, along with quantum events, are potentially responsible for information processing and thus consciousness. This work attempts to solve the unknown, that is, how, at the spark of life, the phenomenon of cellular information processing first appears. This study posits that the spatially distributed wave energy of the molecules of an incepting cell interacts with space and generates a rotating bioinformation field, forming a vortex. This vortex, the local energy maximum, whose inbound and outbound energy fluxes represent signal reception and dispersal, is a critical step in the spark of life responsible for information storage, and with incremental wave superpositions, exhibits information processing. The vorticity of the rotating field is computed, and the obtained field characteristics indicated the emergence of a prebiotic complex to initiate information processing. Furthermore, the developed system model explains how perturbations from the environment are converted into response signals for the emanation of sense, locomotion, nutrition, and asexual reproduction, the fundamental evolutionary building blocks of prokaryotes. Further research directions include explaining how the energy potential available in the bio-information field and the vortex leads to the first formation of genetic material, emergence of cytoskeleton, and extension of bio-information field to multi-cellular organisms.
