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- Agnati, LF, et al.
(author)
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Man is a "Rope" Stretched Between Virosphere and Humanoid Robots: On the Urgent Need of an Ethical Code for Ecosystem Survival
- 2022
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In: Foundations of science. - : Springer Science and Business Media LLC. - 1233-1821 .- 1572-8471. ; 27:2, s. 311-325
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Journal article (peer-reviewed)abstract
- In this paper we compare the strategies applied by two successful biological components of the ecosystem, the viruses and the human beings, to interact with the environment. Viruses have had and still exert deep and vast actions on the ecosystem especially at the genome level of most of its biotic components. We discuss on the importance of the human being as contraptions maker in particular of robots, hence of machines capable of automatically carrying out complex series of actions. Beside the relevance of designing and assembling these contraptions, it is of basic importance the goal for which they are assembled and future scenarios of their possible impact on the ecosystem. We can’t procrastinate the development and implementation of a highly inspired and stringent “ethical code” for human beings and humanoid robots because it will be a crucial aspect for the wellbeing of the mankind and of the entire ecosystem.
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- Fuxe, K, et al.
(author)
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Heterodimers and receptor mosaics of different types of G-protein-coupled receptors
- 2008
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In: Physiology (Bethesda, Md.). - : American Physiological Society. - 1548-9213 .- 1548-9221. ; 23:6, s. 322-332
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Journal article (peer-reviewed)abstract
- Through an assembly of interacting GPCRs, heterodimers and high-order heteromers (termed receptor mosaics) are formed and lead to changes in the agonist recognition, signaling, and trafficking of participating receptors via allosteric mechanisms, sometimes involving the appearance of cooperativity. This field has now become a major research area, and this review deals with their physiology being integrators of receptor signaling in the CNS and their use as targets for novel drug development based on their unique pharmacology.
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| 9. |
- Fuxe, K., et al.
(author)
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Intramembrane receptor-receptor interactions: a novel principle in molecular medicine
- 2007
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In: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 114:1, s. 49-75
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Journal article (peer-reviewed)abstract
- In 1980/81 Agnati and Fuxe introduced the concept of intramembrane receptor-receptor interactions and presented the first experimental observations for their existence in crude membrane preparations. The second step was their introduction of the receptor mosaic hypothesis of the engram in 1982. The third step was their proposal that the existence of intramembrane receptor-receptor interactions made possible the integration of synaptic (WT) and extrasynaptic (VT) signals. With the discovery of the intramembrane receptor-receptor interactions with the likely formation of receptor aggregates of multiple receptors, so called receptor mosaics, the entire decoding process becomes a branched process already at the receptor level in the surface membrane. Recent developments indicate the relevance of cooperativity in intramembrane receptor-receptor interactions namely the presence of regulated cooperativity via receptor-receptor interactions in receptor mosaics (RM) built up of the same type of receptor (homo-oligomers) or of subtypes of the same receptor (RM type1). The receptor-receptor interactions will to a large extent determine the various conformational states of the receptors and their operation will be dependent on the receptor composition (stoichiometry), the spatial organization (topography) and order of receptor activation in the RM. The biochemical and functional integrative implications of the receptor-receptor interactions are outlined and long-lived heteromeric receptor complexes with frozen RM in various nerve cell systems may play an essential role in learning, memory and retrieval processes. Intramembrane receptor-receptor interactions in the brain have given rise to novel strategies for treatment of Parkinson's disease (A2A and mGluR5 receptor antagonists), schizophrenia (A2A and mGluR5 agonists) and depression (galanin receptor antagonists). The A2A/D2, A2A/D3 and A2A/mGluR5 heteromers and heteromeric complexes with their possible participation in different types of RM are described in detail, especially in the cortico-striatal glutamate synapse and its extrasynaptic components, together with a postulated existence of A2A/D4 heteromers. Finally, the impact of intramembrane receptor-receptor interactions in molecular medicine is discussed outside the brain with focus on the endocrine, the cardiovascular and the immune systems.
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- Guidolin, Andrea, et al.
(author)
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Geometry of spiking patterns in early visual cortex : a topological data analytic approach
- 2022
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In: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 19:196
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Journal article (peer-reviewed)abstract
- In the brain, spiking patterns live in a high-dimensional space of neurons and time. Thus, determining the intrinsic structure of this space presents a theoretical and experimental challenge. To address this challenge, we introduce a new framework for applying topological data analysis (TDA) to spike train data and use it to determine the geometry of spiking patterns in the visual cortex. Key to our approach is a parametrized family of distances based on the timing of spikes that quantifies the dissimilarity between neuronal responses. We applied TDA to visually driven single-unit and multiple single-unit spiking activity in macaque V1 and V2. TDA across timescales reveals a common geometry for spiking patterns in V1 and V2 which, among simple models, is most similar to that of a low-dimensional space endowed with Euclidean or hyperbolic geometry with modest curvature. Remarkably, the inferred geometry depends on timescale and is clearest for the timescales that are important for encoding contrast, orientation and spatial correlations.
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| 13. |
- Guidolin, D, et al.
(author)
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A New Integrative Theory of Brain-Body-Ecosystem Medicine: From the Hippocratic Holistic View of Medicine to Our Modern Society
- 2019
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In: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 16:17
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Journal article (peer-reviewed)abstract
- Humans are increasingly aware that their fate will depend on the wisdom they apply in interacting with the ecosystem. Its health is defined as the condition in which the ecosystem can deliver and continuously renew its fundamental services. A healthy ecosystem allows optimal interactions between humans and the other biotic/abiotic components, and only in a healthy ecosystem can humans survive and efficiently reproduce. Thus, both the human and ecosystem health should be considered together in view of their interdependence. The present article suggests that this relationship could be considered starting from the Hippocrates (460 BC–370 BC) work “On Airs, Waters, and Places” to derive useful medical and philosophical implications for medicine which is indeed a topic that involves scientific as well as philosophical concepts that implicate a background broader than the human body. The brain-body-ecosystem medicine is proposed as a new more complete approach to safeguarding human health. Epidemiological data demonstrate that exploitation of the environment resulting in ecosystem damage affects human health and in several instances these diseases can be detected by modifications in the heart-brain interactions that can be diagnosed through the analysis of changes in heart rate variability.
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| 22. |
- Agnati, LF, et al.
(author)
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Functional roles of three cues that provide nonsynaptic modes of communication in the brain: electromagnetic field, oxygen, and carbon dioxide
- 2018
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In: Journal of neurophysiology. - : American Physiological Society. - 1522-1598 .- 0022-3077. ; 119:1, s. 356-368
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Journal article (peer-reviewed)abstract
- The integrative actions of the brain depend on the exchange of information among its computational elements. Hence, this phenomenon plays the key role in driving the complex dynamics of the central nervous system, in which true computations interact with noncomputational dynamical processes to generate brain representations of the body and of the body in the external world, and hence the finalistic behavior of the organism. In this context, it should be pointed out that, besides the intercellular interactions mediated by classical electrochemical signals, other types of interactions, namely, “cues” and “coercions,” also appear to be exploited by the system to achieve its function. The present review focuses mainly on cues present in the environment and on those produced by cells of the body, which “pervade” the brain and contribute to its dynamics. These cues can also be metabolic substrates, and, in most cases, they are of fundamental importance to brain function and the survival of the entire organism. Three of these highly pervasive cues will be analyzed in greater detail, namely, oxygen, carbon dioxide, and electromagnetic fields (EMF). Special emphasis will be placed on EMF, since several authors have suggested that these highly pervasive energy fluctuations may play an important role in the global integrative actions of the brain; hence, EMF signaling may transcend classical connectionist models of brain function. Thus the new concept of “broadcasted neuroconnectomics” has been introduced, which transcends the current connectomics view of the brain.
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| 33. |
- Agnati, LF, et al.
(author)
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Possible relevance of receptor-receptor interactions between viral- and host-coded receptors for viral-induced disease
- 2007
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In: TheScientificWorldJournal. - : Hindawi Limited. - 1537-744X. ; 7, s. 1073-1081
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Journal article (peer-reviewed)abstract
- It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers), but clusters of receptors (receptor mosaics), altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.
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| 37. |
- Agnati, LF, et al.
(author)
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Role of iso-receptors in receptor-receptor interactions with a focus on dopamine iso-receptor complexes
- 2016
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In: Reviews in the neurosciences. - : Walter de Gruyter GmbH. - 2191-0200 .- 0334-1763. ; 27:1, s. 1-25
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Journal article (peer-reviewed)abstract
- Intercellular and intracellular communication processes consist of signals and recognition/decoding apparatuses of these signals. In humans, the G protein-coupled receptor (GPCR) family represents the largest family of cell surface receptors. More than 30 years ago, it has been proposed that GPCR could form dimers or higher-order oligomers (receptor mosaics [RMs] at the plasma membrane level and receptor-receptor interactions [RRIs] have been proposed as a new integrative mechanism for chemical signals impinging on cell plasma membranes). The basic phenomena involved in RRIs are allostery and cooperativity of membrane receptors, and the present paper provides basic information concerning their relevance for the integrative functions of RMs. In this context, the possible role of iso-receptor RM is discussed (with a special focus on dopamine receptor subtypes and on some of the RMs they form with other dopamine iso-receptors), and it is proposed that two types of cooperativity, namely, homotropic and heterotropic cooperativity, could allow distinguishing two types of functionally different RMs. From a general point of view, the presence of iso-receptors and their topological organization within RMs allow the use of a reduced number of signals for the intercellular communication processes, since the target cells can recognize and decode the same signal in different ways. This theoretical aspect is further analyzed here by means of an analogy with artificial information systems. Thus, it is suggested that the ‘multiplexer’ and ‘demultiplexer’ concepts could, at least in part, model the role of RMs formed by iso-receptors in the information handling by the cell.
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| 40. |
- Agnati, LF, et al.
(author)
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The multi-facet aspects of cell sentience and their relevance for the integrative brain actions: role of membrane protein energy landscape
- 2016
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In: Reviews in the neurosciences. - : Walter de Gruyter GmbH. - 2191-0200 .- 0334-1763. ; 27:4, s. 347-363
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Journal article (peer-reviewed)abstract
- Several ion channels can be randomly and spontaneously in an open state, allowing the exchange of ion fluxes between extracellular and intracellular environments. We propose that the random changes in the state of ion channels could be also due to proteins exploring their energy landscapes. Indeed, proteins can modify their steric conformation under the effects of the physicochemical parameters of the environments with which they are in contact, namely, the extracellular, intramembrane and intracellular environments. In particular, it is proposed that the random walk of proteins in their energy landscape is towards attractors that can favor the open or close condition of the ion channels and/or intrinsic activity of G-protein-coupled receptors. The main aspect of the present proposal is that some relevant physicochemical parameters of the environments (e.g. molecular composition, temperature, electrical fields) with which some signaling-involved plasma membrane proteins are in contact alter their conformations. In turn, these changes can modify their information handling via a modulatory action on their random walk towards suitable attractors of their energy landscape. Thus, spontaneous and/or signal-triggered electrical activities of neurons occur that can have emergent properties capable of influencing the integrative actions of brain networks. Against this background, Cook’s hypothesis on ‘cell sentience’ is developed by proposing that physicochemical parameters of the environments with which the plasma-membrane proteins of complex cellular networks are in contact fulfill a fundamental role in their spontaneous and/or signal-triggered activity. Furthermore, it is proposed that a specialized organelle, the primary cilium, which is present in most cells (also neurons and astrocytes), could be of peculiar importance to pick up chemical signals such as ions and transmitters and to detect physical signals such as pressure waves, thermal gradients, and local field potentials.
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