Related Articles

Synthesis and Biological Evaluation of Novel Triple-Modified Colchicine Derivatives as Potent Tubulin-Targeting Anticancer Agents.

Cells. 2018 Nov 19;7(11):

Authors: Majcher U, Klejborowska G, Kaik M, Maj E, Wietrzyk J, Moshari M, Preto J, Tuszynski JA, Huczyński A

Abstract
Specific modifications of colchicine followed by synthesis of its analogues have been tested in vitro with the objective of lowering colchicine toxicity. Our previous studies have clearly shown the anticancer potential of double-modified colchicine derivatives in C-7 and C-10 positions. Here, a series of novel triple-modified colchicine derivatives is reported. They have been obtained following a four-step strategy. In vitro cytotoxicity of these compounds has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo, and LoVo/DX). Additionally, the mode of binding of the synthesized compounds was evaluated in silico using molecular docking to a 3D structure of β-tubulin based on crystallographic data from the Protein Data Bank and homology methodology. Binding free energy estimates, binding poses, and MlogP values of the compounds were obtained. All triple-modified colchicine derivatives were shown to be active at nanomolar concentrations against three of the investigated cancer cell lines (A549, MCF-7, LoVo). Four of them also showed higher potency against tumor cells over normal cells as confirmed by their high selectivity index values. A vast majority of the synthesized derivatives exhibited several times higher cytotoxicity than colchicine, doxorubicin, and cisplatin.

PMID: 30463236 [PubMed]

Related Articles

Antiproliferative Activity and Molecular Docking of Novel Double-Modified Colchicine Derivatives.

Cells. 2018 Nov 01;7(11):

Authors: Majcher U, Klejborowska G, Moshari M, Maj E, Wietrzyk J, Bartl F, Tuszynski JA, Huczyński A

Abstract
Microtubules are tubulin polymer structures, which are indispensable for cell growth and division. Its constituent protein β-tubulin has been a common drug target for various diseases including cancer. Colchicine has been used to treat gout, but it has also been an investigational anticancer agent with a known antimitotic effect on cells. However, the use of colchicine as well as many of its derivatives in long-term treatment is hampered by their high toxicity. To create more potent anticancer agents, three novel double-modified colchicine derivatives have been obtained by structural modifications in C-4 and C-10 positions. The binding affinities of these derivatives of colchicine with respect to eight different isotypes of human β-tubulin have been calculated using docking methods. In vitro cytotoxicity has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo and LoVo/DX). Computer simulations predicted the binding modes of these compounds and hence the key residues involved in the interactions between tubulin and the colchicine derivatives. Two of the obtained derivatives, 4-bromothiocolchicine and 4-iodothiocolchicine, were shown to be active against three of the investigated cancer cell lines (A549, MCF-7, LoVo) with potency at nanomolar concentrations and a higher relative affinity to tumor cells over normal cells.

PMID: 30388878 [PubMed]

Related Articles

Synthesis, antiproliferative activity and molecular docking of thiocolchicine urethanes.

Bioorg Chem. 2018 12;81:553-566

Authors: Majcher U, Urbaniak A, Maj E, Moshari M, Delgado M, Wietrzyk J, Bartl F, Chambers TC, Tuszynski JA, Huczyński A

Abstract
A number of naturally occurring compounds such as paclitaxel, vinblastine, combretastatin, and colchicine exert their therapeutic effect by changing the dynamics of tubulin and its polymer form, microtubules. The identification of tubulin as a potential target for anticancer drugs has led to extensive research followed by clinical development of numerous compounds from several families. In this paper we report on the design, synthesis and in vitro evaluation of a group of thiocolchicine derivatives, modified at ring-B, labelled here compounds 4-14. These compounds have been obtained in a simple reaction of 7-deacetyl-10-thiocolchicine 3 with eleven different alcohols in the presence of triphosgene. These novel agents have been checked for anti-proliferative activity against four human cancer cell lines and their mode of action has been confirmed as colchicine binding site inhibition (CBSI) using molecular docking. Molecular simulations provided rational tubulin binding models for the tested compounds. On the basis of in vitro tests, derivatives 4-8 and 14 demonstrated the highest potency against MCF-7, LoVo and A549 tumor cell lines (IC50 values = 0.009-0.014 μM). They were more potent and characterized by a higher selectivity index than several standard chemotherapeutics including cisplatin and doxorubicin as well as unmodified colchicine. Further, studies revealed that colchicine and its several derivatives arrested MCF-7 cells in mitosis, while its selected derivatives caused microtubule depolymerization.

PMID: 30248507 [PubMed - indexed for MEDLINE]

Related Articles

Tubulin's response to external electric fields by molecular dynamics simulations.

PLoS One. 2018;13(9):e0202141

Authors: Timmons JJ, Preto J, Tuszynski JA, Wong ET

Abstract
Tubulin heterodimers are the building blocks of microtubules and disruption of their dynamics is exploited in the treatment of cancer. Electric fields at certain frequencies and magnitudes are believed to do the same. Here, the tubulin dimer's response to external electric fields was determined by atomistic simulation. External fields from 50 to 750 kV/cm, applied for 10 ns, caused significant conformational rearrangements that were dependent upon the field's directionality. Charged and flexible regions, including the α:H1-B2 loop, β:M-loop, and C-termini, were susceptible. Closer inspection of the α:H1-B2 loop in lower strength fields revealed that these effects were consistent and proportional to field strength, and the findings indicate that external electric fields modulate the stability of microtubules through conformational changes to key loops involved in lateral contacts. We also find evidence that tubulin's curvature and elongation are affected, and external electric fields may bias tubulin towards depolymerization.

PMID: 30231050 [PubMed - indexed for MEDLINE]

Related Articles

Virtual screening using covalent docking to find activators for G245S mutant p53.

PLoS One. 2018;13(9):e0200769

Authors: Omar SI, Lepre MG, Morbiducci U, Deriu MA, Tuszynski JA

Abstract
TP53 is the most mutated gene in all cancers. The mutant protein also accumulates in cells. The high frequency of p53 mutations makes the protein a promising target for anti-cancer therapy. Only a few molecules have been found, using in vitro screening, to reactivate the mutant protein. APR-246 is currently the most successful mutant p53 activator, which reactivates the transcriptional activity of p53 by covalently binding to C124 of the protein. We have recently created in silico models of G245S-mp53 in its apo and DNA-bound forms. In this paper we further report on our in silico screening for potential activators of G245S-mp53. We filtered the ZINC15 database (13 million compounds) to only include drug-like molecules with moderate to standard reactivity. Our filtered database of 130,000 compounds was screened using the DOCKTITE protocol in the Molecular Operating Environment software. We performed covalent docking at C124 of G245S-mp53 to identify potential activators of the mutant protein. The docked compounds were ranked using a consensus scoring approach. We also used ADMET Predictor™ to predict pharmacokinetics and the possible toxicities of the compounds. Our screening procedure has identified compounds, mostly thiosemicarbazones and halo-carbonyls, with the best potential as G245S-mp53 activators, which are described in this work. Based on its binding scores and ADMET risk score, compound 2 is likely to have the best potential as a G245S-mp53 activator compared to the other top hits.

PMID: 30192754 [PubMed - indexed for MEDLINE]

Related Articles

Nonlinear calcium ion waves along actin filaments control active hair-bundle motility.

Biosystems. 2018 Nov;173:181-190

Authors: Tuszynski JA, Sataric MV, Sekulic DL, Sataric BM, Zdravkovic S

Abstract
Calcium ions (Ca2+) tune and control numerous diverse aspects of cochlear and vestibular physiological processes. This paper is focused on the Ca2+ control of mechanotransduction in sensory hair cells in the context of polyelectrolyte properties of actin filaments within the hair-bundles of inner ear. These actin filaments appear to serve as efficient pathways for the flow of Ca2+ ions inside stereocilia. We showed how this can be utilized for tuning of force-generating myosin motors. In an established model, we unified the Ca2+ nonlinear dynamics involved in the control of myosin adaptation motors with mechanical displacements of hair-bundles. The model shows that the characteristic time scales fit reasonably well with the available experimental data for spontaneous oscillations in the inner ear. This scenario promises to fill a gap in our understanding of the role of Ca2+ ions in the regulation of processes in the auditory cells of the inner ear.

PMID: 30179640 [PubMed - indexed for MEDLINE]

Related Articles

Integration of intracellular signaling: Biological analogues of wires, processors and memories organized by a centrosome 3D reference system.

Biosystems. 2018 Nov;173:191-206

Authors: Barvitenko N, Lawen A, Aslam M, Pantaleo A, Saldanha C, Skverchinskaya E, Regolini M, Tuszynski JA

Abstract
BACKGROUND: Myriads of signaling pathways in a single cell function to achieve the highest spatio-temporal integration. Data are accumulating on the role of electromechanical soliton-like waves in signal transduction processes. Theoretical studies strongly suggest feasibility of both classical and quantum computing involving microtubules.
AIM: A theoretical study of the role of the complex composed of the plasma membrane and the microtubule-based cytoskeleton as a system that transmits, stores and processes information.
METHODS: Theoretical analysis presented here refers to (i) the Penrose-Hameroff theory of consciousness (Orchestrated Objective Reduction; Orch OR), (ii) the description of the centrosome as a reference system for construction of the 3D map of the cell proposed by Regolini, (iii) the Heimburg-Jackson model of the nerve pulse propagation along axons' lipid bilayer as soliton-like electro-mechanical waves.
RESULTS AND CONCLUSION: The ideas presented in this paper provide a qualitative model for the decision-making processes in a living cell undergoing a differentiation process.
OUTLOOK: This paper paves the way for the real-time live-cell observation of information processing by microtubule-based cytoskeleton and cell fate decision making.

PMID: 30142359 [PubMed - indexed for MEDLINE]

Related Articles

Using Spectral Representation to Classify Proteins' Conformational States.

Int J Mol Sci. 2018 Jul 18;19(7):

Authors: Saberi Fathi SM, Tuszynski JA

Abstract
Numerous proteins are molecular targets for drug action and hence are important in drug discovery. Structure-based computational drug discovery relies on detailed information regarding protein conformations for subsequent drug screening in silico. There are two key issues in analyzing protein conformations in virtual screening. The first considers the protein's conformational change in response to physical and chemical conditions. The second is the protein's atomic resolution reconstruction from X-ray crystallography or nuclear magnetic resonance (NMR) data. In this latter problem, information is needed regarding the sample's position relative to the source of X-rays. Here, we introduce a new measure for classifying protein conformational states using spectral representation and Wigner's D-functions. Predictions based on the new measure are in good agreement with conformational states of proteins. These results could also be applied to improve conformational alignment of the snapshots given by protein crystallography.

PMID: 30021967 [PubMed - indexed for MEDLINE]

Related Articles

A computational approach for predicting off-target toxicity of antiviral ribonucleoside analogues to mitochondrial RNA polymerase.

J Biol Chem. 2018 06 22;293(25):9696-9705

Authors: Freedman H, Winter P, Tuszynski J, Tyrrell DL, Houghton M

Abstract
In the development of antiviral drugs that target viral RNA-dependent RNA polymerases, off-target toxicity caused by the inhibition of the human mitochondrial RNA polymerase (POLRMT) is a major liability. Therefore, it is essential that all new ribonucleoside analogue drugs be accurately screened for POLRMT inhibition. A computational tool that can accurately predict NTP binding to POLRMT could assist in evaluating any potential toxicity and in designing possible salvaging strategies. Using the available crystal structure of POLRMT bound to an RNA transcript, here we created a model of POLRMT with an NTP molecule bound in the active site. Furthermore, we implemented a computational screening procedure that determines the relative binding free energy of an NTP analogue to POLRMT by free energy perturbation (FEP), i.e. a simulation in which the natural NTP molecule is slowly transformed into the analogue and back. In each direction, the transformation was performed over 40 ns of simulation on our IBM Blue Gene Q supercomputer. This procedure was validated across a panel of drugs for which experimental dissociation constants were available, showing that NTP relative binding free energies could be predicted to within 0.97 kcal/mol of the experimental values on average. These results demonstrate for the first time that free-energy simulation can be a useful tool for predicting binding affinities of NTP analogues to a polymerase. We expect that our model, together with similar models of viral polymerases, will be very useful in the screening and future design of NTP inhibitors of viral polymerases that have no mitochondrial toxicity.

PMID: 29739852 [PubMed - indexed for MEDLINE]

Related Articles

Computational Characterization of Small Molecules Binding to the Human XPF Active Site and Virtual Screening to Identify Potential New DNA Repair Inhibitors Targeting the ERCC1-XPF Endonuclease.

Int J Mol Sci. 2018 Apr 30;19(5):

Authors: Gentile F, Barakat KH, Tuszynski JA

Abstract
The DNA excision repair protein ERCC-1-DNA repair endonuclease XPF (ERCC1-XPF) is a heterodimeric endonuclease essential for the nucleotide excision repair (NER) DNA repair pathway. Although its activity is required to maintain genome integrity in healthy cells, ERCC1-XPF can counteract the effect of DNA-damaging therapies such as platinum-based chemotherapy in cancer cells. Therefore, a promising approach to enhance the effect of these therapies is to combine their use with small molecules, which can inhibit the repair mechanisms in cancer cells. Currently, there are no structures available for the catalytic site of the human ERCC1-XPF, which performs the metal-mediated cleavage of a DNA damaged strand at 5′. We adopted a homology modeling strategy to build a structural model of the human XPF nuclease domain which contained the active site and to extract dominant conformations of the domain using molecular dynamics simulations followed by clustering of the trajectory. We investigated the binding modes of known small molecule inhibitors targeting the active site to build a pharmacophore model. We then performed a virtual screening of the ZINC Is Not Commercial 15 (ZINC15) database to identify new ERCC1-XPF endonuclease inhibitors. Our work provides structural insights regarding the binding mode of small molecules targeting the ERCC1-XPF active site that can be used to rationally optimize such compounds. We also propose a set of new potential DNA repair inhibitors to be considered for combination cancer therapy strategies.

PMID: 29710850 [PubMed - indexed for MEDLINE]

Related Articles

Comparative analyses and structural insights of the novel cytochrome P450 fusion protein family CYP5619 in Oomycetes.

Sci Rep. 2018 04 26;8(1):6597

Authors: Bamal HD, Chen W, Mashele SS, Nelson DR, Kappo AP, Mosa RA, Yu JH, Tuszynski JA, Syed K

Abstract
Phylogenetic and structural analysis of P450 proteins fused to peroxidase/dioxygenase has not been reported yet. We present phylogenetic and in silico structural analysis of the novel P450 fusion family CYP5619 from the deadliest fish pathogenic oomycete, Saprolegnia diclina. Data-mining and annotation of CYP5619 members revealed their unique presence in oomycetes. CYP5619 members have the highest number of conserved amino acids among eukaryotic P450s. The highest number of conserved amino acids (78%) occurred in the peroxidase/dioxygenase domain compared to the P450 domain (22%). In silico structural analysis using a high-quality CYP5619A1 model revealed that CYP5619A1 has characteristic P450 structural motifs including EXXR and CXG. However, the heme-binding domain (CXG) in CYP5619 members was found to be highly degenerated. The in silico substrate binding pattern revealed that CYP5619A1 have a high affinity to medium chain fatty acids. Interestingly, the controlling agent of S. diclina malachite green was predicted to have the highest binding affinity, along with linoleic acid. However, unlike fatty acids, none of the active site amino acids formed hydrogen bonds with malachite green. The study's results will pave the way for assessing CYP5619A1's role in S. diclina physiology, including the nature of malachite green binding.

PMID: 29700357 [PubMed - indexed for MEDLINE]

Related Articles

A Novel Interaction Between the TLR7 and a Colchicine Derivative Revealed Through a Computational and Experimental Study.

Pharmaceuticals (Basel). 2018 Feb 16;11(1):

Authors: Gentile F, Deriu MA, Barakat K, Danani A, Tuszynski J

Abstract
The Toll-Like Receptor 7 (TLR7) is an endosomal membrane receptor involved in the innate immune system response. Its best-known small molecule activators are imidazoquinoline derivatives such as imiquimod (R-837) and resiquimod (R-848). Recently, an interaction between R-837 and the colchicine binding site of tubulin was reported. To investigate the possibility of an interaction between structural analogues of colchicine and the TLR7, a recent computational model for the dimeric form of the TLR7 receptor was used to determine a possible interaction with a colchicine derivative called CR42-24, active as a tubulin polymerization inhibitor. The estimated values of the binding energy of this molecule with respect to the TLR7 receptor were comparable to the energies of known binders as reported in a previous study. The binding to the TLR7 was further assessed by introducing genetic transformations in the TLR7 gene in cancer cell lines and exposing them to the compound. A negative shift of the IC50 value in terms of cell growth was observed in cell lines carrying the mutated TLR7 gene. The reported study suggests a possible interaction between TLR7 and a colchicine derivative, which can be explored for rational design of new drugs acting on this receptor by using a colchicine scaffold for additional modifications.

PMID: 29462934 [PubMed]

Related Articles

Conformational Dynamics and Stability of U-Shaped and S-Shaped Amyloid β Assemblies.

Int J Mol Sci. 2018 Feb 14;19(2):

Authors: Grasso G, Rebella M, Muscat S, Morbiducci U, Tuszynski J, Danani A, Deriu MA

Abstract
Alzheimer's disease is the most fatal neurodegenerative disorder characterized by the aggregation and deposition of Amyloid β (Aβ) oligomers in the brain of patients. Two principal variants of Aβ exist in humans: Aβ1-40 and Aβ1-42. The former is the most abundant in the plaques, while the latter is the most toxic species and forms fibrils more rapidly. Interestingly, fibrils of Aβ1-40 peptides can only assume U-shaped conformations while Aβ1-42 can also arrange as S-shaped three-stranded chains, as recently discovered. As alterations in protein conformational arrangement correlate with cell toxicity and speed of disease progression, it is important to characterize, at molecular level, the conformational dynamics of amyloid fibrils. In this work, Replica Exchange Molecular Dynamics simulations were carried out to compare the conformational dynamics of U-shaped and S-shaped Aβ17-42 small fibrils. Our computational results provide support for the stability of the recently proposed S-shaped model due to the maximized interactions involving the C-terminal residues. On the other hand, the U-shaped motif is characterized by significant distortions resulting in a more disordered assembly. Outcomes of our work suggest that the molecular architecture of the protein aggregates might play a pivotal role in formation and conformational stability of the resulting fibrils.

PMID: 29443891 [PubMed - indexed for MEDLINE]

Related Articles

Destabilizing the AXH Tetramer by Mutations: Mechanisms and Potential Antiaggregation Strategies.

Biophys J. 2018 01 23;114(2):323-330

Authors: Grasso G, Morbiducci U, Massai D, Tuszynski JA, Danani A, Deriu MA

Abstract
The AXH domain of protein Ataxin 1 is thought to play a key role in the misfolding and aggregation pathway responsible for Spinocerebellar ataxia 1. For this reason, a molecular level understanding of AXH oligomerization pathway is crucial to elucidate the aggregation mechanism, which is thought to trigger the disease. This study employs classical and enhanced molecular dynamics to identify the structural and energetic basis of AXH tetramer stability. Results of this work elucidate molecular mechanisms behind the destabilizing effect of protein mutations, which consequently affect the AXH tetramer assembly. Moreover, results of the study draw attention for the first time, to our knowledge, to the R638 protein residue, which is shown to play a key role in AXH tetramer stability. Therefore, R638 might be also implicated in the AXH oligomerization pathway and stands out as a target for future experimental studies focused on self-association mechanisms and fibril formation of full-length ATX1.

PMID: 29401430 [PubMed - indexed for MEDLINE]

Related Articles

Optomechanical proposal for monitoring microtubule mechanical vibrations.

Phys Rev E. 2017 Jul;96(1-1):012404

Authors: Barzanjeh S, Salari V, Tuszynski JA, Cifra M, Simon C

Abstract
Microtubules provide the mechanical force required for chromosome separation during mitosis. However, little is known about the dynamic (high-frequency) mechanical properties of microtubules. Here, we theoretically propose to control the vibrations of a doubly clamped microtubule by tip electrodes and to detect its motion via the optomechanical coupling between the vibrational modes of the microtubule and an optical cavity. In the presence of a red-detuned strong pump laser, this coupling leads to optomechanical-induced transparency of an optical probe field, which can be detected with state-of-the art technology. The center frequency and line width of the transparency peak give the resonance frequency and damping rate of the microtubule, respectively, while the height of the peak reveals information about the microtubule-cavity field coupling. Our method opens the new possibilities to gain information about the physical properties of microtubules, which will enhance our capability to design physical cancer treatment protocols as alternatives to chemotherapeutic drugs.

PMID: 29347215 [PubMed - indexed for MEDLINE]

Related Articles

Electromagnetic fields and optomechanics in cancer diagnostics and treatment.

Front Biosci (Landmark Ed). 2018 03 01;23:1391-1406

Authors: Salari V, Barzanjeh S, Cifra M, Simon C, Scholkmann F, Alirezaei Z, Tuszynski JA

Abstract
In this paper, we discuss biological effects of electromagnetic (EM) fields in the context of cancer biology. In particular, we review the nanomechanical properties of microtubules (MTs), the latter being one of the most successful targets for cancer therapy. We propose an investigation on the coupling of electromagnetic radiation to mechanical vibrations of MTs as an important basis for biological and medical applications. In our opinion, optomechanical methods can accurately monitor and control the mechanical properties of isolated MTs in a liquid environment. Consequently, studying nanomechanical properties of MTs may give useful information for future applications to diagnostic and therapeutic technologies involving non-invasive externally applied physical fields. For example, electromagnetic fields or high intensity ultrasound can be used therapeutically avoiding harmful side effects of chemotherapeutic agents or classical radiation therapy.

PMID: 29293441 [PubMed - indexed for MEDLINE]

Related Articles

Are there optical communication channels in the brain?

Front Biosci (Landmark Ed). 2018 03 01;23:1407-1421

Authors: Zarkeshian P, Kumar S, Tuszynski J, Barclay P, Simon C

Abstract
Despite great progress in neuroscience, there are still fundamental unanswered questions about the brain, including the origin of subjective experience and consciousness. Some answers might rely on new physical mechanisms. Given that biophotons have been discovered in the brain, it is interesting to explore if neurons use photonic communication in addition to the well-studied electro-chemical signals. Such photonic communication in the brain would require waveguides. Here we review recent work (S. Kumar, K. Boone, J. Tuszynski, P. Barclay, and C. Simon, Scientific Reports 6, 36508 (2016)) suggesting that myelinated axons could serve as photonic waveguides. The light transmission in the myelinated axon was modeled, taking into account its realistic imperfections, and experiments were proposed both in vivo and in vitro to test this hypothesis. Potential implications for quantum biology are discussed.

PMID: 29293442 [PubMed - indexed for MEDLINE]

Related Articles

Self-Assembled Ligands Targeting TLR7: A Molecular Level Investigation.

Langmuir. 2017 12 19;33(50):14460-14471

Authors: Deriu MA, Cangiotti M, Grasso G, Licandro G, Lavasanifar A, Tuszynski JA, Ottaviani MF, Danani A

Abstract
Toll-like receptors (TLRs) are pattern recognition transmembrane proteins that play an important role in innate immunity. In particular, TLR7 plays a role in detecting nucleic acids derived from viruses and bacteria. The huge number of pathologies in which TLR7 is involved has led to an increasing interest in developing new compounds targeting this protein. Several conjugation strategies were proposed for TLR7 agonists to increase the potency while maintaining a low toxicity. In this work, we focus the attention on two promising classes of TLR7 compounds derived from the same pharmacophore conjugated with phospholipid and polyethylene glycol (PEG). A multidisciplinary investigation has been carried out by molecular dynamics (MD), dynamic light scattering (DLS), electron paramagnetic resonance (EPR), and cytotoxicity assessment. DLS and MD indicated how only the phospholipid conjugation provides the compound abilities to self-assemble in an orderly fashion with a maximal pharmacophore exposition to the solvent. Further EPR and cytotoxicity experiments highlighted that phospholipid compounds organize in stable aggregates and well interact with TLR7, whereas PEG conjugation was characterized by poorly stable aggregates at the cells surface. The methodological framework proposed in this study may be used to investigate, at a molecular level, the interactions generally occurring between aggregated ligands, to be used as drugs, and protein receptors.

PMID: 29200306 [PubMed - indexed for MEDLINE]

Related Articles

A dialogue on the issue of the "quantum brain" between consciousness and unconsciousness.

J Integr Neurosci. 2017;16(s1):S13-S18

Authors: Cocchi M, Gabrielli F, Tonello L, Tuszynski J

Abstract
In this paper, we present some diverse points of view on the issue of the quantum brain.The paper is structured in the form of opening statements by each of the co-authors followed by comments and critique presented by the other co-authors. The main focus of the discussion is on the interplay between the state of being alive and consciousness, both of which possess characteristics of quantum physical states.

PMID: 29125495 [PubMed - indexed for MEDLINE]

Related Articles

Document of Trapani on animal consciousness and quantum brain function: A hypothesis.

J Integr Neurosci. 2017;16(s1):S99-S103

Authors: Cocchi M, Bernroider G, Rasenick M, Tonello L, Gabrielli F, Tuszynski JA

PMID: 29125501 [PubMed - indexed for MEDLINE]