The nature of reality is experienced as determined by the information-processing capabilities of ... more The nature of reality is experienced as determined by the information-processing capabilities of our brains. While the processing of sensory inputs at the level of the sensory organs operates near optimal performance and the response properties of sensory neurons are optimal for the encoding of stimuli, the processing at later stages within the brain may lose that optimality. Limitations exist at several levels, imposed by neurophysiology as well as psychology, from the unreliability of cell-to-cell contact through synapses to the restrictions of the mental functions derived from their own logical features. It is a fundamental goal of neuroscience to understand the limitations of information processing in nervous systems and particularly in the mammalian brain, not only to better comprehend cognitive functions and the perception of reality but also to characterize pathological mental/brain states. Equally important is another of the main goals of contemporary neuroscience, the understanding of self-consciousness, that is, that the brain is not only aware of its surroundings but also of its own functioning. This scheme contains the implicit assumption that brain states like the "self" can be comprehended by the brain itself. The constraints imposed by autonomous neural/mental activity and internal brain architecture have to be acknowledged as much as those imposed by the environment. In addition to the limits imposed by the intricacy of the brain's cellular circuitry, other logical limitations may also play a role, specifically the highly debatable issue of whether the fundamental limitative theorems in mathematical logic can also apply or are relevant to the mind as a formal system. This special issue contains works that deal with different aspects of brain and machine information processing and from distinct perspectives: mathematical, physical, and philosophical, as the examination of these queries requires a multidisciplinary approach. We hope that these contributions will stimulate readers to further explore the complexities of the mental world that brains create.
The control of cell adhesion at polymer surfaces is of great interest for applications in medicin... more The control of cell adhesion at polymer surfaces is of great interest for applications in medicine and biotechnology research. We present a method of polystyrene (PS) surface treatment by UV laser irradiation (laser wavelength l=193 nm) for the improvement of adhesion of Chinese hamster ovary (CHO) cells. We irradiated the PS foils with a total fluence of 200 mJ/cm2 in a circular spot. The irradiation led to formation of specific micro pattern at the surface (assessed by AFM and SEM). Depending on the position at the spot, the pattern structure varies. There is a specific ring area (B in , where seeded CHO cells show effective adhesion and pronounced spreading. The cells display here a preferential alignment along the ring. The topography of this area has a height variation of 5 to 10 nm, while the surface region irradiated with higher laser intensity (A in has a higher roughness of hundreds of nm. This area is less favorable for CHO cells adhesion as indicated by the round cell morphology, similar to the flat area outside the ring. (Supported by the Austrian NANO Initiative in the projects NSI_NBPF and NSI_PolyModEUV. We present a microfluidic device for measuring affinities of biomolecular interactions. Previous work in our group has led to the development of microfluidic mixing devices, a method for biophysically characterizing molecular interactions, a platform for in situ protein expression from arrays of DNA templates, and the ability to independently address rows of the array. By combining these techniques, we can generate titration curves for a single species of a fluorescently labeled molecule against as many as 48 interaction partners in a single experiment. This approach consumes less than a picomole of the labeled molecule per titration curve, of particular use when the material is precious and of low abundance. Sorting and detection technologies have become an important part of industrial and medical practice. Recently, innovation in lab-on-a-chip technologies promises smaller, less expensive, and more portable devices for these applications. Labeling efficiency, specificity and throughput are challenges that must be overcome in developing such technologies. We introduce a continuous-flow magnetic flow focusing, sorting and detection scheme for unlabeled particles on the size order of cells. Unlabeled particles are focused and sorted by size in the apparatus using the magnetophoretic force in a specially crafted highgradient magnetic field. The magnetic scheme is orthogonal to other sorting techniques, allowing other physical properties to be explored. We demonstrate using the light pressure force from a laser to actively sort a focused stream of flowing particles and use the balance between the light pressure force and the magnetic force as an additional physical axis on which particles can be sorted. We show that the positions and distribution of the particles conform to their theoretical expectations, and use the theory to explore the limitations of this technology in practice. We propose a single molecule fluorescence-based approach to rapidly locate specific sequences on DNA. Using the roughly 50,000 base pair lambda-DNA as a model molecule, we demonstrate that patterns of targeted sequences can be detected using peptide nucleic acid (PNA)-based probes. These bisP-NAs, modified with biotin and Tamra on opposing ends, bind to target sequences on double-stranded lambda-DNA. While PNA probes were chosen for their specificity and versatility, they are prone to bind to non-target sites that differ from the target site by one terminal base pair. PNA binding to these single-end mismatch (SEMM) sites can be minimized by a moderate amount of additional heating following the binding reaction and this step must be optimized to achieve the requisite specificity.
Characterization of the AXH domain of ataxin-1 using enhanced sampling and functional mode analysis
Proteins, Jan 15, 2016
Ataxin-1 is the protein responsible for the Spinocerebellar ataxia type 1, an incurable neurodege... more Ataxin-1 is the protein responsible for the Spinocerebellar ataxia type 1, an incurable neurodegenerative disease caused by polyglutamine expansion. The AXH domain plays a pivotal role in physiological functions of Ataxin-1. In Spinocerebellar ataxia 1, the AXH domain is involved in the misfolding and aggregation pathway. Here molecular modeling is applied to investigate the protein-protein interactions contributing to the AXH dimer stability. Particular attention is focused on: i) the characterization of AXH monomer-monomer interface; ii) the molecular description of the AXH monomer-monomer interaction dynamics. Technically, an approach based on functional mode analysis, here applied to replica exchange molecular dynamics trajectories, was employed. The findings of this study are consistent with previous experimental results and elucidate the pivotal role of the I580 residue in mediating the AXH monomer-monomer interaction dynamics. This article is protected by copyright. All right...
Dissipationless Transfer of Visual Information From Retina to the Primary Visual Cortex in the Human Brain
Activitas Nervosa Superior, 2012
ABSTRACT Recently, the experiments on photosynthetic systems via “femto-second laser spectroscopy... more ABSTRACT Recently, the experiments on photosynthetic systems via “femto-second laser spectroscopy” methods have indicated that a “quantum-coherence” in the system causes a highly efficient transfer of energy to the “reaction center” (efficiency is approximately equal to 100%). A recent experiment on a single neuron has indicated that it can conduct light. Also, a re-emission of light from both photosynthetic systems and single neurons has been observed, which is called “delayed luminescence”. This can be supposed as a possibility for dissipationless transfer of visual information to the human brain. In addition, a long-range Fröhlich coherence in microtubules can be a candidate for efficient transfer of light through “noisy” and complex structures of the human brain. From an informational point of view it is a legitimate question to ask how human brain can receive subtle external quantum information of photons intact when photons are in a quantum superposition and pass through very noisy and complex pathways from the eye to the brain? Here, we propose a coherent model in which quantum states of photons can be rebuilt in the human brain.
Chicoric acid binds to two sites and decreases the activity of the YopH bacterial virulence factor
Oncotarget, 2016
Chicoric acid (CA) is a phenolic compound present in dietary supplements with a large spectrum of... more Chicoric acid (CA) is a phenolic compound present in dietary supplements with a large spectrum of biological properties reported ranging from antioxidant, to antiviral, to immunostimulatory properties. Due to the fact that chicoric acid promotes phagocytic activity and was reported as an allosteric inhibitor of the PTP1B phosphatase, we examined the effect of CA on YopH phosphatase from pathogenic bacteria, which block phagocytic processes of a host cell. We performed computational studies of chicoric acid binding to YopH as well as validation experiments with recombinant enzymes. In addition, we performed similar studies for caffeic and chlorogenic acids to compare the results. Docking experiments demonstrated that, from the tested compounds, only CA binds to both catalytic and secondary binding sites of YopH. Our experimental results showed that CA reduces activity of recombinant YopH phosphatase from Yersinia enterocolitica and human CD45 phosphatase. The inhibition caused by CA ...
Microtubules (MTs) are important cytoskeletal superstructures implicated in neuronal morphology a... more Microtubules (MTs) are important cytoskeletal superstructures implicated in neuronal morphology and function, which are involved in vesicle trafficking, neurite formation and differentiation and other morphological changes. The structural and functional properties of MTs depend on their high intrinsic charge density and functional regulation by the MT depolymerising properties of changes in Ca 2+ concentration. Recently, we reported on remarkable properties of isolated MTs, which behave as biomolecular transistors capable of amplifying electrical signals (Priel et al., Biophys J 90:4639-4643, 2006). Here, we demonstrate that MT-bathing (cytoplasmic) Ca 2+ concentrations modulate the electrodynamic properties of MTs. Electrical amplification by MTs was exponentially dependent on the Ca 2+ concentration between 10 −7 and 10 −2 M. However, the electrical connectivity (coupling) of MTs was optimal at a narrower window of Ca 2+ concentrations. We observed that while raising bathing Ca 2+ concentration increased electrical amplification by MTs, energy transfer was highest in the presence of ethylene glycol tetraacetic acid (lowest Ca 2+ concentration). Our data indicate that Ca 2+ is an important modulator of electrical amplification by MTs, supporting the hypothesis that this divalent cation, which adsorbs onto the polymer's surface, plays an important role as a regulator of the electrical properties of MTs. The Ca 2+ -dependent ability of MTs to modulate and amplify electrical signals may provide a novel means of cell signaling, likely contributing to neuronal function.
Josephin Domain Structural Conformations Explored by Metadynamics in Essential Coordinates
PLoS computational biology, 2016
The Josephin Domain (JD), i.e. the N-terminal domain of Ataxin 3 (At3) protein, is an interesting... more The Josephin Domain (JD), i.e. the N-terminal domain of Ataxin 3 (At3) protein, is an interesting example of competition between physiological function and aggregation risk. In fact, the fibrillogenesis of Ataxin 3, responsible for the spinocerebbellar ataxia 3, is strictly related to the JD thermodynamic stability. Whereas recent NMR studies have demonstrated that different JD conformations exist, the likelihood of JD achievable conformational states in solution is still an open issue. Marked differences in the available NMR models are located in the hairpin region, supporting the idea that JD has a flexible hairpin in dynamic equilibrium between open and closed states. In this work we have carried out an investigation on the JD conformational arrangement by means of both classical molecular dynamics (MD) and Metadynamics employing essential coordinates as collective variables. We provide a representation of the free energy landscape characterizing the transition pathway from a JD ...
In this paper we argue that, in addition to electrical and chemical signals propagating in the ne... more In this paper we argue that, in addition to electrical and chemical signals propagating in the neurons of the brain, signal propagation takes place in the form of biophoton production. This statement is supported by recent experimental confirmation of photon guiding properties of a single neuron. We have investigated the interaction of mitochondrial biophotons with microtubules from a quantum mechanical point of view. Our theoretical analysis indicates that the interaction of biophotons and microtubules causes transitions/fluctuations of microtubules between coherent and incoherent states. A significant relationship between the fluctuation function of microtubules and alpha-EEG diagrams is elaborated on in this paper. We argue that the role of biophotons in the brain merits special attention.
In studying biological systems, conventional approaches based on the laws of physics almost alway... more In studying biological systems, conventional approaches based on the laws of physics almost always require introducing appropriate approximations. We argue that a comprehensive approach that integrates the laws of physics and principles of inference provides a better conceptual framework than these approaches to reveal emergence in such systems. The crux of this comprehensive approach hinges on entropy. Entropy is not merely a physical quantity. It is also a reasoning tool to process information with the least bias. By reviewing three distinctive examples from protein folding dynamics to drug design, we demonstrate the developments and applications of this comprehensive approach in the area of biological systems.
It is known that the Arrhenius equation, based on the Boltzmann distribution, can model only a pa... more It is known that the Arrhenius equation, based on the Boltzmann distribution, can model only a part (e.g. half of the activation energy) for retinal discrete dark noise observed for vertebrate rod and cone pigments. Luo et al (Science, 332, 1307-312, 2011) presented a new approach to explain this discrepancy by showing that applying the Hinshelwood distribution instead the Boltzmann distribution in the Arrhenius equation solves the problem successfully. However, a careful reanalysis of the methodology and results shows that the approach of Luo et al is questionable and the results found do not solve the problem completely.
Bioorganic Medicinal Chemistry Letters, Mar 15, 2011
A series of 1,5-diaryl-substituted tetrazole derivatives was synthesized via conversion of readil... more A series of 1,5-diaryl-substituted tetrazole derivatives was synthesized via conversion of readily available diaryl amides into corresponding imidoylchlorides followed by reaction with sodium azide. All compounds were evaluated by cyclooxygenase (COX)
The Penrose-Hameroff (`Orch OR') model of quantum computation in brain microtubules has been crit... more The Penrose-Hameroff (`Orch OR') model of quantum computation in brain microtubules has been criticized as regards the issue of environmental decoherence. A recent report by Tegmark finds that microtubules can maintain quantum coherence for only $10^{-13}$ s, far too short to be neurophysiologically relevant. Here, we critically examine the assumptions behind Tegmark's calculation and find that: 1) Tegmark's commentary is not aimed at an existing model in the literature but rather at a hybrid that replaces the superposed protein conformations of the `Orch OR' theory with a soliton in superposition along the microtubule, 2) Tegmark predicts decreasing decoherence times at lower temperature, in direct contradiction of the observed behavior of quantum states, 3) recalculation after correcting Tegmark's equation for differences between his model and the `Orch OR' model (superposition separation, charge vs. dipole, dielectric constant) lengthens the decoherence time to $10^{-5} - 10^{-4}$ s and invalidates a critical assumption of Tegmark's derivation, 4) incoherent metabolic energy supplied to the collective dynamics ordering water in the vicinity of microtubules at a rate exceeding that of decoherence can counter decoherence effects (in the same way that lasers avoid decoherence at room temperature), and 5) phases of actin gelation may enhance the ordering of water around microtubule bundles, further increasing the decoherence-free zone by an order of magnitude and the decoherence time to $10^{-2} - 10^{-1}$ s. These revisions bring microtubule decoherence into a regime in which quantum gravity can interact with neurophysiology.
We develop a physiologically-based lattice model for the transport and metabolism of drugs in the... more We develop a physiologically-based lattice model for the transport and metabolism of drugs in the functional unit of the liver, called the lobule. In contrast to earlier studies, we have emphasized the dominant role of convection in well-vascularized tissue with a given structure. Estimates of convective, diffusive and reaction contributions are given. We have compared drug concentration levels observed exiting the lobule with their predicted detailed distribution inside the lobule, assuming that most often the former is accessible information while the latter is not.
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Papers by Jack Tuszynski