DNA as Topological Quantum Computer

This article represents a vision about how DNA might act as a topological quantum computer (tqc). Tqc means that the braidings of braid strands define tqc programs and M-matrix (generalization of S-matrix in zero energy ontology) defining the entanglement between states assignable to the end points of strands define the tqc usually coded as unitary time evolution for Schödinger equation. One can ends up to the model in the following manner. a) Darwinian selection for which the standard theory of self-organization provides a model, should apply also to tqc programs. Tqc programs should correspond to asymptotic self-organization patterns selected by dissipation in the presence of metabolic energy feed. The spatial and temporal pattern of the metabolic energy feed characterizes the tqc program - or equivalently - sub-program call. b) Since braiding characterizes the tqc program, the self-organization pattern should correspond to a hydrodynamical flow or a pattern of magnetic field inducing the braiding. Braid strands must correspond to magnetic flux tubes of the magnetic body of DNA. If each nucleotide is transversal magnetic dipole it gives rise to transversal flux tubes, which can also connect to the genome of another cell. As a matter fact, the flux tubes would correspond to what I call wormhole magnetic fields having pairs of space-time sheets carrying opposite magnetic fluxes. c) The output of tqc sub-program is probability distribution for the outcomes of state function reduction so that the sub-program must be repeated very many times. It is represented as four-dimensional patterns for various rates (chemical rates, nerve pulse patterns, EEG power distributions, ...) having also identification as temporal densities of zero energy states in various scales. By the fractality of TGD Universe there is a hierarchy of tqcs corresponding to p-adic and dark matter hierarchies. Programs (space-time sheets defining coherence regions) call programs in shorter scale. If the self-organizing system has a periodic behavior each tqc module defines a large number of almost copies of itself asymptotically. Generalized EEG could naturally define this periodic pattern and each period of EEG would correspond to an initiation and halting of tqc. This brings in mind the periodically occurring sol-gel phase transition inside cell near the cell membrane. There is also a connection with hologram idea: EEG rhythm corresponds to reference wave and nerve pulse patters to the wave carrying the information and interfering with the reference wave. d) Fluid flow must induce the braiding which requires that the ends of braid strands must be anchored to the fluid flow. Recalling that lipid mono-layers of the cell membrane are liquid crystals and lipids of interior mono-layer have hydrophilic ends pointing towards cell interior, it is easy to guess that DNA nucleotides are connected to lipids by magnetic flux tubes and hydrophilic lipid ends are stuck to the flow. e) The topology of the braid traversing cell membrane cannot be affected by the hydrodynamical flow. Hence braid strands must be split during tqc. This also induces the desired magnetic isolation from the environment. Halting of tqc reconnects them and make possible the communication of the outcome of tqc. The model makes several testable predictions about DNA itself. In particular, matter-antimatter asymmetry and slightly broken isospin symmetry have counterparts at DNA level induced from the breaking of these symmetries for quarks and antiquarks associated with the flux tubes. DNA cell membrane system is not the only possible system that could perform tqc like activities and store memories in braidings: flux tubes could connect biomolecules and the braiding could provide an almost definition for what it is to be living. Even water memory might reduce to braidings. The model leads also to an improved understanding of other roles of the magnetic flux tubes containing dark matter. Phase transitions changing the value of Planck constant for the magnetic flux tubes could be key element of bio-catalysis and electromagnetic long distance communications in living matter. For instance, one ends up to what might be called code for protein folding and bio-catalysis. There is also a fascinating connection with Peter Gariaev's work suggesting that the phase transitions changing Planck constant have been observed and wormhole magnetic flux tubes containing dark matter have been photographed in his experiments

Second Generation General System Theory: Perspectives in Philosophy and Approaches in Complex Systems

Following the classical work of Norbert Wiener, Ross Ashby, Ludwig von Bertalanffy and many others, the concept of System has been elaborated in different disciplinary fields, allowing interdisciplinary approaches in areas such as Physics, Biology, Chemistry, Cognitive Science, Economics, Engineering, Social Sciences, Mathematics, Medicine, Artificial Intelligence, and Philosophy. The new challenge of Complexity and Emergence has made the concept of System even more relevant to the study of problems with high contextuality. This Special Issue focuses on the nature of new problems arising from the study and modelling of complexity, their eventual common aspects, properties and approaches—already partially considered by different disciplines—as well as focusing on new, possibly unitary, theoretical frameworks. This Special Issue aims to introduce fresh impetus into systems research when the possible detection and correction of mistakes require the development of new knowledge. This book contains contributions presenting new approaches and results, problems and proposals. The context is an interdisciplinary framework dealing, in order, with electronic engineering problems; the problem of the observer; transdisciplinarity; problems of organised complexity; theoretical incompleteness; design of digital systems in a user-centred way; reaction networks as a framework for systems modelling; emergence of a stable system in reaction networks; emergence at the fundamental systems level; behavioural realization of memoryless functions

Protein Structure

Since the dawn of recorded history, and probably even before, men and women have been grasping at the mechanisms by which they themselves exist. Only relatively recently, did this grasp yield anything of substance, and only within the last several decades did the proteins play a pivotal role in this existence. In this expose on the topic of protein structure some of the current issues in this scientific field are discussed. The aim is that a non-expert can gain some appreciation for the intricacies involved, and in the current state of affairs. The expert meanwhile, we hope, can gain a deeper understanding of the topic

The Amazing World of IDPs in Human Diseases

It is now clearly established that some proteins or protein regions are devoid of any stable secondary and/or tertiary structure under physiological conditions, but still possess fundamental biological functions. These intrinsically disordered proteins (IDPs) or regions (IDRs) have peculiar features due to their plasticity such as the capacity to bind their biological targets with high specificity and low affinity, and the possibility of interaction with numerous partners. A correlation between intrinsic disorder and various human diseases such as cancer, diabetes, amyloidoses and neurodegenerative diseases is now evident, highlighting the great importance of the topic. In this volume, we have collected recent high-quality research about IDPs and human diseases. We have selected nine papers which deal with a wide range of topics, from neurodegenerative disease to cancer, from IDR-mediated interactions to bioinformatics tools, all related to IDP peculiar features. Recent advances in the IDPs/IDRs issue are here presented, contributing to the progress of knowledge of the intrinsic disorder field in human disease

Functionally Relevant Macromolecular Interactions of Disordered Proteins

Disordered proteins are relatively recent newcomers in protein science. They were first described in detail by Wright and Dyson, in their J. Mol. Biol. paper in 1999. First, it was generally thought for more than a decade that disordered proteins or disordered parts of proteins have different amino acid compositions than folded proteins, and various prediction methods were developed based on this principle. These methods were suitable for distinguishing between the disordered (unstructured) and structured proteins known at that time. In addition, they could predict the site where a folded protein binds to the disordered part of a protein, shaping the latter into a well-defined 3D structure. Recently, however, evidence has emerged for a new type of disordered protein family whose members can undergo coupled folding and binding without the involvement of any folded proteins. Instead, they interact with each other, stabilizing their structure via “mutual synergistic folding” and, surprisingly, they exhibit the same residue composition as the folded protein. Increasingly more examples have been found where disordered proteins interact with non-protein macromolecules, adding to the already large variety of protein–protein interactions. There is also a very new phenomenon when proteins are involved in phase separation, which can represent a weak but functionally important macromolecular interaction. These phenomena are presented and discussed in the chapters of this book

Insights into the structures and dynamics of the pathogen secreted effectors AVR3A11 and tarp through the application of NMR spectroscopy

The lifecycles of obligate pathogenic and parasitic microorganisms depend on a myriad of interactions with their hosts at the molecular level. The class of bacterial proteins directly responsible for these inter-organism interactions have been termed e�ector proteins and can function in either an extracellular or, once secreted into the host cell, an intracellular environment. Primarily through the use of nuclear magnetic resonance spectroscopy (NMR), I have investigated the biophysical properties of two such bacterial e�ector proteins. TARP (translocated actin recruiting protein) is a largely disordered 100 kDa e�ector, common to all chlamydial species, which functions to remodel the host actin cytoskeleton to facilitate the internalisation of the chlamydial cell. Using constructs of TARP comprising an expected actin binding domain, I have shown through NMR chemical shift indexing and 15N relaxation that although the unbound domain is intrinsically disordered a short region, which aligns to other helical actin binding domains, maintains some helical propensity. Furthermore, these residues map to chemical shift variations in the bound state and the Kd for the interaction has also been determined using isothermal titration calorimetry. AVR3a11 is an 8 kDa e�ector from the pepper pathogen Phytophthora capsici that has been shown to inhibit plant programmed cell death. Using a combination of 2D and 3D NMR experiments I have assigned the majority of the backbone and side-chain resonances from the structured regions of AVR3a11. Through the acquisition and analysis of 13C and 15N edited HSQCNOESY spectra I have also calculated a water re�ned, structural ensemble for AVR3a11. Additionally, analysis of the slow (H:D exchange) and fast (T1, T2 and heteronuclear NOE) dynamic regimes, describes AVR3a11 as a relatively tightly folded helical bundle which also exhibits a signi�cant degree of conformational exchange

Dichotomic role of NAADP/two-pore channel 2/Ca2+ signaling in regulating neural differentiation of mouse embryonic stem cells

Poster Presentation - Stem Cells and Pluripotency: abstract no. 1866The mobilization of intracellular Ca2+stores is involved in diverse cellular functions, including cell proliferation and differentiation. At least three endogenous Ca2+mobilizing messengers have been identified, including inositol trisphosphate (IP3), cyclic adenosine diphosphoribose (cADPR), and nicotinic adenine acid dinucleotide phosphate (NAADP). Similar to IP3, NAADP can mobilize calcium release in a wide variety of cell types and species, from plants to animals. Moreover, it has been previously shown that NAADP but not IP3-mediated Ca2+increases can potently induce neuronal differentiation in PC12 cells. Recently, two pore channels (TPCs) have been identified as a novel family of NAADP-gated calcium release channels in endolysosome. Therefore, it is of great interest to examine the role of TPC2 in the neural differentiation of mouse ES cells. We found that the expression of TPC2 is markedly decreased during the initial ES cell entry into neural progenitors, and the levels of TPC2 gradually rebound during the late stages of neurogenesis. Correspondingly, perturbing the NAADP signaling by TPC2 knockdown accelerates mouse ES cell differentiation into neural progenitors but inhibits these neural progenitors from committing to the final neural lineage. Interestingly, TPC2 knockdown has no effect on the differentiation of astrocytes and oligodendrocytes of mouse ES cells. Overexpression of TPC2, on the other hand, inhibits mouse ES cell from entering the neural lineage. Taken together, our data indicate that the NAADP/TPC2-mediated Ca2+signaling pathway plays a temporal and dichotomic role in modulating the neural lineage entry of ES cells; in that NAADP signaling antagonizes ES cell entry to early neural progenitors, but promotes late neural differentiation.postprin