Quantum Theory and the Nature of Consciousness

Our interest focusses on the idea, that consciousness is a powerful acting entity. Up to now there does not exist a scientific concept for this idea. This is not due to problems within the field of psychology or brain research, but rather in resisting theories of modern physics. That is, why we have to search for a solution in the field of physics. A solution can be found in a new understanding of the basics of physical theory. That could be given by abstract and absolute quantum bits of information (AQI bits). To avoid the popular misunderstanding of “information” as “meaningful” it was necessary to find a new word for the free-of-meaning AQI bits: the AQI bits establish a quantum pre-structure termed “Protyposis” (Greek: “pre-formation”), out of which real objects can be formed, starting from energetical and material elementary particles. The Protyposis AQI bits provide a pre-structure for all entities in natural sciences. They are the basic entities, whereof the physical nature of the brain, on the one hand, and the mental nature of consciousness, on the other hand, were formed during the cosmological and the following biological evolution. A deeper understanding of quantum structures may help to overcome the resistance against quantum theory in the field of brain research and consciousness. The key for an understanding is the concept of Protyposis, which means an abstract quantum information free of any definite meaning. With the AQI bits of the Protyposis, both, massless and massive quantum particles can be constructed. Even quantum information with special meanings, in example grammatically formulated thoughts, eventually could be explained. As long as the fundamental basis of quantum theory is misunderstood as being formed by a manifold of some small objects like atoms, quarks, or strings, the problem of understanding consciousness has no solution. If instead we understand quantum theory as based on truly simple quantum structures, there would be no longer fundamental problems for an understanding of consciousness.     

Approximation,Mad Men and the Death of JFK

In this article I take the US television series Mad Men (2007—present) as an exemplary ‘approximation’, a term I adopt to signal the way in which certain texts construct a changeable, fluid ‘truth’ resulting from collisions, exchange and dialectical argument. Approximations are layered, their formal layerings mirroring a layered, multifaceted argument. Mad Men integrates and represents real historical events within a fictional setting, and act that suggests that an event or action can never be finished, fixed and not open to reassessment. Specifically, this article examines ‘The Grown Ups’, Episode 12 of Season 3, which charts the events of 22 November 1963, the day Kennedy was assassinated. Although we might be able to bring to mind the images and conspiracy theories that have been made available since (such Abraham Zapruder’s 8 mm home movie footage of the assassination), these images were not available at the time. Mad Men as a series always strives to represent its historical milieu as authentically as possible, so the characters re-enact 22 November 1963 as authentically as possible by watching only what was on television that day (the news bulletin, Walter Kronkite’s announcement that Kennedy is dead). The contemporary backdrop to these events, including the resonances of ‘9/11’ through Mad Men, inform and collide with the authenticity on the screen.     

Prion protein cleavage fragments regulate adult neural stem cell quiescence through redox modulation of mitochondrial fission and SOD2 expression

Neurogenesis continues in the post-developmental brain throughout life. The ability to stimulate the production of new neurones requires both quiescent and actively proliferating pools of neural stem cells (NSCs). Actively proliferating NSCs ensure that neurogenic demand can be met, whilst the quiescent pool makes certain NSC reserves do not become depleted. The processes preserving the NSC quiescent pool are only just beginning to be defined. Herein, we identify a switch between NSC proliferation and quiescence through changing intracellular redox signalling. We show that N-terminal post-translational cleavage products of the prion protein (PrP) induce a quiescent state, halting NSC cellular growth, migration, and neurite outgrowth. Quiescence is initiated by the PrP cleavage products through reducing intracellular levels of reactive oxygen species. First, inhibition of redox signalling results in increased mitochondrial fission, which rapidly signals quiescence. Thereafter, quiescence is maintained through downstream increases in the expression and activity of superoxide dismutase-2 that reduces mitochondrial superoxide. We further observe that PrP is predominantly cleaved in quiescent NSCs indicating a homeostatic role for this cascade. Our findings provide new insight into the regulation of NSC quiescence, which potentially could influence brain health throughout adult life.     

Bridging the molecular and biological functions of the oxysterol-binding protein family

Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a large eukaryotic gene family that transports and regulates the metabolism of sterols and phospholipids. The original classification of the family based on oxysterol-binding activity belies the complex dual lipid-binding specificity of the conserved OSBP homology domain (OHD). Additional protein- and membrane-interacting modules mediate the targeting of select OSBP/ORPs to membrane contact sites between organelles, thus positioning the OHD between opposing membranes for lipid transfer and metabolic regulation. This unique subcellular location, coupled with diverse ligand preferences and tissue distribution, has identified OSBP/ORPs as key arbiters of membrane composition and function. Here, we will review how molecular models of OSBP/ORP-mediated intracellular lipid transport and regulation at membrane contact sites relate to their emerging roles in cellular and organismal functions.     

Imaging of oxygen and hypoxia in cell and tissue samples

Molecular oxygen (O₂) is a key player in cell mitochondrial function, redox balance and oxidative stress, normal tissue function and many common disease states. Various chemical, physical and biological methods have been proposed for measurement, real-time monitoring and imaging of O₂ concentration, state of decreased O₂ (hypoxia) and related parameters in cells and tissue. Here, we review the established and emerging optical microscopy techniques allowing to visualize O₂ levels in cells and tissue samples, mostly under in vitro and ex vivo, but also under in vivo settings. Particular examples include fluorescent hypoxia stains, fluorescent protein reporter systems, phosphorescent probes and nanosensors of different types. These techniques allow high-resolution mapping of O₂ gradients in live or post-mortem tissue, in 2D or 3D, qualitatively or quantitatively. They enable control and monitoring of oxygenation conditions and their correlation with other biomarkers of cell and tissue function. Comparison of these techniques and corresponding imaging setups, their analytical capabilities and typical applications are given.     

Degradation of the mitochondrial complex I assembly factor TMEM126B under chronic hypoxia

Cell stress such as hypoxia elicits adaptive responses, also on the level of mitochondria, and in part is mediated by the hypoxia-inducible factor (HIF) 1α. Adaptation of mitochondria towards acute hypoxic conditions is reasonably well understood, while regulatory mechanisms, especially of respiratory chain assembly factors, under chronic hypoxia remains elusive. One of these assembly factors is transmembrane protein 126B (TMEM126B). This protein is part of the mitochondrial complex I assembly machinery. We identified changes in complex I abundance under chronic hypoxia, in association with impaired substrate-specific mitochondrial respiration. Complexome profiling of isolated mitochondria of the human leukemia monocytic cell line THP-1 revealed HIF-1α-dependent deficits in complex I assembly and mitochondrial complex I assembly complex (MCIA) abundance. Of all mitochondrial MCIA members, we proved a selective HIF-1-dependent decrease of TMEM126B under chronic hypoxia. Mechanistically, HIF-1α induces the E3-ubiquitin ligase F-box/WD repeat-containing protein 1A (β-TrCP1), which in turn facilitates the proteolytic degradation of TMEM126B. Attenuating a functional complex I assembly appears critical for cellular adaptation towards chronic hypoxia and is linked to destruction of the mitochondrial assembly factor TMEM126B.     

Defining G protein-coupled receptor peptide ligand expressomes and signalomes in human and mouse islets

Introduction

Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.

Materials and methods

GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC. The pathways connecting GPCR peptide ligands with their receptors were identified by manual searches in the PubMed, IUPHAR and Ingenuity databases. Distribution of PYY protein in mouse and human islets was determined by immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets was measured by radioimmunoassay.

Results

We have quantified GPCR peptide ligand mRNA expression in human and mouse islets and created specific signalomes mapping the pathways by which islet peptide ligands regulate human and mouse GPCR signalling. We also identified species-specific islet expression of several GPCR ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than human islets, suggesting a more important role of locally secreted Pyy in mouse islets. This was confirmed by IHC and functional experiments measuring insulin, glucagon and somatostatin secretion.

Discussion

The detailed human and mouse islet GPCR peptide ligand atlases will allow accurate translation of mouse islet functional studies for the identification of GPCR/peptide signalling pathways relevant for human physiology, which may lead to novel treatment modalities of diabetes and metabolic disease.