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Ionic Currents: The Spark of Life

2008-07-21T22:03:00Z

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Xanya Sofra-Weiss. Ph.D, (2008) Ionic Currents: The Spark of Life and Directional Force in Cellular Metabolism and Energetics. The aging process cannot be conceptualized by examining a single gene or a single pathway, but can best be addressed at the systems level. Aging is not only the sum total of shortened telomeres, denatured proteins and DNA molecules, or oxidative damage in the mitochondria. Aging attacks key regulatory nodes crucial for the biological network stability. It is the dynamic process of increasing imbalances in the systemic organization of degenerating biological processes. DNA and stem cells engineering have successfully reversed certain individual components of time attrition resulting in rejuvenation and aging delay. So far, research has merely followed a sequential process that goes from the part to the whole, identifying aging genes and engineering stem cells, etc. However, discovering pieces of the puzzle still requires identification of the interconnections between matching pieces before the solution emerges. The old, the ill, and the injured all suffer from misarranged patterns of atoms. A single substitution an A for a G in a DNA molecule can cause a significant change in the conductance of the molecule leading to cancer. Such research findings demonstrate how the sequence and interrelations of amino acids in a protein, or the sequence of base pairs in a DNA molecule can become determining factors between health and disease, aging and youth. Gene expression is stronger when the gene is attached to the nuclear envelope (the membrane that surrounds the nucleus) than when it moves away from the nuclear envelope (see image). In other words, cells make use of the nuclear architecture to code epigenetic information. The DNA sequence alone doesn't determine everything. The importance of the spatial organization or nuclear architecture in regulating gene expression begs for scientific observation that does not merely focus on the study of atoms and molecules, (the basic components of a Gestalt); but on the interrelations, sequence, orientation and spatial organization of these atoms and molecules (the dynamic whole or Gestalt). Recent research has shown that DNA, proteins, cells, including stem cells, appear to be electrical in that they demonstrate conductivity or the presence of ionic currents. Since electricity is a dynamic entity emerging out of the interactions of atoms and molecules, we propose that perhaps the simplest way of focusing on the entire system is by decoding the complex electrical signals that map biological interactions with respect to spatial organization. Biological signals must be analyzed in terms of their amperage, frequency, voltage, interactions, orientation, spatial organization. Next will be their translation into electronic signals that comply with the specifications of amperage, frequency, voltage or biological signals. Electronic signals will then be intertwined to orchestrate a Gestalt waveform built on the basis of information attained from observations of biological interactions and architecture – a process similar to that done in Pollock’s lab (1990-2004). This Gestalt waveform will act as an electronic diplomat to awaken biological processes that have diminished with aging or disease by signaling the recuperation and activation of biological reparative mechanisms leading to extended longevity.

Understanding Zero Point Energy

2008-07-18T20:32:00Z

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Thomas Valone, M.A., P.E. Integrity Research Institute (1999) Zero point energy has been called "the ultimate quantum free lunch" (Science, Vol. 275, 1/10/97). During the early years of quantum mechanics, Paul Dirac theorized that the vacuum was actually filled with particles in negative energy states (Proc. R. Soc. London A, 126, 360, 1930) thus giving rise to the concept of the "physical vacuum" which is not empty at all. Quantum mechanics also predicted that invisible particles could become materialized for a short time and that these virtual particle appearances should exert a force that is measurable. Hendrik B. G. Casimir (Phys. Rev. 73, 360, 1948) not only predicted the presence of such a force but also explained why van der Waals forces dropped off unexpectedly at long range separation between atoms, predicting that force F=K/d4 where K=p hc/480. Though the Casimir effect subsequently was verified using non-conductive plates, there was always a scientific need for a verification of the Casimir force using conductive plates based on Casimir's 1948 paper. For the first time, Dr. Lamoreaux, now at the Los Alamos Labs, performed the experiment with less than one micrometer (micron) spacing between gold-plated parallel plates attached to a torsion pendulum (Phys. Rev. Ltrs., 78, 1, 97). In retrospect, he found it to one of the most intellectually satisfying experiments that he ever performed since the results matched the theory so closely (within 5%). The Casimir effect has been posited as a force produced solely by activity in the vacuum. The Casimir force is also very powerful at small distances. Besides being independent of temperature, it is inversely proportional to the fourth power of the distance between the plates! Therefore, as the plates are brought closer, the virtual particles outside the plates increasingly overpower the decreasing quantity of virtual particles appearing between the plates with an exponentially increasing force. (Also notable is the fact that its frequency dependence is a third power and the force can be altered with dielectrics or resonate with narrow-band mirrors—see Phys. Lett. A 225, 1997, 188-194.) Lamoreaux's results come as no surprise to anyone familiar with quantum electrodynamics (QED), but they serve as a material confirmation of an unusual theoretical prediction that QED predicts the all-pervading vacuum continuously spawns particles and waves that spontaneously pop in and out of existence. Their time of existence is strictly limited by the uncertainty principle but they create some havoc while they bounce around during their brief lifespan. The churning quantum foam extends throughout the universe even filling the empty space within the atoms. A diagram showing "The Shape of Nothing" (The New York Times 1/21/97) is pictured to be not only subatomic but subelementary particle in size. Physical theories predict that on an infinitesimally small scale, far, far smaller than the diameter of atomic nucleus, quantum fluctuations produce a foam of erupting and collapsing, virtual particles, visualized as a topographic distortion of the fabric of space time.

Biological Dynamics of Anti-aging

2008-07-18T19:27:00Z

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Xanya Sofra-Weiss, Ph.D (2008) Dynamic Healthy Anti-Aging. The biological components of youth act independently and yet in synch with each other. Imagine a very large jazz orchestra where everyone is doing his or her own thing while being perfectly in step and in tune with the whole. Viewed from the above macroscopic point of view, the biological system appears to be an organic gestalt (an organic whole that is greater than the parts that compose it) and where these parts are interconnected by a multiplicity of electro-biochemical signals.

The Casimir Effect

2008-07-17T20:18:00Z

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Quantum mechanics was one of the most outstanding physical theories of the twentieth century. It revealed Nature at the microscopic scale as a strange and fascinating scientific object which seems to defy natural human intuition developed through our every day experience. Though this quantum character is present everywhere as the building block of the physical world, it seldom revels itself at a macroscopic level. The Casimir effect is one of those rare exceptions where a quantum effect can have significant consequences beyond the atomic level. The simplest form of the Casimir effect was predicted in 1948 by H.B.G. Casimir and consists in the attraction between a pair of neutral, parallel conducting plates placed in the vacuum. This attractive force has a purely quantum origin and cannot be obtained using the classical description of electromagnetic field since it is a direct consequence of the existence of Zero-Point Fluctuations: a turmoil of virtual particles that come in and out of existence and that can violate the energy-momentum conservation of the system for very short periods of time, as described by Heisenberg's uncertainty principle.

Electrical Aspects of Neurons

2008-07-16T23:01:00Z

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Power Point Presentation of Electrical Signals carried by Ions. The concentration of ions within the cell is different than the concentration outside of the cell. Some ions have higher concentration inside (K+). Some ions have higher concentrations outside: Na+, Cl-, Ca++

Cellular Proliferation and Differentiation

2008-07-16T22:56:00Z

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Nicolas Goardon, Julie A Lambert, Patrick Rodriguez, Philippe Nissaire, Sabine Herblot, Pierre Thibault, Dominique Dumenil, John Strouboulis, Paul-Henri Romeo, and Trang Hoang (2006) The passage from proliferation to terminal differentiation is critical for normal development and is often perturbed in malignancies. In blood cells, cell cycle arrest is intimately linked with terminal erythroid cell maturation, suggesting that the proliferation and differentiation need to be coordinately regulated.

G Protein in Human Cytotoxic T Lymphocytes

2008-07-16T22:02:00Z

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H.-W. MITTRUCKER & B. FLEISCHER (1992) Cytotoxic T lymphocytes can be triggered by the guanosine triphosphate (GTP) analogue GTPyS to release the contents of their granula by exocytosis (the process of cellular secretion). GTPyS triggers exocytosis in permeabilized human cytotoxic Tlymphocytes. That the response was only seen after introduction of GTPyS but not of ATPyS suggests that indeed a G-protein is mediating this exocytotic response.

The Casimir Force

2008-07-16T20:25:00Z

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Something from Nothing? The Casimir force arises from one of those unlikely sounding real world manifestations of quantum mechanics. It begins with considerations of what exactly is a vacuum. In the classical everyday sense we think of a vacuum as what is left after we have removed all of the stuff, molecules atoms etc. But that still leaves photons, so if we remove those as well, including all the thermal energy then surely we should now have an absolute vacuum which contains precisely nothing. Therein lies the problem. Heisenberg's uncertainty principle, describes the limitation on the knowledge of pairs of parameters in terms of Planck's constant; most well known being position and momentum. An equally important pairing is energy and time, and quantum mechanics forbids the precise independent knowledge of these two parameters. The absolute energy of a system is thus unknowable as a single parameter, including the unique value of zero. So we cannot have a vacuum of absolute zero energy because it violates the uncertainty principle. The theoretical physics resolution of this paradox is to assume the existence of virtual particles which pop out of the vacuum and wander around for an undefined time and then pop back, thus giving the vacuum an average zero point energy, but without disturbing the real world too much. One of the most remarkable results of Quantum Field Theory is the existence of vacuum fields, particles and zero-point energy. Vacuum is not a tranquil void but a quantum state made up of matter fields and energy fields.

A Modular Network Model of Aging

2008-07-16T03:07:00Z

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Huiling Xue, Bo Xian, Dong Dong, Kai Xia, Shanshan Zhu, Zhongnan Zhang, Lei Hou, Qingpeng Zhang, Yi Zhang & Jing-Dong J Han (2007) Many fundamental questions on aging are still unanswered or are under intense debate. These questions are frequently not addressable by examining a single gene or a single pathway, but can best be addressed at the systems level. Here we examined the modular structure of the protein–protein interaction (PPI) networks during fruitfly and human brain aging. In both networks, there are two modules associated with the cellular proliferation to differentiation temporal switch that display opposite aging-related changes in expression. During fly aging, another couple of modules are associated with the oxidative–reductive metabolic temporal switch. These network modules and their relationships demonstrate (1) that aging is largely associated with a small number, instead of many network modules, (2) that some modular changes might be reversible and (3) that genes connecting different modules through PPIs are more likely to affect aging/longevity, a conclusion that is experimentally validated by Caenorhabditis elegans lifespan analysis. Network simulations further suggest that aging might preferentially attack key regulatory nodes that are important for the network stability, implicating a potential molecular basis for the stochastic nature of aging.

Understanding Biological Functions Through Molecular Networks

2008-07-16T02:27:00Z

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Jing-Dong Jackie Han (2008) To understand biological processes beyond single gene analyses, molecular biologists and geneticists often examine biomolecules in the framework of pathways and networks. This way the relationships of the molecules and the logic of operations can be readily captured and visualized. Experimental, statistical and mathematical modeling approaches have been employed to study the structure, function and dynamics of molecular networks, and begin to reveal important links of various network properties to the functions of the biological systems. In agreement with these functional links, evolutionary selection of a network is apparently based on the function, rather than directly on the structure of the network. Dynamic modularity is one of the prominent features of molecular networks. Taking advantage of such a feature may simplify network-based biological studies through construction of process-specific modular networks and provide functional and mechanistic insights linking genotypic variations to complex traits or diseases, which is likely to be a key approach in the next wave of understanding complex human diseases. With the development of ready-to-use network analysis and modeling tools the networks approaches will be infused into everyday biological research in the near future.

Nanosecond Pulsed Electric Fields Cause Melanomas to Self-Destruct

2008-07-16T02:21:00Z

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Richard Nuccitelli, Uwe Pliquett, Xinhua Chen, Wentia Ford, R. James Swanson, Stephen J. Beebe, Juergen F. Kolb, Karl H. Schoenbach (2006) We have discovered a new, drug-free therapy for treating solid skin tumors. Pulsed electric ﬁelds greater than 20 kV/cm with rise times of 30 ns and durations of 300 ns penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood ﬂow to stop. Melanomas shrink by 90% within two weeks following a cumulative ﬁeld exposure time of 120 ls. A second treatment at this time can result in complete remission. This new technique provides a highly localized targeting of tumor cells with only minor eﬀects on overlying skin. Each pulse deposits 0.2 J and 100 pulses increase the temperature of the treated region by only 3 °C, ten degrees lower than the minimum temperature for hyperthermia eﬀects.

Ionic Currents in Pacemaker Cells

2008-07-15T20:09:00Z

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Prof. Dario Di Francesco, Prof. Michele Mazzanti, Dr. Andrea Barbuti, Dr. Mirko Baruscotti, Dr. Enzo Mancinelli (April 9, 2008) Molecular Physiology and Neurobiology Unit investigates the properties of different ion channels. A major project involves the pacemaker ("funny") channel, originally described in cardiac "pacemaker" cells of the sinoatrial node (SAN) (Brown, DiFrancesco & Noble, 1979, Nature 280, 235) and actively investigated since in cardiac myocytes and in neurons. Cardiac rhythmic activity is generated by "pacemaker" cells, which in mammals are located in the sino-atrial node. Action potentials of SAN cells have a special phase, called diastolic (or pacemaker) depolarization, which at the end of an action potential slowly takes the membrane voltage up to threshold for firing of a new action potential, thus inducing repetitive activity. Activation of If is the mechanism underlying the pacemaker depolarization. The If current is also modulated by intracellular cAMP, according to a mechanism responsible for the neurotransmitter-induced modulation of cardiac rate. A similar pacemaker current (Ih) is also expressed in neurons. In sensory neurons Ih is involved in the perception of external stimuli, or in modulating the transduction of sensory stimuli into electrical signalling. Ih is also expressed in pre-synaptic membranes, where it is involved in plasticity phenomena.

Specific reduction of calcium-binding protein and gene expression in aging

2008-07-15T01:36:00Z

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ANTHONY M. IACOPINO AND SYLVIA CHRISTAKOS (1990) Department of Biochemistry and Molecular Biology, Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, NJ. The present studies establish that there are specific, significant decreases in the neuronal calcium-binding protein (28-kDa calbindin-D) gene expression in aging and in neurodegenerative diseases. The specificity of the changes observed in calbindin mRNA levels was tested by reprobing blots with calmodulin, cyclophilin, and B-actin cDNAs. Gross brain regions of the aging rat exhibited specific, significant decreases (60-80%) in calbindin mRNA and protein levels in the cerebellum, corpus striatum, and brain-stem region but not in the cerebral cortex or hippocampus. Discrete areas of the aging human brain exhibited significant decreases in calbindin protein and mRNA in the cerebellum, corpus striatum, and nucleus basalis but not in the neocortex, hippocampus, amygdala, locus ceruleus, or nucleus raphe dorsalis. Comparison of diseased human brain tissue with age- and sex-matched controls yielded significant decreases (60488%) in calbindin protein and mRNA in the substantia nigra (Parkinson disease), in the corpus striatum (Huntington disease), in the nucleus basalis (Alzheimer disease), and in the hippocampus and nucleus raphe dorsalis (Parkinson, Huntington, and Alzheimer diseases) but not in the cerebellum, neocortex, amygdala, or locus ceruleus. Since calbindin gene expression decreased specifically in brain areas known to be particularly affected in aging and in each of the neurodegenerative diseases, these findings suggest that decreased calbindin gene expression may lead to a failure of calcium buffering or intraneuronal calcium homeostasis, which contributes to calcium-mediated cytotoxic events during aging and in the pathogenesis of neurodegenerative diseases.

Effect of Microcurrent Electrical Tissue

2008-07-15T00:19:00Z

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Yi-lo Lin, DVM, MSc; Hugo Moolenaar, PhD; P. René van Weeren, DVM, PhD; Chris H. A. van de Lest, PhD (2006) Application of microcurrent of moderate intensity increased cell proliferation and DNA content, with greater increases with multiple versus single application. Application of microcurrent of moderate intensity once or twice increased protein content, but application 3 times decreased protein content. Application of current a single time did not significantly alter apoptosis rate; however, application twice or 3 times resulted in significant increases in apoptosis rate, and there were significant linear (second order) correlations between current intensity and apoptosis rate when current was applied twice or 3 times.

The Biological Determinants of Aging

2008-07-14T01:32:00Z

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Rattan SI. (1996) Department of Chemistry, Aarhus University, Denmark. The highly complex nature of the process of ageing implicates both genetic and epigenetic causative factors. A progressive failure of maintenance underlines and typifies this process. The instability of the nuclear and the mitochondrial genomes is an important determinant of ageing. Infidelity and misregulation of genetic information transfer, loss of cellular proliferative capacity, altered cellular responsiveness and defective pathways of signal transduction are major aspects of the failure of homeostasis. These are also the basis of age-related diseases and impairments, such as osteoporosis, arthritis, immune deficiency, altered drug clearance and altered functioning of the brain. Studies directed towards understanding the mechanisms of interaction and inter-dependence of various genes involved in maintenance and repair networks are the most promising research strategies for identifying gerontogenes... The highly complex nature of the process of ageing implicates both genetic and epigenetic causative factors. A progressive failure of maintenance underlines and typifies this process. The instability of the nuclear and the mitochondrial genomes is an important determinant of ageing. Infidelity and misregulation of genetic information transfer, loss of cellular proliferative capacity, altered cellular responsiveness and defective pathways of signal transduction are major aspects of the failure of homeostasis. These are also the basis of age-related diseases and impairments, such as osteoporosis, arthritis, immune deficiency, altered drug clearance and altered functioning of the brain. Studies directed towards understanding the mechanisms of interaction and inter-dependence of various genes involved in maintenance and repair networks are the most promising research strategies for identifying gerontogenes.