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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.

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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.

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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.

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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.

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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.

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Matthew R. James, John Gough (2007) The purpose of this paper is to give a description of quantum dissipative systems that combines perspectives from the quantum physics and control engineering communities. The resulting theory provides useful methods for analysis and design of dissipative quantum systems. We describe the interaction of the plant and a class of exosystems in general quantum network terms. Our results include an infinitesimal characterization of the dissipation property, which generalizes the well-known Positive Real and Bounded Real Lemmas, and is used to study some properties of quantum dissipative systems. We also show how to formulate control design problems using quantum network models, which implements Willems’ “control by interconnection” for open quantum systems. This control design formulation includes, for example, standard problems of stabilization, regulation, robust control.

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Mark K. Shigenaga, Toiy M. Hagen, and Bruce N. Ames* (Division of Biochemistry and Molecular Biology, University of California, Berkeley, 1994) We argue for the critical role of oxidative damage in causing the mitochondrial dysfunction of aging. Oxidants generated by nito dria appear to be the major source of the oxidative lesions that accumulate with age. Several mitochondrial fumctins decline with age. The contributing factors include the intrinsic rate of proton leakage across the inner mitochondrial membrane (a correlate of oxidant formation), decreased membrane fluidity, and decreased levels and function of cardiolipin, which supports the function of many of the proteins of the inner mitochondrial membrane. Acetyl-L-carnitine, a high-energy mitochondrial substrate, appears to reverse many age-aciated dec in cellular function, in part by increasing cellular ATP production. Such evidence supports the suggeston that age-associated accumulation of mitochondrial deficits due to oxidative damage is likely to be a major contributor to cellular, tissue, and organismal apg.

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Shun-ya Takahashi Shigeki Mitaku, Shigeki Mitaku; Genome Informatics 11: 418–419 (2000). Dumbbell-type proteins have two domains linked by a long helical segment. Typical examples of dumbbell-type proteins are calmodulin and troponin C, which have regulating function of other proteins. The function seems to be closely related to the dumbbell shape of this protein. Upon binding of calcium, calmodulin changes its structure and strongly interacts with other protein, modulating the function of the bound protein. Troponin C also binds with other proteins, tropomyosin, and regulates the muscle contraction. Therefore, if proteins of dumbbell-type proteins can be predicted from amino acid sequences of total proteome, the method will be useful for inferring the protein-protein interaction and the regulating function of the proteins.In this work, we first analyzed the 3D-structures of proteins in protein data bank (PDB), selecting all dumbbell-type proteins in PDB. Then, we tested various physical parameters of amino acid sequences that may stabilize the dumbbell shape of proteins and constructed an algorithm for predicting dumbbell-type proteins from amino acid sequences alone.

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EDWARD CARMELIET (1999) Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias. Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias. Physiol. Rev. 79:917–1017, 1999.—The aim of this review is to provide basic information on the electrophysiological changes during acute ischemia and reperfusion from the level of ion channels up to the level of multicellular preparations. After an introduction, section II provides a general description of the ion channels and electrogenic transporters present in the heart, more specifically in the plasma membrane, in intracellular organelles of the sarcoplasmic reticulum and mitochondria, and in the gap junctions. The description is restricted to activation and permeation characterisitics, while modulation is incorporated in section III. This section (ischemic syndromes) describes the biochemical (lipids, radicals, hormones, neurotransmitters, metabolites) and ion concentration changes, the mechanisms involved, and the effect on channels and cells. Section IV (electrical changes and arrhythmias) is subdivided in two parts, with first a description of the electrical changes at the cellular and multicellular level, followed by an analysis of arrhythmias during ischemia and reperfusion. The last short section suggests possible developments in the study of ischemiarelated phenomena.

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Making Daughters Different: How Immune Cells Take Divergent Paths When Fighting Infections (2007) Credit: John Chang, M.D., and Steven Reiner, M.D., University of Pennsylvania, School of Medicine; ScienceDaily (Mar. 7, 2007) — How do immune cells decide to respond to invading microbes by either fighting to the death or becoming the body's memory for future infections? Researchers at the University of Pennsylvania School of Medicine have discovered that immune cells can differ in their inheritance of molecules that regulate cell fate, and therefore what role they play in fighting infection. The research appears this week in an early online issue of Science. "These findings will change the way we look at how vaccines work," says lead author Steven Reiner, MD, Professor of Medicine. "Until now, wehave pretty much been in the dark as to how we generate the spectrum of immune cells that are needed to fight off infections. We've always known the end result -- that more than one type of cell is needed -- but not the initial events that generate cell diversity. Now we have information that may one day be applied to a more targeted approach to developing vaccines."