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Emma Teixeiro, Patricia Fuentes, Begon Galocha, Balbino Alarco, and Rafael Bragado (2002) The results suggest that an altered signaling cascade leading to an imbalance in mitogen-activated protein kinase activities is involved in the selective impairment of apoptosis in these mutant cells.

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Xanya Sofra-Weiss, Ph.D (2008) Modern electronics and molecular biology research are combined to deduce the specifications for a technology that promotes Healthy Anti-aging. Resonating the firings, spatial organization and rhythms of electrically excitable cells leads to healing and rejuvenation in a completely safe, noninvasive method. The pervasive presence of ionic currents in core biological functions: (1) signal transduction, (2) the electrical conductivity of DNA, (3) the electromagnetic dynamics of protein conformation, render nanoelectricity the common denominator of all integral parts composing the Gestalt of a living organism. However, to date, few devices pay attention to waveform formation that reflects the essence of cellular communications. A simple square waveform is too impoverished to resonate the harmonious complexity of a biological system, the way a two piece band is insufficient in delivering the musical richness of a symphony. The waveform is as important in cellular resonance as language is in verbal communication. Language is confined by grammar and syntax rules in order to convey a message correctly. Similarly, a waveform is confined by the spatial organization and rhythm of endogenous electrical signals that cells use in their multifaceted networking. Ion resonance has a harmonic specificity that has to be encompassed before a device is designed. There is a lot to be gained by developing a device that can emit signals capable of intertwining with those of signal transduction receptors (including G proteins, gene transcription and the activation of T cells). Such a device will not only become the protagonist in Anti-aging but it will have sufficient sophistication to heal disease and enhance overall immune efficiency.

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M Komatsu, T Ueno, S Waguri, Y Uchiyama, E Kominami and K Tanaka (2007) Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan. Investigations pursued during the last decade on neurodegenerative diseases have revealed a common mechanism underlying the development of such diseases: conformational disorder of certain proteins leads to the formation of misfolded protein oligomers, which subsequently develop into large protein aggregates. These aggregates entangle other denatured proteins and lipids to form disease-specific inclusion bodies. The failure of the ubiquitin-proteasome system to shred the protein aggregates has led investigators to focus their attention to autophagy, a bulk degradative system coupled with lysosomes, which is involved in non-selective shredding of large amounts of cytoplasmicm components. Research in this field has demonstrated the accumulation of autophagic vacuoles and intracytoplasmic protein aggregates in patients with various neurodegenerative diseases. Although autophagy fails to degrade large protein aggregates once they are formed in the cytoplasm, drug-induced activation of autophagy is effective in preventing aggregate deposition, indicating that autophagy significantly contributes to the clearance of aggregate-prone proteins. The pivotal role of autophagy in the clearance of aggregate-prone proteins has been confirmed by a deductive approach using a brain-specific autophagy-ablated mouse model. In this review, we discuss the consequences of autophagy deficiency in neurons.

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R. Lovlin, W. Cottle, I. Pyke, M. Kavanagh, and A. N. Belcastro (1987) Department of Physical Education and Sport Studies, University of Alberta, Edmonton, Alberta Canada, T6G 2H9. The possibility that plasma levels of malonaldehyde (MDA) are altered by exercise has been examined. The presence of MDA has been recognized to reflect peroxidation of lipids resulting from reactions with free radicals. Maximal exercise, eliciting 100% of maximal oxygen consumption. Short periods of intermittent exercise, the intensity of which was varied, indicated a correlation between lactate and MDA (r 2=0.51) (p<0.001). Blood lactate concentrations increased throughout this exercise regimen. A significant decrease (10.3%) in plasma MDA occurred at 40%. At 70% plasma MDA was still below resting values, however the trend to an increase in MDA with exercise intensity was evident. At exhaustion, plasma MDA and lactate were significantly greater than at rest. These results suggest, that exhaustive maximal exercise induces free radical generation while short periods of submaximal exercise may inhibit it and lipid peroxidation.

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J.W. Zmijewski*†, A. Landar*†, N. atanabe*†‡, D.A. Dickinson†§, N. Noguchi*†‡ and V.M. Darley-Usmar*†1 *Department of Pathology, University of Alabama at Birmingham, AL, U.S.A. (2005) The controlled formation of ROS (reactive oxygen species) and RNS (reactive nitrogen species) is now known to be critical in cellular redox signalling. As with the more familiar phosphorylation-dependent signal transduction pathways, control of protein function is mediated by the post-translational modification at specific amino acid residues, notably thiols. Two important classes of oxidant-derived signalling molecules are the lipid oxidation products, including those with electrophilic reactive centres, and decomposition products such as lysoPC (lysophosphatidylcholine). The mechanisms can be direct in the case of electrophiles, as they can modify signalling proteins by post-translational modification of thiols. In the case of lysoPC, it appears that secondary generation of ROS/RNS, dependent on intracellular calcium fluxes, can cause the secondary induction of H2O2 in the cell. In either case, the intracellular source of ROS/RNS has not been defined. In this respect, the mitochondrion is particularly interesting since it is now becoming apparent that the formation of superoxide from the respiratory chain can play an important role in cell signalling, and oxidized lipids can stimulate ROS formation from an undefined source. In this short overview, we describe recent experiments that suggest that the cell signalling mediated by lipid oxidation products involves their interaction with mitochondria. The implications of these results for our understanding of adaptation and the response to stress in cardiovascular disease are discussed.

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John V. Forrester Noemi Lois Min Zhao Colin McCaig, University of Aberdeen , Aberdeen, UK 2007) Endogenous electric fields (EF) have long been known to influence cell behavior during development, neural cell tropism, wound healing and cell behavior generally. The effect is based on short circuiting of electrical potential differences across cell and tissue boundaries generated by ionic segregation. Recent in vitro and in vivo studies have shown that EF regulate not only cell movement but orientation of cells during mitosis, an effect which may underlie shaping of tissues and organs. The molecular basis of this effect is founded on receptor-mediated cell signalling events and alterations in cytoskeletal function as revealed in studies of gene deficient cells.

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Clyde Freeman Herreid (2008) “Well, you definitely are correct. In Exhibit E you see the nuclear membranes again disolving, and in Exhibit F the chromosomes are lining up in the middle of the cell, just like in mitosis and it doesn’t matter how they get into a line as long as they do it. Then the spindle fibers attach to their chromatids and Exhibit G shows the fibers pulling them apart. This way each side of the cell gets a complete set of instructions. Then, the cell divides. That’s it. Meiosis is finished. If everything is perfect, each cell at the end has one complete set of instructions. Each sperm has 23 chromosomes. And, of course, there are four of them produced. In the first stage of meiosis we produced two cells, and then in the second stage each of these divided again and produced two. That makes four, doesn’t it?"

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J. Bejma and L. L. Ji (1999) Department of Kinesiology, University of Wisconsin-Madison, Madison, Wisconsin. Reactive oxygen species (ROS) are implicated in the mechanism of biological aging and exercise-induced oxidative damage. The present study examined the effect of an acute bout of exercise on intracellular ROS production, lipid and protein peroxidation, and GSH status in the skeletal muscle. Strenuous physical exercise increases ROS production and causes various forms of oxidative damage in skeletal muscle. However, because of the lack of reliable and convenient methods to measure ROS, only scarce data exist regarding ROS generation in skeletal muscle during exercise. Using electron spin resonance (ESR) spectroscopy, Jackson et al. (1985) reported that free radical signals in intact muscle fibers were increased during stimulated contraction. Although ESR provides great sensitivity, quantitation of ROS production is relatively poor. With greater precision, Reid et al. (1992) showed that the oxidation rate of dichlorofluorescin (DCFH), a synthetic probe for intracellular oxidants, was dramatically increased in contracting diaphragmmuscle compared with restingmuscle, wherein superoxide radicals were suggested to be the primary oxidant causing DCFH oxidation.

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Lukas Burger and Erik van Nimwegen (2008) Biozentrum, the University of Basel, and Swiss Institute of Bioinformatics, Basel, Switzerland. Accurate and large-scale prediction of protein–protein interactions directly from amino-acid sequences is one of the great challenges in computational biology. Here we present a new Bayesian network method that predicts interaction partners using only multiple alignments of amino-acid sequences of interacting protein domains, without tunable parameters, and without the need for any training examples. We first apply the method to bacterial two-component systems and comprehensively reconstruct two-component signaling networks across all sequenced bacteria. Comparisons of our predictions with known interactions show that our method infers interaction partners genome-wide with high accuracy. To demonstrate the general applicability of our method we show that it also accurately predicts interaction partners in a recent dataset of polyketide synthases. Analysis of the predicted genome-wide two-component signaling networks shows that cognates (interacting kinase/regulator pairs, which lie adjacent on the genome) and orphans (which lie isolated) form two relatively independent components of the signaling network in each genome. In addition, while most genes are predicted to have only a small number of interaction partners, we find that 10% of orphans form a separate class of ‘hub’ nodes that distribute and integrate signals to and from up to tens of different interaction partners.

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Philipp Oberdoerffer and David A. Sinclair (2007) Eukaryotes come in many shapes and sizes, yet one thing that they all seem to share is a decline in vitality and health over time — a process known as ageing. If there are conserved causes of ageing, they may be traced back to common biological structures that are inherently difficult to maintain throughout life. One such structure is chromatin, the DNA–protein complex that stabilizes the genome and dictates gene expression. Studies in the budding yeast Saccharomyces cerevisiae have pointed to chromatin reorganization as a main contributor to ageing in that species, which raises the possibility that similar processes underlie ageing in more complex organisms. The long-term maintenance of the nuclear architecture is vital for the normal functioning of cells and tissues over a lifetime. The dramatic effect of a disturbed nuclear architecture is exemplified by utchinson–Gilford progeria syndrome (HGPS), in which a mutation that disrupts the nuclear architecture leads to a disease with symptoms that resemble aspects of normal human ageing, such as loss of hair, restricted joint mobility and atherosclerosis. Even cells from normal individuals undergo significant nuclear architecture changes in response to stress, and there are early hints that normal human ageing is associated with alterations in nuclear architecture.