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Cell Repair Devices

2008-04-29T03:00:00Z

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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.

Constitutive autophagy: vital role in clearance of unfavorable proteins in neurons

2008-04-28T22:49:00Z

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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.

Are indices of free radical damage related the exercise intensity?

2008-04-28T21:48:00Z

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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.

Cell Signaling and the Role of Reactive Oxygen Species in the Endothelium

2008-04-26T03:15:00Z

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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.

The Spark of Life: The Role of Electric Fields in Regulating Cell Behaviour Using the Eye as a Model System

2008-04-26T02:52:00Z

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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.

The Case of The Dividing Cell

2008-04-26T02:46:00Z

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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?"

Aging and acute exercise enhance free radical generation

2008-04-26T02:28:00Z

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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.

Accurate prediction of protein–protein interactions

2008-04-26T02:18:00Z

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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.

The role of nuclear architecture

2008-04-24T00:54:00Z

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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.

Similar gene expression patterns characterize aging

2008-04-21T23:33:00Z

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Gary N. Landis*, Diana Abdueva*, Dmitriy Skvortsov*, Junsheng Yang*, Beth E. Rabin*, James Carrick*, Simon Tavare´*†, and John Tower (2003) *Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-1340; and †Department of Oncology, Cambridge University, Cambridge, United Kingdom: Affymetrix GeneChips were used to measure RNA abundance for 13,500 Drosophila genes in young, old, and 100% oxygen stressed flies. Data were analyzed by using a recently developed background correction algorithm and a robust multichip modelbased statistical analysis that dramatically increased the ability to identify changes in gene expression. Aging and oxidative stress responses shared the up-regulation of purine biosynthesis, heat shock protein, antioxidant, and innate immune response genes. Results were confirmed by using Northerns and transgenic reporters. Immune response gene promoters linked to GFP allowed longitudinal assay of gene expression during aging in individual flies. Immune reporter expression in young flies was partially predictive of remaining life span, suggesting their potential as biomonitors of aging.

Aging and Chromatin

2008-04-10T21:35:00Z

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Andreas Ladurner PhD (2008), University of Cambridge, UK. Chromatin packages our cellular DNA, protects it from damage and ensures access by the right machines, at the right time. The smallest unit of chromatin is the nucleosome, a tightly-knit and stable assembly of histones and DNA. Yet, chromatin is a dynamic and versatile (“plastic”) substrate. We now know that it regulates gene expression and the inheritance of our genome. Biochemical and proteomic approaches show that proteins rarely act in isolation. Rather, they often form larger molecular assemblies. Importantly, it is often only in the context of these larger protein complexes that many proteins reveal their specific activity. In an on-going, ambitious project with Damian Brunner in EMBL’s Cell Biology Unit and with Robin Allshire at the Wellcome Trust Centre for Cell Biology in Edinburgh (UK), we are seeking to identify novel protein complexes involved in heterochromatin formation and in centromere function in a model organism, the fission yeast S. pombe. We will report progress on this challenging project in future reports.

Functional ion channels in human embryonic stem cells

2008-04-05T21:32:00Z

Johns Hopkins Medical Institutions (2008) Researchers from Johns Hopkins have discovered the presence of functional ion channels in human embryonic stem cells (ESCs). These ion channels act like electrical wires and permit ESCs, versatile cells that possess the unique ability to become all cell types of the body, to conduct and pass along electric currents. If researchers could selectively block some of these channels in implanted cells, derived from stem cells, they may be able to prevent potential tumor development. The paper appears Aug. 5 online in the journal Stem Cells. "A major concern for human ESC-based therapies is the potential for engineered grafts to go haywire after transplantation and form tumors, for instance, due to contamination by only a few undifferentiated human ESCs," says Ronald A. Li, Ph.D., an assistant professor of medicine at The Johns Hopkins University School of Medicine and senior author of the study. "Our discovery of functional ion channels, which are valves in a cell's outer membrane allowing the passage of charged atoms, the basis of electricity, provides an important link to the differentiation, or maturation, and cell proliferation, or growth of human ESCs." Because human ESCs can potentially provide an unlimited supply of even highly specialized cells, such as brain and heart cells, for transplantation and cell-based therapies, they may provide an ultimate solution to limited donor availability. In an earlier study, Li's lab genetically engineered heart cells derived from human ESCs, suggesting the possibility of transplanting unlimited supplies of healthy, specialized cells into damaged organs. "We do not want to be taking any chances of tumor formation. Based on our previous research, we therefore decided to explore the existence of ion channels in pluripotent, or versatile, human ESCs because electrical activity is known to regulate cell differentiation and proliferation," says Li. "To my knowledge, the electrical properties of human ESCs were never studied up to this point." In the current study, the researchers measured the electric currents of single human ESCs, discovered several channels that allow and control passage of potassium, and observed the electric current's effect on cell differentiation and proliferation. "In a number of different cell types, from cancer to T-lymphocytes, potassium channels are responsible for altering the membrane voltage of cells," says Li. "This in turn is required for the progression of certain cells into the next phase of a cell cycle." Li hopes the targeting of specific potassium channels will give scientists more understanding and control in engineering healthy cells for transplantation. "We found that blocking potassium channels in ESCs also slowed their growth," says Li. "Our findings may lead to genetic strategies that suppress undesirable cell division after transplantation, not only for ESCs and their derivatives, but perhaps for adult stem cells as well." Li adds that much more work is necessary to know for sure.

Anti-oxidant Effects of Ultra-Low Microcurrents

2008-03-17T08:14:00Z

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Bok Y. Lee, MD, FACS, Alfred J. Koonin, M.B., Ch, B., Ph.D., FRCS, Keith Wendell, Ph.D., John Hillard, RN (2005) In conclusion, 25 chronic skin ulcers present for an average of 18.5 months and not responding to standard conservative treatment in a hospital setting were treated with the ultra-low current, ultra-low frequency device. 100% showed response to the treatment. 100% healed in a maximum time of 7 weeks. Average time of healing was 48 hours of treatment over 16 days. Surgical debridement was unnecessary as the necrotic tissue appeared to disappear spontaneously. The ages of the patients ranged between 20 and 85 years of age. Many studies have shown that the rate of wound healing of an individual is directly proportional to their age. From this study it can be seen that treating chronic skin ulcers with the ultra-low current device eliminates the age factor by equalizing the healing rate at all ages (fig.14). The only limiting factor in healing time with this method seems to be the duration of the lesion (fig.15). This study therefore suggests that treatment with the ultra-low current device eliminates the restrictions that aging brings to the healing process.

Advances in Nanomedicine

2008-03-15T05:02:00Z

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X Weiss, (2008) Aging is not just the sum total of individually deteriorating cells. Aging is the dynamic process of increasing imbalances in the systemic organization of these cells. Anti-aging reflects a multilevel approach that simultaneously targets a number of biological network modules. Identifying these dynamically organized network modules will be very important in formulating a model of how and why the aging process takes place and whether or not we can reverse aging by reorganizing an aged network model. The old, the ill, and the injured all suffer from disarranged patterns of atoms, whether disarranged by aging and accumulated free radicals, invading viruses, or unfortunate accidents. Aged and young are the Gestalts on opposite poles composed of variations in the arrangement of their dynamically organized networks. 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.

Dynamic Model of Anti-Aging

2008-03-15T04:21:00Z

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X Weiss, (2008) Aging is not just the sum total of individually deteriorating cells. Aging is the dynamic process of increasing imbalances in the systemic organization of these cells. Anti-aging reflects a multilevel approach that simultaneously targets a number of biological network modules. Identifying these dynamically organized network modules will be very important in formulating a model of how and why the aging process takes place and whether or not we can reverse aging by reorganizing an aged network model. How can a biological network be reorganized? The old, the ill, and the injured all suffer from disarranged patterns of atoms, whether disarranged by aging and accumulated free radicals, invading viruses, or unfortunate accidents. Aged and young are the Gestalts on opposite poles composed of variations in the arrangement of their dynamically organized networks.