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Min Zhao, Bing Song, Jin Pu, Teiji Wada, Brian Reid, Guangping Tai, Fei Wang, Aihua Guo, Petr Walczysko, Yu Gu, Takehiko Sasaki, Akira Suzuki, John V. Forrester, Henry R. Bourne, Peter N. Devreotes, Colin D. McCaig & Josef M. Penninger. Vol 442|27 July 2006|doi:10.1038/nature04925. Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing. The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol–phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-g (PI(3)Kg) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kg and PTEN control electrotaxis.

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Th. Förster, C. Jassoy, D. Petersohn, K. Schlotmann und M. Waldmann-Laue Systematic evaluation of new active substances and cosmetics. Paper on the occasion of the 4th annual meeting of the Gesellschaft für Dermopharmazie (Dermopharmacy Society) in Freiburg on 24 May 2000. In young skin, the lower part of the skin, the dermis, has a very regular structure. This regularity is no longer so clear-cut in older skin. The dermis contains irregular structures and flaws and appears less compact. The next highest layer, the epidermis, is somewhat thinner in older skin than in younger. More noticeable than this slight change in the thickness of the epidermis, however, is the disappearance of the curvature of the epidermal-dermal interface. In older skin this interface is flat, so that the cohesion between dermis and epidermis is weaker. Finally, in the upper layer, the stratum corneum, scarcely any differences can be observed under the microscope. The main changes are therefore in the deeper layers of the skin, especially the dermis. One of the biological causes is the major change in the collagen metabolism. Collagens are the main component of skin, accounting for around 60% of its dry substance. If, as a measure of synthesis activity, the mRNA of the fibroblasts of a group of young subjects is studied in comparison with that of an older group, it is found that for procollagen type I, for example, synthesis activity in the older group has decreased by approximately 60%.

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F.W. van Leeuwena,!, L. Gerezb, R. Benneb, E.M. Hola (University of Amsterdam 2002) Molecular misreading is an expression used to describe errors in RNA that lead to the translation of mutated proteins. If the resulting mutant transcripts escape RNA quality control systems, they are translated into +1 proteins. If functional domains are located downstream of the frameshift site, the result will be a protein with either a partial or complete loss of function. A clear example is ubiquitin+1 (UBB+1), which has lost its capacity to ubiquitinate, i.e. tagging proteins destined for proteasomal degradation. This is an important step in regulating the degradation of misfolded proteins and transcription factors. In fact, UBB+1 seems to block the proteasome. UBB+1 and other proteins accumulate in the neuropathological hallmarks of Alzheimer’s disease (AD), which suggests a causal relationship. We have hypothesized that quality control mechanisms for both transcripts and proteins work less efficiently during aging. In this manner +1 proteins may become manifest and contribute to age-related diseases.

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Vogel SN, Fitzgerald KA, and Fenton MJ. TLRs: Differential Adapter Utilization by Toll-Like Receptors Mediates TLR-Specific Patterns of Gene Expression. Mol. Interv. 2003; 3:466-77. Toll-like receptors (TLRs) are signaling molecules that recognize different microbial products during infection and serve as an important link between the innate and adaptive immune responses.

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Nobuyuki Uchikoga, Shun-Ya Takahashi, Runcong Ke, Masashi Sonoyama and Shigeki Mitaku. Protein Sci. 2005 14: 74-80; originally published online Dec 2, 2004. Extended proteins such as calmodulin and troponin C have two globular terminal domains linked by a central region that is exposed to water and often acts as a function-regulating element. The mechanisms that stabilize the tertiary structure of extended proteins appear to differ greatly from those of globular proteins. Identifying such differences in physical properties of amino acid sequences between extended proteins and globular proteins can provide clues useful for identification of extended proteins from complete genomes including orphan sequences. In the present study, we examined the structure and amino acid sequence of extended proteins. We found that extended proteins have a large net electric charge, high charge density, and an even balance of charge between the terminal domains, indicating that electrostatic interaction is a dominant factor in stabilization of extended proteins. Additionally, the central domain exposed to water contained many amphiphilic residues. Extended proteins can be identified from these physical properties of the tertiary structure, which can be deduced from the amino acid sequence. Analysis of physical properties of amino acid sequences can provide clues to the mechanism of protein folding. Also, structural changes in extended proteins may be caused by formation of molecular complexes. Long-range effects of electrostatic interactions also appear to play important roles in structural changes of extended proteins.

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MITSUHIKO YAMADA, ATSUSHI INANOBE, AND YOSHIHISA KURACH Department of Pharmacology II, Faculty of Medicine, Osaka University, Osaka, Japan (1998) Accordingly, the affinity of particular G protein subunits for the KG channel may not be sufficient to explain specific activation of KACh channel by GK. Actually, various combinations of recombinant G!" (except for G!1"1) have similar efficacy and potency in activating KACh channels (Wickman et al., 1994). However, the receptor specificity in cardiac atrial myocytes is well documented by extensive studies (Kurachi, 1995). It is often argued that receptor specificity could arise from compartmentalization of the appropriate receptors and channels, although little evidence has been shown for such compartmentalization. We do not know whether different mechanisms underlie receptor specificity in different organs. In other words, we have not yet fully answered the question how information specifically passes from a membrane receptor to the effector, the KG channel, via G proteins.

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Aoi INOMATA, Takeshi SHIMOMURA, Seiji HEIKE3, Masaaki FUJIMORI, Tomihiro HASHIZUME, and Kohzo ITO; Journal of the Physical Society of Japan Vol. 75, No. 7, July, 2006, 074803. We measured the electrical current-voltage characteristics of !DNA in vacuum using fine electrodes with a gap of about 200 nm. It was found that the electrical resistance of !DNA molecules between the fine electrodes had a large variation: from 7.8M! to values larger than 1 T!. This was consistent with the controversial results given in previous reports. The temperature dependence of conductivity was explained well by the Arrhenius equation. In addition, the conductivity of a single molecule of double-stranded DNA was measured by a ‘‘one-by-one’’ cutting method using atomic force microscopy (AFM). The conductivity was determined to be 3 " 101 S/cm, which is about the same order as that of semiconductors.

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RONALD W. SKADSEN AND JOE H. CHERRY Plant Physiol. (1983) 71, 861-868. Cotyledons of Light-grown soybean (GbvJne mar L. var Wayne) seedlings were used as a model system to study the possibility that aging requires qualitative changes in protein synthesis. Cotyledons reached a final stage of senescence and then abscised about 22 days after imbibition. Cotyledon senescence was reversed at 20 days after germination by epicotyl removal. Thereafter, the cotyledons regained much of the chlorophyll, RNA, protein, and polyribosomes lost during aging.

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10 March 2008, André Brown, Physics World. Colin Nuckolls of Columbia University, Jacqueline Barton of Caltech and colleagues were able to make reliable conductivity measurements by inventing a new and consistent way of connecting a single DNA molecule to two carbon nanotubes (Nature Nanotechnology 3 163). Past methods had struggled to make a reliable connection between a DNA molecule — which is only about 2 nm wide— and two electrodes. Poor connectivity is thought to be behind many of the inconsistencies in previous measurements.

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Real-Time Tracking of the Transcription of Linear DNA Templates: Dr. Peter H. Von Hippel University of Oregon: Institute of Molecular Biology, Eugene, Oregon (2007) Kinetic regulation of the termination-elongation switch during RNA transcriptional regulation has long been postulated (von Hippel & Yager). However, the time resolution of the approaches previously used to measure the rates of dissociation during termination of transcription has limited the progress in understanding this aspect of transcriptional regulation. The binding and dissociation events between RNA polymerase and the immobilized DNA template were clearly visible and the dissociation rates, under salt challenge, of the RNA polymerase from initiation complexes were compared with those from stalled elongation complexes. Template directed synthesis of the nascent RNA was also detected by changes in SPR signal and further analyzed by denaturing PAGE. Finally, dissociation of the elongation complexes at termination positions was observed and was consistent with the known termination efficiencies of the terminators analyzed.