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991.
992.
Acid-sensing ion channels (ASIC) are ligand-gated cation channels that are highly expressed in peripheral sensory and central neurons. ASIC are transiently activated by decreases in extracellular pH and are thought to play important roles in sensory perception, neuronal transmission, and excitability, and in the pathology of neurological conditions, such as brain ischemia. We demonstrate here that the heavy metals Ni(2+) and Cd(2+) dose-dependently inhibit ASIC currents in hippocampus CA1 neurons and in Chinese hamster ovary (CHO) cells heterologously expressing these channels. The effects of both Ni(2+) and Cd(2+) were voltage-independent, fast, and reversible. Neither metal affected activation and desensitization kinetics but rather decreased pH-sensitivity. Moreover, distinct ASIC isoforms were differentially inhibited by Ni(2+) and Cd(2+). External application of 1 mM Ni(2+) rapidly inhibited homomeric ASIC1a and heteromeric ASIC1a/2a channels without affecting ASIC1b, 2a, and ASIC3 homomeric channels and ASIC1a/3 and 2a/3 heteromeric channels. In contrast, external Cd(+) (1 mM) inhibited ASIC2a and ASIC3 homomeric channels and ASIC1a/2a, 1a/3, and 2a/3 heteromeric channels but not ASIC1a homomeric channels. The acid-sensing current in isolated rat hippocampus CA1 neurons, thought to be carried primarily by ASIC1a and 1a/2a, was inhibited by 1 mM Ni(2+). The current study identifies ASIC as a novel target for the neurotoxic heavy metals Cd(2+) and Ni(2+). 相似文献
993.
Veiga E Guttman JA Bonazzi M Boucrot E Toledo-Arana A Lin AE Enninga J Pizarro-Cerdá J Finlay BB Kirchhausen T Cossart P 《Cell host & microbe》2007,2(5):340-351
Infection by the bacterium Listeria monocytogenes depends on host cell clathrin. To determine whether this requirement is widespread, we analyzed infection models using diverse bacteria. We demonstrated that bacteria that enter cells following binding to cellular receptors (termed "zippering" bacteria) invade in a clathrin-dependent manner. In contrast, bacteria that inject effector proteins into host cells in order to gain entry (termed "triggering" bacteria) invade in a clathrin-independent manner. Strikingly, enteropathogenic Escherichia coli (EPEC) required clathrin to form actin-rich pedestals in host cells beneath adhering bacteria, even though this pathogen remains extracellular. Furthermore, clathrin accumulation preceded the actin rearrangements necessary for Listeria entry. These data provide evidence for a clathrin-based entry pathway allowing internalization of large objects (bacteria and ligand-coated beads) and used by "zippering" bacteria as part of a general mechanism to invade host mammalian cells. We also revealed a nonendocytic role for clathrin required for extracellular EPEC infections. 相似文献
994.
995.
Protocols for the synthesis of the microbicidal polycation N,N-dodecyl,methyl-polyethylenimine and coating (painting) of glass slides with this polycation's butanol solution are described. Subsequently detailed are the procedures for validating that the resultant coated slides are essentially 100% lethal to the human bacterial pathogens, Staphylococcus aureus and Escherichia coli, as well as to two common strains of influenza virus. The time required to prepare and apply the cationic polymer and to test its microbicidal efficiency is conservatively estimated to be <4 weeks. 相似文献
996.
Derek G. Shendell Melannie S. Alexander Lauren Lorentzson Frances A. McCarty 《International journal of biometeorology》2010,54(4):441-448
Adults have been increasingly motivated to compete in recreational endurance sports events. Amateurs may lack a complete understanding
of recommended strategies for handling heat and humidity, making heat-related illnesses increasingly possible. This is compounded
by global climate change and increasing average surface and air temperatures, especially in urban areas of industrialized
nations in Europe and North America that have hosted most events to date. We conducted an on-line, secure survey at the 2nd
Annual ING Georgia Marathon and Half-Marathon in Atlanta, Georgia, in 2008. We included previously validated questions on
participant socio-demographics, training locations, and knowledge and awareness of heat-related illnesses. Participants were
aware of heat illnesses, and of heat stroke as a serious form of heat stress. However, the majority, across age and gender,
did not understand the potential severity of heat stroke. Furthermore, 1-in-5 participants did not understand the concept
of heat stress as a form of heat-related illness, and how heat stress may result from buildup of muscle-generated heat in
the body. Adult recreational endurance athletes are another susceptible, vulnerable population sub-group for applied research
and public health educational interventions, especially in urban areas of industrialized nations in Europe and North America. 相似文献
997.
998.
Cell polarization generally occurs along a single well-defined axis that is frequently determined by environmental cues such as chemoattractant gradients or cell-cell contacts, but polarization can also occur spontaneously in the apparent absence of such cues, through a process called symmetry breaking. In Saccharomyces cerevisiae, cells are born with positional landmarks that mark the poles of the cell and guide subsequent polarization and bud emergence to those sites, but cells lacking such landmarks polarize towards a random cortical site and proliferate normally. The landmarks employ a Ras-family GTPase, Rsr1p, to communicate with the conserved Rho-family GTPase Cdc42p, which is itself polarized and essential for cytoskeletal polarization. We found that yeast Cdc42p was effectively polarized to a single random cortical site even in the combined absence of landmarks, microtubules and microfilaments. Among a panel of Cdc42p effectors and interacting proteins, we found that the scaffold protein Bem1p was uniquely required for this symmetry-breaking behaviour. Moreover, polarization was dependent on GTP hydrolysis by Cdc42p, suggesting that assembly of a polarization site involves cycling of Cdc42p between GTP- and GDP-bound forms, rather than functioning as a simple on/off switch. 相似文献
999.
Alexander Bürkle Graziella Caselli Claudio Franceschi Erminia Mariani Paolo Sansoni Angela Santoni Giancarlo Vecchio Jacek M Witkowski Calogero Caruso 《Immunity & ageing : I & A》2007,4(1):4-8
On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo,
Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed.
In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the
life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different
strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is
essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life. 相似文献
1000.
Alexander Kaever Thomas Lingner Kirstin Feussner Cornelia G?bel Ivo Feussner Peter Meinicke 《BMC bioinformatics》2009,10(1):92