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Indirect Action (indirect + action)
Selected AbstractsDirect and Indirect Actions of Fibroblast Growth Factor 2 on Osteoclastic Bone Resorption in CulturesJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2000Hiroshi Kawaguchi M.D., Ph.D. Abstract Fibroblast growth factor 2 (FGF-2 or basic FGF) is known to show variable actions on bone formation and bone resorption. This study was undertaken to elucidate the mechanisms whereby FGF-2 affects bone metabolism, especially bone resorption, using three different culture systems. FGF-2 at 10,9 M and higher concentrations induced osteoclastic cell formation in the coculture system of mouse osteoblastic cells and bone marrow cells, and this induction was abrogated by nonsteroidal anti-inflammatory drugs (NSAIDs). 45Ca release from prelabeled cultured mouse calvariae stimulated by FGF-2 (10,8 M) was also inhibited by NSAIDs, and the inhibition was stronger by NSAIDs, which are more selective for inhibition of cyclooxygenase 2 (COX-2) than COX-1, suggesting the mediation of COX-2 induction. COX-2 was highly expressed and its messenger RNA (mRNA) level was stimulated by FGF-2 in osteoblastic cells whereas it was undetectable or not stimulated by FGF-2 in cells of osteoclast lineage. To further investigate the direct actions of FGF-2 on osteoclasts, resorbed pit formation was compared between cultures of purified osteoclasts and unfractionated bone cells from rabbit long bones. FGF-2 (,10,12 M) stimulated resorbed pit formation by purified osteoclasts with a maximum effect of 2.0-fold at 10,11 M, and no further stimulation was observed at higher concentrations. However, FGF-2 at 10,9 M , 10,8 M stimulated resorbed pit formation by unfractionated bone cells up to 9.7-fold. NS-398, a specific COX-2 inhibitor, did not affect the FGF-2 stimulation on purified osteoclasts but inhibited that on unfractionated bone cells. We conclude that FGF-2 at low concentrations (,10,12 M) acts directly on mature osteoclasts to resorb bone moderately, whereas at high concentrations (,10,9 M) it acts on osteoblastic cells to induce COX-2 and stimulates bone resorption potently. [source] Mechanism for gastric cancer development by Helicobacter pylori infectionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8pt1 2008Tsutomu Chiba Abstract Helicobacter pylori (H. pylori) infection plays a crucial role in the development of gastric cancer. There are two major pathways for the development of gastric cancer by H. pylori infection: the indirect action of H. pylori on gastric epithelial cells through inflammation, and the direct action of the bacteria on epithelial cells through the induction of protein modulation and gene mutation. Both pathways work together to promote gastric carcinogenesis. [source] Oxidative gating of water channels (aquaporins) in Chara by hydroxyl radicalsPLANT CELL & ENVIRONMENT, Issue 9 2004T. HENZLER ABSTRACT Hydroxyl radicals (*OH) as produced in the Fenton reaction (Fe2+ + H2O2 = Fe3+ + OH, + *OH) have been used to reversibly inhibit aquaporins in the plasma membrane of internodes of Chara corallina. Compared to conventional agents such as HgCl2, *OH proved to be more effective in blocking water channels and was less toxic to the cell. When internodes were treated for 30 min, cell hydraulic conductivity (Lp) decreased by 90% or even more. This effect was reversed within a few minutes after removing the radicals from the medium. In contrast to HgCl2, radical treatment reduced membrane permeability of small lipophilic organic solutes (ethanol, acetone, 1-propanol, and 2-propanol) by only 24 to 52%, indicating some continued limited movement of these solutes across aquaporins. The biggest effect of *OH treatment on solute permeability was found for isotopic water (HDO), which largely used water channels to cross the membrane. Inhibition of aquaporins reduced the diffusional water permeability (Pd) by about 70%. For the organic test solutes, which mainly use the bilayer to cross the membrane, channel closure caused anomalous (negative) osmosis; that is, cells had negative reflection coefficients (,s) and were transiently swelling in a hypertonic medium. From the ratio of bulk (Lp or osmotic permeability coefficient, Pf) to diffusional (Pd) permeability of water, the number (N) of water molecules that align in water channels was estimated to be N = Pf/Pd = 46 (on average). Radical treatment decreased N from 46 to 11, a value still larger than unity, which would be expected for a membrane lacking pores. The gating of aquaporins by *OH radicals is discussed in terms of a direct action of the radicals when passing the pores or by an indirect action via the bilayer. The rapid recovery of inhibited channels may indicate an easy access of cytoplasmic antioxidants to closed water channels. As hydrogen peroxide is a major signalling substance during different biotic and abiotic stresses, the reversible closure of water channels by *OH (as produced from H2O2 in the apoplast in the presence of transition metals such as Fe2+ or Cu+) may be downstream of the H2O2 signalling. This may provide appropriate adjustments in water relations (hydraulic conductivity), and a common response to different kinds of stresses. [source] Knitting and untying the protein network: Modulation of protein ensembles as a therapeutic strategyPROTEIN SCIENCE, Issue 3 2009Susana Gordo Abstract Proteins constitute the working machinery and structural support of all organisms. In performing a given function, they must adopt highly specific structures that can change with their level of activity, often through the direct or indirect action of other proteins. Indeed, proteins typically function within an ensemble, rather than individually. Hence, they must be sufficiently flexible to interact with each other and execute diverse tasks. The discovery that errors within these groups can ultimately cause disease has led to a paradigm shift in drug discovery, from an emphasis on single protein targets to a holistic approach whereby entire ensembles are targeted. [source] Hermit crabs, humans and Mozambique mangrovesAFRICAN JOURNAL OF ECOLOGY, Issue 3 2001David K. A. Barnes Abstract There is a complex interrelationship between upper shore hermit crabs (such as Coenobita sp. and Clibanarius sp.), coastal human populations and mangrove forests in Mozambique. The abundance, activity, shell selection and behaviour of three species of hermit crab are related to the level of mangrove cover. With increased density of mangrove trees, the study species of hermit crab changed in abundance, tended to become diurnal, spent more time feeding and were clustered in larger groups when doing so, and selected longer spired shells. All five of the same variables are also linked to the proximity and activity of humans through both direct and indirect actions. Direct effects included a tendency to nocturnal activity with proximity to human activity; indirect effects included increased and more clumped food supplies, and shell middens from intertidal harvesting and deforestation. Mangroves are important to local human populations as well as to hermit crabs, for a wide variety of (similar) reasons. Mangroves provide storm shelter, fisheries and fishery nursery grounds for adjacent human settlements, but they also harbour mosquito populations and their removal provides valuable building materials and fuel. Hermit crabs may be useful (indirectly) to coastal human populations by being a source of food to certain commercial species, and by quickly consuming rotting/discarded food and faeces (thereby reducing disease and pests). They can also cause minor problems to coastal human populations because they use shells of (fisheries) target mollusc species and can be more abundant than the living molluscs, thereby slowing down effective hand collection through confusion over identification. The mixture of positive and negative attributes that the three groups impart to each other in the Quirimba Archipelago, northern Mozambique, is discussed. Résumé Il existe des interrelations complexes entre les Bernard-l'Ermite du haut littoral (tels que Coenobita sp. Et Clibanarius sp.), les populations humaines côtières et les forêts de mangroves au Mozambique. L'abondance, l'activité, le choix de la coquille et le comportement de trois espèces de Bernard-l'Ermite sont liés au degré de couverture de la mangrove. Lorsque la densité des arbres de la mangrove augmente, l'abondance des espèces étudiées de Bernard-l'Ermite change, ils ont tendance à devenir diurnes, passent plus de temps à se nourrir et se rassemblent à ces moments-là en plus grands groupes, et ils choisissent aussi de plus longues coquilles. Les cinq mêmes variables sont aussi liées à la proximité et à l'activité des hommes, directement et indirectement. Parmi les effets directs, on compte une tendance à une activité nocturne lorsque les activités humaines sont proches ; les effets indirects incluent des apports de nourriture et de débris de coquilles accrus et plus regroupés résultant des marées et de la déforestation. Les mangroves sont aussi importantes pour les populations locales que pour les Bernard-l'Ermite, pour toute une série de raisons (semblables). Les mangroves constituent un abri en cas de tempête, un terrain de pêche et de frai dont bénéficient les populations humaines voisines, mais elles renferment aussi beaucoup de moustiques, et leur bois fournit un bon matériau de construction et du combustible. Les Bernard-l'Ermite peuvent être (indirectement) utiles aux populations côtières car certaines espèces commerciales sont comestibles et que tous consomment rapidement les restes de nourriture en décomposition et les excréments (réduisant ainsi les risques de maladie et d'animaux nuisibles). Ils peuvent aussi causer des problèmes mineurs aux populations côtières parce qu'ils utilisent la coquille d'espèces de mollusques qui font l'objet de la pêche et qu'ils peuvent être plus abondants que les mollusques eux-mêmes, ce qui ralentit la pêche manuelle à cause du besoin d'identification. On discute le mélange de qualités négatives et positives que les trois groupes représentent les uns pour les autres dans l'Archipel de Quirimba, au nord du Mozambique. [source] Axonal branching patterns of nucleus accumbens neurons in the ratTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 22 2010Anushree Tripathi Abstract The patterns of axonal collateralization of nucleus accumbens (Acb) projection neurons were investigated in the rat by means of single-axon tracing techniques using the anterograde tracer biotinylated dextran amine. Seventy-three axons were fully traced, originating from either the core (AcbC) or shell (AcbSh) compartment, as assessed by differential calbindin D28k-immunoreactivity. Axons from AcbC and AcbSh showed a substantial segregation in their targets; target areas were either exclusively or preferentially innervated from AcbC or AcbSh. Axon collaterals in the subthalamic nucleus were found at higher than expected frequencies; moreover, these originated exclusively in the dorsal AcbC. Intercompartmental collaterals were observed from ventral AcbC axons into AcbSh, and likewise, interconnections at pallidal and mesencephalic levels were also observed, although mostly from AcbC axons toward AcbSh targets, possibly supporting crosstalk between the two subcircuits at several levels. Cell somata giving rise to short-range accumbal axons, projecting to the ventral pallidum (VP), were spatially intermingled with others, giving rise to long-range axons that innervated VP and more caudal targets. This anatomical organization parallels that of the dorsal striatum and provides the basis for possible dual direct and indirect actions from a single axon on either individual or small sets of neurons. J. Comp. Neurol. 518:4649,4673, 2010. © 2010 Wiley-Liss, Inc. [source] The effect of intracellular acidification on the relationship between cell volume and membrane potential in amphibian skeletal muscleTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005James A. Fraser The relationship between cell volume (Vc) and membrane potential (Em) in Rana temporaria striated muscle fibres was investigated under different conditions of intracellular acidification. Confocal microscope xz -scanning monitored the changes in Vc, whilst conventional KCl and pH-sensitive microelectrodes measured Em and intracellular pH (pHi), respectively. Applications of Ringer solutions with added NH4Cl induced rapid reductions in Vc that rapidly reversed upon their withdrawal. These could be directly attributed to the related alterations in extracellular tonicity. However: (1) a slower and persistent decrease in Vc followed the NH4Cl withdrawal, leaving Vc up to 10% below its resting value; (2) similar sustained decreases in resting Vc were produced by the addition and subsequent withdrawal of extracellular solutions in which NaCl was isosmotically replaced with NH4Cl; (3) the same manoeuvres also produced a marked intracellular acidification, that depended upon the duration of the preceding exposure to NH4Cl, of up to 0.53 ± 0.10 pH units; and (4) the corresponding reductions in Vc similarly increased with this exposure time. These reductions in Vc persisted and became more rapid with Cl, deprivation, thus excluding mechanisms involving either direct or indirect actions of pHi upon Cl, -dependent membrane transport. However they were abolished by the Na+,K+ -ATPase inhibitor ouabain. The Em changes that accompanied the addition and withdrawal of NH4+ conformed to a Nernst equation modified to include realistic NH4+ permeability terms, and thus the withdrawal of NH4+ restored Em to close to control values despite a persistent change in Vc. Finally these Em changes persisted and assumed faster kinetics with Cl, deprivation. The relative changes in Vc, Em and pHi were compared to predictions from the recent model of Fraser and Huang published in 2004 that related steady-state values of Vc and Em to the mean charge valency (zx) of intracellular membrane-impermeant anions, X,i. By assuming accepted values of intracellular buffering capacity (,i), intracellular acidification was shown to produce quantitatively predictable decreases in Vc. These findings thus provide experimental evidence that titration of the anionic zx by increased intracellular [H+] causes cellular volume decrease in the presence of normal Na+,K+ - ATPase activity, with Cl, -dependent membrane fluxes only influencing the kinetics of such changes. [source] | |||||||||||||