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Parallel Pathways (parallel + pathway)
Selected AbstractsESX-1-dependent cytolysis in lysosome secretion and inflammasome activation during mycobacterial infectionCELLULAR MICROBIOLOGY, Issue 9 2008Ingrid C. Koo Summary Exocytosis of lysosomes from macrophages has been described as a response to microbial cytotoxins and haemolysins, as well as for releasing pro-inflammatory cytokines interleukin (IL)-1, and IL-18 during inflammasome activation. The mycobacterial ESX-1 secretion system, encoded in part by the Region of Difference-1, is a virulence factor necessary for phagosome escape and host cell lysis by a contact-dependent haemolysin in Mycobacterium marinum. Here we show that ESX-1 from M. marinum and M. tuberculosis is required for Ca2+ -dependent induction of lysosome secretion from macrophages. Mycobacteria-induced lysosome secretion was concurrent to release of IL-1, and IL-18, dependent on phagocytosis of bacteria containing ESX-1. Synthesis but not release of IL-1, and IL-18 occurred in response to dead bacilli and bacteria lacking ESX-1, indicating that only cytokine release was regulated by ESX-1. Release of these cytokines and exocytosis of lysosomes were independent of intracellular mycobacterial growth, yet correlated with mycobacteria-encoded haemolytic activity, demonstrating a parallel pathway for the two responses. We further identified inflammasome components caspase-1, ASC and NALP3, but not Ipaf, required for release of IL-1, and IL-18. Collectively, these results reveal a role for ESX-1 in triggering secretion of lysosomes, as well as release of IL-1, and IL-18 during mycobacteria infection. [source] Mitogen-activated protein kinase signal transduction in skeletal muscle: effects of exercise and muscle contractionACTA PHYSIOLOGICA, Issue 3 2001U. Widegren Exercise has numerous growth and metabolic effects in skeletal muscle, including changes in glycogen metabolism, glucose and amino acid uptake, protein synthesis and gene transcription. However, the mechanism(s) by which exercise regulates intracellular signal transduction to the transcriptional machinery in the nucleus, thus modulating gene expression, is largely unknown. This review will provide insight on potential intracellular signalling mechanisms by which muscle contraction/exercise leads to changes in gene expression. Mitogen-activated protein kinase (MAPK) cascades are associated with increased transcriptional activity. The MAPK family members can be separated into distinct parallel pathways including the extracellular signal-regulated kinase (ERK) 1/2, the stress-activated protein kinase cascades (SAPK1/JNK and SAPK2/p38) and the extracellular signal-regulated kinase 5 (ERK5). Acute exercise elicits signal transduction via MAPK cascades in direct response to muscle contraction. Thus, MAPK pathways appear to be potential physiological mechanisms involved in the exercise-induced regulation of gene expression in skeletal muscle. [source] Harvesting Excitons Via Two Parallel Channels for Efficient White Organic LEDs with Nearly 100% Internal Quantum Efficiency: Fabrication and Emission-Mechanism AnalysisADVANCED FUNCTIONAL MATERIALS, Issue 1 2009Qi Wang Abstract By incorporating two phosphorescent dyes, namely, iridium(III)[bis(4,6-difluorophenyl)-pyridinato-N,C2,]picolinate (FIrpic) for blue emission and bis(2-(9,9-diethyl-9H -fluoren-2-yl)-1-phenyl-1H -benzoimidazol-N,C3)iridium(acetylacetonate) ((fbi)2Ir(acac)) for orange emission, into a single-energy well-like emissive layer, an extremely high-efficiency white organic light-emitting diode (WOLED) with excellent color stability is demonstrated. This device can achieve a peak forward-viewing power efficiency of 42.5,lm,W,1, corresponding to an external quantum efficiency (EQE) of 19.3% and a current efficiency of 52.8,cd,A,1. Systematic studies of the dopants, host and dopant-doped host films in terms of photophysical properties (including absorption, photoluminescence, and excitation spectra), transient photoluminescence, current density,voltage characteristics, and temperature-dependent electroluminescence spectra are subsequently performed, from which it is concluded that the emission natures of FIrpic and (fbi)2Ir(acac) are, respectively, host,guest energy transfer and a direct exciton formation process. These two parallel pathways serve to channel the overall excitons to both dopants, greatly reducing unfavorable energy losses. It is noteworthy that the introduction of the multifunctional orange dopant (fbi)2Ir(acac) (serving as either hole-trapping site or electron-transporting channel) is essential to this concept as it can make an improved charge balance and broaden the recombination zone. Based on this unique working model, detailed studies of the slight color-shift in this WOLED are performed. It is quantitatively proven that the competition between hole trapping on orange-dopant sites and undisturbed hole transport across the emissive layer is the actual reason. Furthermore, a calculation of the fraction of trapped holes on (fbi)2Ir(acac) sites with voltage shows that the hole-trapping effect of the orange dopant is decreased with increasing drive voltage, leading to a reduction of orange emission. [source] High-performance liquid chromatographic/tandem mass spectrometric identification of the phototransformation products of tebuconazole on titanium dioxideJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 6 2002Paola Calza Abstract Tebuconazole is a widely used fungicide. The formation of by-products on irradiated titanium dioxide as a photocatalyst was evaluated. Several species derived from tebuconazole degradation were identified and characterized by HPLC/MSn. A pattern of reactions accounting for the observed intermediates is proposed. Different parallel pathways are operating (and through these pathways the transformation of the molecule proceeds), leading to a wide range of intermediate compounds. All these molecules are more hydrophylic than tebuconazole. The main steps involved are (1) the hydroxylation of the molecule with the formation of three species having [M + H]+ 324; the hydroxylation occurs on the C-1 carbon and on the aromatic ring in the two ortho -positions; (2) the cleavage of a C,C bond with the release of the tert -butyl moiety and the formation of a species having m/z 250; analogously to step 1, also on this species a further hydroxylation reaction occurs; (3) through the loss of the triazole moiety with the formation of a structure with m/z 257. Copyright © 2002 John Wiley & Sons, Ltd. [source] Activity Switches of Rhodopsin,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2008Eglof Ritter Rhodopsin, the visual pigment of the rod photoreceptor cell contains as its light-sensitive cofactor 11- cis retinal, which is bound by a protonated Schiff base between its aldehyde group and the Lys296 side chain of the apoprotein. Light activation is achieved by 11- cis to all- trans isomerization and subsequent thermal relaxation into the active, G protein-binding metarhodopsin II state. Metarhodopsin II decays via two parallel pathways, which both involve hydrolysis of the Schiff base eventually to opsin and released all- trans retinal. Subsequently, rhodopsin's dark state is regenerated by a complicated retinal metabolism, termed the retinoid cycle. Unlike other retinal proteins, such as bacteriorhodopsin, this regeneration cycle cannot be short cut by light, because blue illumination of active metarhodopsin II does not lead back to the ground state but to the formation of largely inactive metarhodopsin III. In this review, mechanistic details of activating and deactivating pathways of rhodopsin, particularly concerning the roles of the retinal, are compared. Based on static and time-resolved UV/Vis and FTIR spectroscopic data, we discuss a model of the light-induced deactivation. We describe properties and photoreactions of metarhodopsin III and suggest potential roles of this intermediate for vision. [source] A unified mechanism for protein folding: Predetermined pathways with optional errorsPROTEIN SCIENCE, Issue 3 2007Mallela M.G. Krishna Abstract There is a fundamental conflict between two different views of how proteins fold. Kinetic experiments and theoretical calculations are often interpreted in terms of different population fractions folding through different intermediates in independent unrelated pathways (IUP model). However, detailed structural information indicates that all of the protein population folds through a sequence of intermediates predetermined by the foldon substructure of the target protein and a sequential stabilization principle. These contrary views can be resolved by a predetermined pathway,optional error (PPOE) hypothesis. The hypothesis is that any pathway intermediate can incorporate a chance misfolding error that blocks folding and must be reversed for productive folding to continue. Different fractions of the protein population will then block at different steps, populate different intermediates, and fold at different rates, giving the appearance of multiple unrelated pathways. A test of the hypothesis matches the two models against extensive kinetic folding results for hen lysozyme which have been widely cited in support of independent parallel pathways. The PPOE model succeeds with fewer fitting constants. The fitted PPOE reaction scheme leads to known folding behavior, whereas the IUP properties are contradicted by experiment. The appearance of a conflict with multipath theoretical models seems to be due to their different focus, namely on multitrack microscopic behavior versus cooperative macroscopic behavior. The integration of three well-documented principles in the PPOE model (cooperative foldons, sequential stabilization, optional errors) provides a unifying explanation for how proteins fold and why they fold in that way. [source] Direction selectivity in V1 of alert monkeys: evidence for parallel pathways for motion processingTHE JOURNAL OF PHYSIOLOGY, Issue 2 2007Moshe Gur In primary visual cortex (V1) of macaque monkeys, motion selective cells form three parallel pathways. Two sets of direction selective cells, one in layer 4B, and the other in layer 6, send parallel direct outputs to area MT in the dorsal cortical stream. We show that these two outputs carry different types of spatial information. Direction selective cells in layer 4B have smaller receptive fields than those in layer 6, and layer 4B cells are more selective for orientation. We present evidence for a third direction selective pathway that flows through V1 layers 4Cm (the middle tier of layer 4C) to layer 3. Cells in layer 3 are very selective for orientation, have the smallest receptive fields in V1, and send direct outputs to area V2. Layer 3 neurons are well suited to contribute to detection and recognition of small objects by the ventral cortical stream, as well as to sense subtle motions within objects, such as changes in facial expressions. [source] | |||||||||||||