Lack of influence of the COX inhibitors metamizol and diclofenac on platelet GPIIb/IIIa and P-selectin expression in vitro

BACKGROUND: The effect of non-steroidal anti-inflammatory drugs (NSAIDs) for reduced platelet aggregation and thromboxane A(2 )synthesis has been well documented. However, the influence on platelet function is not fully explained. Aim of this study was to examine the influence of the COX-1 inhibiting NSAIDs, diclofenac and metamizol on platelet activation and leukocyte-platelet complexes, in vitro. Surface expression of GPIIb/IIIa and P-selectin on platelets, and the percentage of platelet-leukocyte complexes were investigated. METHODS: Whole blood was incubated with three different concentrations of diclofenac and metamizol for 5 and 30 minutes, followed by activation with TRAP-6 and ADP. Rates of GPIIb/IIIa and P-selectin expression, and the percentage of platelet-leukocyte complexes were analyzed by a flow-cytometric assay. RESULTS: There were no significant differences in the expression of GPIIb/IIIa and P-selectin, and in the formation of platelet-leukocyte complexes after activation with ADP and TRAP-6, regarding both the time of incubation and the concentrations of diclofenac and metamizol. CONCLUSIONS: Accordingly, the inhibitory effect of diclofenac and metamizol on platelet aggregation is not related to a reduced surface expression of P-selectin and GPIIb/IIIa on platelets

A Reaction-Diffusion Model to Capture Disparity Selectivity in Primary Visual Cortex

Decades of experimental studies are available on disparity selective cells in visual cortex of macaque and cat. Recently, local disparity map for iso-orientation sites for near-vertical edge preference is reported in area 18 of cat visual cortex. No experiment is yet reported on complete disparity map in V1. Disparity map for layer IV in V1 can provide insight into how disparity selective complex cell receptive field is organized from simple cell subunits. Though substantial amounts of experimental data on disparity selective cells is available, no model on receptive field development of such cells or disparity map development exists in literature. We model disparity selectivity in layer IV of cat V1 using a reaction-diffusion two-eye paradigm. In this model, the wiring between LGN and cortical layer IV is determined by resource an LGN cell has for supporting connections to cortical cells and competition for target space in layer IV. While competing for target space, the same type of LGN cells, irrespective of whether it belongs to left-eye-specific or right-eye-specific LGN layer, cooperate with each other while trying to push off the other type. Our model captures realistic 2D disparity selective simple cell receptive fields, their response properties and disparity map along with orientation and ocular dominance maps. There is lack of correlation between ocular dominance and disparity selectivity at the cell population level. At the map level, disparity selectivity topography is not random but weakly clustered for similar preferred disparities. This is similar to the experimental result reported for macaque. The details of weakly clustered disparity selectivity map in V1 indicate two types of complex cell receptive field organization

Electron shuttle-mediated microbial Fe(III) reduction under alkaline conditions

Purpose: Extracellular Fe(III) reduction plays an important role in a variety of biogeochemical processes. Several mechanisms for microbial Fe(III) reduction in pH-neutral environments have been proposed, but pathways of microbial Fe(III) reduction within alkaline conditions have not been clearly identified. Alkaline soils are vastly distributed; thus, a better understanding of microbial Fe(III) reduction under alkaline conditions is of significance. The purpose of this study is to explore the dominant mechanism of bacterial iron reduction in alkaline environments. Materials and methods: We used antraquinone-2,6-disulfonate (AQDS) as a representative of quinone moities of humic substances and elemental sulfur and sulfate as sulfur species to investigate the potential role of humic substances and sulfur species in mediating microbial Fe(III) reduction in alkaline environments. We carried out thermodynamic calculations to predict the ability of bacteria to reduce Fe(III) (oxyhydr)oxides under alkaline conditions and the ability of AQDS and sulfur species to serve as electron acceptors for microbial anaerobic respiration in an assumed alkaline soil environments. A series of incubation experiments with two model dissimilatory metal reducing bacteria, Shewanella oneidensis MR-1 and Geobacter sulfurreducens PCA as well as mixed bacteria enriched from a soil were performed to confirm the contribution of AQDS and sulfur species to Fe(III) reduction under alkaline conditions. Results and discussion: Based on thermodynamic calculations, we predicted that, under alkaline conditions, the enzymatic reduction of Fe(III) (oxyhydr)oxides would be thermodynamically feasible but very weak. In our incubation experiments, the reduction of ferrihydrite by anaerobic cultures of Shewanella oneidensis MR-1, Geobacter sulfurreducens PCA or microbes enriched from a soil was significantly increased in the presence of S0 or AQDS. Notably, AQDS contributed more to promoting Fe(III) reduction as a soluble electron shuttle than S0 did under the alkaline conditions probably because of different mechanisms of microbial utilization of AQDS and S0. Conclusions: These results suggest that microbial reduction of Fe(III) (oxyhydr)oxides under alkaline conditions may proceed via a pathway mediated by electron shuttles such as AQDS and S0. Considering the high ability of electron shuttling and vast distribution of humic substances, we suggest that humic substance-mediated Fe(III) reduction may potentially be the dominant mechanism for Fe(III) reduction in alkaline environments

Direct gating and mechanical integrity of Drosophila auditory transducers require TRPN1

The elusive transduction channels for hearing are directly gated mechanically by the pull of gating springs. We found that the transient receptor potential (TRP) channel TRPN1 (NOMPC) is essential for this direct gating of Drosophila auditory transduction channels and that the channel-spring complex was disrupted if TRPN1 was lost. Our results identify TRPN1 as a mechanical constituent of the fly's auditory transduction complex that may act as the channel and/or gating spring

The Effect of Intracortical Competition on the Formation of Topographic Maps in Models of Hebbian Learning

Correlation based learning models (CBL) and self-organizing maps (SOM) are two classes of Hebbian models that have both been proposed to explain the activity driven formation of cortical maps. Both models differ significantly in the way lateral cortical interactions are treated leading to different predictions for the formation of receptive fields. The linear CBL models predict that receptive field profiles are determined by the average values and the spatial correlations of second order of the afferent activity patterns, wheras SOM models map stimulus features. Here we investigate a class of models which are characterized by a variable degree of lateral competition and which have the CBL and SOM models as limit cases. We show that there exists a critical value for intracortical competition below which the model exhibits CBL properties and above which feature mapping sets in. The class of models is then analyzed with respect to the formation of topographic maps between two layers of ne..

The joint development of orientation and ocular dominance: Role of constraints

Piepenbrock C, Ritter H, Obermayer K. The joint development of orientation and ocular dominance: Role of constraints. Neural computation. 1997;9(5):959-970.Correlation-based learning (CBL) has been suggested as the mechanism that underlies the development of simple-cell receptive fields in the primary visual cortex of cats, including orientation preference (OR) and ocular dominance (OD) (Linsker, 1986; Miller, Keller, & Shyker, 1989). CBL has been applied successfully to the development of OR and OD individually (Miller, Keller, & Stryker, 1989; Miller, 1994; Miyashita & Tanaka, 1991; Erwin, Obermayer, & Schulten, 1995), but the conditions for their joint development have not been studied (but see Erwin & Miller, 1995, for independent work on the same question) in contrast to competitive Hebbian models (Obermayer, Blasdel, & Schulten, 1992). In this article, we provide insight into why this has been the case: OR and OD decouple in symmetric CBL models, and a joint development of OR and OD is possible only in a parameter regime that depends on nonlinear mechanisms

Solving Large Systems of Differential Equations in Parallel Using Covers and Skeletons

The design and implementation of parallel algorithms for distributed memory architectures is much harder than the development of sequential algorithms. This is mainly due to the communication and synchronization that is necessary to manage distributed data correctly. This paper applies a methodology for the transformational derivation of parallel programs using data distribution algebras that enable an abstract description of data distribution issues. Algorithms are formulated using skeletons, that is, specialized higher-order functions with particular parallel implementations. The methodology is applied to a the solution of a system of ordinary differential equations where convolutions can be computed using the Fast Fourier transformation. The example illustrates the practical optimization problems for a development model of the visual system that involves large scale neural network simulations. Finally, this algorithm is compared to an implementation of the same system of equations i..