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Selected AbstractsSynaptic Transmission: Inhibition of Neurotransmitter Release by Botulinum ToxinsHEADACHE, Issue 2003Oliver Dolly MSc Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation. At the neuromuscular junction, the presynaptic nerve ending is packed with synaptic vesicles filled with acetylcholine, and clustered at the tip of the folds of the postsynaptic muscle membrane are the acetylcholine receptors. Synaptic vesicles fuse with the membrane in response to an elevation of intraneuronal calcium concentration and undergo release of their transmitter by exocytosis. Intracellular proteins that contribute to the fusion of the vesicles with the plasma membrane during exocytosis include synaptosomal protein with a molecular weight of 25 kDa (SNAP-25); vesicle-associated membrane protein (VAMP), also known as synaptobrevin; and syntaxin. Through their proteolytic action on these proteins, botulinum toxins prevent exocytosis, thereby inhibiting the release of acetylcholine. There are 7 serotypes of this toxin,A, B, C1, D, E, F, and G,and each cleaves a different intracellular protein or the same target at distinct bonds. The separate cleavage sites in SNAP-25 for botulinum toxin types A and E contribute to their dissimilar durations of muscle relaxation. This report describes the molecular basis for the inhibition by botulinum toxins of neuroexocytosis and subsequent functional recovery at the neuromuscular junction. [source] The number of CD34+ cells in peripheral blood as a predictor of the CD34+ yield in patients going to autologous stem cell transplantationJOURNAL OF CLINICAL APHERESIS, Issue 2 2006A.L. Basquiera Abstract The number of CD34+ cells in peripheral blood (PB) is a guide to the optimal timing to harvest peripheral blood progenitor cells (PBPC). The objective was to determine the number of CD34+ cells in PB that allows achieving a final apheresis product containing ,1.5 × 106 CD34+ cells/kg, performing up to three aphereses. Between March 1999 and August 2003, patients with hematological and solid malignancies who underwent leukapheresis for autologous bone marrow transplantation were prospectively evaluated. Seventy-two aphereses in 48 patients were performed (mean 1.45 per patient; range 1,3). PBPC were mobilized with cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (G-CSF) (n = 40), other chemotherapy drugs plus G-CSF (n = 7), or G-CSF alone (n = 1). We found a strong correlation between the CD34+ cells count in peripheral blood and the CD34+ cells yielded (r = 0.903; P < 0.0001). Using receiver-operating characteristic (ROC) curves, the minimum number of CD34+ cells in PB to obtain ,1.5 × 106/kg in the first apheresis was 16.48 cells/,L (sensitivity 100%; specificity 95%). The best cut-off point necessary to obtain the same target in the final harvest was 15.48 cells/,L, performing up to three aphereses (sensitivity 89%; specificity 100%). In our experience, ,15 CD34+ cells/,L is the best predictor to begin the apheresis procedure. Based on this threshold level, it is possible to achieve at least 1.5 × 106/kg CD34+ cells in the graft with ,3 collections. J. Clin. Apheresis 2005. © 2005 Wiley-Liss, Inc. [source] The diverse CheC-type phosphatases: chemotaxis and beyondMOLECULAR MICROBIOLOGY, Issue 5 2008Travis J. Muff Summary A new class of protein phosphatases has emerged in the study of bacterial/archaeal chemotaxis, the CheC-type phosphatases. These proteins are distinct and unrelated to the well-known CheY-P phosphatase CheZ, though they have convergently evolved to dephosphorylate the same target. The family contains a common consensus sequence D/S-X3 -E-X2 -N-X22 -P that defines the phosphatase active site, of which there are often two per protein. Three distinct subgroups make up the family: CheC, FliY and CheX. Further, the CheC subgroup can be divided into three classes. Bacillus subtilis CheC typifies the first class and might function as a regulator of CheD. Class II CheCs likely function as phosphatases in systems other than chemotaxis. Class III CheCs are found in the archaeal class Halobacteria and might function as class I CheCs. FliY is the main phosphatase in the B. subtilis chemotaxis system. CheX is quite divergent from the rest of the family, forms a dimer and some may function outside chemotaxis. A model for the evolution of the family is discussed. [source] Cognitive processes facilitated by contextual cueing: Evidence from event-related brain potentialsPSYCHOPHYSIOLOGY, Issue 3 2009Andrea Schankin Abstract Finding a target in repeated search displays is faster than finding the same target in novel ones (contextual cueing). It is assumed that the visual context (the arrangement of the distracting objects) is used to guide attention efficiently to the target location. Alternatively, other factors, e.g., facilitation in early visual processing or in response selection, may play a role as well. In a contextual cueing experiment, participant's electrophysiological brain activity was recorded. Participants identified the target faster and more accurately in repeatedly presented displays. In this condition, the N2pc, a component reflecting the allocation of visual-spatial attention, was enhanced, indicating that attention was allocated more efficiently to those targets. However, also response-related processes, reflected by the LRP, were facilitated, indicating that guidance of attention cannot account for the entire contextual cueing benefit. [source] Three-dimensional distribution of no sources in a primary mechanosensory integration center in the locust and its implications for volume signalingTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 15 2010Daniel Münch Abstract Nitric oxide (NO) is an evolutionarily conserved mediator of neural plasticity. Because NO is highly diffusible, signals from multiple sources might combine in space and time to affect the same target. Whether such cooperative effects occur will depend on the effective signaling range and on the distances of NO sources to one another and to their targets. These anatomical parameters have been quantified in only few systems. We analyzed the 3D architecture of NO synthase (NOS) expression in a sensory neuropil, the ventral association center (VAC) of the locust. High-resolution confocal microscopy revealed NOS immunoreactive fiber boutons in submicrometer proximity to both the axon terminals of sensory neurons and their postsynaptic target, interneuron A4I1. Pharmacological manipulation of NO signaling affected the response of A4I1 to individual wind-puff stimuli and the response decrement during repetitive stimulation. Mapping NOS immunoreactivity in defined volumes around dendrites of A4I1 revealed NOS-positive fiber boutons within 5 ,m of nearly every surface point. The mean distances between neighboring NOS-boutons and between any point within the VAC and its nearest NOS-bouton were likewise about 5 ,m. For an NO signal to convey the identity of its source, the effective signaling range would therefore have to be less than 5 ,m, and shorter still when multiple boutons release NO simultaneously. The architecture is therefore well suited to support the cooperative generation of volume signals by interaction between the signals from multiple active boutons. J. Comp. Neurol. 518:2903,2916, 2010. © 2010 Wiley-Liss, Inc. [source] Three-dimensional distribution of NO sources in a primary mechanosensory integration center in the locust and its implications for volume signalingTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 15 2010Daniel Münch Abstract Nitric oxide (NO) is an evolutionarily conserved mediator of neural plasticity. Because NO is highly diffusible, signals from multiple sources might combine in space and time to affect the same target. Whether such cooperative effects occur will depend on the effective signaling range and on the distances of NO sources to one another and to their targets. These anatomical parameters have been quantified in only few systems. We analyzed the 3D architecture of NO synthase (NOS) expression in a sensory neuropil, the ventral association center (VAC) of the locust. High-resolution confocal microscopy revealed NOS immunoreactive fiber boutons in submicrometer proximity to both the axon terminals of sensory neurons and their postsynaptic target, interneuron A4I1. Pharmacological manipulation of NO signaling affected the response of A4I1 to individual wind-puff stimuli and the response decrement during repetitive stimulation. Mapping NOS immunoreactivity in defined volumes around dendrites of A4I1 revealed NOS-positive fiber boutons within 5 ,m of nearly every surface point. The mean distances between neighboring NOS-boutons and between any point within the VAC and its nearest NOS-bouton were likewise about 5 ,m. For an NO signal to convey the identity of its source, the effective signaling range would therefore have to be less than 5 ,m, and shorter still when multiple boutons release NO simultaneously. The architecture is therefore well suited to support the cooperative generation of volume signals by interaction between the signals from multiple active boutons. J. Comp. Neurol. 518:2903,2916, 2010. © 2010 Wiley-Liss, Inc. [source] Multi-sensor track-to-track fusion via linear minimum variance sense estimatorsASIAN JOURNAL OF CONTROL, Issue 3 2008Li-Wei Fong Abstract An integrated approach that consists of sensor-based filtering algorithms, local processors, and a global processor is employed to describe the distributed fusion problem when several sensors execute surveillance over a certain area. For the sensor tracking systems, each filtering algorithm utilized in the reference Cartesian coordinate system is presented for target tracking, with the radar measuring range, bearing, and elevation angle in the spherical coordinate system (SCS). For the local processors, each track-to-track fusion algorithm is used to merge two tracks representing the same target. The number of 2-combinations of a set with N distinct sensors is considered for central track fusion. For the global processor, the data fusion algorithms, simplified maximum likelihood (SML) estimator and covariance matching method (CMM), based on linear minimum variance (LMV) estimation fusion theory, are developed for use in a centralized track-to-track fusion situation. The resulting global fusers can be implemented in a parallel structure to facilitate estimation fusion calculation. Simulation results show that the proposed SML estimator has a more robust capability of improving tracking accuracy than the CMM and the LMV estimators. Copyright © 2008 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society [source] Eye,hand coordination in essential tremorMOVEMENT DISORDERS, Issue 3 2006Peter Trillenberg MD Abstract Patients with essential tremor (ET) or with cerebellar lesions have in common oculomotor abnormalities, with the exception of saccadic eye movements, which do not seem to be involved in ET. Since grasping is prolonged in ET and might be related to saccadic dysmetria, we tested whether simultaneous hand pointing could unmask it. Twelve ET patients and 14 controls performed saccades with and without simultaneous pointing movements to the same targets, and with and without a gap between the disappearance of the fixation point and the appearance of the target. Eye movements were recorded with the magnetic search-coil method, hand movements with an ultrasound-emitting probe. ET patients did not have saccadic dysmetria, and contrary to normal subjects their saccadic latency did not decrease during combined eye,hand movements compared with saccades performed in isolation. Hand movements had a longer duration in ET patients, with decreased peak acceleration, an increased latency of the peak velocity, and peak deceleration. In conclusion, this first study on eye,hand coordination in ET revealed abnormal kinematic changes in the early phase of pointing movements. These changes might be related to cerebellar disease but they are independent of the intention tremor component and saccade performance. © 2005 Movement Disorder Society [source] Pulmonary mucus: Pediatric perspectivePEDIATRIC PULMONOLOGY, Issue 3 2003Duncan F. Rogers PhD Abstract Airway mucus hypersecretion is a clinical feature of a number of childhood diseases, including asthma and bronchitis-associated conditions. However, compared with adults, there is relatively scarce information concerning mucus pathophysiology in respiratory diseases in children. The available evidence indicates many similarities between adult and childhood respiratory hypersecretory conditions, including goblet-cell hyperplasia and submucosal gland hypertrophy, and airway mucus plugging in asthma. Consequently, it is likely that treatments that are effective in adults would be effective in children. Numerous therapeutic targets are linked to the pathophysiology of airway mucus hypersecretion in experimental models and adults with respiratory disease. Whether or not these same targets are relevant in children is for the most part unclear. These targets include the inflammatory cells mediating the inflammatory response that generates the hypersecretory phenotype, and highly specific cellular elements such as epidermal growth factor receptor tyrosine kinase and calcium-activated chloride (CACL) channels. Identification of these factors is linked with the development of different classes of pharmacotherapeutic molecules directed at these targets. Compounds with a broader spectrum of anti-inflammatory activity are likely to be more effective than compounds with restricted activity. However, certain highly specific targets, such as human CACL1 channels, appear to be strongly associated with the development of an airway hypersecretory phenotype. Data from current clinical trials in adults with blockers of these specific targets are awaited with great interest. The hope is that, if effective, pediatric trials with these compounds could be initiated with a view to alleviation of the clinical impact of airway mucus hypersecretion in children. A significant challenge to the therapeutic progression of these new compounds is effective delivery to the airways in children, with the research effort into development of new compounds matched by advances in inhaler design. Pediatr Pulmonol. 2003; 36:178,188. © 2003 Wiley-Liss, Inc. [source] | |||||||||||||