962 research outputs found

    Two-photon photochemical long-period grating fabrication in hydrogenated photonic crystal fiber

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    We report on the photochemical fabrication of a long-period grating in photonic crystal fiber. The characteristic fluence value for inscription is an order of magnitude less than that for standard telecom fiber

    Muscarinic Receptor Sequestration in SH-SY5Y Neuroblastoma Cells Is Inhibited when Clathrin Distribution Is Perturbed

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    The possibility that clathrin plays a role in the agonist-mediated sequestration of muscarinic cholinergic receptors in human SH-SY5Y neuroblastoma cells has been investigated by the application of experimental paradigms previously established to perturb clathrin distribution and receptor cycling events. Preincubation of SH-SY5Y cells under hypertonic conditions resulted in a pronounced inhibition of agonist-induced muscarinic receptor sequestration (70–80% at 550 mOsm), which was reversed when cells were returned to isotonic medium. Depletion of intracellular K + or acidification of the cytosol also resulted in >80% inhibition of muscarinic receptor sequestration. Under conditions of hypertonicity, depletion of intracellular K + , or acidification of cytosol, muscarinic receptor-stimulated phosphoinositide hydrolysis and Ca 2+ signaling events were either unaffected or markedly less inhibited than receptor sequestration. That these same experimental conditions did perturb clathrin distribution was verified by immunofluorescence studies. Hypertonicity and depletion of intracellular K + resulted in a pronounced accumulation of clathrin in the perinuclear region, whereas acidification of the cytosol resulted in the appearance of microaggregates of clathrin throughout the cytoplasm and at the plasma membrane. The results are consistent with the possibility that muscarinic receptors in SH-SY5Y cells are endocytosed via a clathrin-dependent mechanism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66348/1/j.1471-4159.1996.66010186.x.pd

    Immunocytochemical Localization of (Na + ,K + )-ATPase in the Goldfish Optic Nerve

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    Antiserum to the catalytic subunit of goldfish brain (Na + ,K + )-ATPase has been employed at the electron microscopic level by means of the peroxidase-antiperoxidase immunohistochemical method. In optic nerve, an-tigenic sites are restricted to the nodes of Ranvier. No reaction product is detected in underlying internodal neurolemma. Outgrowing neurites for cultured retinal explants devoid of glial ensheathment exhibit a continuous distribution of the enzyme subunit. Antibodies against eel electroplax (Na + , K + )-ATPase cross-react with the goldfish brain enzyme and show a similar immunocytochemical distribution pattern.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65862/1/j.1471-4159.1981.tb02384.x.pd

    Immunocytochemical Demonstration of Na + ,K + -ATPase in Internodal Axolemma of Myelinated Fibers of Rat Sciatic and Optic Nerves

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    We used postembedding electron microscopic immunocytochemistry with colloidal gold to determine the ultrastructural distribution of Na + ,K + -ATPase in the sciatic and optic nerves of the rat. Using a polyclonal antiserum raised against the denatured catalytic subunit of brain Na + ,K + -ATPase, we found immunoreactivity along the internodal axolemma of myelinated fibers in both nerves. This antiserum did not produce labeling of nodal axolemma. These results suggest that an important site of energy-dependent sodium-potassium exchange is along the internodal axolemma of myelinated fibers in the mammalian CNS and PNS and that there may be differences between the internodal and nodal forms of the enzyme.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66444/1/j.1471-4159.1991.tb02114.x.pd

    Instantaneous frequency and amplitude of complex signals based on quaternion Fourier transform

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    The ideas of instantaneous amplitude and phase are well understood for signals with real-valued samples, based on the analytic signal which is a complex signal with one-sided Fourier transform. We extend these ideas to signals with complex-valued samples, using a quaternion-valued equivalent of the analytic signal obtained from a one-sided quaternion Fourier transform which we refer to as the hypercomplex representation of the complex signal. We present the necessary properties of the quaternion Fourier transform, particularly its symmetries in the frequency domain and formulae for convolution and the quaternion Fourier transform of the Hilbert transform. The hypercomplex representation may be interpreted as an ordered pair of complex signals or as a quaternion signal. We discuss its derivation and properties and show that its quaternion Fourier transform is one-sided. It is shown how to derive from the hypercomplex representation a complex envelope and a phase. A classical result in the case of real signals is that an amplitude modulated signal may be analysed into its envelope and carrier using the analytic signal provided that the modulating signal has frequency content not overlapping with that of the carrier. We show that this idea extends to the complex case, provided that the complex signal modulates an orthonormal complex exponential. Orthonormal complex modulation can be represented mathematically by a polar representation of quaternions previously derived by the authors. As in the classical case, there is a restriction of non-overlapping frequency content between the modulating complex signal and the orthonormal complex exponential. We show that, under these conditions, modulation in the time domain is equivalent to a frequency shift in the quaternion Fourier domain. Examples are presented to demonstrate these concepts

    Tyrosine Phosphorylation of Botulinum Neurotoxin Protease Domains

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    Botulinum neurotoxins are most potent of all toxins. Their N-terminal light chain domain (Lc) translocates into peripheral cholinergic neurons to exert its endoproteolytic action leading to muscle paralysis. Therapeutic development against these toxins is a major challenge due to their in vitro and in vivo structural differences. Although three-dimensional structures and reaction mechanisms are very similar, the seven serotypes designated A through G vastly vary in their intracellular catalytic stability. To investigate if protein phosphorylation could account for this difference, we employed Src-catalyzed tyrosine phosphorylation of the Lc of six serotypes namely LcA, LcB, LcC1, LcD, LcE, and LcG. Very little phosphorylation was observed with LcD and LcE but LcA, LcB, and LcG were maximally phosphorylated by Src. Phosphorylation of LcA, LcB, and LcG did not affect their secondary and tertiary structures and thermostability significantly. Phosphorylation of Y250 and Y251 made LcA resistant to autocatalysis and drastically reduced its kcat/Km for catalysis. A tyrosine residue present near the essential cysteine at the C-terminal tail of LcA, LcB, and LcG was readily phosphorylated in vitro. Inclusion of a competitive inhibitor protected Y426 of LcA from phosphorylation, shedding light on the role of the C-terminus in the enzyme’s substrate or product binding

    Effects of ethacrynic acid on ion transport and energy metabolism in slices of avian salt gland and of mammalian liver and kidney cortex

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    Ethacrynic acid greatly inhibited net transport of ions and aerobic, energyconserving metabolism in slices of avian salt gland, rat liver, and rat and guinea-pig kidney cortex. The effects of increasing concentrations of ethacrynic acid on the transport of Na + , K + and Cl − ran closely parallel to its effects on tissue ATP levels and respiration. The concentration needed for maximal inhibition of transport reduced ATP levels by 80–90%. Respiration was reduced by 80–90% in salt gland and kidney cortex, and by a maximum of 30% in liver slices. The effects of low concentrations of ethacrynic acid required time to become fully manifest in some tissues, and the development of transport inhibition followed a similar course to decline of respiration and ATP levels. Ca 2+ extrusion by liver cells was inhibited by ethacrynic acid. The concentration dependence of the inhibition was similar to that shown by the other transport systems inhibited. There was no distinction evident between the sensitivity of Na + extrusion and of K + accumulation to the diuretic. Lactate production increased as respiration decreased in the presence of increasing concentrations of ethacrynic acid. We conclude that ethacrynic acid acted primarily as an inhibitor of mitochondrial respiration and ATP synthesis in the tissue slices, and that inhibition of ion transport was a nonspecific consequence of the failure of the energy supply.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48027/1/232_2005_Article_BF01933482.pd

    Spontaneous Variability and Circadian Distribution of Ectopic Activity in Patients With Malignant Ventricular Arrhythmia

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    Day to day variability of ventricular ectopic activity was analyzed in 45 patients with a history of malignant ventricular tachyarrhythmias who underwent two successive 24 h periods of ambulatory electrocardiographic (ECG) monitoring in the absence of antiarrhythmic drugs; 26 were male and 19 female, with a mean age of 56 years (range 15 to 76). The total number of single ventricular premature beats, couplets and ventricular tachycardia beats and runs on days 1 and 2 demonstrated a consistent overall correlation (r = 0.76 to 0.84). Individual variability was evaluated by regression analysis with determination of 95% confidence limits.The minimal decrease in arrhythmia density necessary to distinguish true drug effect from spontaneous variability was 64% for single ventricular premature beats, 83% for couplets, 90% for ventricular tachycardia runs and 93% for ventricular tachycardia beats. To meet the criteria for arrhythmia aggravation, the arrhythmia density had to increase by 400, 877, 1,500 and 2,400%, respectively. Multivariate analysis disclosed an inverse relation between day to day arrhythmia variability and baseline arrhythmia density and age. Variability was more pronounced in patients with coronary artery disease but was not influenced by the type of presenting arrhythmia or left ventricular function.The diurnal distribution of arrhythmias and heart rate followed a distinct circadian pattern. These data indicate that, despite good group reproducibility, spontaneous arrhythmia variability in individuals is substantial, necessitating standards to define both drug effect and arrhythmia aggravation
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