Calcium/calmodulin-dependent protein kinase II increases glutamate and noradrenaline release from synaptosomes

A variety of evidence indicates that calcium-dependent protein phosphorylation modulates the release of neurotransmitter from nerve terminals. For instance, the injection of rat calcium/calmodulin-dependent protein kinase II (Ca2+/CaM-dependent PK II) into the preterminal digit of the squid giant synapse leads to an increase in the release of a so-far unidentified neurotransmitter induced by presynaptic depolarization. But until now, it has not been demonstrated that Ca2+/CaM-dependent PK II can also regulate neurotransmitter release in the vertebrate nervous system. Here we report that the introduction of Ca2+/CaM-dependent PK II, autoactivated by thiophosphorylation, into rat brain synaptosomes (isolated nerve terminals) increases the initial rate of induced release of two neurotransmitters, glutamate and noradrenaline. We also show that introduction of a selective peptidergic inhibitor of Ca2+/CaM-dependent PK II inhibits the initial rate of induced glutamate release. These results support the hypothesis that activation of Ca2+/CaM-dependent PK II in the nerve terminal removes a constraint on neurotransmitter release.     

A nanometre-scale electronic switch consisting of a metal cluster and redox-addressable groups

So-called bottom-up fabrication methods aim to assemble and integrate molecular components exhibiting specific functions into electronic devices that are orders of magnitude smaller than can be fabricated by lithographic techniques. Fundamental to the success of the bottom-up approach is the ability to control electron transport across molecular components. Organic molecules containing redox centres-chemical species whose oxidation number, and hence electronic structure, can be changed reversibly-support resonant tunnelling and display promising functional behaviour when sandwiched as molecular layers between electrical contacts, but their integration into more complex assemblies remains challenging. For this reason, functionalized metal nanoparticles have attracted much interest: they exhibit single-electron characteristics (such as quantized capacitance charging) and can be organized through simple self-assembly methods into well ordered structures, with the nanoparticles at controlled locations. Here we report scanning tunnelling microscopy measurements showing that organic molecules containing redox centres can be used to attach metal nanoparticles to electrode surfaces and so control the electron transport between them. Our system consists of gold nanoclusters a few nanometres across and functionalized with polymethylene chains that carry a central, reversibly reducible bipyridinium moiety. We expect that the ability to electronically contact metal nanoparticles via redox-active molecules, and to alter profoundly their tunnelling properties by charge injection into these molecules, can form the basis for a range of nanoscale electronic switches.     

Evaluation of a program to control hydatid disease in central Utah

Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 st1\:*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} A program to control hydatid disease in central Utah was evaluated by: (1) surveillance of infection in dogs and sheep, (2) questioning adult residents of two Sanpete County communities (Fountain Green and Spring City) about their knowledge of hydatid disease and their attitudes toward preventive measures, (3) interviewing local officials to evaluate the proposed implementation of proper community-wide measures, (4) analyzing records of prophylactic treatment of dogs with praziquantel, and (5) comparing scores of tests given to third and fourth grade students before and after they colored an educational pamphlet about hydatid disease. Infection rates of Echinococcus granulosus in dogs brought to volunteer diagnostic clinics dropped from 28.3 percent in 1972 to 1.0 percent in 1979, but increased to 9.8 percent in 1981. This last rise was due mainly to the fact that some dogs were examined that belonged to range sheepmen who had either not attended a field clinic recently or had never attended at all. Prevalence of the parasite in slaughtered sheep decreased steadily from 13.2 percent in 1972 to 2.8 percent in 1981. With regard to the questionnaire phase of the project, 87.3 percent and 84.3 percent of the respondents understood the role of dogs in the life cycle of E. granulosus in Fountain Green and Spring City, respectively. Over 50 percent of the respondents of these two communities had worked directly with sheep sometime in their life. In general, residents were more willing to practice preventive measures involving sheep than they were to implement measures involving dogs alone. However, many of the recommended community-wide preventive measures were not implemented. With the coloring book, students answered an average of 62.5 percent of the questions correctly before they colored the pamphlet and 83.3 percent afterward. Overall, our results suggest that residents of Sanpete County are knowledgeable about hydatid disease and its mode of transmission, and that, in general, progress has been made in control of hydatid disease in central Utah.       

Induction of formation of presynaptic terminals in neuroblastoma cells by synapsin IIb

The synapsins are a family of closely related phosphoproteins (termed synapsins Ia, Ib, IIa and IIb) associated with synaptic vesicles and implicated in the short-term regulation of neurotransmitter release from nerve endings. During development, expression of the synapsins correlates temporally with synapse formation, but there has been no direct evidence that they are involved in synaptogenesis. Here we report that overexpression of synapsin IIb in the neuroblastoma x glioma hybrid clonal cell line NG108-15 leads, during cell differentiation, to marked increases in the number of neuritic varicosities and in the numbers of small clear vesicles and large dense core vesicles per varicosity, as well as to the appearance of synapse-like cell-cell contacts. Thus, synapsin IIb may be involved in the regulation of synapse formation and, as a result, in long-term neuronal signalling.     

KATP channels as molecular sensors of cellular metabolism

In responding to cytoplasmic nucleotide levels, ATP-sensitive potassium (K(ATP)) channel activity provides a unique link between cellular energetics and electrical excitability. Over the past ten years, a steady drumbeat of crystallographic and electrophysiological studies has led to detailed structural and kinetic models that define the molecular basis of channel activity. In parallel, the uncovering of disease-causing mutations of K(ATP) has led to an explanation of the molecular basis of disease and, in turn, to a better understanding of the structural basis of channel function.