Evidence for transmitter operated electrical synapses (TOES) in ampullary electroreceptor organs

Afferent fibres of ampullary electroreceptor organs in electrosensitive fish fire spontaneously, that is, they fire without external stimulus. In the past it has been postulated that the spontaneous activity originates from a sustained level of neurotransmitter release delivered by the electroreceptor cells. The spontaneous activity can be modulated by electrical stimuli. Blocking of the chemical synapse, however, reduces the susceptibility to electrical stimuli to 2% or less, but the spontaneous activity to 60% only. By evaluating existing experimental evidence it is concluded that spontaneous firing of afferents is based on two processes. (1) A membrane bound oscillator, which does not depend on transmitter release, is almost free of frequency fluctuations, and is described by Hodgkin/Huxley-equations (HH-equations). (2) Release of neurotransmitter, which increases the firing level, adds frequency noise, and raises the susceptibility of the afferent to electrical stimuli. There is evidence that neurotransmitter release acts as a gating process, which makes the generator area of the afferents directly accessible to electrical stimuli from the outside. Apparently, the activated synapse behaves as a transmitter operated electrical synapse (TOES).     

Enhanced Expression and Activation of the Alternative Oxidase during Infection of Arabidopsis with Pseudomonas syringae pv tomato

Cyanide-resistant ("alternative") respiration was studied in Arabidopsis during incompatible and compatible infection with Pseudomonas syringae pv tomato DC3000. Total leaf respiration increased as the leaves became necrotic, as did the cyanide-resistant component that was sensitive to salicylhydroxamic acid. Infiltration of leaves with an avirulent strain rapidly induced alternative oxidase (AOX) mRNA, whereas the increase was delayed in the compatible combination. The increase in mRNA correlated with the increase in AOX protein. Increased expression was confined to the infected leaves, in contrast to the pathogenesis-related protein-1, which was induced systemically. Virtually all of the AOX protein was in the reduced (high-activity) form. Using transgenic NahG and mutant npr1-1 and etr1-1 plants, we established that the rapid induction of the AOX was associated with necrosis and that ethylene, but not salicylic acid, was required for its induction. Increased pyruvate levels in the infected leaves suggested that increased substrate levels were respired through the alternative pathway; however, in the control leaves and the infected leaves, respiration was not inhibited by salicylhydroxamic acid alone. Increased respiration appeared to be associated primarily with symptom expression rather than resistance reactions.     

β-Arrestin-biased signaling of PTH analogs of the type 1 parathyroid hormone receptor

Parathyroid hormone (PTH) is an anabolic agent that mediates bone formation through activation of the Gα_s-, Gα_q- and β-arrestin-coupled parathyroid hormone receptor type 1 (PTH1R). Pharmacological evidence based on the effect of PTH(7–34), a PTH derivative that is said to preferentially activate β-arrestin signaling through PTH1R, suggests that PTH1R-activated β-arrestin signaling mediates anabolic effects on bone. Here, we performed a thorough evaluation of PTH(7–34) signaling behaviour using quantitative assays for β-arrestin recruitment, Gα_s- and Gα_q-signaling. We found that PTH(7–34) inhibited PTH-induced cAMP accumulation, but was unable to induce β-arrestin recruitment, PTH1R internalization and ERK1/2 phosphorylation in HEK293, CHO and U2OS cells. Thus, the β-arrestin bias of PTH(7–34) is not apparent in every cell type examined, suggesting that correlating in vivo effects of PTH(7–34) to in vitro pharmacology should be done with caution.     

A compact vocabulary of paratope-epitope interactions enables predictability of antibody-antigen binding

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