Arachidonic Acid as a Possible Negative Feedback Inhibitor of Nicotinic Acetylcholine Receptors on Neurons

Neuronal acetylcholine receptors, being highly permeable to calcium, are likely to regulate calcium-dependent events in neurons. Arachidonic acid is a membrane-permeant second messenger that can be released from membrane phospholipids by phospholipases in a calcium-dependent manner. We show here that activation of neuronal acetylcholine receptors triggers release of 3H-arachidonic acid in a calcium-dependent manner from neurons preloaded with the fatty acid. Moreover, low concentrations of arachidonic acid reversibly inhibit the receptors and act most efficiently on receptors likely to have the highest permeability to calcium, namely receptors containing α7 subunits. Low concentrations of arachidonic acid also reversibly inhibit α7- containing receptors expressed in Xenopus oocytes following injection of α7 cRNA. The oocyte results indicate following injection of α7 cRNA. The oocyte results indicate that the inhibition is a feature of the receptors rather than a consequence of neuron-specific machinery. The inhibition is not mediated by specific metabolites of arachidonic acid because the effects can be mimicked by other fatty acids; their effectiveness correlates with their content of double bonds. In contrast to arachidonic effects on calcium currents, inhibition of neuronal nicotinic receptors by the fatty acid cannot be prevented by blocking production of free radicals or by inhibiting protein kinase C. An alternative mechanism is that arachidonic acid binds directly to the receptors or perturbs the local environment in such a manner as to constrain receptor function

Synaptic Currents Generated by Neuronal Acetylcholine Receptors Sensitive to α-Bungarotoxin

AbstractNicotinic acetylcholine receptors are widely distributed throughout the nervous system, but their functions remain largely unknown. One of the most abundant is a class of receptors that contains the α7 gene product, has a high relative permeability to calcium, and binds α-bungarotoxin. Here, we report that receptors sensitive to α-bungarotoxin, though concentrated in perisynaptic clusters on neurons, can generate a large amount of the synaptic current. Residual currents through other nicotinic receptors are sufficient to elicit action potentials, but with slower rise times. This demonstrates a postsynaptic response for α-bungarotoxin-sensitive receptors on neurons and suggests that the functional domain of the postsynaptic membrane is broader than previously recognized

Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus

Neurogenesis in the dentate gyrus occurs throughout adult mammalian life and is essential for proper hippocampal function. Early in their development, adult-born neurons express homomeric α7-containing nicotinic acetylcholine receptors (α7-nAChRs) and receive direct cholinergic innervation. We show here that functional α7-nAChRs are necessary for normal survival, maturation, and integration of adult-born neurons in the dentate gyrus. Stereotaxic retroviral injection into the dentate gyrus of wild-type and α7-knock-out (α7KO) male and female mice was used to label and birthdate adult-born neurons for morphological and electrophysiological measures; BrdU (5-bromo-2-deoxyuridine) injections were used to quantify cell survival. In α7KO mice, we find that adult-born neurons develop with truncated, less complex dendritic arbors and display GABAergic postsynaptic currents with immature kinetics. The neurons also have a prolonged period of GABAergic depolarization characteristic of an immature state. In this condition, they receive fewer spontaneous synaptic currents and are more prone to die during the critical period when adult-born neurons are normally integrated into behaviorally relevant networks. Even those adult-born neurons that survive the critical period retain long-term dendritic abnormalities in α7KO mice. Interestingly, local infection with retroviral constructs to knockdown α7-mRNA mimics the α7KO phenotype, demonstrating that the relevant α7-nAChR signaling is cell autonomous. The results indicate a profound role for α7-nAChRs in adult neurogenesis and predict that α7-nAChR loss will cause progressive impairment in hippocampal circuitry and function over time as fewer neurons are added to the dentate gyrus and those that are added integrate less well.This work was supported by National Institutes of Health Grants NS012601 and N0S35469, and the Tobacco-Related Disease Research Program (16RT-0167). N.R.C. is a Tobacco-Related Disease Research Program predoctoral fellow. C.C.F. is a Fundação Calouste Gulbenkian Graduate Fellow. A.W.F. is a National Research Service Award predoctoral fellow. We thank Gouping Feng (Duke University, Durham, NC) for the GFP-reporter mouse line and Xiao-Yun Wang for expert technical assistance

Public perceptions of behavioral enrichment: Assumptions gone awry

More and more, zoos are integrating behavioral enrichment programs into their management routines. Given the newness of such programs on an official level, however, there are an increasing number of enrichment decisions based on assumption. Enrichment is typically not provided on exhibit, especially for exhibits considered to be more naturalistic, because it is assumed to affect visitors' experience negatively. To test that assumption, visitors were interviewed in front of four exhibits—an outdoor barren grotto, an outdoor vegetated grotto, an indoor immersion exhibit, and an outdoor traditional cage—each with either natural, nonnatural or no enrichment objects present. Specifically, we wanted to know whether (1) the exhibit's perceived educational message, (2) the animal's perceived “happiness,” and (3) the visitor perceptions of enrichment, the naturalism of animal's behavior, and zoo animal well-being changed as a function of object type. Overall, the type of enrichment object had little impact on visitor perceptions. In the outdoor barren grotto, only visitor perceptions of exhibit naturalism were affected by object type. In the outdoor vegetated grotto, object type influenced visitors perceptions of enrichment and exhibit naturalism. For the indoor immersion exhibit, general perceptions of enrichment and the perceived naturalism of the animal's behavior were affected. Finally, in the outdoor traditional cage, perceived educational message and general perceptions of enrichment changed as a function of object type. Zoo Biol 17:525–534, 1998. © 1998 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38477/1/6_ftp.pd

The science of decadence

In the nineteenth century, the concept of decadence was not solely of aesthetic interest but had a number of scientific applications. Decadence itself is an organic metaphor, extending the natural processes of decline and decay to societies and the arts. Rather than rejecting nature outright, decadent authors readily embraced new scientific theories that changed the way people thought about the natural world. The pessimism of nineteenth-century science stemmed from the brutal world of industrial capitalism in which it was developed. Decadent writers then incorporated both scientific ideas and language into a literary style obsessed with decay and decline. Finally, science returned to decadent literature to pathologize certain modes of artistic expression as yet another sign that certain types of individuals were ‘degenerate’. Three key scientific theories of the nineteenth century underpin the decadent fixation on decline, decay, and degeneration: uniformitarianism, evolution, and the conservation of energy. All three theories identify impermanence in natural structures previously believed to be permanent and stable

Functional characterization of a class III acid endochitinase from the traps of the carnivorous pitcher plant genus, Nepenthes

Carnivory in plants is an adaptation strategy to nutrient-poor environments and soils. Carnivorous plants obtain some additional mineral nutrients by trapping and digesting prey; the genus Nepenthes is helped by its specialized pitcher traps. To make the nutrients available, the caught prey needs to be digested, a process that requires the concerted activity of several hydrolytic enzymes. To identify and investigate the various enzymes involved in this process, fluid from Nepenthes traps has been analysed in detail. In this study, a novel type of Nepenthes endochitinase was identified in the digestion fluid of closed pitchers. The encoding endochitinase genes have been cloned from eight different Nepenthes species. Among these, the deduced amino acid sequence similarity was at least 94.9%. The corresponding cDNA from N. rafflesiana was heterologously expressed, and the purified protein, NrChit1, was biochemically characterized. The enzyme, classified as a class III acid endochitinase belonging to family 18 of the glycoside hydrolases, is secreted into the pitcher fluid very probably due to the presence of an N-terminal signal peptide. Transcriptome analyses using real-time PCR indicated that the presence of prey in the pitcher up-regulates the endochitinase gene not only in the glands, which are responsible for enzyme secretion, but at an even higher level, in the glands’ surrounding tissue. These results suggest that in the pitchers’ tissues, the endochitinase as well as other proteins from the pitcher fluid might fulfil a different, primary function as pathogenesis-related proteins

A world of copper: globalizing the Industrial Revolution, 1830-70

For most of human history the smelting of metallic ores has been performed immediately adjacent to the ore body. In the 1830s the copper industry that was centred on Swansea in the UK departed abruptly from that ancient pattern: Swansea smelters shipped in ores from very distant locations, including sites in Australasia, Latin America, and southern Africa. Swansea became the hub of a globally integrated heavy industry, one that deployed capital on a very large scale, implanted British industrial technologies in some very diverse settings, and mobilized a transnational workforce that included British-born ‘labour aristocrats’, Chinese indentured servants, and African slaves. This paper explores the World of Copper between its inception c.1830 and its demise in the aftermath of the American Civil War. It asks what the experience of this precociously globalized industry can contribute to some current concerns in global history

Engineering transcription factors with novel DNA-binding specificity using comparative genomics

The transcriptional program for a gene consists of the promoter necessary for recruiting RNA polymerase along with neighboring operator sites that bind different activators and repressors. From a synthetic biology perspective, if the DNA-binding specificity of these proteins can be changed, then they can be used to reprogram gene expression in cells. While many experimental methods exist for generating such specificity-altering mutations, few computational approaches are available, particularly in the case of bacterial transcription factors. In a previously published computational study of nitrogen oxide metabolism in bacteria, a small number of amino-acid residues were found to determine the specificity within the CRP (cAMP receptor protein)/FNR (fumarate and nitrate reductase regulatory protein) family of transcription factors. By analyzing how these amino acids vary in different regulators, a simple relationship between the identity of these residues and their target DNA-binding sequence was constructed. In this article, we experimentally tested whether this relationship could be used to engineer novel DNA–protein interactions. Using Escherichia coli CRP as a template, we tested eight designs based on this relationship and found that four worked as predicted. Collectively, these results in this work demonstrate that comparative genomics can inform the design of bacterial transcription factors

Sensitivity analysis of periodic matrix population models

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Theoretical Population Biology 82 (2012): 329-339, doi:10.1016/j.tpb.2012.03.008.Periodic matrix models are frequently used to describe cyclic temporal variation (seasonal or interannual) and to account for the operation of multiple processes (e.g., demography and dispersal) within a single projection interval. In either case, the models take the form of peri- odic matrix products. The perturbation analysis of periodic models must trace the e ects of parameter changes, at each phase of the cycle, on output variables that are calculated over the entire cycle. Here, we apply matrix calculus to obtain the sensitivity and elasticity of scalar-, vector-, or matrix-valued output variables. We apply the method to linear models for periodic environments (including seasonal harvest models), to vec-permutation models in which individ- uals are classi ed by multiple criteria, and to nonlinear models including both immediate and delayed density dependence. The results can be used to evaluate management strategies and to study selection gradients in periodic environments.This research was supported by NSF Grant DEB-0816514, by a Research Award from the Alexander von Humboldt Foundation, and by WHOI Academic Programs Funds