Drugs and the brain, the MOOC

How does a MOOC differ in value and impact from previous "distance-learning" technologies? (1) A major additional possibility is the online community that springs up around the course. "Drugs and the Brain" brought some people with real-life interest in drug mechanisms, and others with detailed scientific experience. Quantifying the letter group: of the students who finished the 2012-2013 course and earned "statements of accomplishment", ~ 10% of the students had PHD degrees and 7% had MD degrees, and ~ 7% had professional degrees in pharmacy. This online community requires detailed curation, moderation, and judgment. For the 2013-2014 rendition, we plan to have two undergraduate TA's as curators. (2) A secondary possibility is the concept of instantaneous feedback on exams and quizzes. This can also be incorporated in previous technologies. What are limitations of the MOOC? (1) After all limitations in bandwidth and technology have been overcome, "internet time" will still be constrained by the fact that the world is round. The instructor will be asleep when some students want to communicate, and vice-versa. (2) The course staff must invest formidable effort to optimize the learning experience. In this area, we include analyzing quiz responses, clicks, etc. We also include human evaluation of essays and other student responses. These are both wonderful problems, in the sense that we have too much data

Regions of beta 2 and beta 4 responsible for differences between the steady state dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic receptors

We constructed chimeras of the rat beta 2 and beta 4 neuronal nicotinic subunits to locate the regions that contribute to differences between the acetylcholine (ACh) dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 receptors. Expressed in Xenopus oocytes, the alpha 3 beta 2 receptor displays an EC50 for ACh approximately 20-fold less than the EC50 of the alpha 3 beta 4 receptor. The apparent Hill slope (n(app)) of alpha 3 beta 2 is near one whereas the alpha 3 beta 4 receptor displays an n(app) near two. Substitutions within the first 120 residues convert the EC50 for ACh from one wild-type value to the other. Exchanging just beta 2:104-120 for the corresponding region of beta 4 shifts the EC50 of ACh dose-response relationship in the expected direction but does not completely convert the EC50 of the dose- response relationship from one wild-type value to the other. However, substitutions in the beta 2:104-120 region do account for the relative sensitivity of the alpha 3 beta 2 receptor to cytisine, tetramethylammonium, and ACh. The expression of beta 4-like (strong) cooperativity requires an extensive region of beta 4 (beta 4:1-301). Relatively short beta 2 substitutions (beta 2:104-120) can reduce cooperativity to beta 2-like values. The results suggest that amino acids within the first 120 residues of beta 2 and the corresponding region of beta 4 contribute to an agonist binding site that bridges the alpha and beta subunits in neuronal nicotinic receptors

The transporter-like protein inebriated mediates hyperosmotic stimuli through intracellular signaling

We cloned the inebriated homologue MasIne from Manduca sexta and expressed it in Xenopus laevis oocytes. MasIne is homologous to neurotransmitter transporters but no transport was observed with a number of putative substrates. Oocytes expressing MasIne respond to hyperosmotic stimulation by releasing intracellular Ca(2+), as revealed by activation of the endogenous Ca(2+)-activated Cl(-) current. This Ca(2+) release requires the N-terminal 108 amino acid residues of MasIne and occurs via the inositol trisphosphate pathway. Fusion of the N terminus to the rat gamma-aminobutyric acid transporter (rGAT1) also renders rGAT1 responsive to hyperosmotic stimulation. Immunohistochemical analyses show that MasIne and Drosophila Ine have similar tissue distribution patterns, suggesting functional identity. Inebriated is expressed in tissues and cells actively involved in K(+) transport, which suggests that it may have a role in ion transport, particularly of K(+). We propose that stimulation of MasIne releases intracellular Ca(2+) in native tissues, activating Ca(2+)-dependent K(+) channels, and leading to K(+) transport

Determining Parameters of Cool Giant Stars by Modeling Spectrophotometric and Interferometric Observations Using the SAtlas Program

Context: Optical interferometry is a powerful tool for observing the intensity structure and angular diameter of stars. When combined with spectroscopy and/or spectrophotometry, interferometry provides a powerful constraint for model stellar atmospheres. Aims: The purpose of this work is to test the robustness of the spherically symmetric version of the Atlas stellar atmosphere program, SAtlas, using interferometric and spectrophotometric observations. Methods: Cubes (three dimensional grids) of model stellar atmospheres, with dimensions of luminosity, mass, and radius, are computed to fit observations for three evolved giant stars, \psi Phoenicis, \gamma Sagittae, and \alpha Ceti. The best-fit parameters are compared with previous results. Results: The best-fit angular diameters and values of \chi^2 are consistent with predictions using Phoenix and plane-parallel Atlas models. The predicted effective temperatures, using SAtlas, are about 100 to 200 K lower, and the predicted luminosities are also lower due to the differences in effective temperatures. Conclusions: It is shown that the SAtlas program is a robust tool for computing models of extended stellar atmospheres that are consistent with observations. The best-fit parameters are consistent with predictions using Phoenix models, and the fit to the interferometric data for \psi Phe differs slightly, although both agree within the uncertainty of the interferometric observations.Comment: 5 pages, 6 figures, Accepted for publication in A&A as a Research Not

Regions of β4·β2 subunit chimeras that contribute to the agonist selectivity of neuronal nicotinic receptors

AbstractFifteen chimeric nicotinic receptors β subunits were constructed consisting of N-terminal neuronal β4 sequences and C-terminal β2 sequences. Responses to cytisine, nicotine, or tetramethylammonium were compared to acetylcholine responses for these subunits expressed in Xenopus oocytes with α3 subunits. The results show that (i) two residues in the extracellular domain of chimeric β4·β2 subunits (108β2F/β4V, 110β2S/β4T) account for much of the relative cytisine sensitivity; and (ii) four extracellular residues of chimeric β4·β2 subunits (112β2A/β4V, 113β2V/β4I and 115β2S/β4R, 116β2Y/β4S) account for most of the relative tetramethylammonium sensitivity. The data did not permit localization of nicotine sensitivity to any particular region