The Ventilatory Response to Normoxic Hypercapnia in Male Pet-1 Knockout Mice and the Influence of Female Sex Hormones

Purpose: To determine if the deficiency in the hypercapnic ventilatory response as a result of 70% loss of serotonergic neurons in male Pet-1 knockout mice and the sparing of the female Pet-1 knockout mice can been accounted for and corrected by supplementation with estrogen and progesterone. Methods: Using whole-body flow-through plethysmography, 5 male Pet-1 -/- mice and 5 wild type mice were exposed to room air, 3%, 5%, 7%, and 10% CO2 and VE measured. All mice were then treated with oral 17β-estradiol (2500 nM) for 48 hours followed by a SC injection of progesterone (2 mg/kg). One hour after injection all plethysmography studies were repeated. Results: Before treatment Pet-1 knockout mice showed a trend towards decreased VE at room air, 3%, and 7% CO2, with statistical significance at 5% CO2 (p \u3c0.05), and an identical VE only at 10% CO2. Absolute changes in VE after treatment were insignificant; the differences in VE between genotypes achieved significance at control, 3%, and 5% CO2 (p \u3c0.05) while now VE at 7% and 10% CO2 exposures were identical (p \u3c 0.05). Conclusion: The partial recovery of the male Pet-1 knockout phenotype provides evidence that the remaining serotonergic neurons can recover some chemoreceptor function under the influence of female sex hormones, which in turn may partially explain the female Pet-1 knockout phenotype

Gz, a guanine nucleotide-binding protein with unique biochemical properties

Cloning of a complementary DNA (cDNA) for Gz alpha, a newly appreciated member of the family of guanine nucleotide-binding regulatory proteins (G proteins), has allowed preparation of specific antisera to identify the protein in tissues and to assay it during purification from bovine brain. Additionally, expression of the cDNA in Escherichia coli has resulted in the production and purification of the recombinant protein. Purification of Gz from bovine brain is tedious, and only small quantities of protein have been obtained. The protein copurifies with the beta gamma subunit complex common to other G proteins; another 26- kDa GTP-binding protein is also present in these preparations. The purified protein could not serve as a substrate for NAD-dependent ADP- ribosylation catalyzed by either pertussis toxin or cholera toxin. Purification of recombinant Gz alpha (rGz alpha) from E. coli is simple, and quantities of homogeneous protein sufficient for biochemical analysis are obtained. Purified rGz alpha has several properties that distinguish it from other G protein alpha subunit polypeptides. These include a very slow rate of guanine nucleotide exchange (k = 0.02 min^-1), which is reduced greater than 20-fold in the presence of mM concentrations of Mg2+. In addition, the rate of the intrinsic GTPase activity of Gz alpha is extremely slow. The hydrolysis rate (kcat) for rGz alpha at 30 degrees C is 0.05 min^-1, or 200-fold slower than that determined for other G protein alpha subunits. rGz alpha can interact with bovine brain beta gamma but does not serve as a substrate for ADP-ribosylation catalyzed by either pertussis toxin or cholera toxin. These studies suggest that Gz may play a role in signal transduction pathways that are mechanistically distinct from those controlled by the other members of the G protein family

G protein beta gamma subunits synthesized in Sf9 cells. Functional characterization and the significance of prenylation of gamma

Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) consist of a nucleotide-binding alpha subunit and a high- affinity complex of beta and gamma subunits. There is molecular heterogeneity of beta and gamma, but the significance of this diversity is poorly understood. Different G protein beta and gamma subunits have been expressed both singly and in combinations in Sf9 cells. Although expression of individual subunits is achieved in all cases, beta gamma subunit activity (support of pertussis toxin-catalyzed ADP-ribosylation of rGi alpha 1) is detected only when beta and gamma are expressed concurrently. Of the six combinations of beta gamma tested (beta 1 or beta 2 with gamma 1, gamma 2, or gamma 3), only one, beta 2 gamma 1, failed to generate a functional complex. Each of the other five complexes has been purified by subunit exchange chromatography using Go alpha-agarose as the chromatographic matrix. We have detected differences in the abilities of the purified proteins to support ADP- ribosylation of Gi alpha 1; these differences are attributable to the gamma component of the complex. When assayed for their ability to inhibit calmodulin-stimulated type-I adenylylcyclase activity or to potentiate Gs alpha-stimulated type-II adenylylcyclase, recombinant beta 1 gamma 1 and transducin beta gamma are approximately 10 and 20 times less potent, respectively, than the other complexes examined. Prenylation and/or further carboxyl-terminal processing of gamma are not required for assembly of the beta gamma subunit complex but are indispensable for high affinity interactions of beta gamma with either G protein alpha subunits or adenylylcyclases

Symmetry and structure of carbon-nitrogen complexes in gallium arsenide from infrared spectroscopy and first-principles calculations

Molecular-like carbon-nitrogen complexes in GaAs are investigated both experimentally and theoretically. Two characteristic high-frequency stretching modes at \num{1973} and \SI{2060}{cm^{-1}}, detected by Fourier transform infrared absorption (FTIR) spectroscopy, appear in carbon- and nitrogen-implanted and annealed layers. From isotopic substitution it is deduced that the chemical composition of the underlying complexes is CN$_2$ and C$_2$N, respectively. Piezospectroscopic FTIR measurements reveal that both centers have tetragonal symmetry. For density functional theory (DFT) calculations linear entities are substituted for the As anion, with the axis oriented along the \hkl direction, in accordance with the experimentally ascertained symmetry. The DFT calculations support the stability of linear N-C-N and C-C-N complexes in the GaAs host crystal in the charge states ranging from $+3$ to $-3$. The valence bonds of the complexes are analyzed using molecular-like orbitals from DFT. It turns out that internal bonds and bonds to the lattice are essentially independent of the charge state. The calculated vibrational mode frequencies are close to the experimental values and reproduce precisely the isotopic mass splitting from FTIR experiments. Finally, the formation energies show that under thermodynamic equilibrium CN$_2$ is more stable than C$_2$N

An Empirical Framework for Matching with Imperfectly Transferable Utility

We introduce an empirical framework for models of matching with imperfectly transferable utility and unobserved heterogeneity in tastes. Our framework includes as special cases the classic fully- and non-transferable utility models, collective models, and settings with taxes on transfers, deadweight losses, and risk aversion. We characterize equilibrium and conditions for identification, and derive comparative statics

Influential Article Review - Github: Examining the Gap Between Hierachical and Non Hierachical Types of Organisations

This paper examines organization. We present insights from a highly influential paper. Here are the highlights from this paper: In this edition of the organizational zoo series, we take a closer look at an interesting organization design case—GitHub, a software company from California. Similar to Valve, the subject of the previous article in the series (Puranam and Håkonsson, J Organ Design 4: 2–4, 2015) GitHub is used to delegate the choice of projects and project allocation to its workers, fitting the recent trend in running organizations without bosses. The interesting fact about GitHub is that after years of praising its own unorthodox organizational structure, the company suddenly decided to abandon it for something much more traditional. We asked several renowned organization scientists to share their thoughts on this interesting case and discuss what we can learn from it. For our overseas readers, we then present the insights from this paper in Spanish, French, Portuguese, and German