Intrinsic Gating Properties of a Cloned G Protein-activated Inward Rectifier K^+ Channel

The voltage-, time-, and K^+-dependent properties of a G protein-activated inwardly rectifying K^+ channel (GIRK1/KGA/Kir3.1) cloned from rat atrium were studied in Xenopus oocytes under two-electrode voltage clamp. During maintained G protein activation and in the presence of high external K^+ (V_K = 0 mV), voltage jumps from V_K to negative membrane potentials activated inward GIRK1 K^+ currents with three distinct time-resolved current components. GIRK1 current activation consisted of an instantaneous component that was followed by two components with time constants T_f~50 ms and T_s~400 ms. These activation time constants were weakly voltage dependent, increasing approximately twofold with maximal hyperpolarization from V_K. Voltage-dependent GIRK1 availability, revealed by tail currents at -80 mV after long prepulses, was greatest at potentials negative to V_K and declined to a plateau of approximately half the maximal level at positive voltages. Voltage-dependent GIRK1 availability shifted with V_K and was half maximal at V_K -20 mV; the equivalent gating charge was ~1.6 e^-. The voltage-dependent gating parameters of GIRK1 did not significantly differ for G protein activation by three heterologously expressed signaling pathways: m2 muscarinic receptors, serotonin 1A receptors, or G protein β1y2 subunits. Voltage dependence was also unaffected by agonist concentration. These results indicate that the voltage-dependent gating properties of GIRK1 are not due to extrinsic factors such as agonist-receptor interactions and G protein-channel coupling, but instead are analogous to the intrinsic gating behaviors of other inwardly rectifying K^+ channels

Immune cells and preterm labour:do invariant NKT cells hold the key?

We have developed our original made-to-measure (M2M) algorithm, PRIMAL, with the aim of modelling the Galactic disc from upcoming Gaia data. From a Milky Way like N-body disc galaxy simulation, we have created mock Gaia data using M0III stars as tracers, taking into account extinction and the expected Gaia errors. In PRIMAL, observables calculated from the N-body model are compared with the target stars, at the position of the target stars. Using PRIMAL, the masses of the N-body model particles are changed to reproduce the target mock data, and the gravitational potential is automatically adjusted by the changing mass of the model particles. We have also adopted a new resampling scheme for the model particles to keep the mass resolution of the N-body model relatively constant. We have applied PRIMAL to this mock Gaia data and we show that PRIMAL can recover the structure and kinematics of a Milky Way like barred spiral disc, along with the apparent bar structure and pattern speed of the bar despite the galactic extinction and the observational errors

Lecture notes on sediment transportation and channel stability

These notes have been prepared for a series of lectures on sediment transportation and channel stability given by the authors to a group of engineers and geologists of the U. S. Department of Agriculture assembled at Caltech on September 12-16,1960. The material herein is not intended to serve as a complete textbook, because it covers only subjects of the one-week sequence of lectures Due to limitation of space and time, coverage of many subjects is brief and others are omitted altogether. At the end of each chapter the reader will find a selected list of references for more detailed study

Polylactic Acid (PLA) Scaffolds for Tissue Engineering Applications do not Biodegrade in Physiological Saline at Room Temperature

Three-dimensional (3D) printable scaffolds are advantageous for their ability to be custom made to fill hard tissue defects. In this approach, scaffolds are required to be osteoconductive such that cells (osteoblasts) can attach and proliferate on the scaffolds and subsequently go on to become bone. It is desirable for the scaffold to biodegrade while bone formation occurs. Biodegradation occurs through the process of polymer chains being broken down into smaller chains, resulting in eventual extinction of the polymer altogether. Knowledge of biodegradation rates is important for prediction of scaffold stiffness and strength used in engineering analysis. Polylactic acid, or PLA, is a popular filament used in 3D printing (3DP). Biodegradation of PLA occurs through the process of hydrolysis which utilizes water molecules to break down the polymer chain. In this study, PLA scaffolds were tested to determine their baseline degradation rates. Eight X-type scaffold specimens were selected for the assessment of PLA sustainability due to soaking in cell culture media held at room temperature (20° C). Specimens were weighted, measured, and mechanically tested at the onset of the protocol (t = 0 weeks) and at weeks 1-7, week 10, and week 32. Mechanical compression tests made between steel plates within the elastic limit. Following testing, the structural stiffness (slope of the load-displacement curve) was calculated within the linear elastic region. Statistical analysis using JMP (SAS institute, Cary, NC) was performed to detect degradation in weight and stiffness with soak time. A significant difference is indicated by

The X-ray emission of z>2.5 active galactic nuclei can be obscured by their host galaxies

We present a multi-wavelength study of seven AGN at spectroscopic redshift >2.5 in the 7 Ms Chandra Deep Field South, selected to have good FIR/sub-mm detections. Our aim is to investigate the possibility that the obscuration observed in the X-rays can be produced by the interstellar medium (ISM) of the host galaxy. Based on the 7 Ms Chandra spectra, we measured obscuring column densities N$_{H, X}$ in excess of 7x10$^{22}$ cm$^{-2}$ and intrinsic X-ray luminosities L$_{X}$>10$^{44}$ erg s$^{-1}$ for our targets, as well as equivalent widths for the Fe K$\alpha$ emission line EW>0.5-1 keV. We built the UV-to-FIR spectral energy distributions by using broad-band photometry from CANDELS and Herschel catalogs. By means of an SED decomposition technique, we derived stellar masses (M$_{*}$~10$^{11}$ Msun), IR luminosities (L$_{IR}$>10$^{12}$ Lsun), star formation rates (SFR~190-1680 Msun yr$^{-1}$) and AGN bolometric luminosities (L$_{bol}$~10$^{46}$ erg s$^{-1}$) for our sample. We used an empirically-calibrated relation between gas masses and FIR/sub-mm luminosities and derived M$_{gas}$~0.8-5.4x10$^{10}$ Msun. High-resolution (0.3-0.7'') ALMA data (when available, CANDELS data otherwise) were used to estimate the galaxy size and hence the volume enclosing most of the ISM under simple geometrical assumptions. These measurements were then combined to derive the column density associated with the ISM of the host, on the order of N$_{H, ISM}$~10$^{23-24}$ cm$^{-2}$. The comparison between the ISM column densities and those measured from the X-ray spectral analysis shows that they are similar. This suggests that, at least at high redshift, significant absorption on kpc scales by the dense ISM in the host likely adds to or substitutes that produced by circumnuclear gas on pc scales (i.e., the torus of unified models). The lack of unobscured AGN among our ISM-rich targets supports this scenario.Comment: 15 pages, 3 figures. Accepted for publication in A&

Expression of an atrial G-protein-activated potassium channel in Xenopus oocytes

Injection of rat atrial RNA into Xenopus oocytes resulted in the expression of a guanine nucleotide binding (G) protein-activated K+ channel. Current through the channel could be activated by acetylcholine or, if RNA encoding a neuronal 5HT1A receptor was coinjected with atrial RNA, by serotonin (5HT). A 5HT-evoked current (I5HT) was observed in oocytes injected with ventricle RNA fractions (of 2.5-5.5 kb) and 5HT1A receptor RNA. I5HT displayed strong inward rectification with very little conductance above the K+ equilibrium potential, was highly selective for K+ over Na+, and was blocked by 5-300 µM Ba2+. I5HT was suppressed by intracellular injection of the nonhydrolyzable analog of GDP, guanosine 5'-[ß-thio]diphosphate, but not by treatment with pertussis toxin (PTX), suggesting coupling of the receptor to the G-protein-activated K+ channel via a PTX-insensitive G protein, possibly endogenously present in the oocyte. Coexpression of the subunit of a PTX-sensitive G protein, Gi2, rendered I5HT sensitive to PTX inhibition. Native oocytes displayed a constitutively active inwardly rectifying K+ current with a lower sensitivity to Ba2+ block; expression of a similar current was also directed by atrial or ventricle RNA of 1.5-3 kb. Xenopus oocytes may be employed for cloning of the G-protein-activated K+ channel cDNA and for studying the coupling between this channel and G proteins

Further genetic analysis and linkage relationships of isozyme loci in the pea: Confirmation of the diploid nature of the genome

Allozyme polymorphism is described and the mode of inheritance determined for 15 loci in Pisum sativum. The approximate position on the pea linkage map is described for 12 of these loci. The remaining three loci formed a single group that assorted independently of morphological markers on each of the seven currently recognized linkage groups. Possible cases of gene duplication are identified in the alcohol dehydrogenase and esterase enzyme systems, but in neither case was polyploidy a likely explanation for the paired loci. Nor did the arrangement of the isozyme loci on the linkage map give any indication that the pea genome is of polyploid derivation. We conclude that the "polymeric” genes that have been described in the pea are probably not homologous pairs and do not reflect a polypiold ancestr

Crafting a critical technical practice

In recent years, the category of practice-based research has become an essential component of discourse around public funding and evaluation of the arts in British higher education. When included under the umbrella of public policy concerned with the creative industries", technology researchers often find themselves collaborating with artists who consider their own participation to be a form of practice-based research. We are conducting a study under the Creator Digital Economies project asking whether technologists, themselves, should be considered as engaging in practice-based research, whether this occurs in collaborative situations, or even as a component of their own personal research [1]