A unified form of low-energy nodal electronic interactions in hole-doped cuprate superconductors.

Using angle resolved photoemission spectroscopy measurements of Bi2Sr2CaCu2O8+δ over a wide range of doping levels, we present a universal form for the non-Fermi liquid electronic interactions in the nodal direction in the exotic normal state phase. It is described by a continuously varying power law exponent versus energy and temperature (hence named a Power Law Liquid or PLL), which with doping varies smoothly from a quadratic Fermi Liquid in the overdoped regime, to a linear Marginal Fermi Liquid at optimal doping, to a non-quasiparticle non-Fermi Liquid in the underdoped regime. The coupling strength is essentially constant across all regimes and is consistent with Planckian dissipation. Using the extracted PLL parameters we reproduce the experimental optics and resistivity over a wide range of doping and normal-state temperature values, including the T* pseudogap temperature scale observed in the resistivity curves. This breaks the direct link to the pseudogapping of antinodal spectral weight observed at similar temperature scales and gives an alternative direction for searches of the microscopic mechanism.

Identification of potential stroke targets by lentiviral vector mediated overexpression of HIF-1 alpha and HIF-2 alpha in a primary neuronal model of hypoxia.

The identification of genes differentially regulated by ischemia will lead to an improved understanding of cell death pathways such as those involved in the neuronal loss observed following a stroke. Furthermore, the characterization of such pathways could facilitate the identification of novel targets for stroke therapy. We have used a novel approach to amplify differential gene expression patterns in a primary neuronal model of stroke by employing a lentiviral vector system to specifically bias the transcriptional activation of hypoxically regulated genes. Overexpression of the hypoxia-induced transcription factor subunits HIF-1 alpha and HIF-2 alpha elevated hypoxia-mediated transcription of many known HIF-regulated genes well above control levels. Furthermore, many potentially novel HIF-regulated genes were discovered that were not previously identified as hypoxically regulated. Most of the novel genes identified were activated by a combination of HIF-2 alpha overexpression and hypoxic insult. These included several genes with particular importance in cell survival pathways and of potential therapeutic value. Hypoxic induction of HIF-2 alpha may therefore be a critical factor in mediating protective responses against ischemic injury. Further investigation of the genes identified in this study may provide increased understanding of the neuronal response to hypoxia and may uncover novel therapeutic targets for the treatment of cerebral ischemia.

Effect of pH modification by bicarbonate on pain after subcutaneous lidocaine injection.

OBJECTIVE: To quantify the pain experienced on subcutaneous injection of lidocaine, lidocaine with sodium bicarbonate (NaHCO3) and saline. DESIGN: A double-blind randomized prospective study. SETTING: A clinical research unit in a university-affiliated hospital. PARTICIPANTS: Forty-two healthy adult volunteers who did not have a history of adverse reaction to lidocaine or peripheral neuropathy and were not pregnant. The study was performed in two phases. In Phase 1, 1 mL each of three solutions (2 mL or 8.4% NaHCO3 in 20 mL 1% lidocaine, 2 mL saline in 20 mL lidocaine and saline alone) were injected by an investigator, blinded as to the identity of the solutions, in random order to five volunteers to measure onset and duration of anesthesia and the perceived pain on injection. In Phase 2, 37 volunteers were injected with the three solutions in random order, by an investigator blinded as to the identity of the solutions. MAIN OUTCOME MEASURE: Pain on injection measured with the visual analogue scale. RESULTS: There were no clinically significant differences between onset and duration of action of lidocaine with and without NaHCO3, as determined by Kruskal- Wallis one-way analysis of variance and the Wilcoxon signed-ranks test. Injection of lidocaine with NaHCO3 was significantly less painful than injection of plain lidocaine (p=0.041). Injection of saline was the most painful. CONCLUSION: The addition of NaHCO3 to lidocaine produces significant reduction in pain experienced on injection without significantly affecting the onset or duration of action.

Oligopeptide repeats in the yeast protein Sup35p stabilize intermolecular prion interactions.

The nuclear-encoded Sup35p protein is responsible for the prion-like [PSI(+)] determinant of yeast, with Sup35p existing largely as a high molecular weight aggregate in [PSI(+)] strains. Here we show that the five oligopeptide repeats present at the N-terminus of Sup35p are responsible for stabilizing aggregation of Sup35p in vivo. Sequential deletion of the oligopeptide repeats prevented the maintenance of [PSI(+)] by the truncated Sup35p, although deletants containing only two repeats could be incorporated into pre-existing aggregates of wild-type Sup35p. The mammalian prion protein PrP also contains similar oligopeptide repeats and we show here that a human PrP repeat (PHGGGWGQ) is able functionally to replace a Sup35p oligopeptide repeat to allow stable [PSI(+)] propagation in vivo. Our data suggest a model in which the oligopeptide repeats in Sup35p stabilize intermolecular interactions between Sup35p proteins that initiate establishment of the aggregated state. Modulating repeat number therefore alters the rate of yeast prion conversion in vivo. Furthermore, there appears to be evolutionary conservation of function of the N-terminally located oligopeptide repeats in prion propagation.