Regulation of expression of the rat orthologue of mouse double minute 2 (MDM2) by H2O2-induced oxidative stress in neonatal rat cardiac myocytes.

The Mdm2 ubiquitin ligase is an important regulator of p53 abundance and p53-dependent apoptosis. Mdm2 expression is frequently regulated by a p53 Mdm2 autoregulatory loop whereby p53 stimulates Mdm2 expression and hence its own degradation. Although extensively studied in cell lines, relatively little is known about Mdm2 expression in heart where oxidative stress (exacerbated during ischemia-reperfusion) is an important pro-apoptotic stimulus. We demonstrate that Mdm2 transcript and protein expression are induced by oxidative stress (0.2 mm H(2)O(2)) in neonatal rat cardiac myocytes. In other cells, constitutive Mdm2 expression is regulated by the P1 promoter (5' to exon 1), with inducible expression regulated by the P2 promoter (in intron 1). In myocytes, H(2)O(2) increased Mdm2 expression from the P2 promoter, which contains two p53-response elements (REs), one AP-1 RE, and two Ets REs. H(2)O(2) did not detectably increase expression of p53 mRNA or protein but did increase expression of several AP-1 transcription factors. H(2)O(2) increased binding of AP-1 proteins (c-Jun, JunB, JunD, c-Fos, FosB, and Fra-1) to an Mdm2 AP-1 oligodeoxynucleotide probe, and chromatin immunoprecipitation assays showed it increased binding of c-Jun or JunB to the P2 AP-1 RE. Finally, antisense oligonucleotide-mediated reduction of H(2)O(2)-induced Mdm2 expression increased caspase 3 activation. Thus, increased Mdm2 expression is associated with transactivation at the P2 AP-1 RE (rather than the p53 or Ets REs), and Mdm2 induction potentially represents a cardioprotective response to oxidative stress.

Pseudomonas syringae pv. coryli, the causal agent of bacterial twig dieback of Corylus avellana

Thirty-eight bacterial strains isolated from hazelnut (Corylus avellana) cv. Tonda Gentile delle Langhe showing a twig dieback in Piedmont and Sardinia, Italy, were studied by a polyphasic approach. All strains were assessed by fatty acids analysis and repetitive sequence-based polymerase chain reaction (PCR) fingerprinting using BOX and ERIC primer sets. Representative strains also were assessed by sequencing the 16S rDNA and hrpL genes, determining the presence of the syrB gene, testing their biochemical and nutritional characteristics, and determining their pathogenicity to hazelnut and other plants species or plant organs. Moreover, they were compared with reference strains of other phytopathogenic pseudomonads. The strains from hazelnut belong to Pseudomonas syringae (sensu latu), LOPAT group Ia. Both fatty acids and repetitive-sequence-based PCR clearly discriminate such strains from other Pseudomonas spp., including P. avellanae and other P. syringae pathovars as well as P. syringae pv. syringae strains from hazelnut. Also, the sequencing of 16S rDNA and hrpL genes differentiated them from P. avellanae and from P. syringae pv. syringae. They did not possess the syrB gene. Some nutritional tests also differentiated them from related P. syringae pathovars. Upon artificial inoculation, these strains incited severe twig diebacks only on hazelnut. Our results justify the creation of a new pathovar because the strains from hazelnut constitute a homogeneous group and a discrete phenon. The name of P. syringae pv. coryli is proposed and criteria for routine identification are presented.

Imitation of lateralised body movements: doing it the hard way

Two experiments examined imitation of lateralised body movement sequences presented at six viewing angles (0º, 60º, 120º, 180º, 240º, and 300º rotation relative to the participant’s body). Experiment 1 found that, when participants were instructed simply to ‘‘do what the model does’’, at all viewing angles they produced more actions using the same side of the body as the model (anatomical matches), than actions using the opposite side (anatomical non-matches). In Experiment 2 participants were instructed to produce either anatomical matches or anatomical non-matches of observed actions. When the model was viewed from behind (0º), the anatomically matching group were more accurate than the anatomically non-matching group, but the non-matching group was superior when the model faced the participant (180º and 240º). No reliable differences were observed between groups at 60º, 120º, and 300º. In combination, the results of Experiments 1 and 2 suggest that, when they are confronting a model, people choose to imitate the hard way; they attempt to match observed actions anatomically, in spite of the fact that anatomical matching is more subject to error than anatomical non-matching.

Structural characterization of a new crystal form of the four-way Holliday junction formed by the DNA sequence d(CCGGTACCGG)2: sequence versus lattice?

DNA-strand exchange is a vital step in the recombination process, of which a key intermediate is the four-way DNA Holliday junction formed transiently in most living organisms. Here, the single-crystal structure at a resolution of 2.35 Å of such a DNA junction formed by d(CCGGTACCGG)2, which has crystallized in a more highly symmetrical packing mode to that previously observed for the same sequence, is presented. In this case, the structure is isomorphous to the mismatch sequence d(CCGGGACCGG)2, which reveals the roles of both lattice and DNA sequence in determining the junction geometry. The helices cross at the larger angle of 43.0° (the previously observed angle for this sequence was 41.4°) as a right-handed X. No metal cations were observed; the crystals were grown in the presence of only group I counter-cations.

Advances in continuously profiling the thermodynamic state of the boundary layer: integration of measurements and methods

This paper describes advances in ground-based thermodynamic profiling of the lower troposphere through sensor synergy. The well-documented integrated profiling technique (IPT), which uses a microwave profiler, a cloud radar, and a ceilometer to simultaneously retrieve vertical profiles of temperature, humidity, and liquid water content (LWC) of nonprecipitating clouds, is further developed toward an enhanced performance in the boundary layer and lower troposphere. For a more accurate temperature profile, this is accomplished by including an elevation scanning measurement modus of the microwave profiler. Height-dependent RMS accuracies of temperature (humidity) ranging from 0.3 to 0.9 K (0.5–0.8 g m−3) in the boundary layer are derived from retrieval simulations and confirmed experimentally with measurements at distinct heights taken during the 2005 International Lindenberg Campaign for Assessment of Humidity and Cloud Profiling Systems and its Impact on High-Resolution Modeling (LAUNCH) of the German Weather Service. Temperature inversions, especially of the lower boundary layer, are captured in a very satisfactory way by using the elevation scanning mode. To improve the quality of liquid water content measurements in clouds the authors incorporate a sophisticated target classification scheme developed within the European cloud observing network CloudNet. It allows the detailed discrimination between different types of backscatterers detected by cloud radar and ceilometer. Finally, to allow IPT application also to drizzling cases, an LWC profiling method is integrated. This technique classifies the detected hydrometeors into three different size classes using certain thresholds determined by radar reflectivity and/or ceilometer extinction profiles. By inclusion into IPT, the retrieved profiles are made consistent with the measurements of the microwave profiler and an LWC a priori profile. Results of IPT application to 13 days of the LAUNCH campaign are analyzed, and the importance of integrated profiling for model evaluation is underlined.

Beyond the American century: Walter Lippmann and American grand strategy, 1943-1950

As the United States became a world Power, journalist and intellectual Walter Lippmann feared that it would become its own worst enemy. During and after the Second World War, he tried to steer the country towards coherent statecraft, to define the national interest and the limits of power, and give geopolitical expression to the role of the United States as the core of an Atlantic strategic system. But in response to world war, the Truman Doctrine, and the Korean War, he became pessimistic about the country's ability to conduct strategy effectively. In the prophetic tradition, he believed that a fatal symbiosis between America's growing strength and domestic politics led it towards crisis. Though at times ahistorical, Lippmann's concept of strategy deserves attention for its dialogue between power and identity, for its questioning of “ends” as well as means, and for its focus on the danger of self-defeating behaviour.

Unraveling the electronic structures of low-valent naphthalene and anthracene iron complexes: x-ray, spectroscopic, and density functional theory studies

Naphthalene and anthracene transition metalates are potent reagents, but their electronic structures have remained poorly explored. A study of four Cp*-substituted iron complexes (Cp* = pentamethylcyclopentadienyl) now gives rare insight into the bonding features of such species. The highly oxygen- and water-sensitive compounds [K(18-crown- 6){Cp*Fe(η4-C10H8)}] (K1), [K(18-crown-6){Cp*Fe(η4-C14H10)}] (K2), [Cp*Fe(η4-C10H8)] (1), and [Cp*Fe(η4-C14H10)] (2) were synthesized and characterized by NMR, UV−vis, and 57Fe Mössbauer spectroscopy. The paramagnetic complexes 1 and 2 were additionally characterized by electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility measurements. The molecular structures of complexes K1, K2, and 2 were determined by single-crystal X-ray crystallography. Cyclic voltammetry of 1 and 2 and spectroelectrochemical experiments revealed the redox properties of these complexes, which are reversibly reduced to the monoanions [Cp*Fe(η4-C10H8)]− (1−) and [Cp*Fe(η4-C14H10)]− (2−) and reversibly oxidized to the cations [Cp*Fe(η6-C10H8)]+ (1+) and [Cp*Fe(η6-C14H10)]+ (2+). Reduced orbital charges and spin densities of the naphthalene complexes 1−/0/+ and the anthracene derivatives 2−/0/+ were obtained by density functional theory (DFT) methods. Analysis of these data suggests that the electronic structures of the anions 1− and 2− are best represented by low-spin FeII ions coordinated by anionic Cp* and dianionic naphthalene and anthracene ligands. The electronic structures of the neutral complexes 1 and 2 may be described by a superposition of two resonance configurations which, on the one hand, involve a low-spin FeI ion coordinated by the neutral naphthalene or anthracene ligand L, and, on the other hand, a low-spin FeII ion coordinated to a ligand radical L•−. Our study thus reveals the redox noninnocent character of the naphthalene and anthracene ligands, which effectively stabilize the iron atoms in a low formal, but significantly higher spectroscopic oxidation state.

The transatlantic dimensions of the time lord: Doctor Who and the relationships between British and North American television

This chapter explores some of the textual specificity of the Steven Moffat/Matt Smith Doctor Who, in relation to its positioning within the current transatlantic television landscape. The chapter develops further the existing scholarship on Doctor Who, by both offering a critical assessment of the transatlantic dimensions of the Moffat/Smith-era Doctor Who, and by challenging some of the existing critical arguments about Doctor Who's transatlantic dimensions. Particular attention is paid to the casting, physicality and costuming of actor Matt Smith as the Doctor in relation to notions of Britishness.