Contributors: Robert Hall
... The heterogeneous Sundaland region was assembled by closure of Tethyan oceans and addition of continental fragments. Its Mesozoic and Cenozoic history is illustrated by a new plate tectonic reconstruction. A continental block (Luconia–Dangerous Grounds) rifted from east Asia was added to eastern Sundaland north of Borneo in the Cretaceous. Continental blocks that originated in western Australia from the Late Jurassic are now in Borneo, Java and Sulawesi. West Burma was not rifted from western Australia in the Jurassic. The Banda (SW Borneo) and Argo (East Java–West Sulawesi) blocks separated from western Australia and collided with the SE Asian margin between 110 and 90Ma, and at 90Ma the Woyla intra-oceanic arc collided with the Sumatra margin. Subduction beneath Sundaland terminated at this time. A marked change in deep mantle structure at about 110°E reflects different subduction histories north of India and Australia since 90Ma. India and Australia were separated by a transform boundary that was leaky from 90 to 75Ma and slightly convergent from 75 to 55Ma. From 80Ma, India moved rapidly north with north-directed subduction within Tethys and at the Asian margin. It collided with an intra-oceanic arc at about 55Ma, west of Sumatra, and continued north to collide with Asia in the Eocene. Between 90 and 45Ma Australia remained close to Antarctica and there was no significant subduction beneath Sumatra and Java. During this interval Sundaland was largely surrounded by inactive margins with some strike-slip deformation and extension, except for subduction beneath Sumba–West Sulawesi between 63 and 50Ma. At 45Ma Australia began to move north; subduction resumed beneath Indonesia and has continued to the present. There was never an active or recently active ridge subducted in the Late Cretaceous or Cenozoic beneath Sumatra and Java. The slab subducted between Sumatra and east Indonesia in the Cenozoic was Cretaceous or older, except at the very western end of the Sunda Arc where Cenozoic lithosphere has been subducted in the last 20million years. Cenozoic deformation of the region was influenced by the deep structure of Australian fragments added to the Sundaland core, the shape of the Australian margin formed during Jurassic rifting, and the age of now-subducted ocean lithosphere within the Australian margin.
Contributors: Chloé Mauroy, Thomas Portet, Martin Winterhalder, Elisabeth Bellard, Marie-Claire Blache, Justin Teissié, Andreas Zumbusch, Marie-Pierre Rols
... We present experimental results regarding the effects of electric pulses on giant unilamellar vesicles (GUVs). We have used phase contrast and coherent anti-Stokes Raman scattering (CARS) microscopy as relevant optical approaches to gain insight into membrane changes under electropermeabilization. No addition of exogenous molecules (lipid analogue, fluorescent dye) was needed. Therefore, experiments were performed on pure lipid systems avoiding possible artefacts linked to their use. Structural membrane changes were assessed by loss of contrast inside the GUVs due to sucrose and glucose mixing. Our observations, performed at the single vesicle level, indicate these changes are under the control of the number of pulses and field intensity. Larger number of pulses enhances membrane alterations. A threshold value of the field intensity must be applied to allow exchange of molecules between GUVs and the external medium. This threshold depends on the size of the vesicles, the larger GUVs being affected at lower electric field strengths than the smaller ones. Our experimental data are well described by a simple model in which molecule entry is driven by direct exchange. The CARS microscopic study of the effect of pulse duration confirms that pulses, in the ms time range, induce loss of lipids and membrane deformations facing the electrodes.
Adrenergic deficiency leads to impaired electrical conduction and increased arrhythmic potential in the embryonic mouse heart
Contributors: Candice Baker, David G. Taylor, Kingsley Osuala, Anupama Natarajan, Peter J. Molnar, James Hickman, Sabikha Alam, Brittany Moscato, David Weinshenker, Steven N. Ebert
... To determine if adrenergic hormones play a critical role in the functional development of the cardiac pacemaking and conduction system, we employed a mouse model where adrenergic hormone production was blocked due to targeted disruption of the dopamine β-hydroxylase (Dbh) gene. Immunofluorescent histochemical evaluation of the major gap junction protein, connexin 43, revealed that its expression was substantially decreased in adrenergic-deficient (Dbh−/−) relative to adrenergic-competent (Dbh+/+ and Dbh+/−) mouse hearts at embryonic day 10.5 (E10.5), whereas pacemaker and structural protein staining appeared similar. To evaluate cardiac electrical conduction in these hearts, we cultured them on microelectrode arrays (8×8, 200μm apart). Our results show a significant slowing of atrioventricular conduction in adrenergic-deficient hearts compared to controls (31.4±6.4 vs. 15.4±1.7ms, respectively, p<0.05). To determine if the absence of adrenergic hormones affected heart rate and rhythm, mouse hearts from adrenergic-competent and deficient embryos were cultured ex vivo at E10.5, and heart rates were measured before and after challenge with the β-adrenergic receptor agonist, isoproterenol (0.5μM). On average, all hearts showed increased heart rate responses following isoproterenol challenge, but a significant (p<0.05) 225% increase in the arrhythmic index (AI) was observed only in adrenergic-deficient hearts. These results show that adrenergic hormones may influence heart development by stimulating connexin 43 expression, facilitating atrioventricular conduction, and helping to maintain cardiac rhythm during a critical phase of embryonic development.
Contributors: Kris Kemper, Allissa Lee, Betty J. Simkins
... Many investment companies hold diversified asset portfolios and frequently try to mirror or outperform a market index for each asset class such as stocks and bonds. As Wibaut and Wilford (2009) show, often the same issuers appear in each of those indices and this may lead to undesirable results such as during a crisis period. Our research further explores the topic of diversification with a special focus on the financial crisis period of 2007 through 2009. Our results indicate that there is benefit in terms of correlations from holding bond and stock portfolios. Interestingly, these findings show the benefit is most pronounced during times of market stress.
Two-photon excitation with pico-second fluorescence lifetime imaging to detect nuclear association of flavanols
Contributors: Irene Mueller-Harvey, Walter Feucht, Juergen Polster, Lucie Trnková, Pierre Burgos, Anthony W. Parker, Stanley W. Botchway
... Two-photon excitation enabled for the first time the observation and measurement of excited state fluorescence lifetimes from three flavanols in solution, which were ∼1.0ns for catechin and epicatechin, but <45ps for epigallocatechin gallate (EGCG). The shorter lifetime for EGCG is in line with a lower fluorescence quantum yield of 0.003 compared to catechin (0.015) and epicatechin (0.018).
Regular article - Morphine Decreases Bacterial Phagocytosis by Inhibiting Actin Polymerization through cAMP-, Rac-1-, and p38 MAPK-Dependent Mechanisms
Contributors: Jana Ninković, Sabita Roy
... Morphine increases the susceptibility to opportunistic infection by attenuating bacterial clearance through inhibition of Fcγ receptor (FcgR)–mediated phagocytosis. Mechanisms by which morphine inhibits this process remain to be investigated. Actin polymerization is essential for FcgR-mediated internalization; therefore, disruption of the signaling mechanisms involved in this process is detrimental to the phagocytic ability of macrophages. To our knowledge, this study is the first to propose the modulation of actin polymerization and upstream signaling effectors [cAMP, Rac1-GTP, and p38 mitogen-activated protein kinase (MAPK)] as key mechanisms by which morphine leads to inhibition of pathogen clearance. Our results indicate that long-term morphine treatment in vitro and in vivo, through activation of the μ-opioid receptor, leads to an increase in intracellular cAMP, activation of protein kinase A, and inhibition of Rac1-GTPase and p38 MAPK, thereby attenuating actin polymerization and reducing membrane ruffling. Furthermore, because of long-term morphine treatment, FcgR-mediated internalization of opsonized dextran beads is also reduced. Morphine's inhibition of Rac1-GTPase activation is abolished in J774 macrophages transfected with constitutively active pcDNA3-EGFP-Rac1-Q61L plasmid. Dibutyryl-cAMP inhibits, whereas H89 restores, activation of Rac-GTPase and abolishes morphine's inhibitory effect, implicating cAMP as the key effector in morphine's modulation of actin polymerization. These findings indicate that long-term morphine treatment, by increasing intracellular cAMP and activating protein kinase A, leads to inhibition of Rac1-GTPase and p38 MAPK, causing attenuation of actin polymerization, FcgR-mediated phagocytosis, and decreased bacterial clearance.
Contributors: Alfredo Gonzalez-Sulser, Jing Wang, Gholam K. Motamedi, Massimo Avoli, Stefano Vicini, Rhonda Dzakpasu
... Epileptiform discharges recorded in the 4-aminopyridine (4-AP) in vitro epilepsy model are mediated by glutamatergic and GABAergic signaling. Using a 60-channel perforated multi-electrode array (pMEA) on corticohippocampal slices from 2 to 3 week old mice we recorded interictal- and ictal-like events. When glutamatergic transmission was blocked, interictal-like events no longer initiated in the hilus or CA3/CA1 pyramidal layers but originated from the dentate gyrus granule and molecular layers. Furthermore, frequencies of interictal-like events were reduced and durations were increased in these regions while cortical discharges were completely blocked. Following GABAA receptor blockade interictal-like events no longer propagated to the dentate gyrus while their frequency in CA3 increased; in addition, ictal-like cortical events became shorter while increasing in frequency. Lastly, drugs that affect tonic and synaptic GABAergic conductance modulated the frequency, duration, initiation and propagation of interictal-like events. These findings confirm and expand on previous studies indicating that multiple synaptic mechanisms contribute to synchronize neuronal network activity in forebrain structures.
Basic research study - Assessment of mouse hind limb endothelial function by measuring femoral artery blood flow responses
Contributors: Chao-Hung Wang, Kuo-Ti Chen, Hsiu-Fu Mei, Ju-Fang Lee, Wen-Jin Cherng, Shing-Jong Lin
... Substantial progress has been made in cell therapy strategies and in gene- and cytokine-introduced angiogenesis using a variety of mouse models, such as hind limb ischemia models. Endothelial function is an important target in evaluating the effects and outcomes of these potential therapies. Although animal models have been established for estimating endothelium-dependent function by measuring the blood flow responses in carotid and renal arteries and the abdominal aorta, a model specific for an indicated hind limb by measuring femoral artery blood flow (FABF) has not yet been established.
Phylogeography and epidemiological history of West Nile virus genotype 1a in Europe and the Mediterranean basin
Contributors: Gianguglielmo Zehender, Erika Ebranati, Flavia Bernini, Alessandra Lo Presti, Giovanni Rezza, Mauro Delogu, Massimo Galli, Massimo Ciccozzi
... Aim of this study was to reconstruct the temporal and spatial phylodynamics of WNV-1a, the genotype to which the majority of European/Mediterranean viral strains belongs, by using sequences retrieved from public databases.
Contributors: Byungyong You, Minsung Kim, Dukman Lee, Jookang Lee, J.S. Lee
... In this paper, an iterative learning control (ILC) method is introduced to control molten steel level in a continuous casting process, in the presence of disturbance, noise and initial errors. The general ILC method was originally developed for processes that perform tasks repetitively but it can also be applied to periodic time-domain signals. To propose a more realistic algorithm, an ILC algorithm that consists of a P-type learning rule with a forgetting factor and a switching mechanism is introduced. Then it is proved that the input signal error, the state error and the output error are ultimately bounded in the presence of model uncertainties, periodic bulging disturbances, measurement noises and initial state errors. Computer simulation and experimental results establish the validity of the proposed control method.