1,139 research outputs found
Ultrafast sodium channel block by dietary fish oil prevents dofetilide-induced ventricular arrhythmias in rabbit hearts
9 pages, 4 figures, 1 table.-- et al.Several epidemiologic and clinical studies show that following myocardial infarction, dietary supplements of omega-3 polyunsaturated fatty acids (omega3FA) reduce sudden death. Animal data show that omega3FA have antiarrhythmic properties, but their mechanisms of action require further elucidation. The effects of omega3FA supplementation were studied in female rabbits to analyze whether their antiarrhythmic effects are due to a reduction of triangulation, reverse use-dependence, instability, and dispersion (TRIaD) of the cardiac action potential (TRIaD as a measure of proarrhythmic effects). In Langendorff-perfused hearts challenged by a selective rapidly activating delayed rectifier potassium current inhibitor that has been shown to exhibit proarrhythmic effects (dofetilide; 1 to 100 nM), omega3FA pretreatment (30 days; n=6) prolonged the plateau phase of the monophasic action potential; did not slow the terminal fast repolarization; reduced the dofetilide-induced prolongation of the action potential duration; reduced dofetilide-induced triangulation; and reduced dofetilide-induced reverse use-dependence, instability of repolarization, and dispersion. Dofetilide reduced excitability in omega3FA-pretreated hearts but not in control hearts. Whereas torsades de pointes (TdP) were observed in five out of six in control hearts, none were observed in omega3FA-pretreated hearts. Docosahexaenoic acid (DHA) inhibited the sodium current with ultrafast kinetics. Dietary omega3FA supplementation markedly reduced dofetilide-induced TRIaD and abolished dofetilide-induced TdP. Ultrafast sodium channel block by DHA may account for the antiarrhythmic protection of the dietary supplements of omega3FA against dofetilide-induced proarrhythmia observed in this animal model.This work was funded by Solvay Pharma, Novartis, Grants CICYT
SAF2004-06856 and SAF2007-65868 and Red Temática de Investigación
Cooperativa Grant FIS RD06/0014/0006.Peer reviewe
Overbias Light Emission From Memristive Nanojunctions
A nanoscale dielectric gap clamped between two metal electrodes may undergo a
large resistance change from insulating to highly conducting upon applying an
electrical stress. This sudden resistive switching effect is largely exploited
in memristors for emulating synapses in neuromorphic neural networks. Here, we
show that resistive switching can be accompanied by a release of
electromagnetic radiation spanning the visible spectral region. Importantly, we
find that the spectrum is characterized by photon energies exceeding the
maximum kinetic energy of electrons provided by the switching voltage. This
so-called overbias emission can be described self-consistently by a thermal
radiation model featuring an out-of-equilibrium electron distribution generated
in the device with an effective temperature exceeding 2000~K. The emitted
spectrum is understood in terms of hot electrons radiatively decaying to
resonant optical modes occurring in a nanoscale \ch{SiO2} matrix located
between two \ch{Ag} electrodes. The correlation between resistive switching and
the onset of overbias emission in atomic-scale photonic memristor brings new
venues to generate light on chip and their exploitation in optical
interconnects. Photons emitted during memristive switching can also be
monitored to follow the neural activation pathways in memristor-based networks
Crystal structure of mixed fluorites Ca(1-x)Sr(x)F(2) and Sr(1-x)Ba(x)F(2) and luminescence of Eu(2+) in the crystals
Within the framework of the virtual crystal method implemented in the shell
model and pair potential approximation the crystal structure of mixed fluorites
Ca(1-x)Sr(x)F(2) and Sr(1-x)Ba(x)F(2) has been calculated. The impurity center
Eu(2+) and the distance Eu(2+)-F in this crystals have been also calculated.
The low level position of excited 4f65d configuration of the Eu(2+) ion has
been expressed using phenomenological dependence on distance E(2+)-F. The
dependences of Stokes shift and Huang-Rhys factor on concentration x have been
received for yellow luminescence in Sr(1-x)Ba(x)F(2):Eu(2+). The value x, for
which the eg -level of Eu(2+) ion will be in conduction band in
Sr(1-x)Ba(x)F(2):Eu(2+) has been calculated.Comment: 8 pages, 3 figures. The manuscript is sent to journal 'Physics of the
solid state'. The results will be submitted on inernational conference
SCINTMAT'2002 in oral session (june,20-22,2002,Ekaterinburg,Russia).
Corresponding author e-mail: [email protected]
Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies.
BACKGROUND: In sporadic Tauopathies, neurofibrillary degeneration (NFD) is characterised by the intraneuronal aggregation of wild-type Tau proteins. In the human brain, the hierarchical pathways of this neurodegeneration have been well established in Alzheimer's disease (AD) and other sporadic tauopathies such as argyrophilic grain disorder and progressive supranuclear palsy but the molecular and cellular mechanisms supporting this progression are yet not known. These pathways appear to be associated with the intercellular transmission of pathology, as recently suggested in Tau transgenic mice. However, these conclusions remain ill-defined due to a lack of toxicity data and difficulties associated with the use of mutant Tau.
RESULTS: Using a lentiviral-mediated rat model of hippocampal NFD, we demonstrated that wild-type human Tau protein is axonally transferred from ventral hippocampus neurons to connected secondary neurons even at distant brain areas such as olfactory and limbic systems indicating a trans-synaptic protein transfer. Using different immunological tools to follow phospho-Tau species, it was clear that Tau pathology generated using mutated Tau remains near the IS whereas it spreads much further using the wild-type one.
CONCLUSION: Taken together, these results support a novel mechanism for Tau protein transfer compared to previous reports based on transgenic models with mutant cDNA. It also demonstrates that mutant Tau proteins are not suitable for the development of experimental models helpful to validate therapeutic intervention interfering with Tau spreading
Comparison of gene expression patterns among Leishmania braziliensis clinical isolates showing a different in vitro susceptibility to pentavalent antimony
Introduction. Evaluation of Leishmania drug susceptibility depends on in vitro SbV susceptibility assays, which are labour-intensive and may give a biased view of the true parasite resistance. Molecular markers are urgently needed to improve and simplify the monitoring of SbV-resistance. We analysed here the gene expression profile of 21 L. braziliensis clinical isolates in vitro defined as SbV-resistant and -sensitive, in order to identify potential resistance markers. Methods. The differential expression of 13 genes involved in SbV metabolism, oxidative stress or housekeeping functions was analysed during in vitro promastigote growth. Results. Expression profiles were up-regulated for 5 genes only, each time affecting a different set of isolates (mosaic picture of gene expression). Two genes, ODC (ornithine decarboxylase) and TRYR (trypanothione reductase), showed a significantly higher expression rate in the group of SbV-resistant compared to the group of SbV-sensitive parasites (P<0·01). However, analysis of individual isolates showed both markers to explain only partially the drug resistance. Discussion. Our results might be explained by (i) the occurrence of a pleiotropic molecular mechanism leading to the in vitro SbV resistance and/or (ii) the existence of different epi-phenotypes not revealed by the in vitro SbV susceptibility assays, but interfering with the gene expression pattern
Lentiviral delivery of the human wild-type tau protein mediates a slow and progressive neurodegenerative tau pathology in the rat brain.
Most models for tauopathy use a mutated form of the Tau gene, MAPT, that is found in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and that leads to rapid neurofibrillary degeneration (NFD). Use of a wild-type (WT) form of human Tau protein to model the aggregation and associated neurodegenerative processes of Tau in the mouse brain has thus far been unsuccessful. In the present study, we generated an original "sporadic tauopathy-like" model in the rat hippocampus, encoding six Tau isoforms as found in humans, using lentiviral vectors (LVs) for the delivery of a human WT Tau. The overexpression of human WT Tau in pyramidal neurons resulted in NFD, the morphological characteristics and kinetics of which reflected the slow and sporadic neurodegenerative processes observed in sporadic tauopathies, unlike the rapid neurodegenerative processes leading to cell death and ghost tangles triggered by the FTDP-17 mutant Tau P301L. This new model highlights differences in the molecular and cellular mechanisms underlying the pathological processes induced by WT and mutant Tau and suggests that preference should be given to animal models using WT Tau in the quest to understand sporadic tauopathies
The exchangeability of shape
<p>Abstract</p> <p>Background</p> <p>Landmark based geometric morphometrics (GM) allows the quantitative comparison of organismal shapes. When applied to systematics, it is able to score shape changes which often are undetectable by traditional morphological studies and even by classical morphometric approaches. It has thus become a fast and low cost candidate to identify cryptic species. Due to inherent mathematical properties, shape variables derived from one set of coordinates cannot be compared with shape variables derived from another set. Raw coordinates which produce these shape variables could be used for data exchange, however they contain measurement error. The latter may represent a significant obstacle when the objective is to distinguish very similar species.</p> <p>Results</p> <p>We show here that a single user derived dataset produces much less classification error than a multiple one. The question then becomes how to circumvent the lack of exchangeability of shape variables while preserving a single user dataset. A solution to this question could lead to the creation of a relatively fast and inexpensive systematic tool adapted for the recognition of cryptic species.</p> <p>Conclusions</p> <p>To preserve both exchangeability of shape and a single user derived dataset, our suggestion is to create a free access bank of reference images from which one can produce raw coordinates and use them for comparison with external specimens. Thus, we propose an alternative geometric descriptive system that separates 2-D data gathering and analyzes.</p
Electronic and Magnetic Properties of Partially-Open Carbon Nanotubes
On the basis of the spin-polarized density functional theory calculations, we
demonstrate that partially-open carbon nanotubes (CNTs) observed in recent
experiments have rich electronic and magnetic properties which depend on the
degree of the opening. A partially-open armchair CNT is converted from a metal
to a semiconductor, and then to a spin-polarized semiconductor by increasing
the length of the opening on the wall. Spin-polarized states become
increasingly more stable than nonmagnetic states as the length of the opening
is further increased. In addition, external electric fields or chemical
modifications are usable to control the electronic and magnetic properties of
the system. We show that half-metallicity may be achieved and the spin current
may be controlled by external electric fields or by asymmetric
functionalization of the edges of the opening. Our findings suggest that
partially-open CNTs may offer unique opportunities for the future development
of nanoscale electronics and spintronics.Comment: 6 figures, to appear in J. Am. Chem. So
Simultaneous determination of wave speed and arrival time of reflected waves using the pressure-velocity loop
This is the post print version of the article. The official published version can be found at the link below.In a previous paper we demonstrated that the linear portion of the pressure–velocity loop (PU-loop) corresponding to early systole could be used to calculate the local wave speed. In this paper we extend this work to show that determination of the time at which the PU-loop first deviates from linearity provides a convenient way to determine the arrival time of reflected waves (Tr). We also present a new technique using the PU-loop that allows for the determination of wave speed and Tr simultaneously. We measured pressure and flow in elastic tubes of different diameters, where a strong reflection site existed at known distances away form the measurement site. We also measured pressure and flow in the ascending aorta of 11 anaesthetised dogs where a strong reflection site was produced through total arterial occlusion at four different sites. Wave speed was determined from the initial slope of the PU-loop and Tr was determined using a new algorithm that detects the sampling point at which the initial linear part of the PU-loop deviates from linearity. The results of the new technique for detecting Tr were comparable to those determined using the foot-to-foot and wave intensity analysis methods. In elastic tubes Tr detected using the new algorithm was almost identical to that detected using wave intensity analysis and foot-to-foot methods with a maximum difference of 2%. Tr detected using the PU-loop in vivo highly correlated with that detected using wave intensity analysis (r 2 = 0.83, P < 0.001). We conclude that the new technique described in this paper offers a convenient and objective method for detecting Tr, and allows for the dynamic determination of wave speed and Tr, simultaneously
Determination of the bonding configuration of the metastable molecular oxygen adsorbed on a Si(111)-(7×7) surface
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