186 research outputs found
Endothelial Connexin37 and Connexin40 participate in basal but not agonist-induced NO release.
BACKGROUND: Connexin37 (Cx37) and Cx40 are crucial for endothelial cell-cell communication and homeostasis. Both connexins interact with endothelial nitric oxide synthase (eNOS). The exact contribution of these interactions to the regulation of vascular tone is unknown.
RESULTS: Cx37 and Cx40 were expressed in close proximity to eNOS at cell-cell interfaces of mouse aortic endothelial cells. Absence of Cx37 did not affect expression of Cx40 and a 50 % reduction of Cx40 in Cx40(+/-) aortas did not affect the expression of Cx37. However, absence of Cx40 was associated with reduced expression of Cx37. Basal NO release and the sensitivity for ACh were decreased in Cx37(-/-) and Cx40(-/-) aortas but not in Cx40(+/-) aortas. Moreover, ACh-induced release of constricting cyclooxygenase products was present in WT, Cx40(-/-) and Cx40(+/-) aortas but not in Cx37(-/-) aortas. Finally, agonist-induced NO-dependent relaxations and the sensitivity for exogenous NO were not affected by genotype.
CONCLUSIONS: Cx37 is more markedly involved in basal NO release, release of cyclooxygenase products and the regulation of the sensitivity for ACh as compared to Cx40
Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry.
Diagnostics of myocardial infarction in human post-mortem hearts can be achieved only if ischemia persisted for at least 6-12 h when certain morphological changes appear in myocardium. The initial 4 h of ischemia is difficult to diagnose due to lack of a standardized method. Developing a panel of molecular tissue markers is a promising approach and can be accelerated by characterization of molecular changes. This study is the first untargeted metabolomic profiling of ischemic myocardium during the initial 4 h directly from tissue section. Ischemic hearts from an ex-vivo Langendorff model were analysed using matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) at 15 min, 30 min, 1 h, 2 h, and 4 h. Region-specific molecular changes were identified even in absence of evident histological lesions and were segregated by unsupervised cluster analysis. Significantly differentially expressed features were detected by multivariate analysis starting at 15 min while their number increased with prolonged ischemia. The biggest significant increase at 15 min was observed for m/z 682.1294 (likely corresponding to S-NADHX-a damage product of nicotinamide adenine dinucleotide (NADH)). Based on the previously reported role of NAD <sup>+</sup> /NADH ratio in regulating localization of the sodium channel (Na <sub>v</sub> 1.5) at the plasma membrane, Na <sub>v</sub> 1.5 was evaluated by immunofluorescence. As expected, a fainter signal was observed at the plasma membrane in the predicted ischemic region starting 30 min of ischemia and the change became the most pronounced by 4 h. Metabolomic changes occur early during ischemia, can assist in identifying markers for post-mortem diagnostics and improve understanding of molecular mechanisms
Comparison between direct and reverse electroporation of cells in situ: a simulation study.
The discovery of the human genome has unveiled new fields of genomics, transcriptomics, and proteomics, which has produced paradigm shifts on how to study disease mechanisms, wherein a current central focus is the understanding of how gene signatures and gene networks interact within cells. These gene function studies require manipulating genes either through activation or inhibition, which can be achieved by temporarily permeabilizing the cell membrane through transfection to deliver cDNA or RNAi. An efficient transfection technique is electroporation, which applies an optimized electric pulse to permeabilize the cells of interest. When the molecules are applied on top of seeded cells, it is called “direct” transfection and when the nucleic acids are printed on the substrate and the cells are seeded on top of them, it is termed “reverse” transfection. Direct transfection has been successfully applied in previous studies, whereas reverse transfection has recently gained more attention in the context of high-throughput experiments. Despite the emerging importance, studies comparing the efficiency of the two methods are lacking. In this study, a model for electroporation of cells in situ is developed to address this deficiency. The results indicate that reverse transfection is less efficient than direct transfection. However, the model also predicts that by increasing the concentration of deliverable molecules by a factor of 2 or increasing the applied voltage by 20%, reverse transfection can be approximately as efficient as direct transfection
Search for and Using Genetic Programming Event Selection
We apply a genetic programming technique to search for the double Cabibbo
suppressed decays and .
We normalize these decays to their Cabibbo favored partners and find
\Lambda_c^+ \to p K^+ \pi^-\Lambda_c^+ \to p K^-
\pi^+ and D_s^+ \to K^+ K^+
\pi^-D_s^+ \to K^+ K^- \pi^+ where
the first errors are statistical and the second are systematic. Expressed as
90% confidence levels (CL), we find and respectively.
This is the first successful use of genetic programming in a high energy
physics data analysis.Comment: 10 page
Measurement of the D+ and Ds+ decays into K+K-K+
We present the first clear observation of the doubly Cabibbo suppressed decay
D+ --> K-K+K+ and the first observation of the singly Cabibbo suppressed decay
Ds+ --> K-K+K+. These signals have been obtained by analyzing the high
statistics sample of photoproduced charm particles of the FOCUS(E831)
experiment at Fermilab. We measure the following relative branching ratios:
Gamma(D+ --> K-K+K+)/Gamma(D+ --> K-pi+pi+) = (9.49 +/- 2.17(statistical) +/-
0.22(systematic))x10^-4 and Gamma(Ds+ --> K-K+K+)/Gamma(Ds+ --> K-K+pi+) =
(8.95 +/- 2.12(statistical) +2.24(syst.) -2.31(syst.))x10^-3.Comment: 10 pages, 8 figure
A Non-parametric Approach to the D+ to K*0bar mu+ nu Form Factors
Using a large sample of D+ -> K- pi+ mu+ nu decays collected by the FOCUS
photoproduction experiment at Fermilab, we present the first measurements of
the helicity basis form factors free from the assumption of spectroscopic pole
dominance. We also present the first information on the form factor that
controls the s-wave interference discussed in a previous paper by the FOCUS
collaboration. We find reasonable agreement with the usual assumption of
spectroscopic pole dominance and measured form factor ratios.Comment: 14 pages, 5 figures, and 2 tables. We updated the previous version by
changing some words, removing one plot, and adding two tables. These changes
are mostly stylisti
Measurements of Branching Ratios
Using data collected by the fixed target Fermilab experiment FOCUS, we
measure the branching ratios of the Cabibbo favored decays , , and relative to to be
, , and ,
respectively. We report the first observation of the Cabibbo suppressed decay
and we measure the branching ratio relative to
to be . We also set 90%
confidence level upper limits for and relative to to
be 0.12 and 0.05, respectively. We find an indication of the decays and and set
90% confidence level upper limits for the branching ratios with respect to
to be 0.12 and 1.72, respectively. Finally, we
determine the 90% C.L. upper limit for the resonant contribution relative to to be 0.10.Comment: 14 pages, 8 figure
Dalitz plot analysis of D_s+ and D+ decay to pi+pi-pi+ using the K-matrix formalism
FOCUS results from Dalitz plot analysis of D_s+ and D+ to pi+pi-pi+ are
presented. The K-matrix formalism is applied to charm decays for the first time
to fully exploit the already existing knowledge coming from the light-meson
spectroscopy experiments. In particular all the measured dynamics of the S-wave
pipi scattering, characterized by broad/overlapping resonances and large
non-resonant background, can be properly included. This paper studies the
extent to which the K-matrix approach is able to reproduce the observed Dalitz
plot and thus help us to understand the underlying dynamics. The results are
discussed, along with their possible implications on the controversial nature
of the sigma meson.Comment: To be submitted to Phys.Lett.B A misprint corrected in formula
Measurement of the branching ratio of the decay D^0 -> \pi^-\mu^+\nu relative to D^0 -> K^-\mu^+\nu
We present a new measurement of the branching ratio of the Cabibbo suppressed
decay D^0\to \pi^-\mu^+\nu relative to the Cabibbo favored decay D^0\to
K^-\mu^+\nu and an improved measurement of the ratio
|\frac{f_+^{\pi}(0)}{f_+^{K}(0)}|. Our results are 0.074 \pm 0.008 \pm 0.007
for the branching ratio and 0.85 \pm 0.04 \pm 0.04 \pm 0.01 for the form factor
ratio, respectively.Comment: 13pages, 3 figure
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