38 research outputs found
Adoptive transfer of CD4<sup>+</sup>CD25<sup>−</sup>Nrp1<sup>+</sup> T cells synergize with Rapamycin to prevent allograft rejection.
No full text<p>Heterotopic heart grafts were transplanted from BALB/c mice into C57BL/6 recipients. The recipients received a sub-therapeutic regimen of 1 mg/kg/day i.p. Rapamycin for 10 consecutive days (days 0-9), and/or two dose of freshly isolated Nrp1<sup>+</sup> T cell on day 0 and day 7 (2×10<sup>6</sup>). Rejection was defined as cessation of a palpable impulse. (<b>A</b>) Survival rates were compared using log-rank test. (<b>B</b>) Hematoxylin and eosin staining of representative heart allografts harvested at 7d post transplantation. (<b>C</b>) Quantitative histological evaluation of allografts harvested on 7d post transplantation. SC, syngeneic control, Nrp1<sup>+</sup> T = neuropilin-1-positive T cells, HPF = high power field, rapa = Rapamycin, NS = not significant. Results are presented as mean ± SD. *P<0.05, **P<0.01, ***P<0.001.</p
On the Laplace transform of perpetuities with thin tails
No full textWe consider the random variables which are solutions of the distributional equation R\overset{\cL}{=}MR+Q, where is independent of and \ABS{M}\leq 1. Goldie and Grübel showed that the tails of are no heavier than exponential. In this note we provide the exact lower and upper bounds of the domain of the Laplace transform of
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Additional file 1 of Non-Markovian effects on protein sequence evolution due to site dependent substitution rates
No full textP_NonMarkovian.txt. Ensemble average transition probability matrices for codons according to Eq. 5, where the rate is γ-distributed as in Eq. 3, for various t. The file is structured in 12 columns: the first two contain i and j, the other ten P ~ c ( t ) ij respectively for t=0.06,0.14,0.25,0.4,0.6,0.9,1.3,1.9,2.9,4.3 corresponding to the sequence identities of 95 %,90 %...55 %,50 %. i and j identify codons by alphabetical order: 1=“AAA”, 2=“AAC”... 64=“TTT”. (TXT 550 kb
Additional file 2 of Non-Markovian effects on protein sequence evolution due to site dependent substitution rates
No full textP_Markovian.txt. Probability matrices for codons according to Eq. 2 for various t. The file is structured in 12 columns: the first two contain i and j, the other ten P ij c ( t ) respectively for t=0.05,0.11,0.17,0.235,0.31,0.39,0.48,0.58,0.7,0.84 corresponding to the sequence identities of 95 %,90 %...55 %,50 %. i and j identify codons by alphabetical order: 1=“AAA”, 2=“AAC”... 64=“TTT”. (TXT 550 kb
Hemodynamic Response to Forepaw Stimulation in Anesthetized Mice Somatosensory Cortex
No full textAim: Genetically altered mice are a potentially powerful tool to elucidate the molecular basis of neuro-vascular coupling mechanism.
However, neural activity-induced hemodynamic responses in anesthetized murine cortex remains uncharacterized, which hampers the use of a mice model for functional imaging studies (e.g., fMRI and optical imaging). In the present study, hemodynamic responses to forepaw stimulation in the mice somatosensory cortex were characterized under pentobarbital, ketamine-xylazine, and isoflurane anesthesia, all of which are generally used for repeated animal experiments.
\nMaterials and methods: A total of thirteen male C57B6J mice (23-35 g) were divided into three groups. First group (N = 4) was induced with pentobarbital anesthesia (an initial dose of 90 mg/kg i.p. and supplemental dose of 30-45 mg/kg/h i.p.). Second group (N = 6) was induced with a cocktail of ketamine and xylazine (an initial dose of 60 mg/kg and 10 mg/kg i.m., respectively, and supplementally injected with only ketamine 20 mg/kg i.m. every 20-40 min.). The animals in the third group (N = 3) were ventilated with a mixture of isoflurane (4% for induction and 1.3-1.5% for experiments) and air with supplemental oxygen (a total of 30-35%). Animals in the isoflurane group were intubated and mechanically ventilated, whereas the other two groups breathed spontaneously. After the skin covering the skull was removed, oil was immediately placed to preserve the integrity of the skull. First, intrinsic optical imaging (620-nm wavelength) was performed for the localization of the forepaw area in the primary somatosensory cortex. Then, hemodynamic response was measured with laser-Doppler flowmetry (LDF) on the activation focus induced by electrical forepaw stimulation (rectangular pulses with 0.5-ms pulse width and 0.8-mA current). Stimulation duration was fixed at 10 sec for all experiments and stimulation rate (frequency) was varied (2, 4, 6, 8 and 12 Hz). Preliminary experiments determined a pulse width and current that would not elicit a pain response from the animal.
\nResults and discussion: All animal groups showed clear localization of forepaw area in 620-nm optical imaging. The clearest contrast of activation area was observed with ketamine-xylazine group. Under pentobarbital anesthesia, the hemodynamic response increased with an increase in stimulation frequency. The peak of 10 +/- 12% (Mean +/- SD, N = 4) signal change in LDF was observed at stimulation with 12 Hz. Under ketamine-xylazine anesthesia, the highest signal change (13 +/- 4% at peak) was observed at stimulation with 6 Hz. These results indicate that the optimum frequency differs depending on the anesthesia used, which was consistent with our previous results obtained in rats (Masamoto et al., 2006). In isoflurane-anesthetized group, however, no significant hemodynamic response was observed for any stimulation frequency. This result indicates that the isoflurane may be not a good agent for functional imaging studies with mice, which was not the case in rats anesthetized with isoflurane (Masamoto et al., 2006). In conclusion, mice anesthetized with pentobarbital or ketamine-xylazine can be used for repeated functional imaging studies, which make possible to probe the mechanism of neurovascular coupling with a specific molecular basis.Brain'07 and BrainPET'07conference objec
METAGUI 3: A graphical user interface for choosing the collective variables in molecular dynamics simulations
No full textMolecular dynamics (MD) simulations allow the exploration of the phase space of biopolymers through the integration of equations of motion of their constituent atoms. The analysis of MD trajectories often relies on the choice of collective variables (CVs) along which the dynamics of the system is projected. We developed a graphical user interface (GUI) for facilitating the interactive choice of the appropriate CVs. The GUI allows: defining interactively new CVs; partitioning the configurations into microstates characterized by similar values of the CVs; calculating the free energies of the microstates for both unbiased and biased (metadynamics) simulations; clustering the microstates in kinetic basins; visualizing the free energy landscape as a function of a subset of the CVs used for the analysis. A simple mouse click allows one to quickly inspect structures corresponding to specific points in the landscape
Six-state kinetic model for Na<sup>+</sup>-galactose cotransporter updated to a branched six-state model.
No full text<p>In the absence of ligands, the transporter can be in two states: outward or inward-facing conformation (C1 and C6, respectively). After the binding of Na<sup>+</sup> to the outward conformation (C2Na), the substrate enters the protein and finds its site (C3NaS). This step is then followed by the crucial event that sees the transporter switching to the inward-facing conformation (C4NaS). In case the transport follows the dashed line, namely passing from C2Na to C5Na, a uniport of Na<sup>+</sup> ion happens. From the ligands-loaded inward conformation (C4NaS) the protein can lose at first the substrate (C5Na), as suggested in Ref. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004017#pcbi.1004017-Wright1" target="_blank">[11]</a>, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004017#pcbi.1004017-Eskandari1" target="_blank">[48]</a>, or, based on our results (blue region), in an independent way characterized by similar barriers, the ion (C5S).</p
Distribution of variability of <i>θ</i><sub>1</sub> and <i>θ</i><sub>3</sub> angles for different values of <i>λ</i><sub>1</sub> for a 7 degrees of freedom chain.
No full text<p>In this case it is not possible to change a single dof without altering the others: as a consequence a rescaling of <i>λ</i><sub>1</sub> affects the distributions of <i>θ</i><sub>1</sub> as well as of the other angles (shown: <i>θ</i><sub>3</sub>). In this case the effect of changing the rigidity of one or more parameters is the same as rescaling the step size used during the simulation.</p
Explicit Characterization of the Free-Energy Landscape of a Protein in the Space of All Its C<sub>α</sub> Carbons
No full textBy using an approach that allows computing the free energy
in high-dimensional
spaces together with a clustering technique capable of identifying
kinetic attractors stabilized by conformational disorder, we analyze
a molecular dynamics trajectory of the Villin headpiece from Lindorff-Larsen,
K.; et al. How fast-folding proteins fold. Science 2011, 334, 517–520. We compute
its free-energy landscape in the space of all its Cα carbons. This landscape has the shape of a 12-dimensional funnel
with the free energy decreasing monotonically as a function of the
native contacts. There are no significant folding barriers. The funnel
can be partitioned in five regions, three mainly folded and two unfolded,
which behave as Markov states. The slowest relaxation time among these
states corresponds to the folding transition. The second slowest time
is only twice smaller and corresponds to a transition within the unfolded
state. This indicates that the unfolded part of the funnel has a nontrivial
shape, which induces a sizable kinetic barrier between disordered
states
