293 research outputs found
Functional and molecular analysis of proprioceptive sensory neuron excitability in mice
Neurons located in dorsal root ganglia (DRG) are crucial for transmitting peripheral sensations such as proprioception, touch, temperature, and nociception to the spinal cord before propagating these signals to higher brain structures. To date, difficulty in identifying modality-specific DRG neurons has limited our ability to study specific populations in detail. As the calcium-binding protein parvalbumin (PV) is a neurochemical marker for proprioceptive DRG cells we used a transgenic mouse line expressing green fluorescent protein (GFP) in PV positive DRGs, to study the functional and molecular properties of putative proprioceptive neurons. Immunolabeled DRGs showed a 100% overlap between GFP positive (GFP+) and PV positive cells, confirming the PVeGFP mouse accurately labeled PV neurons. Targeted patch-clamp recording from isolated GFP+ and GFP negative (GFPâ) neurons showed the passive membrane properties of the two groups were similar, however, their active properties differed markedly. All GFP+ neurons fired a single spike in response to sustained current injection and their action potentials (APs) had faster rise times, lower thresholds and shorter half widths. A hyperpolarization-activated current (Ih) was observed in all GFP+ neurons but was infrequently noted in the GFPâ population (100% vs. 11%). For GFP+ neurons, Ih activation rates varied markedly, suggesting differences in the underlying hyperpolarization-activated cyclic nucleotide-gated channel (HCN) subunit expression responsible for the current kinetics. Furthermore, quantitative polymerase chain reaction (qPCR) showed the HCN subunits 2, 1, and 4 mRNA (in that order) was more abundant in GFP+ neurons, while HCN 3 was more highly expressed in GFPâ neurons. Likewise, immunolabeling confirmed HCN 1, 2, and 4 protein expression in GFP+ neurons. In summary, certain functional properties of GFP+ and GFPâ cells differ markedly, providing evidence for modality-specific signaling between the two groups. However, the GFP+ DRG population demonstrates considerable internal heterogeneity when hyperpolarization-activated cyclic nucleotide-gated channel (HCN channel) properties and subunit expression are considered. We propose this heterogeneity reflects the existence of different peripheral receptors such as tendon organs, muscle spindles or mechanoreceptors in the putative proprioceptive neuron population
Capillary Condensation and Interface Structure of a Model Colloid-Polymer Mixture in a Porous Medium
We consider the Asakura-Oosawa model of hard sphere colloids and ideal
polymers in contact with a porous matrix modeled by immobilized configurations
of hard spheres. For this ternary mixture a fundamental measure density
functional theory is employed, where the matrix particles are quenched and the
colloids and polymers are annealed, i.e. allowed to equilibrate. We study
capillary condensation of the mixture in a tiny sample of matrix as well as
demixing and the fluid-fluid interface inside a bulk matrix. Density profiles
normal to the interface and surface tensions are calculated and compared to the
case without matrix. Two kinds of matrices are considered: (i) colloid-sized
matrix particles at low packing fractions and (ii) large matrix particles at
high packing fractions. These two cases show fundamentally different behavior
and should both be experimentally realizable. Furthermore, we argue that
capillary condensation of a colloidal suspension could be experimentally
accessible. We find that in case (ii), even at high packing fractions, the main
effect of the matrix is to exclude volume and, to high accuracy, the results
can be mapped onto those of the same system without matrix via a simple
rescaling.Comment: 12 pages, 9 figures, submitted to PR
Minibeam radiation therapy enhanced tumor delivery of PEGylated liposomal doxorubicin in a triple-negative breast cancer mouse model
Background: Minibeam radiation therapy is an experimental radiation therapy utilizing an array of parallel submillimeter planar X-ray beams. In preclinical studies, minibeam radiation therapy has been shown to eradicate tumors and cause significantly less damage to normal tissue compared to equivalent radiation doses delivered by conventional broadbeam radiation therapy, where radiation dose is uniformly distributed. Methods: Expanding on prior studies that suggested minibeam radiation therapy increased perfusion in tumors, we compared a single fraction of minibeam radiation therapy (peak dose:valley dose of 28 Gy:2.1 Gy and 100 Gy:7.5 Gy) and broadbeam radiation therapy (7 Gy) in their ability to enhance tumor delivery of PEGylated liposomal doxorubicin and alter the tumor microenvironment in a murine tumor model. Plasma and tumor pharmacokinetic studies of PEGylated liposomal doxorubicin and tumor microenvironment profiling were performed in a genetically engineered mouse model of claudin-low triple-negative breast cancer (T11). Results: Minibeam radiation therapy (28 Gy) and broadbeam radiation therapy (7 Gy) increased PEGylated liposomal doxorubicin tumor delivery by 7.1-fold and 2.7-fold, respectively, compared to PEGylated liposomal doxorubicin alone, without altering the plasma disposition. The enhanced tumor delivery of PEGylated liposomal doxorubicin by minibeam radiation therapy is consistent after repeated dosing, is associated with changes in tumor macrophages but not collagen or angiogenesis, and nontoxic to local tissues. Our study indicated that the minibeam radiation therapyâs ability to enhance the drug delivery decreases from 28 to 100 Gy peak dose. Discussion: Our studies suggest that low-dose minibeam radiation therapy is a safe and effective method to significantly enhance the tumor delivery of nanoparticle agents
Sub-femto-g free fall for space-based gravitational wave observatories: LISA pathfinder results
We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2 ± 0.1 fm sâ2/âHz or (0.54 ± 0.01) Ă 10â15 g/âHz, with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8 ± 0.3) fm/âHz, about 2 orders of magnitude better than requirements. At f †0.5 mHz we observe a low-frequency tail that stays below 12 fm sâ2/âHz down to 0.1 mHz. This performance would allow for a space-based gravitational wave
observatory with a sensitivity close to what was originally foreseen for LISA
Evidence of Color Coherence Effects in W+jets Events from ppbar Collisions at sqrt(s) = 1.8 TeV
We report the results of a study of color coherence effects in ppbar
collisions based on data collected by the D0 detector during the 1994-1995 run
of the Fermilab Tevatron Collider, at a center of mass energy sqrt(s) = 1.8
TeV. Initial-to-final state color interference effects are studied by examining
particle distribution patterns in events with a W boson and at least one jet.
The data are compared to Monte Carlo simulations with different color coherence
implementations and to an analytic modified-leading-logarithm perturbative
calculation based on the local parton-hadron duality hypothesis.Comment: 13 pages, 6 figures. Submitted to Physics Letters
Distribuição espacial da meleira do mamoeiro em zonas de trĂłpico Ășmido e trĂłpico semi-ĂĄrido
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