Physiological and theoretical analysis of K+ currents controlling discharge in neonatal rat mesencephalic trigeminal neurons

Whole cell voltage- and current-clamp recordings were obtained from mesencephalic trigeminal sensory (Mes 5) neurons identified visually in thin brain stem slices of neonatal rats with the use of infrared video microscopy. These cells exhibited accommodation in spike discharge responses to depolarizing current injection protocols whose duration differed as a function of holding potential (-50 vs. -65 mV). Several spikes were elicited before the membrane response accommodated from -50 mV, whereas from -65 mV only single action potentials were evoked. In response to similar protocols, application of the K+ channel blocker 4-aminopyridine (4-AP) (50 microM to 2 mM) caused sustained repetitive spiking whereas tetraethylammonium (TEA) (10-30 mM) did not cause repetitive spiking. In voltage clamp, 4-AP application (100 microM) revealed a sustained outward current (I4-AP) that was active between -60 and -30 mV. I4-AP was responsible for suppressing sustained repetitive spiking behavior, producing accommodation under normal circumstances. TEA application in voltage clamp revealed a sustained outward current evoked positive to -40 mV. Two transient outward currents (TOCs) were identified by prepulse protocols typically used to characterize A-type currents: a 4-AP-insensitive fast TOC, and a slow TOC (ITOC-S) sensitive to 4-AP (> 500 microM). A Ca(2+)-dependent outward current that activated positive to -30 mV was also characterized. A mathematical model of a Mes 5 neuron was assembled from our voltage-clamp records to simulate the dynamic interaction of outward currents during membrane excitation. We conclude that in Mes 5 neurons, the 4-AP-sensitive currents ITOC-S and I4-AP determine the duration of spike trains. In particular, the noninactivating I4-AP determines whether cells exhibit sustained repetitive discharge or accommodate in response to depolarizing current. Neurotransmitter modulation of this current or modulation of the resting membrane potential could modify the output properties of Mes 5 neurons, and therefore the properties of these currents must be incorporated into our current understanding of how these cells contribute to shaping oral-motor pattern generation.     

MR monitoring of focused ultrasonic surgery of renal cortex: experimental and simulation studies

The aim of the study was to test the hypothesis that magnetic resonance (MR) imaging-guided and -monitored noninvasive ultrasonic surgery can be performed in highly perfused tissues from outside the body. A simulation study was performed to evaluate the optimal sonication parameters. An MR-compatible positioning device was then used to manipulate a focused ultrasound transducer in an MR imager, which was used to sonicate kidneys of five rabbits at various power levels and different durations. Temperature elevation during sonication was monitored with a T1-weighted spoiled gradient-echo sequence. The simulation study demonstrated that a sharply focused transducer and relatively short sonication times (30 seconds or less) are necessary to prevent damage to the overlying skin and muscle tissue, which have a much lower blood perfusion rate than kidney. The experiments showed that the imaging sequence was sensitive enough to show temperature elevation during sonication, thereby indicating the location of the beam focus. Histologic evaluations showed that kidney necrosis could be consistently induced without damage to overlying skin and muscle. The study demonstrated that highly perfused tissues such as the renal cortex can be coagulated from outside the body with focused ultrasound and that MR imaging can be used to guide and monitor this surgery.     

Feedback Specificity, Learning Opportunities, and Learning.

Although increasing feedback specificity is generally beneficial for immediate performance, it can undermine certain aspects of the learning needed for later, more independent performance. The results of the present transfer experiment demonstrate that the effects of increasing feedback specificity on learning depended on what was to be learned, and these effects were partially mediated through the opportunities to learn how to respond to different task conditions during practice. More specific feedback was beneficial for learning how to respond to good performance and detrimental for learning how to respond to poor performance. The former relationship was partially mediated by feedback specificity's effect on learning opportunities during practice. The results have implications for designing feedback interventions and training to maximize the learning of various aspects of a task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Eruption times of third molars in young rural Nigerians

The mechanical stability of proximal femoral osteotomies fixed by the tension band wire technique was studied in flexion-compression and torsion tests. The fixation consisted in crossing the section with two Kirschner wires and with a wire cerclage applied to the tension surface. The study was conducted in three steps. First, cyclinders of wood were cut either transversely or at 30 degrees of inclination in relation to the long axis of the specimen, and fixed with two Kirschner wires and a wire cerclage. We concluded that the inclination of the plane of section significantly increased the stability of fixation. No significant difference was observed when oblique sections were made in the reverse orientation. Second, 30 degrees subtrochanteric varus osteotomies were performed in dog femurs, so that the section plane was transverse in one group and oblique in another, after closing the osteotomy. In both groups the fixation was achieved by two Kirschner wires that crossed the osteotomy and a wire cerclage placed on the lateral cortex (tension surface). We concluded that inclination of the osteotomy plane increased the stability of osteosynthesis in bone specimens, as already seen with the wood pieces. Third, the stability of tension band wire fixation was compared with that provided by the AO/ASIF paediatric angled plate. Varus osteotomies (30 degrees) were created at the subtrochanteric level of paired dog femurs. On one side, the femur was fixed with Kirschner wires and a wire cerclage as described previously. For the other femur, the osteotomy was fixed with the angled plate. We found that both types of fixation presented the same stability in flexion-compression tests. However, under torsion the tension band wire fixation was 30%-50% less stable than the plate fixation.     

Tissue factor pathway inhibitor in endothelial cells colocalizes with glycolipid microdomains/caveolae. Regulatory mechanism(s) of the anticoagulant properties of the endothelium

Tissue factor pathway inhibitor (TFPI), the main downregulator of the procoagulant activity of tissue factor.factor VIIa complex, locates in human endothelial cells (EC) in culture as well-defined clusters uniformly distributed both on the cell surface and intracellularly. We here demonstrate by immunofluorescence that TFPI colocalizes in EC with caveolin, urokinase-type plasminogen activator receptor, and glycosphingolipids. The localization of TFPI in caveolae in resting endothelium is proved by double immunogold electron microscopy for TFPI and caveolin. After ultracentrifugation of rat lung or EC homogenates through density gradients of Nycodenz, TFPI was highly enriched at densities of 1.05 to 1.08 g/mL, together with caveolin and alkaline phosphatase. By ELISA, more than half of the cellular TFPI was detected in Triton X-100-insoluble extracts of EC. TFPI incorporates [1-3H]ethanolamine and is cleaved from the cell surface by phosphatidylinositol-phospholipase C, indicating a specific glycosylphosphatidylinositol-anchorage mechanism for TFPI in the plasma membrane. Clustering of TFPI and its localization in caveolae are dependent on the presence of cholesterol in the membrane. Agonist-induced stimulation of EC caused marked changes of distribution for both TFPI and caveolin at subcellular level, with subsequent increase of the cell surface-associated inhibitory activity toward tissue factor.factor VIIa. Our findings suggest that, beside their function in transcytosis, potocytosis, cell surface proteolysis, and regulation of signal transduction, caveolae also play a direct role in the regulation of EC anticoagulant properties.     

A human homologue of the Drosophila Toll protein signals activation of adaptive immunity

Induction of the adaptive immune response depends on the expression of co-stimulatory molecules and cytokines by antigen-presenting cells. The mechanisms that control the initial induction of these signals upon infection are poorly understood. It has been proposed that their expression is controlled by the non-clonal, or innate, component of immunity that preceded in evolution the development of an adaptive immune system in vertebrates. We report here the cloning and characterization of a human homologue of the Drosophila toll protein (Toll) which has been shown to induce the innate immune response in adult Drosophila. Like Drosophila Toll, human Toll is a type I transmembrane protein with an extracellular domain consisting of a leucine-rich repeat (LRR) domain, and a cytoplasmic domain homologous to the cytoplasmic domain of the human interleukin (IL)-1 receptor. Both Drosophila Toll and the IL-1 receptor are known to signal through the NF-kappaB pathway. We show that a constitutively active mutant of human Toll transfected into human cell lines can induce the activation of NF-kappaB and the expression of NF-kappaB-controlled genes for the inflammatory cytokines IL-1, IL-6 and IL-8, as well as the expression of the co-stimulatory molecule B7.1, which is required for the activation of naive T cells.