Phasic modulation of corticomotor excitability during passive movement of the upper limb: effects of movement frequency and muscle specificity

Modulations in the excitability of spinal reflex pathways during passive rhythmic movements of the lower limb have been demonstrated by a number of previous studies [4]. Less emphasis has been placed on the role of supraspinal pathways during passive movement, and on tasks involving the upper limb. In the present study, transcranial magnetic stimulation (TMS) was delivered to subjects while undergoing passive flexion-extension movements of the contralateral wrist. Motor evoked potentials (MEPs) of flexor carpi radialis (FCR) and abductor pollicus brevis (APB) muscles were recorded. Stimuli were delivered in eight phases of the movement cycle during three different frequencies of movement. Evidence of marked modulations in pathway excitability was found in the MEP amplitudes of the FCR muscle, with responses inhibited and facilitated from static values in the extension and flexion phases, respectively. The results indicated that at higher frequencies of movement there was greater modulation in pathway excitability. Paired-pulse TMS (sub-threshold conditioning) at short interstimulus intervals revealed modulations in the extent of inhibition in MEP amplitude at high movement frequencies. In the APE muscle, there was some evidence of phasic modulations of response amplitude, although the effects were less marked than those observed in FCR. It is speculated that these modulatory effects are mediated via Ia afferent pathways and arise as a consequence of the induced forearm muscle shortening and lengthening. Although the level at which this input influences the corticomotoneuronal pathway is difficult to discern, a contribution from cortical regions is suggested. (C) 2001 Published by Elsevier Science B.V.

Substrate evaluation for a microbeam endstation using unstained cell imaging.

A cellular imaging system, optimized for unstained cells seeded onto a thin substrate, is under development. This system will be a component of the endstation for the microbeam cell-irradiation facility at the University of Surrey. Previous irradiation experiments at the Gray Cancer Institute (GCI) have used Mylar film to support the cells [Folkard, M., Prise, K., Schettino, G., Shao, C., Gilchrist, S., Vojnovic, B., 2005. New insights into the cellular response to radiation using microbeams. Nucl. Instrum. Methods B 231, 189-194]. Although suitable for fluorescence microscopy, the Mylar often creates excessive optical noise when used with non-fluorescent microscopy. A variety of substrates are being investigated to provide appropriate optical clarity, cell adhesion, and radiation attenuation. This paper reports on our investigations to date.

Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures.

Sertraline and fluoxetine are selective serotonin re-uptake inhibitors (SSRIs) that are widely prescribed to treat depression. They exert their effects by inhibiting the presynaptic plasma membrane serotonin transporter (SERT). All SSRIs possess halogen atoms at specific positions, which are key determinants for the drugs' specificity for SERT. For the SERT protein, however, the structural basis of its specificity for SSRIs is poorly understood. Here we report the crystal structures of LeuT, a bacterial SERT homolog, in complex with sertraline, R-fluoxetine or S-fluoxetine. The SSRI halogens all bind to exactly the same pocket within LeuT. Mutation at this halogen-binding pocket (HBP) in SERT markedly reduces the transporter's affinity for SSRIs but not for tricyclic antidepressants. Conversely, when the only nonconserved HBP residue in both norepinephrine and dopamine transporters is mutated into that found in SERT, their affinities for all the three SSRIs increase uniformly. Thus, the specificity of SERT for SSRIs is dependent largely on interaction of the drug halogens with the protein's HBP.

Tailoring the AMC and EBG characteristics of periodic metallic arrays printed on grounded dielectric substrate

The artificial magnetic conductor (AMC) and electromagnetic band gap (EBG) characteristics of planar periodic metallic arrays printed on grounded dielectric substrate are investigated. The currents induced on the arrays are presented for the first time and their study reveals two distinct resonance phenomena associated with these surfaces. A new technique is presented to tailor the spectral position of the AMC operation and the EBG. Square patch arrays with fixed element size and variable periodicities are employed as working examples to demonstrate the dependence of the spectral AMC and EBG characteristics on array parameters. It is revealed that as the array periodicity is increased, the AMC frequency is increased, while the EBG frequency is reduced. This is shown to occur due to the different nature of the resonance phenomena and the associated underlying physical mechanisms that produce the two effects. The effect of substrate thickness is also investigated. Full wave method of moments (MoM) has been employed for the derivation of the reflection characteristics, the currents and the dispersion relations. A uniplanar array with simultaneous AMC and EBG operation is demonstrated theoretically and experimentally.

Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation

Insulin resistance and diabetes might promote neurodegenerative disease, but a molecular link between these disorders is unknown. Many factors are responsible for brain growth, patterning, and survival, including the insulin-insulin-like growth factor (IGF)-signaling cascades that are mediated by tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. Irs2 signaling mediates peripheral insulin action and pancreatic beta-cell function, and its failure causes diabetes in mice. In this study, we reveal two important roles for Irs2 signaling in the mouse brain. First, disruption of the Irs2 gene reduced neuronal proliferation during development by 50%, which dissociated brain growth from Irs1-dependent body growth. Second, neurofibrillary tangles containing phosphorylated tau accumulated in the hippocampus of old Irs2 knock-out mice, suggesting that Irs2 signaling is neuroprotective. Thus, dysregulation of the Irs2 branch of the insulin-Igf-signaling cascade reveals a molecular link between diabetes and neurodegenerative disease.

How many processes underline category-based induction? Effect of conclusion specificity and cognitive ability

Two studies investigated participants' sensitivity to the amount and diversity of the evidence when reasoning inductively about categories. Both showed that participants are more sensitive to characteristics of the evidence for arguments with general rather than specific conclusions. Both showed an association between cognitive ability and sensitivity to these evidence characteristics, particularly when the conclusion category was general. These results suggest that a simple associative process may not be sufficient to capture some key phenomena of category-based induction. They also support the claim that the need to generate a superordinate category is a complicating factor in category-based reasoning and that adults' tendency to generate such categories while reasoning has been overestimated.