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“Consideration was given to means of increasing the reliability and muscle specificity of
paired associative stimulation (PAS) by utilising the phenomenon of crossed-facilitation. Eight participants completed three separate sessions: isometric flexor contractions of the left wrist at 20% of maximum voluntary contraction CB-839 (MVC) simultaneously with PAS (20s intervals; 14 min duration) delivered at the right median nerve and left primary motor cortex (MI); isometric contractions at 20% of MVC: and PAS only ( 14 min). Eight further participants completed two sessions of longer duration PAS (28 min): either alone or in conjunction with flexion contractions of the left wrist. Thirty motor potentials (MEPs) were evoked in the right flexor (rFCR) and extensor (rECR) carpi radialis muscles by magnetic stimulation of left M1 Prior to the interventions, immediately post-intervention, and 10 min post-intervention. Both 14 and 28 min of combined PAS and (left wrist flexion) contractions resulted in reliable increases in rFCR MEP amplitude, which were not present in rECR. In the AZD3965 in vitro PAS only conditions, 14 min of stimulation gave rise to unreliable increases in MEP amplitudes in rFCR and rECR, whereas 28 min of PAS induced small (unreliable) changes only for rFCR. These results support the conclusion that changes in the excitability of the corticospinal pathway induced by PAS interact with those associated with contraction of
the muscles ipsilateral to the site of cortical stimulation. Furthermore, focal contractions applied by the opposite limb increase
the extent and muscle specificity of the induced changes in excitability associated with PAS. (C) 2008 Elsevier Ireland Ltd. Guanylate cyclase 2C All rights reserved.”
“Human immunodeficiency virus type 1 (HIV-1) neutralization can be effected by several classes of inhibitors that target distinct regions of gp41 that are accessible in the prehairpin intermediate (PHI) state and block the formation of the six-helix bundle (6-HB) conformation of gp41. The N-heptad repeat (N-HR) of gp41 is the site of action of two classes of inhibitors. One class binds to the trimeric N-HR coiled coil, while the other, exemplified by the peptide N-36Mut(e,N-g), disrupts the trimer and sequesters the PHI through the formation of heterotrimers. We recently reported a neutralizing Fab (Fab 3674), selected from a nonimmune phage library, that binds to the trimeric N-HR coiled coil through an epitope that remains exposed in the 6-HB and is also present in heterotrimers of the N-HR and N36(Mut(e,g)) peptide. Here we show that N36(Mut(e,g)) prolongs the temporal window during which the virus is susceptible to neutralization by the bivalent Fab 3674 and that bivalent Fab 3674 and N36(Mut(e,g)) neutralize HXB2 and SF162 strains of HIV-1, as well as isolates of diverse primary B and C HIV-1 strains, synergistically in a Env-pseudotyped virus neutralization assay.