Anti-TBCD monoclonal antibody Made to order

Microtubules are highly dynamic tubulin polymers that are required for a variety of cellular functions. Despite the importance of a cellular population of tubulin dimers, we have incomplete information about the mechanisms involved in the biogenesis of alpha beta-tubulin heterodimers. In addition to prefoldin and the TCP-1 Ring Complex, five tubulin-specific chaperones, termed cofactors A-E (TBCA-E), and GTP are required for the folding of alpha- and beta-tubulin subunits and assembly into heterodimers. We recently described the purification of a novel trimer, TBCD.ARL2.beta-tubulin. Here, we employed hydrogen/deuterium exchange coupled with mass spectrometry to explore the dynamics of each of the proteins in the trimer. Addition of guanine nucleotides resulted in changes in the solvent accessibility of regions of each protein that led to predictions about each's role in tubulin folding. Initial testing of that model confirmed that it is ARL2, and not beta-tubulin, that exchanges GTP in the trimer. Comparisons of the dynamics of ARL2 monomer to ARL2 in the trimer suggested that its protein interactions were comparable to those of a canonical GTPase with an effector. This was supported by the use of nucleotide-binding assays that revealed an increase in the affinity for GTP by ARL2 in the trimer. We conclude that the TBCD.ARL2.beta-tubulin complex represents a functional intermediate in the beta-tubulin folding pathway whose activity is regulated by the cycling of nucleotides on ARL2. The co-purification of guanine nucleotide on the beta-tubulin in the trimer is also shown, with implications to modeling the pathway. (C) 2017 Elsevier Ltd. All rights reserved.

Speech inversion is a way of estimating articulatory trajectories or vocal tract configurations from the acoustic speech signal. Traditionally, articulator flesh-point or pellet trajectories have been used in speech-inversion research; however such information introduces additional variability into the inverse problem given they are head-centered, task-neutral measures. This paper proposes the use of vocal tract constriction variables (TVs) that are less variable for speech-inversion since they are constriction-based, task-specific measures. TVs considered in this study consist of five constriction degree variables, lip aperture (LA), tongue body constriction degree (TBCD), tongue tip constriction degree (TTCD), velum (VEL), and glottis (GLO); and three constriction location variables, lip protrusion (LP), tongue tip constriction location (TTCL) and tongue body constriction location (TBCL). Six different flesh-point trajectories were considered that were measured with transducers placed on the upper lip (UL), lower lip (LL) and four positions on the tongue (T1, T2, T3 and T4) between the tongue tip and the tongue dorsum. Speech inversion using a simple neural network architecture shows that the TVs can be estimated relatively more accurately than the pellet trajectories. Further statistical investigation reveals that the non-uniqueness is reduced in the TVs compared to the pellet trajectories for phones which are known to appreciably suffer from non-uniqueness. Finally we perform word recognition experiments using the estimated TVs as opposed to the pellet trajectories and show that the former offers greater word recognition accuracy both in clean and noisy speech, indicating that the TVs are a better choice for speech recognition systems.