Anti-F2 monoclonal antibody

Impairment of vowel production in dysarthria has been highly valued. This study aimed to explore the vowel production of Mandarin-speakers with post-stroke spastic dysarthria in connected speech and to explore the influence of gender and tone on the vowel production. Multiple vowel acoustic metrics, including F1 range, F2 range, vowel space area (VSA), vowel articulation index (VAI) and formant centralization ratio (FCR), were analyzed from vowel tokens embedded in connected speech produced. The participants included 25 clients with spastic dysarthria secondary to stroke (15 males, 10 females) and 25 speakers with no history of neurological disease (15 males, 10 females). Variance analyses were conducted and the results showed that the main effects of population, gender, and tone on F2 range, VSA, VAI, and FCR were all significant. Vowel production became centralized in the clients with post-stroke spastic dysarthria. Vowel production was found to be more centralized in males compared to females. Vowels in neutral tone (T0) were the most centralized among the other tones. The quantitative acoustic metrics of F2 range, VSA, VAI, and FCR were effective in predicting vowel production in Mandarin-speaking clients with post-stroke spastic dysarthria, and hence may be used as powerful tools to assess the speech performance for this population.

Kindlin-3, a protein 4.1, ezrin, radixin, and moesin (FERM) domain-containing adaptor in hematopoietic cells, is essentially required for supporting the bidirectional integrin ( )alpha IIb beta 3 signaling in platelets by binding to the integrin beta 3 cytoplasmic tail. However, the structural details of kindlin-3's FERM domain remain unknown. In this study, we crystalized the kindlin-3's FERM domain protein and successfully solved its 3-dimensional structure. The structure shows that the 3 kindlin-3's FERM subdomains (F1, F2, and F3) compact together and form a cloverleaf-shaped conformation, which is stabilized by the binding interface between the F1 and F3 subdomains. Interestingly, the FERM domain of kindlin-3 exists as a monomer in both crystal and solution, which is different from its counterpart in kindlin-2 that is able to form a F2 subdomain-swapped dimer nonetheless, dimerization is required for kindlin-3 to support integrin alpha IIb beta 3 activation, indicating that kindlin-3 may use alternative mechanisms for formation of a functional dimer in cells. To evaluate the functional importance of the cloverleaf-like FERM structure in kindlin-3, structure-based mutations were introduced into kindlin-3 to disrupt the F1/F3 interface. The results show that integrin alpha IIb beta 3 activation is significantly suppressed in platelets expressing the kindlin-3 mutant compared with those expressing wild-type kindlin-3. In addition, introduction of equivalent mutations into kindlin-1 and kindlin-2 also significantly compromises their ability to support integrin alpha IIb beta 3 activation in CHO cells. Together, our findings suggest that the cloverleaf-like FERM domain in kindlins is structurally important for supporting integrin alpha IIb beta 3 activation.