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1.
Nat Commun ; 15(1): 2362, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491006

RESUMEN

The axon-initial-segment (AIS) of mature neurons contains microtubule (MT) fascicles (linear bundles) implicated as retrograde diffusion barriers in the retention of MT-associated protein (MAP) tau inside axons. Tau dysfunction and leakage outside of the axon is associated with neurodegeneration. We report on the structure of steady-state MT bundles in varying concentrations of Mg2+ or Ca2+ divalent cations in mixtures containing αß-tubulin, full-length tau, and GTP at 37 °C in a physiological buffer. A concentration-time kinetic phase diagram generated by synchrotron SAXS reveals a wide-spacing MT bundle phase (Bws), a transient intermediate MT bundle phase (Bint), and a tubulin ring phase. SAXS with TEM of plastic-embedded samples provides evidence of a viscoelastic intervening network (IN) of complexes of tubulin oligomers and tau stabilizing MT bundles. In this model, αß-tubulin oligomers in the IN are crosslinked by tau's MT binding repeats, which also link αß-tubulin oligomers to αß-tubulin within the MT lattice. The model challenges whether the cross-bridging of MTs is attributed entirely to MAPs. Tubulin-tau complexes in the IN or bound to isolated MTs are potential sites for enzymatic modification of tau, promoting nucleation and growth of tau fibrils in tauopathies.


Asunto(s)
Tubulina (Proteína) , Proteínas tau , Microtúbulos/metabolismo , Dispersión del Ángulo Pequeño , Proteínas tau/metabolismo , Tubulina (Proteína)/metabolismo , Difracción de Rayos X , Humanos
2.
PLoS One ; 18(11): e0293322, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37917746

RESUMEN

Disparities for women and minorities in science, technology, engineering, and math (STEM) careers have continued even amidst mounting evidence for the superior performance of diverse workforces. In response, we launched the Diversity and Science Lecture series, a cross-institutional platform where junior life scientists present their research and comment on diversity, equity, and inclusion in STEM. We characterize speaker representation from 79 profiles and investigate topic noteworthiness via quantitative content analysis of talk transcripts. Nearly every speaker discussed interpersonal support, and three-fifths of speakers commented on race or ethnicity. Other topics, such as sexual and gender minority identity, were less frequently addressed but highly salient to the speakers who mentioned them. We found that significantly co-occurring topics reflected not only conceptual similarity, such as terms for racial identities, but also intersectional significance, such as identifying as a Latina/Hispanic woman or Asian immigrant, and interactions between concerns and identities, including the heightened value of friendship to the LGBTQ community, which we reproduce using transcripts from an independent seminar series. Our approach to scholar profiles and talk transcripts serves as an example for transmuting hundreds of hours of scholarly discourse into rich datasets that can power computational audits of speaker diversity and illuminate speakers' personal and professional priorities.


Asunto(s)
Diversidad, Equidad e Inclusión , Etnicidad , Femenino , Humanos , Grupos Minoritarios , Tecnología
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