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1.
Artigo em Inglês | MEDLINE | ID: mdl-39018573

RESUMO

BACKGROUND: Despite widespread acceptance of the importance of diversity in leadership, systemic challenges in leadership attainment in orthopaedic surgery still exist for several groups. We hypothesize that women, underrepresented in medicine groups, and Asians have decreased odds of achieving program director and chairperson positions compared with peers. METHODS: Demographic data were collected from the Association of American Medical Colleges for faculty, program directors, and chairpersons in orthopaedic surgery. Odds ratios were calculated treating race, ethnicity, or sex as the predictor variables and attainment of a leadership position as the outcome, comparing the composition of program directors in 2020 and chairpersons in 2019 with faculty in 2019. RESULTS: Significantly decreased odds were found for women at 0.37 (0.264 to 0.51 [P < 0.0001]) and the Other category at 0.16 (0.065 to 0.3864 [P = 0.0001]) while significantly increased odds were found for White and Black/African American faculty at 1.32 (1.02 to 1.71 [P = 0.0314]) and 1.95 (1.17 to 3.26 [P = 0.011]), respectively, in holding program director positions. Significantly decreased odds of attaining chairpersonship were found for women at 0.17 (0.07 to 0.41 [P = 0.0075]) and Asian faculty at 0.33 (0.14 to 0.75 [P = 0.0062]) while White faculty demonstrated significantly increased odds at 2.43 (1.41 to 4.19 [P = 0.0013]). CONCLUSIONS: Women showed markedly decreased odds of leadership attainment while Black/African American faculty had increased likelihood of becoming program directors but were not markedly more likely to become chairs. Asian faculty were less likely to become program directors and markedly less likely to become chairs. While decreased odds for women were expected based on current literature, decreased odds of Asians becoming chairs and an increased likelihood of Black/African American orthopaedic surgeons becoming program directors but not attaining the role of chairs at the same rate were novel findings, revealing concerning trends for these groups.

2.
Structure ; 31(12): 1589-1603.e6, 2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-37776857

RESUMO

Human thirty-eight-negative kinase-1 (TNK1) is implicated in cancer progression. The TNK1 ubiquitin-associated (UBA) domain binds polyubiquitin and plays a regulatory role in TNK1 activity and stability. No experimentally determined molecular structure of this unusual UBA domain is available. We fused the UBA domain to the 1TEL variant of the translocation ETS leukemia protein sterile alpha motif (TELSAM) crystallization chaperone and obtained crystals diffracting as far as 1.53 Å. GG and GSGG linkers allowed the UBA to reproducibly find a productive binding mode against its host 1TEL polymer and crystallize at protein concentrations as low as 0.2 mg/mL. Our studies support a mechanism of 1TEL fusion crystallization and show that 1TEL fusion crystals require fewer crystal contacts than traditional protein crystals. Modeling and experimental validation suggest the UBA domain may be selective for both the length and linkages of polyubiquitin chains.


Assuntos
Chaperonas Moleculares , Poliubiquitina , Humanos , Poliubiquitina/química , Ligação Proteica , Cristalização , Estrutura Terciária de Proteína , Domínios Proteicos , Chaperonas Moleculares/metabolismo , Proteínas Fetais/metabolismo , Proteínas Tirosina Quinases/metabolismo
3.
bioRxiv ; 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37398013

RESUMO

Human thirty-eight-negative kinase-1 (TNK1) is implicated in cancer progression. The TNK1-UBA domain binds polyubiquitin and plays a regulatory role in TNK1 activity and stability. Sequence analysis suggests an unusual architecture for the TNK1 UBA domain, but an experimentally-validated molecular structure is undetermined. To gain insight into TNK1 regulation, we fused the UBA domain to the 1TEL crystallization chaperone and obtained crystals diffracting as far as 1.53 Å. A 1TEL search model enabled solution of the X-ray phases. GG and GSGG linkers allowed the UBA to reproducibly find a productive binding mode against its host 1TEL polymer and to crystallize at protein concentrations as low as 0.1 mg/mL. Our studies support a mechanism of TELSAM fusion crystallization and show that TELSAM fusion crystals require fewer crystal contacts than traditional protein crystals. Modeling and experimental validation suggest the UBA domain may be selective for both the length and linkages of polyubiquitin chains.

4.
Open Biol ; 12(3): 210271, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35232248

RESUMO

While conducting pilot studies into the usefulness of fusion to TELSAM polymers as a potential protein crystallization strategy, we observed novel properties in crystals of two TELSAM-target protein fusions, as follows. (i) A TELSAM-target protein fusion can crystallize more rapidly and with greater propensity than the same target protein alone. (ii) TELSAM-target protein fusions can be crystallized at low protein concentrations. This unprecedented observation suggests a route to crystallize proteins that can only be produced in microgram amounts. (iii) The TELSAM polymers themselves need not directly contact one another in the crystal lattice in order to form well-diffracting crystals. This novel observation is important because it suggests that TELSAM may be able to crystallize target proteins too large to allow direct inter-polymer contacts. (iv) Flexible TELSAM-target protein linkers can allow target proteins to find productive binding modes against the TELSAM polymer. (v) TELSAM polymers can adjust their helical rise to allow fused target proteins to make productive crystal contacts. (vi). Fusion to TELSAM polymers can stabilize weak inter-target protein crystal contacts. We report features of these TELSAM-target protein crystal structures and outline future work needed to validate TELSAM as a crystallization chaperone and determine best practices for its use.


Assuntos
Chaperonas Moleculares , Polímeros , Cristalização , Cristalografia por Raios X , Chaperonas Moleculares/química , Polímeros/química
5.
CBE Life Sci Educ ; 16(4)2017.
Artigo em Inglês | MEDLINE | ID: mdl-29196430

RESUMO

Recent calls for improvement in undergraduate education within STEM (science, technology, engineering, and mathematics) disciplines are hampered by the methods used to evaluate teaching effectiveness. Faculty members at research universities are commonly assessed and promoted mainly on the basis of research success. To improve the quality of undergraduate teaching across all disciplines, not only STEM fields, requires creating an environment wherein continuous improvement of teaching is valued, assessed, and rewarded at various stages of a faculty member's career. This requires consistent application of policies that reflect well-established best practices for evaluating teaching at the department, college, and university levels. Evidence shows most teaching evaluation practices do not reflect stated policies, even when the policies specifically espouse teaching as a value. Thus, alignment of practice to policy is a major barrier to establishing a culture in which teaching is valued. Situated in the context of current national efforts to improve undergraduate STEM education, including the Association of American Universities Undergraduate STEM Education Initiative, this essay discusses four guiding principles for aligning practice with stated priorities in formal policies: 1) enhancing the role of deans and chairs; 2) effectively using the hiring process; 3) improving communication; and 4) improving the understanding of teaching as a scholarly activity. In addition, three specific examples of efforts to improve the practice of evaluating teaching are presented as examples: 1) Three Bucket Model of merit review at the University of California, Irvine; (2) Evaluation of Teaching Rubric, University of Kansas; and (3) Teaching Quality Framework, University of Colorado, Boulder. These examples provide flexible criteria to holistically evaluate and improve the quality of teaching across the diverse institutions comprising modern higher education.


Assuntos
Cultura , Políticas , Pesquisa/educação , Recompensa , Ensino , Universidades , Currículo , Feminino , Humanos , Masculino , Modelos Educacionais , Estudantes
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