As literature indicates, historic racism and implicit bias throughout academia have been profound metrics leading to a lack of diversity, as related to people from underrepresented groups according to race and ethnicity, among biomedical sciences graduate students in U.S. universities. Recognizing such challenges, a team of biomedical scientists and inclusivity educators developed and implemented a pilot training program within an academic health sciences center as an initial step to educate faculty and staff regarding their roles in the promotion of an inclusive academic environment, receptive to all students, including underrepresented students. The 3-h workshop included didactic modules, videos, teaching modules, and active attendee participation. Faculty and staff were presented common terminology and ways to promote the development of an inclusive and diverse academic workforce. Compared with pre-workshop, post-workshop survey results indicated a statistically significant improvement in attendee knowledge of correctly identifying definitions of “implicit bias,” “status leveling,” “color-blind racial attitudes,” “tokenism,” and “failure to differentiate.” Additionally, by the end of the workshop, participants had a statistically significant increase in self-perceptions regarding the importance of improving diversity and recognizing biases and stereotypes in graduate education, knowing what to say when interacting with people from different cultures, and the ability to acknowledge bias when mentoring students from groups underrepresented in the biomedical field. This preliminary initiative was successful in the introduction of faculty and staff to the importance of fostering an inclusive academic environment and thereby developing a diverse workforce.

This study describes the design and implementation of remote Summer undergraduate research programs during the COVID-19 pandemic, including program strengths and recommendations for improvement from the perspectives of undergraduate researchers.

The mechanism of Nedd4-2 has been quantitatively explored for the first time using biochemically defined kinetic assays examining rates of I-polyubiquitin chain assembly as a functional readout. We demonstrate that Nedd4-2 exhibits broad specificity for E2 paralogs of the Ubc4/5 clade to assemble Lys-linked polyubiquitin chains. Full-length Nedd4-2 catalyzes free I-polyubiquitin chain assembly by hyperbolic Michaelis-Menten kinetics with respect to Ubc5B∼ubiquitin thioester concentration ( = 44 ± 6 nm; = 0.020 ± 0.007 s) and substrate inhibition above 0.5 μm ( = 2.5 ± 1.3 μm) that tends to zero velocity, requiring ordered binding at two functionally distinct E2∼ubiquitin-binding sites. The Ubc5BC85A product analog non-competitively inhibits Nedd4-2 ( = 2.0 ± 0.5 μm), consistent with the presence of the second E2-binding site. In contrast, the isosteric Ubc5BC85S-ubiquitin oxyester substrate analog exhibits competitive inhibition at the high-affinity Site 1 ( = 720 ± 340 nm) and non-essential activation at the lower-affinity Site 2 ( = 750 ± 260 nm). Additional studies utilizing Ubc5BF62A, defective in binding the canonical E2 site, demonstrate that the cryptic Site 1 is associated with thioester formation, whereas binding at the canonical site (Site 2) is associated with polyubiquitin chain elongation. Finally, previously described Ca-dependent C2 domain-mediated autoinhibition of Nedd4-2 is not observed under our reported experimental conditions. These studies collectively demonstrate that Nedd4-2 catalyzes polyubiquitin chain assembly by an ordered two-step mechanism requiring two dynamically linked E2∼ubiquitin-binding sites analogous to that recently reported for E6AP, the founding member of the Hect ligase family.

Undergraduates participating in remote research programs experienced gains in scientific self-efficacy similar those observed in in-person research. Students experienced gains in scientific identity, graduate and career intentions, and perceptions of benefits and costs of doing research only if they started their remote undergraduate research experiences at lower levels.

Edited by George N. DeMartino The NEDD4-2 (neural precursor cell-expressed developmentally down-regulated 4-2) HECT ligase catalyzes polyubiquitin chain assembly by an ordered two-step mechanism requiring two functionally distinct E2ϳubiquitin-binding sites, analogous to the trimeric E6AP/UBE3A HECT ligase. This conserved catalytic mechanism suggests that NEDD4-2, and presumably all HECT ligases, requires oligomerization to catalyze polyubiquitin chain assembly. To explore this hypothesis, we examined the catalytic mechanism of NEDD4-2 through the use of biochemically defined kinetic assays examining rates of 125 I-labeled polyubiquitin chain assembly and biophysical techniques. The results from gel filtration chromatography and dynamic light-scattering analyses demonstrate for the first time that active NEDD4-2 is a trimer. Homology modeling to E6AP revealed that the predicted intersubunit interface has an absolutely conserved Phe-823, substitution of which destabilized the trimer and resulted in a >10 4-fold decrease in k cat for polyubiquitin chain assembly. The small-molecule Phe-823 mimic, N-acetylphenylalanyl-amide, acted as a noncompetitive inhibitor (K i ‫؍‬ 8 ؎ 1.2 mM) of polyubiquitin chain elongation by destabilizing the active trimer, suggesting a mechanism for therapeutically targeting HECT ligases. Additional kinetic experiments indicated that monomeric NEDD4-2 catalyzes only HECTϳubiquitin thioester formation and monoubiquitination, whereas polyubiquitin chain assembly requires NEDD4-2 oligomerization. These results provide evidence that the previously identified sites 1 and 2 of NEDD4-2 function in trans to support chain elongation, explicating the requirement for oligomerization. Finally, we identified a conserved catalytic ensemble comprising Glu-646 and Arg-604 that supports HECT-ubiquitin thioester exchange and isopeptide bond formation at the active-site Cys-922 of NEDD4-2.

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A large body of theoretically supported experimental and observational research describes how stereotypes impede the participation and advancement of individuals from groups underrepresented in academia, especially in science. As a result, there is a lack of diversity of graduate students in US universities with individuals from groups underrepresented in biomedical sciences encompassing only 10% of doctorate degrees earned. Implicit biases, hidden biases, or unconscious biases are bits of knowledge about social groups that are learned at an early age, developed, and established throughout our lifetime. We all carry hidden biases from exposure to cultural attitudes about age, gender, race, ethnicity, religion, social class, sexuality, disability status, and nationality which play a major role in establishing individual implicit bias. These unconscious perceptions govern many important decisions we make and can have profound effects on our personal and professional lives. Implicit biases can create added obstacles for individuals from groups underrepresented in biomedical sciences entering graduate programs. In academia, graduate faculty mentors have a major influence on shaping their students' skills, attitudes, and careers. It is therefore imperative for academic institutions of higher learning to educate research faculty and graduate students on implicit bias to improve inclusiveness in their cultural educational environment. To address this need, we have developed an interactive workshop series for faculty research mentors and graduate students. The 4‐hour workshop will include teaching modules, a simulation video, and discussions to focus on how to recognize implicit bias through increased awareness, introspection, authenticity, humility, and compassion for all people. The facilitators will discuss topics including: 1) What is the importance of a diverse academic environment? 2) What is unconscious bias? 3) How do we become more aware of our own unconscious biases? 4) Strategies to overcome bias, and 5) What biases have you witnessed regarding graduate education or training? Attendees will use the interactive video simulation, “Fair Play”, funded by the Univ. of Wisconsin, NIH NIGMS, and Gates Foundation which provides the opportunity to take the perspective of Jamal Davis, an African American graduate student. The simulation presents real‐life examples of bias concepts such as microaggressions, colorblind racial attitudes, tokenism, and highlights many of the obstacles that sometimes prevent individuals from groups underrepresented in biomedical sciences from excelling in graduate education and their future careers. Upon completion, the attendees will reflect on their attitudes while walking in the shoes of Jamal Davis. Attendees will be encouraged to become aware of their implicit biases, intervene, and change the behaviors. Additionally, ways to develop more consciousness of implicit bias in decision making will be discussed. A Likert scale of diversity and cultural awareness, as well as, multiple‐choice quiz regarding diversity and implicit bias terms will be used for pre‐ and post‐tests. Upon completion of the workshop, it is hoped that faculty and graduate students will develop a mutual understanding and introspective awareness towards the inclusion and improved mentoring of a diverse group of future scientists.Support or Funding InformationAPS Teaching Career Enhancement Award, R25GM121189This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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