RESUMO
My experience of the COVID-19 pandemic, and trying to write through it, has been profoundly shaped by my identity as a mother. Like me, many women-mothers in particular-have had their voices muted by the demands of domestic labor. Trying to find a way to continue telling the stories that matter to me during these times has made me see how important it is for mothers to unmute and claim a space for our voices, even if our voices must change in order to be heard.
RESUMO
We used two approaches to design proteins with shape and chemical complementarity to the receptor binding domain (RBD) of SARS-CoV-2 Spike protein near the binding site for the human ACE2 receptor. Scaffolds were built around an ACE2 helix that interacts with the RBD, or de novo designed scaffolds were docked against the RBD to identify new binding modes. In both cases, designed sequences were optimized first in silico and then experimentally for target binding, folding and stability. Nine designs bound the RBD with affinities ranging from 100pM to 10nM, and blocked bona fide SARS-CoV-2 infection of Vero E6 cells with IC50 values ranging from 35 pM to 35 nM; the most potent of these -- 56 and 64 residue hyperstable proteins made using the second approach -- are roughly six times more potent on a per mass basis (IC50 ~ 0.23 ng/ml) than the best monoclonal antibodies reported thus far. Cryo-electron microscopy structures of the SARS-CoV-2 spike ectodomain trimer in complex with the two most potent minibinders show that the structures of the designs and their binding interactions with the RBD are nearly identical to the computational models, and that all three RBDs in a single Spike protein can be engaged simultaneously. These hyperstable minibinders provide promising starting points for new SARS-CoV-2 therapeutics, and illustrate the power of computational protein design for rapidly generating potential therapeutic candidates against pandemic threats.
RESUMO
Incorporating metacognitive strategies in the classroom helps students monitor and adjust their learning strategies throughout the semester, and helps students progress from novice to expert learners in a subject. Journaling (i.e., reflective writing) is one metacognitive task that allows students to contemplate and articulate their skill development as they learn a new subject. The research reported here examines the use of 'blogs' (i.e., online journals) in an upper level undergraduate human anatomy course. The blogs both facilitated development of students' metacognitive skills and provided researchers insight into student metacognitive process. Data were examined from 92 students from three successive semesters (spring 2010, 2012 and 2014). Each student reviewed 10 radiology online cases throughout the semester and then reflected on their understanding of anatomy and radiology in an online blog for each case. A total of 927 blogs were examined for this research. The researchers used a grounded theory approach to analyze the blog narratives and develop a codebook based on common themes. The 927 blogs yielded 11,082 statements that were coded with the codebook. As the semester progressed, the blog entries showed that students demonstrated greater self-confidence in their abilities to understand the subject matter, expressed greater enthusiasm for anatomy in general, and they improved their metacognitive skills. This research illustrates that reflective writing in an undergraduate anatomy course not only facilitates improvement in student metacognitive skills, but also provides the instructor with evidence how a student progresses from novice to more experienced learner in anatomy.