The cardiac glycosides ouabain and
digitoxin, established Na+/K+ ATPase inhibitors,
were found to inhibit MDA-MB-231
breast cancer cell migration through an unbiased chemical genetics
screen for cell motility. The Na+/K+ ATPase
acts both as an ion-transporter and as a receptor for cardiac glycosides.
To delineate which function is related to breast cancer cell migration,
structure–activity relationship (SAR) profiles of cardiac glycosides
were established at the cellular (cell migration inhibition), molecular
(Na+/K+ ATPase inhibition), and atomic (computational
docking) levels. The SAR of cardiac glycosides and their analogs revealed
a similar profile, a decrease in potency when the parent cardiac glycoside
structure was modified, for each activity investigated. Since assays
were done at the cellular, molecular, and atomic levels, correlation
of SAR profiles across these multiple assays established links between
cellular activity and specific protein–small molecule interactions.
The observed antimigratory effects in breast cancer cells are directly
related to the inhibition of Na+/K+ transport.
Specifically, the orientation of cardiac glycosides at the putative
cation permeation path formed by transmembrane helices αM1–M6
correlates with the Na+ pump activity and cell migration.
Other Na+/K+ ATPase inhibitors that are structurally
distinct from cardiac glycosides also exhibit antimigratory activity,
corroborating the conclusion that the antiport function of Na+/K+ ATPase and not the receptor function is important
for supporting the motility of MDA-MB-231 breast cancer cells. Correlative
SAR can establish new relationships between specific biochemical functions
and higher-level cellular processes, particularly for proteins with
multiple functions and small molecules with unknown or various modes
of action.
Objective
At the New York University College of Dentistry, we are faced with the challenge of teaching Head and Neck Anatomy to a class of approximately 380 first‐year students. We have developed an innovative anatomy curriculum that has proven effective in facilitating students’ learning and long‐term retention of the material. It has the added benefit of being time‐ and cost‐efficient. Here, we share the structure of our curriculum and examine the student outcomes and student feedback.
Materials and Methods
In this paper, we describe the evidence‐based methods used in our course and present measures of student success. We also surveyed students about aspects of the anatomy curriculum.
Results
Our curriculum efficiently manages cost, instructional time, and classroom space, while promoting student success. Over the last 9 years, NYU Dentistry students have achieved a mean first‐time pass rate of 98.6% and an average anatomy score of 1.74 standard deviations above the national mean on the National Board Dental Examination Part I. Students agree with instructor assessments of which features of the curriculum are valuable and state that the course helps them prepare for clinical courses.
Conclusion
We believe that the main factors in the success of our course are the small group setting, the benefits of spaced repetition and frequent quizzes, and the use of plastinated specimens in place of wet cadavers.
Photon correlation spectroscopy (PCS) is routinely used to investigate the dynamics of colloidal particles undergoing Brownian motion. This technique is applicable to low-density colloidal suspensions in which the effects of multiple light scattering are minimal. We introduce a new low-coherence heterodyne PCS technique that allows direct investigation of colloidal suspensions of higher concentration than previously accessible with standard PCS. In this technique, low-coherence optical heterodyne interferometry is used tosuppress multiple light scattering, allowing preferential detection of single-scattering events.
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