From EMT to HSC to AML: ZEB2 is a cell fate switch.

In this issue of Blood, complimentary studies by J. Li et al1 and H. Li et al2 identify the transcription factor ZEB2 as a critical regulator of multilineage differentiation in both normal and malignant hematopoiesis. In particular, these studies show that ZEB2 is an inhibitor of normal granulocyte production, and in acute myeloid leukemia (AML), antagonizing ZEB2 function releases the granulocytic differentiation block, creating an antileukemic therapeutic effect

Analyzing Machupo virus-receptor binding by molecular dynamics simulations

In many biological applications, we would like to be able to computationally predict mutational effects on affinity in protein-protein interactions. However, many commonly used methods to predict these effects perform poorly in important test cases. In particular, the effects of multiple mutations, non-alanine substitutions, and flexible loops are difficult to predict with available tools and protocols. We present here an existing method applied in a novel way to a new test case; we interrogate affinity differences resulting from mutations in a host-virus protein-protein interface. We use steered molecular dynamics (SMD) to computationally pull the machupo virus (MACV) spike glycoprotein (GP1) away from the human transferrin receptor (hTfR1). We then approximate affinity using the maximum applied force of separation and the area under the force-versus-distance curve. We find, even without the rigor and planning required for free energy calculations, that these quantities can provide novel biophysical insight into the GP1/hTfR1 interaction. First, with no prior knowledge of the system we can differentiate among wild type and mutant complexes. Moreover, we show that this simple SMD scheme correlates well with relative free energy differences computed via free energy perturbation. Second, although the static co-crystal structure shows two large hydrogen-bonding networks in the GP1/hTfR1 interface, our simulations indicate that one of them may not be important for tight binding. Third, one viral site known to be critical for infection may mark an important evolutionary suppressor site for infection-resistant hTfR1 mutants. Finally, our approach provides a framework to compare the effects of multiple mutations, individually and jointly, on protein-protein interactions.Comment: 33 pages, 8 figures, 5 table

'A boy would be friends with boys... and a girl... with girls' : gender norms in early adolescent friendships in Egypt and Belgium

Purpose: A gender analysis was conducted to illuminate the key elements of friendships highlighted by early adolescent girls and boys in two sites for the purpose of better understanding the impact of gender norms on adolescent friendships in different contexts. Methods: Narrative interviews with early adolescents were conducted in two sites: Assiut, Egypt (n = 37) and Ghent, Belgium (n = 30). The interviews were recorded, transcribed, translated into English, and coded using Atlas.ti for analysis. Results: In both Assiut and Ghent, early adolescents reported some similarities in defining key characteristics of their same-sex friends as well as in the activities they share. However, differences were noticed among boys and girls within each site. In addition, the scope of shared activity was broader in Ghent than in Assiut. In both sites, few opposite-sex friendships were reported. Gender norms influenced choice of friends as well as the type and place of shared activities. Conclusions: Building on knowledge that adolescent friendships guide and reinforce attitudes, beliefs, and behaviors that impact immediate and long-term health, our findings indicate that gender norms inform early adolescent friendships, which may impact healthy development

Chart a Course for Holistic Admissions Transformation Using an Interprofessional Model

Implementing comprehensive holistic admissions requires schools to evaluate, and perhaps think differently, about recruitment and marketing, admission and retention practices, as well as the extent to which these practices align with the institutional mission and goals. Developing and implementing holistic admissions is time, and resource intensive and requires tremendous leadership and faculty support. This course is designed to give physical therapy educators background rationale and a formal structure to operationalize comprehensive holistic admissions, from recruitment to workforce placement, including strategies for gaining higher administration support. The Dean, former Associate Dean for Academic Affairs, and Admissions Committee Chair of the College of Allied Health Professions (CAHP) at the University of Nebraska Medical Center will share their experience with developing, implementing and evaluating comprehensive holistic admissions for the entire college, consisting of 14 programs. The interactive course format will invite participants to engage the presenters as it pertains to the participants’ unique journeys with implementing holistic admission practices at their own institutions, allowing for a rich exchange of information and experiences.https://digitalcommons.unmc.edu/cahp_pres/1000/thumbnail.jp

Universal systole bounds for arithmetic locally symmetric spaces

The systole of a closed Riemannian manifold is the minimal length of a non-contractible closed loop. We give a uniform lower bound for the systole for large classes of simple arithmetic locally symmetric orbifolds. We establish new bounds for the translation length of a semisimple element x in SL_n(R) in terms of its associated Mahler measure. We use these geometric methods to prove the existence of extensions of number fields in which fixed sets of primes have certain prescribed splitting behavior