Control of developmentally primed erythroid genes by combinatorial co-repressor actions

How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced. A combination of proteomics, functional genomics and in vivo studies presented here identifies known and novel co-repressors, most notably the ETO2 and IRF2BP2 proteins, involved in maintaining this primed state. The ETO2-IRF2BP2 axis, interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of the vast majority of archetypical erythroid genes and pathways until its decommissioning at the onset of terminal erythroid differentiation. Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interplay between activating and repressing components that determines lineage-specific gene expression and cellular differentiation

Rapid Adaptation to Remote Didactics and Learning in GME

Weekly didactic conference in emergency medicine education has traditionally united residents and faculty for learning and fostered community within the residency program. The global pandemic Coronavirus Disease-19 (COVID-19) has fueled a rapid transition to remote learning that has disrupted the typical in-person format. To maintain ACGME educational experiences and requirements for residents in a safe manner, many residencies have moved to videoconferencing platforms such as Zoom™, Teams™, and WebEX.™ Given the importance of didactic conference as a ritual, educational experience and community-building activity, most residency programs have worked to maintain an active and robust didactic conference despite the many logistical challenges. Engaging residency program members in the transition to remote learning and utilizing opportunities for innovation can help to maintain normalcy and combat isolation resulting from the loss of weekly in-person contact. Herein, we propose practical tips for optimizing remote learning for weekly emergency medicine residency didactics

Pharmaceutical Creep: U.S. Military Power and the Global and Transnational Mobility of Psychopharmaceuticals

In 2006, the United States Department of Defense developed for the first time official criteria for the use of psychopharmaceuticals “in theater”—in the physical and tactical spaces of military operations including active combat. Based on fieldwork with Army soldiers and veterans, this article explores the transnational and global dimensions of military psychopharmaceutical use in the post‐9/11 wars. I consider the spatial, material, and symbolic dimensions of what I call “pharmaceutical creep”—the slow drift of psychopharmaceuticals from the civilian world into theater and into the military corporate body. While pharmaceutical creep is managed by the U.S. military as a problem of gatekeeping and of supply and provisioning, medications can appear as the solution to recruitment and performance problems once in theater. Drawing on soldiers’ accounts of medication use, I illuminate the possibilities, but also the frictions, that arise when routine psychopharmaceuticals are remade into technologies of global counterinsurgency

The impact of sleep and psychiatric symptoms on alcohol consequences among young adults

OBJECTIVE: Independent lines of research have documented links between psychiatric symptoms and poor sleep quality, psychiatric symptoms and alcohol use, and alcohol use and poor sleep quality. The current study examined the synergistic effect of poor sleep quality and psychiatric symptoms on alcohol-related consequences in heavy-drinking young adults. METHOD: Matriculating college students reporting at least one heavy drinking episode over the first nine weeks of the semester (N = 385, 52% female) were categorized as experiencing ‘good’ (n = 280) versus ‘poor’ sleep quality (n = 105) and screening ‘positive’ (n = 203) or ‘negative’ (n = 182) for a psychiatric disorder. Sleep quality was assessed using the Pittsburgh Sleep Quality Index; psychiatric diagnosis was assessed using the Psychiatric Diagnostic Screening Questionnaire; and alcohol-related consequences were assessed using the Brief Young Adult Alcohol Consequences Questionnaire. General linear models were used to examine the main effects and interaction between sleep quality and psychiatric symptoms on alcohol-related consequences. RESULTS: Sleep quality moderated the association between psychiatric screen and alcohol-related consequences among heavy-drinking college students, such that psychiatric symptoms were associated with more alcohol-related consequences in the context of poor sleep quality. CONCLUSIONS: The combination of poor sleep quality and psychiatric symptoms is associated with increased alcohol-related consequences among heavy-drinking college students. Given the significant interaction between these symptoms, healthcare providers are encouraged to screen for the presence of sleep and psychiatric disorders among heavy-drinking young adults and to provide empirically-supported treatments as appropriate

RF Performance of InAlN/GaN HFETs and MOSHFETs with fTxLG up to 21GHz*um

The RF performance of lattice-matched InAlN/GaN heterostructure field-effect transistors (HFETs) and Al2O3/InAlN/GaN metal-oxide-semiconductor HFETs (MOSHFETs) with varied gate length was evaluated. The current gain cutoff frequency f(T) and the maximum oscillation frequency f(max) for the HFETs with 0.3-mu m gate length were 54 and 58 GHz, respectively. An increase of f(T) to 61 GHz and of f(max) to 70 GHz was obtained for the MOSHFETs. The HFETs and MOSHFETs with different gate length yielded an f(T) x L-G product of 18 and 21 GHz . mu m, respectively. These are higher values than reported yet on InAlN/GaN devices and similar to those known for AlGaN/GaN HFETs

Culturally congruent mentorship can reduce disruptive behavior among elementary school students: results from a pilot study

Abstract Background Our study objective was to examine the feasibility of implementing a culturally congruent mentorship pilot program, Youth-First (YF), that targets behavior modification among elementary school-aged children with disruptive behavior and a history of school suspension. We hypothesize that it is feasible to implement the YF program to reduce disruptive behaviors and recidivism of level III/IV infractions in school settings among at-risk African American students. Methods We assessed program feasibility based on the success of program acceptance by parents/guardians, study enrollment, and intervention compliance by students. A pre/posttest study design was used to examine whether the YF program reduced recidivism of disruptive behavior among enrolled at-risk African American elementary school children between September 2016 and January 2017. Generalized linear mixed models examined whether student behavioral scores improved over time and varied by program mentor. A McNemar test examined the reduction in cumulative incidence of level III/IV infractions pre-post YF program intervention. Results Intervention acceptance, enrollment, and compliance were 100% (95% confidence interval [CI] 86 to 100%), 100% (95% CI 86 to 100%), and 67% (95% CI 45 to 84%), respectively (N = 24). Overall, student behavioral scores improved and plateaued over time (Time2 effect: b = − 0.01, 95% CI − 0.02, < 0.01); a two-week period was associated with a seven-point improvement (effect size: Cohen’s d = 0.47, 95% CI 0.03, 0.94) in behavioral scores. Behavioral score improvements were class-specific, based on respectfulness behavior (b = 0.11, 95% CI < 0.01, 0.26). No recidivism of level III/IV infractions was reported during and post YF intervention. Conclusion The integration of culturally congruent mentorship in elementary school-settings is feasible and can reduce risk of disruptive behaviors among at-risk African American students. Future studies should use randomized clinical trials to determine the effectiveness of culturally congruent mentorship interventions (void of potential selection and confounding biases) in reducing disruptive behavior, level III/IV infractions, and school suspensions among at-risk children