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As ambush-hunting predators that consume large prey after long intervals of fasting, Burmese pythons evolved with unique adaptations for modulating organ structure and function. Among these is cardiac hypertrophy that develops within three days following a meal (Andersen et al., 2005, Secor, 2008), which we previously showed was initiated by circulating growth factors (Riquelme et al., 2011). Postprandial cardiac hypertrophy in pythons also rapidly regresses with subsequent fasting (Secor, 2008); however, the molecular mechanisms that regulate the dynamic cardiac remodeling in pythons during digestion are largely unknown. In this study, we employed a multiomics approach coupled with targeted molecular analyses to examine remodeling of the python ventricular transcriptome and proteome throughout digestion. We found that forkhead box protein O1 (FoxO1) signaling was suppressed prior to hypertrophy development and then activated during regression, which coincided with decreased and then increased expression, respectively, of FoxO1 transcriptional targets involved in proteolysis. To define the molecular mechanistic role of FoxO1 in hypertrophy regression, we used cultured mammalian cardiomyocytes treated with postfed python plasma. Hypertrophy regression both in pythons and in vitro coincided with activation of FoxO1-dependent autophagy; however, the introduction of a FoxO1-specific inhibitor prevented both regression of cell size and autophagy activation. Finally, to determine whether FoxO1 activation could induce regression, we generated an adenovirus expressing a constitutively active FoxO1. FoxO1 activation was sufficient to prevent and reverse postfed plasma-induced hypertrophy, which was partially prevented by autophagy inhibition. Our results indicate that modulation of FoxO1 activity contributes to the dynamic ventricular remodeling in postprandial Burmese pythons. [ABSTRACT FROM AUTHOR]

Undergraduate science education curricula are traditionally composed of didactic instruction with a small number of laboratory courses that provide introductory training in research techniques. Research on learning methodologies suggests this model is relatively ineffective, whereas participation in independent research projects promotes enhanced knowledge acquisition and improves retention of students in science. However, availability of faculty mentors and limited departmental budgets prevent the majority of students from participating in research. A need therefore exists for this important component in undergraduate education in both small and large university settings. A course was designed to provide students with the opportunity to engage in a research project in a classroom setting. Importantly, the course collaborates with a sponsor's laboratory, producing a symbiotic relationship between the classroom and the laboratory and an evolving course curriculum. Students conduct a novel gene expression study, with their collective data being relevant to the ongoing research project in the sponsor's lab. The success of this course was assessed based on the quality of the data produced by the students, student perception data, student learning gains, and on whether the course promoted interest in and preparation for careers in science. In this paper, we describe the strategies and outcomes of this course, which represents a model for efficiently providing research opportunities to undergraduates.

YY1 is a transcription factor that can activate or repress transcription of a variety of genes and is involved in several developmental processes. YY1 is a repressor of transcription in differentiated H9C2 cells and in neonatal cardiac myocytes but an activator of transcription in undifferentiated H9C2 cells. We now present a detailed analysis of the functional domains of YY1 when it is acting as a repressor or an activator and identify the mechanism whereby its function is regulated in the differentiation of H9C2 cells. We show that histone deacetylase 5 (HDAC5) is localized to the cytoplasm in undifferentiated H9C2 ceils and that this localization is dependent on [Ca.sup.2+]/calmodulin-dependent kinase IV (CaMKIV) and/or protein kinase D (PKD). In differentiated cells, HDAC5 is nuclear and interacts with YY1. Finally, we show that HDAC5 localization in differentiated cells is dependent on phosphatase 2A (PP2A). Our results suggest that a signaling mechanism that involves CaMKIV/PKD and PP2A controls YY1 function through regulation of HDAC5 and is important in the maintenance of muscle differentiation. differentiation