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OBJECTIVES/GOALS: The goal of this study was to understand the impact of a high sodium diet on gene networks in the kidney that correlate with blood pressure in female primates, and translating findings to women. METHODS/STUDY POPULATION: Sodium-naïve female baboons (n=7) were fed a low-sodium (LS) diet for 6 weeks followed by a high sodium (HS) diet for 6 weeks. Sodium intake, serum 17 beta-estradiol, and ultrasound-guided kidney biopsies for RNA-Seq were collected at the end of each diet. Blood pressure was continuously measured for 64-hour periods throughout the study by implantable telemetry devices. Weighted gene coexpression network analysis was performed on RNA-Seq data to identify transcripts correlated with blood pressure on each diet. Network analysis was performed on transcripts highly correlated with BP, and in silico findings were validated by immunohistochemistry of kidney tissues. RESULTS/ANTICIPATED RESULTS: On the LS diet, Na+ intake and serum 17 beta-estradiol concentration correlated with BP. Cell type composition of renal biopsies was consistent among all animals for both diets. Kidney transcriptomes differed by diet; analysis by unbiased weighted gene co-expression network analysis revealed modules of genes correlated with BP on the HS diet. Network analysis of module genes showed causal networks linking hormone receptors, proliferation and differentiation, methylation, hypoxia, insulin and lipid regulation, and inflammation as regulators underlying variation in BP on the HS diet. Our results show variation in BP correlated with novel kidney gene networks with master regulators PPARG and MYC in female baboons on a HS diet. DISCUSSION/SIGNIFICANCE: Previous studies in primates to identify molecular networks dysregulated by HS diet focused on males. Current clinical guidelines do not offer sex-specific treatment plans for sodium sensitive hypertension. This study leveraged variation in BP as a first step to identify correlated kidney regulatory gene networks in female primates after a HS diet.
The last 50 years have seen an increasing dependence on academic institutions to develop and commercialize new biomedical innovations, a responsibility for which many universities are ill-equipped. To address this need, we created LEAP, an asset development and gap fund program at Washington University in St. Louis (WUSTL). Beyond awarding funds to promising projects, this program aimed to promote a culture of academic entrepreneurship, and thus improve WUSTL technology transfer, by providing university inventors with individualized consulting and industry expert feedback. The purpose of this work is to document the structure of the LEAP program and evaluate its impact on the WUSTL entrepreneurial ecosystem. Our analysis utilizes program data, participant surveys, and WUSTL technology transfer office records to demonstrate that LEAP consistently attracted new investigators and that the training provided by the program was both impactful and highly valued by participants. We also show that an increase in annual WUSTL start-up formation during the years after LEAP was established and implicate the program in this increase. Taken together, our results illustrate that programs like LEAP could serve as a model for other institutions that seek to support academic entrepreneurship initiatives.
How expansive are the social meanings inferred by a nonstandard syntactic variant, and how are these social meanings constructed? This chapter suggests that the social meanings of syntax lie at the nexus of pragmatics and social distribution. Furthermore, the analysis shows that certain social meanings are enriched when syntactic items co-occur with specific phonetic variants. Drawing upon an ethnographic study of adolescents, this chapter focuses on the social meanings of negative concord by exploring the correlation between social class, social practice, topic of talk, nonstandard phonetic variants and instances of negative concord. Negative concord increases across social groups in-line with their placement on a pro-/anti-school continuum, but a topic analysis suggests that this a consequence of different groups talking about different things: there is more negative concord in talk about delinquent behaviour than there is in talk about non-delinquent behaviour (irrespective of social group). In exploring why negative concord is a useful device for talking about delinquency, the pragmatics of the construction itself are examined, exposing a relationship between social distribution and pragmatic function. Finally, an analysis of the relationship between negative concord and co-occurring phonetic variants suggests that different levels of linguistic architecture work synergistically to create social meaning.