CHARACTERIZATION OF SPONTANEOUS HYPERTENSION IN CHLOROCEBUS AETHIOPS SABAEUS, THE AFRICAN GREEN MONKEY

Hypertension is a complex multifactorial pathology that is a major risk factor for the development of cardiovascular disease, stroke, and end stage renal disease. In the United States, hypertension affects over 1 in 3 adults and comprises an annual cost of over $58 billion in the healthcare industry. While remarkable strides in the diagnosis and treatment of hypertension have been made since the pathology was first treated in the 1960s, a remarkable 13% of patients with elevated blood pressures are classified as resistant hypertensive, where blood pressure remains uncontrolled while on three or more classes of anti-hypertensive drugs. This treatment gap suggests that researchers need to develop and utilize translational models that recapitulate the pathologies seen in patient populations. Non-human primates (NHP) are highly similar to humans in terms of physiology, circadian rhythmicity, behavior, and gene sequence and structure. Development of NHP models that spontaneously develop pathologies, like spontaneous hypertension, provide novel and vital tools to studying disease. Overall, this dissertation is a comparative analysis of the mechanisms that drive the development of spontaneous hypertension in Chlorocebus aethiops sabaeus, an Old World non-human primate, and known mediators of essential hypertension in human populations. Chapter 2 presents how hypertensive (HT) African Green Monkeys (AGMs) are older, with elevated heart rates, increased renal vascular wall/lumen ratios, and altered glomerular morphologies compared to normotensive (NT) controls. Chapter 3 describes metabolic studies performed in a large cohort of animals that identified elevated proteinuria and ion excretion in HT AGMs compared to NT animals. Chapter 4 focuses on the contribution of sympathetic nervous system to the development of hypertension in this animal model and describes the significant left ventricular hypertrophy and elevation of adrenergic receptor mRNA in HT AGMs. Chapter 5 examines how age affects hypertension and renal function in the NT and HT AGMs. Together these data provide a foundational basis for the development of spontaneous hypertension in the AGM and provide a novel translational model for the study of cardiovascular disease

A Galaxy at z = 6.545 and Constraints on the Epoch of Reionization

We report the discovery of a Lyman-alpha-emitting galaxy at redshift z=6.545 serendipitously identified in the course of spectroscopic follow-up of hard X-ray sources on behalf of the Serendipitous Extragalactic X-Ray Source Identification (SEXSI) survey. The line flux of the galaxy, 2.1e-17 erg/cm2/s, is similar to line fluxes probed by narrow-band imaging surveys; the 5.2 square-arcminutes surveyed implies a surface density of z~6.5 Lyman-alpha emitters somewhat higher than that inferred from narrow-band surveys. This source marks the sixth Lyman-alpha-emitting galaxy identified at z~6.5, a redshift putatively beyond the epoch of reionization when the damping wings of the neutral hydrogen of the intergalactic medium is capable of severely attenuating Lyman-alpha emission. By comparing the Lyman-alpha emitter luminosity functions at z~5.7 and z~6.5, we infer that the intergalactic medium may remain largely reionized from the local universe out to z~6.5.Comment: 16 pages, 4 figures; submitted to the Astrophysical Journa

Resource: A curated database of brain-related functional gene sets (Brain.GMT)

Transcriptional profiling has become a common tool for investigating the nervous system. During analysis, differential expression results are often compared to functional ontology databases, which contain curated gene sets representing well-studied pathways. This dependence can cause neuroscience studies to be interpreted in terms of functional pathways documented in better studied tissues (e.g., liver) and topics (e.g., cancer), and systematically emphasizes well-studied genes, leaving other findings in the obscurity of the brain “ignorome”. To address this issue, we compiled a curated database of 918 gene sets related to nervous system function, tissue, and cell types (“Brain.GMT”) that can be used within common analysis pipelines (GSEA, limma, edgeR) to interpret results from three species (rat, mouse, human). Brain.GMT includes brain-related gene sets curated from the Molecular Signatures Database (MSigDB) and extracted from public databases (GeneWeaver, Gemma, DropViz, BrainInABlender, HippoSeq) and published studies containing differential expression results. Although Brain.GMT is still undergoing development and currently only represents a fraction of available brain gene sets, “brain ignorome” genes are already better represented than in traditional Gene Ontology databases. Moreover, Brain.GMT substantially improves the quantity and quality of gene sets identified as enriched with differential expression in neuroscience studies, enhancing interpretation. • We compiled a curated database of 918 gene sets related to nervous system function, tissue, and cell types (“Brain.GMT”). • Brain.GMT can be used within common analysis pipelines (GSEA, limma, edgeR) to interpret neuroscience transcriptional profiling results from three species (rat, mouse, human). • Although Brain.GMT is still undergoing development, it substantially improved the interpretation of differential expression results within our initial use cases

COS Ambassadors

A collection of materials and resources for COS ambassadors