Developing Computerized Screening for Early Detection of Tuberculosis in Peru

Role of the Aryl hydrocarbon receptor in hematopoietic stem cells

The aryl hydrocarbon receptor (Ahr) mediates the toxicity of certain environmental pollutants including dioxins. Accidental dioxin exposure to humans has been correlated with blood malignancies such as leukemia and lymphoma. Dioxin exposure suppresses immune responses in mammals via Ahr by several mechanisms including altering the functional ability of hematopoietic progenitors to seed the thymus. Also, exposure alters population of the spleen and reconstitution of peripheral blood and bone marrow. The Ahr is a ligand-activated transcription factor without any established endogenous ligand or physiological role in hematopoietic cells. To explain the decreased reconstitution of bone marrow, I hypothesized that dioxin exposure alters the numbers of hematopoietic stem/progenitor cells and/or the trafficking of these populations to the bone marrow. Furthermore, I hypothesized that these cellular consequences of TCDD exposure are secondary to an alteration of transcriptionally regulated pathways related to cell-to-cell signaling and cellular movement. Colony-forming assays and competitive repopulation experiments were used to quantify sub-populations of LSKs. In vivo dioxin exposure increased the numbers of multipotent progenitors but did not change the numbers of functional hematopoietic stem cells (HSCs). Trafficking of LSKs to the bone marrow in vivo, and to the chemokine Cxcl12 in vitro were decreased. Transcripts involved in cell-to-cell signaling (Ccl3, Cd69, Cxcl2, Cox-2, Mmp8) and cellular movement (Scin, Mmp8), as well as hematological system development and function (Egr-1, Ccl3, Cd69, Cxcl2, Cox-2) were altered in TCDD-exposed LSKs. Altogether these data support a physiological role of the Ahr to regulate homeostasis in HSCs. Disruption of Ahr expression or activity may predispose more differentiated populations to acquire malignant behaviors and reduce the ability of HSCs to respond to stress or injury.

Forest Molecular Genetics and Biotechnology

The genera Populus and Salix (family Salicaceae) are populated by fast-growing woody species that are widely planted as short-rotation tree crops for biomass. Their uses range from pulp and bioenergy production that have commercial value, to phytoremediation and carbon sequestration that are of environmental significance. Since biomass productivity depends on simultaneous selection for growth and ¿fitness¿ traits, such as those affecting nutrient retention and protection against biotic and abiotic stresses, tree improvement programs can benefit from a thorough comprehension of the growth-fitness tradeoffs. Foliar phenolic glycosides (PGs) and condensed tannins (CTs) are important fitness determinants in Populus and Salix (Lindroth and Hwang 1996; Driebe and Whitham 2000; Orians, 2000). They are the predominant secondary metabolites in these species and can accumulate to high levels (e.g., up to 35% leaf dry weight) that correctlate negatively with growth and, therefore, may incur growth-impacting metabolic costs (Lindroth and Hwang 1996; Kleiner et al. 1999; Ruuhola and Julkunen-Titto 2003). To understand the molecular mechanisms orchestrating resource allocation between growth and fitness, natural cottonwood and willow hybrids were investigated using traditional analysis of leaf phenolics coupled with metabolic profiling and cDNA microarray hybridization.