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1.  Lymphatic/Blood Endothelial Cell Connections at the Capillary Level in Adult Rat Mesentery 
Analyses of microvascular networks with traditional tracer filling techniques suggest that the blood and lymphatic systems are distinct without direct communications, yet involvement of common growth factors during angiogenesis and lymphangiogenesis suggest that interactions at the capillary level are possible. In order to investigate the structural basis for lymphatic/blood endothelial cell connections during normal physiological growth, the objective of this study was to characterize the spatial relations between lymphatic and blood capillaries in adult rat mesenteric tissue. Using immunohistochemical methods, adult male Wistar rat mesenteric tissues were labeled with antibodies against PECAM (an endothelial marker) and LYVE-1, Prox-1, or Podoplanin (lymphatic endothelial markers) or NG2 (a pericyte marker). Positive PECAM labeling identified apparent lymphatic/blood endothelial cell connections at the capillary level characterized by direct contact or direct alignment with one another. In PECAM labeled networks, a subset of the lymphatic and blood capillary blind ends were connected with each other. Intravital imaging of FITC-Albumin injected through the femoral vein did not identify lymphatic vessels. At contact sites, lymphatic endothelial markers did not extend along blood capillary segments. However, PECAM positive lymphatic sprouts, structurally similar to blood capillary sprouts, lacked observable lymphatic marker labeling. These observations suggest that non-lumenal lymphatic/blood endothelial cell interactions exist in unstimulated adult microvascular networks and highlight the potential for lymphatic/blood endothelial cell plasticity.
PMCID: PMC3000855  PMID: 20648570
Microcirculation; Angiogenesis; Lymphangiogenesis; Endothelial Cell
2.  Proteomic and network analysis characterize stage-specific metabolism in Trypanosoma cruzi 
BMC Systems Biology  2009;3:52.
Trypanosoma cruzi is a Kinetoplastid parasite of humans and is the cause of Chagas disease, a potentially lethal condition affecting the cardiovascular, gastrointestinal, and nervous systems of the human host. Constraint-based modeling has emerged in the last decade as a useful approach to integrating genomic and other high-throughput data sets with more traditional, experimental data acquired through decades of research and published in the literature.
We present a validated, constraint-based model of the core metabolism of Trypanosoma cruzi strain CL Brener. The model includes four compartments (extracellular space, cytosol, mitochondrion, glycosome), 51 transport reactions, and 93 metabolic reactions covering carbohydrate, amino acid, and energy metabolism. In addition, we make use of several replicate high-throughput proteomic data sets to specifically examine metabolism of the morphological form of T. cruzi in the insect gut (epimastigote stage).
This work demonstrates the utility of constraint-based models for integrating various sources of data (e.g., genomics, primary biochemical literature, proteomics) to generate testable hypotheses. This model represents an approach for the systematic study of T. cruzi metabolism under a wide range of conditions and perturbations, and should eventually aid in the identification of urgently needed novel chemotherapeutic targets.
PMCID: PMC2701929  PMID: 19445715

Results 1-2 (2)