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Full-Text Articles in Medicine and Health Sciences

Embryonic Stem Cell-Derived Hematopoietic Stem Cells, Yuan Wang, Frank Yates, Olaia Naveiras, Patricia Ernst, George Q. Daley Dec 2005

Embryonic Stem Cell-Derived Hematopoietic Stem Cells, Yuan Wang, Frank Yates, Olaia Naveiras, Patricia Ernst, George Q. Daley

Dartmouth Scholarship

Despite two decades of studies documenting the in vitro blood-forming potential of murine embryonic stem cells (ESCs), achieving stable long-term blood engraftment of ESC-derived hematopoietic stem cells in irradiated mice has proven difficult. We have exploited the Cdx-Hox pathway, a genetic program important for blood development, to enhance the differentiation of ESCs along the hematopoietic lineage. Using an embryonic stem cell line engineered with tetracycline-inducible Cdx4 , we demonstrate that ectopic Cdx4 expression promotes hematopoietic mesoderm specification, increases hematopoietic progenitor formation, and, together with HoxB4, enhances multilineage hematopoietic engraftment of lethally irradiated adult mice. Clonal analysis of retroviral integration sites …


A Drosophila Deg/Enac Channel Subunit Is Required For Male Response To Female Pheromones, Heping Lin, Kevin J. Mann, Elena Starostina, Ronald D. Kinser, Claudio W. Pikielny Sep 2005

A Drosophila Deg/Enac Channel Subunit Is Required For Male Response To Female Pheromones, Heping Lin, Kevin J. Mann, Elena Starostina, Ronald D. Kinser, Claudio W. Pikielny

Dartmouth Scholarship

Odorants and pheromones as well as sweet- and bitter-tasting small molecules are perceived through activation of G protein-coupled chemosensory receptors. In contrast, gustatory detection of salty and sour tastes may involve direct gating of sodium channels of the DEG/ENaC family by sodium and hydrogen ions, respectively. We have found that ppk25, a Drosophila melanogaster gene encoding a DEG/ENaC channel subunit, is expressed at highest levels in the male appendages responsible for gustatory and olfactory detection of female pheromones: the legs, wings, and antennae. Mutations in the ppk25 gene reduce or even abolish male courtship response to females in the dark, …


The Cns Role Of Toll-Like Receptor 4 In Innate Neuroimmunity And Painful Neuropathy, Flobert Y. Tanga, Nancy Nutile-Mcmenemy, Joyce A. Deleo Apr 2005

The Cns Role Of Toll-Like Receptor 4 In Innate Neuroimmunity And Painful Neuropathy, Flobert Y. Tanga, Nancy Nutile-Mcmenemy, Joyce A. Deleo

Dartmouth Scholarship

Neuropathic pain remains a prevalent and persistent clinical problem because of our incomplete understanding of its pathogenesis. This study demonstrates for the first time, to our knowledge, a critical role for CNS innate immunity by means of microglial Toll-like receptor 4 (TLR4) in the induction phase of behavioral hypersensitivity in a mouse and rat model of neuropathy. We hypothesized that after L5 nerve transection, CNS neuroimmune activation and subsequent cytokine expression are triggered by the stimulation of microglial membrane-bound TLR4. To test this hypothesis, experiments were undertaken to assess tactile and thermal hypersensitivity in genetically altered (i.e., TLR4 knockout and …


Role For Akt3/Protein Kinase Bγ In Attainment Of Normal Brain Size, Rachel M. Easton, Han Cho, Kristin Roovers, Diana W. Shineman Mar 2005

Role For Akt3/Protein Kinase Bγ In Attainment Of Normal Brain Size, Rachel M. Easton, Han Cho, Kristin Roovers, Diana W. Shineman

Dartmouth Scholarship

Studies of Drosophila and mammals have revealed the importance of insulin signaling through phosphatidylinositol 3-kinase and the serine/threonine kinase Akt/protein kinase B for the regulation of cell, organ, and organismal growth. In mammals, three highly conserved proteins, Akt1, Akt2, and Akt3, comprise the Akt family, of which the first two are required for normal growth and metabolism, respectively. Here we address the function of Akt3. Like Akt1, Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size. However, in contrast to Akt1/ mice, which display a …