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Full-Text Articles in Life Sciences

Functional Group Interactions Of A 5-Ht3r Antagonist, Padmavati Venkataraman, Prasad Joshi, Srinivasan P. Venkatachalan, Mani Mathalagi, Harish S. Parihar, Karen S. Kirschbaum, Marvin K. Schulte Jan 2002

Functional Group Interactions Of A 5-Ht3r Antagonist, Padmavati Venkataraman, Prasad Joshi, Srinivasan P. Venkatachalan, Mani Mathalagi, Harish S. Parihar, Karen S. Kirschbaum, Marvin K. Schulte

PCOM Scholarly Works

Background: Lerisetron, a competitive serotonin type 3 receptor (5-HT 3R) antagonist, contains five functional groups capable of interacting with amino acids in the 5-HT3R binding site. Site directed mutagenesis studies of the 5-HT3AR have revealed several amino acids that are thought to form part of the binding domain of this receptor. The specific functional groups on the ligand that interact with these amino acids are, however, unknown. Using synthetic analogs of lerisetron as molecular probes in combination with site directed mutagenesis, we have identified some of these interactions and have proposed a model of the lerisetron binding site. Results: Two …


Polarized Fluorescence Depletion Reports Orientation Distribution And Rotational Dynamics Of Muscle Cross-Bridges, Marcus G. Bell, Robert E. Dale, Uulke A. Van Der Heide, Yale E. Goldman Jan 2002

Polarized Fluorescence Depletion Reports Orientation Distribution And Rotational Dynamics Of Muscle Cross-Bridges, Marcus G. Bell, Robert E. Dale, Uulke A. Van Der Heide, Yale E. Goldman

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The method of polarized fluorescence depletion (PFD) has been applied to enhance the resolution of orientational distributions and dynamics obtained from fluorescence polarization (FP) experiments on ordered systems, particularly in muscle fibers. Previous FP data from single fluorescent probes were limited to the 2nd- and 4th-rank order parameters, and , of the probe angular distribution (ß) relative to the fiber axis and , a coefficient describing the extent of rapid probe motions. We applied intense 12-µs polarized photoselection pulses to transiently populate the triplet state of rhodamine probes and measured the polarization of the ground-state depletion using a weak interrogation …


Stat6 Mediates Interleukin-4 Growth Inhibition In Human Breast Cancer Cells, Jennifer L. Gooch, B. Christy, D. Yee Jan 2002

Stat6 Mediates Interleukin-4 Growth Inhibition In Human Breast Cancer Cells, Jennifer L. Gooch, B. Christy, D. Yee

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In addition to acting as a hematopoietic growth factor, interleukin-4 (IL-4) inhibits growth of some transformed cells in vitro and in vivo. In this study, we show that insulin receptor substrate (IRS)-1, IRS-2, and signal transducer and activator of transcription 6 (STAT6) are phosphorylated following IL-4 treatment in MCF-7 breast cancer cells. STAT6 DNA binding is enhanced by IL-4 treatment. STAT6 activation occurs even after IRS-1 depletion, suggesting the two pathways are independent. To examine the role of STAT6 in IL-4-mediated growth inhibition and apoptosis, a full-length STAT6 cDNA was transfected into MCF-7 cells. Transient overexpression of STAT6 resulted in …


The Osteopetrotic Mutation Toothless (Tl) Is A Loss-Of-Function Frameshift Mutation In The Rat Csf1 Gene: Evidence Of A Crucial Role For Csf-1 In Osteoclastogenesis And Endochondral Ossification, Liesbeth Van Wesenbeeck, Paul R. Odgren, Carole A. Mackay, Marina D'Angelo, Fayez F. Safadi, Steven N. Popoff, Wim Van Hul, Sandy C. Marks Jr. Jan 2002

The Osteopetrotic Mutation Toothless (Tl) Is A Loss-Of-Function Frameshift Mutation In The Rat Csf1 Gene: Evidence Of A Crucial Role For Csf-1 In Osteoclastogenesis And Endochondral Ossification, Liesbeth Van Wesenbeeck, Paul R. Odgren, Carole A. Mackay, Marina D'Angelo, Fayez F. Safadi, Steven N. Popoff, Wim Van Hul, Sandy C. Marks Jr.

PCOM Scholarly Works

The toothless (tl) mutation in the rat is a naturally occurring, autosomal recessive mutation resulting in a profound deficiency of bone-resorbing osteoclasts and peritoneal macrophages. The failure to resorb bone produces severe, unrelenting osteopetrosis, with a highly sclerotic skeleton, lack of marrow spaces, failure of tooth eruption, and other pathologies. Injections of CSF-1 improve some, but not all, of these. In this report we have used polymorphism mapping, sequencing, and expression studies to identify the genetic lesion in the tl rat. We found a 10-base insertion near the beginning of the open reading of the Csf1 gene that yields a …