10 research outputs found
Nutraceutical and functional food regulations in the European Union
Our chapter explores the US Food and Drug Administrations (USFDAs) regulation of medical foods, a growing industry that lies between pharmaceutical drugs and food.In addition to an overall discussion of the short regulatory history of medical foods, we cover the agencys recently released revised draft guidance and other regulatory requirements for medical foods, including the applicable Current Good Manufacturing Practices and import/export requirements, as well as FDAs enforcement actions to date
Dimerization of the exocyst protein Sec6p and its interaction with the t-SNARE Sec9p
Vesicles in eukaryotic cells transport cargo between functionally distinct membrane-bound organelles and the plasma membrane for growth and secretion. Trafficking and fusion of vesicles to specific target sites are highly regulated processes that are not well understood at the molecular level. At the plasma membrane, tethering and fusion of secretory vesicles require the exocyst complex. As a step toward elucidation of the molecular architecture and biochemical function(s) of the exocyst complex, we expressed and purified the exocyst subunit Sec6p and demonstrated that it is a predominantly helical protein. Biophysical characterization of purified Sec6p by gel filtration and analytical ultracentrifugation experiments revealed that Sec6p is a dimer. Limited proteolysis defined an independently folded C-terminal domain (residues 300-805) that equilibrated between a dimer and monomer in solution. Removal of residues 300-410 from this construct yielded a well-folded, monomeric domain. These results demonstrate that residues 300-410 are necessary for dimerization, and the presence of the N-terminal region (1-299) increases dimer stability. Moreover, we found that the dimer of Sec6p binds to the plasma membrane t-SNARE Sec9p and inhibits the interaction between Sec9p and its partner t-SNARE Sso1p. This direct interaction between the exocyst complex and the t-SNARE implicates the exocyst in SNARE complex regulation
ARF and p53 coordinate tumor suppression of an oncogenic IFN-β-STAT1-ISG15 signaling axis
SummaryThe ARF and p53 tumor suppressors are thought to act in a linear pathway to prevent cellular transformation in response to various oncogenic signals. Here, we show that loss of p53 leads to an increase in ARF protein levels, which function to limit the proliferation and tumorigenicity of p53-deficient cells by inhibiting an IFN-β-STAT1-ISG15 signaling axis. Human triple-negative breast cancer (TNBC) tumor samples with coinactivation of p53 and ARF exhibit high expression of both STAT1 and ISG15, and TNBC cell lines are sensitive to STAT1 depletion. We propose that loss of p53 function and subsequent ARF induction creates a selective pressure to inactivate ARF and propose that tumors harboring coinactivation of ARF and p53 would benefit from therapies targeted against STAT1 and ISG15 activation
Class of 2003, Indiana University School of Law
Pictured:
Marc O. Abplanalp, Kristin Acuff, Jonathon R. Albright, Sandra J. Ante, Joseph M. Banyash, Jenifer J. Baumann, Anastasia Benarski, David Beslow, Sarah Bierley, Neal R. Blythe, William J. Brinkerhoff, Marcie Brown, Aija Bryson, Elizabeth Ann Bumbales, Brenton Campbell, Adrienne R. Champine, Frank T. Chen, Hyun Suk Choi, Jason T. Clagg, Doris L. Clark, Nicole D. Clark, Jason P. Cleveland, Paul R. Colbert, Atto Commey, Michael P. Commons, Amy C. Conner, Matthew E. Conrad, Nicholas Conway, Cynthia Cross, Nicole A. Cunningham, Levi C. Czubaroff, Larry Dailey, Sarah Dansker, Joshua M. Davis, Maria DeFord, Stephen DePaul, Andrea Dick, Shawn J. Donahue, April R. Drake, Yolanda D. Edwards, Jill Ellis, Marius Escolar, Julia M. Fidaleo, Carmen Fisher, Mavis R. Gee, Mitchell J. Gerber, Matthew A. Gernand, Rebecca Greene, Emily C. Guenin-Hodson, Luiey G. Haddad, Stephen Hamilton, Ryan D. Hammer, Joy M. Hanson, James R. Harris, Lakshmi, Hasanadka, Brett Haworth, Charles C. Hayes, Deborah Hea, Michael Heintz, Sarah Herkamp, Jennifer M. Herrmann, Kristin L. Herrmann, Jennifer M. Hess, Scott S. Holmes, William Hope, Janet Horvath, Michele Huckstep-Neary, Christopher Humphreys, Ryan M. Hurley, A. Costance Hyun, Cynthia DeNardi Ipsen, Leigh Erin Irons, Brandy Jones, John T. Jones Jr., Brandon S. Judkins, Eunsook Jung, Derek Kaczmarek, John Kaminski, Carolyn Kang, Angela Kelver, Matthew R. King, Karen E. Klein, Chad Kleinheksel, Daniel J. Kopp, Leilani K. Krashin, Aaron Krolik, Scott N. Kumis, Sarah Kyle, Lauren S. Lark, Andrew D. LeMar, Christopher Lee, David Y. Lee, Ariel J. Leinwand, Tonya Lengar, Nicholas Levi, Ann E. Liefer, Phil Lodato, Michele Lofthouse, Sean McAndrew, Jonna McGinley, David McPherson, Hannah L. Meils, Teresa L. Melton, Russell Menyhart, Crystal M. Merlau, Petra R. Micu, Alyce Miller, Samuel F. Miller, Benjamin W. Mills, Derek M. Mills, Robb A. Minich, Eugene S. Miyata, Jill Morgan, Jonas I. Moskowitz, Kristy L. Murphy, Paul Newman, Shinobu Nishida, Andrew P. O\u27Brien, Michael O\u27Neal, Alexander O\u27Neill, Patrick Omillan, Christine Painter, Davina L. Patterson, Janell M. Payne, Samuel J. Perry, Daniel A. Pfaff, Joshlene A. Pollock, Matthew V. Pontius, Rachel M. Rabideau, Andrew J. Reitz, Benjamin Riddle, Rae R. Ridley, Jacob Rigney, David B. Rivera, Zachary Rosenbarger, Jane E. Rueger, Mark A. Ryan, Deborah Salons, Charles R. Salter, Anne E. Sanders, Christohper Saporita, Erica L. Schilke, Gregory S. Schnarr, Gary Schutte, Allen Sebastian, Jennifer L. Shea, Jesse Sheley, Deborah K. Shepier, Aaron M. Silver, Matt Silverman, Emily D. Smith, Gwendolyn L. Smith, Lena Snethen, Tichelle Sorensen, William Spalding, Mark Stalcup, Aaron M. Staser, Jennifer P. Stephens, Benjamin G. Stevenson, Terrance Stroud, Sara L. Swaney, John Sweeney, Julie Swinney, Valerie Tachtiris, Andrea Taylor, Jeremy Teipen, Terrance T. Tharpe, Jaime Turley, Matthew Van Sickle, Eric Voigt, Matthew P. Voors, Jeremy Wallace, Joseph Walterman, Kenneth Washington, M. Danniel Weatherford, Jennifer Weber, Hillary L. Weigle, Dale D. Wengler, Campbell White, Geoffrey Wiegand, David B. Wilford, Andrew Wood, Minhee Yang, Zhiqiang Zhao, and Stephanie Ziegler.
Not Pictured: Christopher Anderson, Vivek Boray, Cheryl Carson, Ralph Cerveny, Kelli Davis, Mark Delgado, Scott Dillon, Christopher Donovan, Matthew Douthat, Cara Fedewa, Kathryn Gordon, Elizabeth Henthorn, Kiyoaki Kojima, Jaime Lebitz, Matthew Lloyd, Peter Mikolaitis, Charles Overheul, Elizabeth Pitts, Jason Riley, Steven Rininger, Jennifer Risen, Kevin Rogers, Malavika Sahai, Bradley Scheick, Thomas Snider, and Shaun Thistlethwaite.
The Recognition Ceremony Program for the Class of 2003 can be found here.https://www.repository.law.indiana.edu/composite/1029/thumbnail.jp
Class of 2003, Indiana University School of Law
Pictured:
Marc O. Abplanalp, Kristin Acuff, Jonathon R. Albright, Sandra J. Ante, Joseph M. Banyash, Jenifer J. Baumann, Anastasia Benarski, David Beslow, Sarah Bierley, Neal R. Blythe, William J. Brinkerhoff, Marcie Brown, Aija Bryson, Elizabeth Ann Bumbales, Brenton Campbell, Adrienne R. Champine, Frank T. Chen, Hyun Suk Choi, Jason T. Clagg, Doris L. Clark, Nicole D. Clark, Jason P. Cleveland, Paul R. Colbert, Atto Commey, Michael P. Commons, Amy C. Conner, Matthew E. Conrad, Nicholas Conway, Cynthia Cross, Nicole A. Cunningham, Levi C. Czubaroff, Larry Dailey, Sarah Dansker, Joshua M. Davis, Maria DeFord, Stephen DePaul, Andrea Dick, Shawn J. Donahue, April R. Drake, Yolanda D. Edwards, Jill Ellis, Marius Escolar, Julia M. Fidaleo, Carmen Fisher, Mavis R. Gee, Mitchell J. Gerber, Matthew A. Gernand, Rebecca Greene, Emily C. Guenin-Hodson, Luiey G. Haddad, Stephen Hamilton, Ryan D. Hammer, Joy M. Hanson, James R. Harris, Lakshmi, Hasanadka, Brett Haworth, Charles C. Hayes, Deborah Hea, Michael Heintz, Sarah Herkamp, Jennifer M. Herrmann, Kristin L. Herrmann, Jennifer M. Hess, Scott S. Holmes, William Hope, Janet Horvath, Michele Huckstep-Neary, Christopher Humphreys, Ryan M. Hurley, A. Costance Hyun, Cynthia DeNardi Ipsen, Leigh Erin Irons, Brandy Jones, John T. Jones Jr., Brandon S. Judkins, Eunsook Jung, Derek Kaczmarek, John Kaminski, Carolyn Kang, Angela Kelver, Matthew R. King, Karen E. Klein, Chad Kleinheksel, Daniel J. Kopp, Leilani K. Krashin, Aaron Krolik, Scott N. Kumis, Sarah Kyle, Lauren S. Lark, Andrew D. LeMar, Christopher Lee, David Y. Lee, Ariel J. Leinwand, Tonya Lengar, Nicholas Levi, Ann E. Liefer, Phil Lodato, Michele Lofthouse, Sean McAndrew, Jonna McGinley, David McPherson, Hannah L. Meils, Teresa L. Melton, Russell Menyhart, Crystal M. Merlau, Petra R. Micu, Alyce Miller, Samuel F. Miller, Benjamin W. Mills, Derek M. Mills, Robb A. Minich, Eugene S. Miyata, Jill Morgan, Jonas I. Moskowitz, Kristy L. Murphy, Paul Newman, Shinobu Nishida, Andrew P. O\u27Brien, Michael O\u27Neal, Alexander O\u27Neill, Patrick Omillan, Christine Painter, Davina L. Patterson, Janell M. Payne, Samuel J. Perry, Daniel A. Pfaff, Joshlene A. Pollock, Matthew V. Pontius, Rachel M. Rabideau, Andrew J. Reitz, Benjamin Riddle, Rae R. Ridley, Jacob Rigney, David B. Rivera, Zachary Rosenbarger, Jane E. Rueger, Mark A. Ryan, Deborah Salons, Charles R. Salter, Anne E. Sanders, Christohper Saporita, Erica L. Schilke, Gregory S. Schnarr, Gary Schutte, Allen Sebastian, Jennifer L. Shea, Jesse Sheley, Deborah K. Shepier, Aaron M. Silver, Matt Silverman, Emily D. Smith, Gwendolyn L. Smith, Lena Snethen, Tichelle Sorensen, William Spalding, Mark Stalcup, Aaron M. Staser, Jennifer P. Stephens, Benjamin G. Stevenson, Terrance Stroud, Sara L. Swaney, John Sweeney, Julie Swinney, Valerie Tachtiris, Andrea Taylor, Jeremy Teipen, Terrance T. Tharpe, Jaime Turley, Matthew Van Sickle, Eric Voigt, Matthew P. Voors, Jeremy Wallace, Joseph Walterman, Kenneth Washington, M. Danniel Weatherford, Jennifer Weber, Hillary L. Weigle, Dale D. Wengler, Campbell White, Geoffrey Wiegand, David B. Wilford, Andrew Wood, Minhee Yang, Zhiqiang Zhao, and Stephanie Ziegler.
Not Pictured: Christopher Anderson, Vivek Boray, Cheryl Carson, Ralph Cerveny, Kelli Davis, Mark Delgado, Scott Dillon, Christopher Donovan, Matthew Douthat, Cara Fedewa, Kathryn Gordon, Elizabeth Henthorn, Kiyoaki Kojima, Jaime Lebitz, Matthew Lloyd, Peter Mikolaitis, Charles Overheul, Elizabeth Pitts, Jason Riley, Steven Rininger, Jennifer Risen, Kevin Rogers, Malavika Sahai, Bradley Scheick, Thomas Snider, and Shaun Thistlethwaite.
The Recognition Ceremony Program for the Class of 2003 can be found here.https://www.repository.law.indiana.edu/composite/1029/thumbnail.jp
Androgen-induced migration in NIH3T3 mouse fibroblasts: role of AR association with Filamin A.
Androgen stimulation triggers rapid activation of various signaling effectors in target cells (Migliaccio et al. 2000; Castoria et al. 2003). This occurs through a direct interaction of classical steroid receptors with proto-oncogenic tyrosine kinase (Src), the p85-regulatory subunit of Phosphatidylinositol 3-kinase (PI3K) and other signaling components. Activation of these pathways fosters cell cycle, prevents apoptosis and leads to cytoskeleton changes in reproductive as well as non reproductive cells.
The role of signaling activation in steroid action has been corroborated by findings showing that mouse embryo NIH3T3 fibroblasts express very low amount of classical androgen receptor (AR) which does not activate gene transcription. This receptor, through rapid and extra nuclear action, triggers migration upon stimulation with physiological concentrations (10nM) of the non aromatizable androgen, R1881 (Castoria et al. 2003).
By combining different approaches, it was observed that filamin A (FlnA) has an important role in androgen-stimulated migration.
In NIH3T3 cells, 10 nM R1881 rapidly induces interaction of AR with filamin A at cytoskeleton. AR/FlnA complex recruits and activates integrin beta1. Androgen assembled AR/FlnA/integrin beta1 complex activates both Ras-related C3 botulinum toxin substrate 1 (Rac1) and focal adhesion kinase (FAK), which independently of each other coordinate cytoskeletal changes and cell motility of fibroblasts.
Collected data indicate that AR/FlnA interaction in the extra-nuclear compartment of target cells plays a master role for the access of androgen to the signalling leading to cell migration. Such an interaction may impact human organ development as well as cancer progression and may offer new hints to gain a more tailored therapy of androgen-dependent human cancers
