Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II

The classically recognized functions of the renin–angiotensin system are mediated by type 1 (AT1) angiotensin receptors. Whereas man possesses a single AT1 receptor, there are two AT1 receptor isoforms in rodents (AT1A and AT1B) that are products of separate genes (Agtr1a and Agtr1b). We have generated mice lacking AT1B (Agtr1b −/−) and both AT1A and AT1B receptors (Agtr1a −/−Agtr1b −/−). Agtr1b −/− mice are healthy, without an abnormal phenotype. In contrast, Agtr1a −/−Agtr1b −/− mice have diminished growth, vascular thickening within the kidney, and atrophy of the inner renal medulla. This phenotype is virtually identical to that seen in angiotensinogen-deficient (Agt−/−) and angiotensin-converting enzyme-deficient (Ace −/−) mice that are unable to synthesize angiotensin II. Agtr1a −/−Agtr1b −/− mice have no systemic pressor response to infusions of angiotensin II, but they respond normally to another vasoconstrictor, epinephrine. Blood pressure is reduced substantially in the Agtr1a −/− Agtr1b −/− mice and following administration of an angiotensin converting enzyme inhibitor, their blood pressure increases paradoxically. We suggest that this is a result of interruption of AT2-receptor signaling. In summary, our studies suggest that both AT1 receptors promote somatic growth and maintenance of normal kidney structure. The absence of either of the AT1 receptor isoforms alone can be compensated in varying degrees by the other isoform. These studies reaffirm and extend the importance of AT1 receptors to mediate physiological functions of the renin–angiotensin system.

Regulation of blood pressure by the type 1A angiotensin II receptor gene.

The renin-angiotensin system plays a critical role in sodium and fluid homeostasis. Genetic or acquired alterations in the expression of components of this system are strongly implicated in the pathogenesis of hypertension. To specifically examine the physiological and genetic functions of the type 1A receptor for angiotensin II, we have disrupted the mouse gene encoding this receptor in embryonic stem cells by gene targeting. Agtr1A(-/-) mice were born in expected numbers, and the histomorphology of their kidneys, heart, and vasculature was normal. AT1 receptor-specific angiotensin II binding was not detected in the kidneys of homozygous Agtr1A(-/-) mutant animals, and Agtr1A(+/-) heterozygotes exhibited a reduction in renal AT1 receptor-specific binding to approximately 50% of wild-type [Agtr1A(+/+)] levels. Pressor responses to infused angiotensin II were virtually absent in Agtr1A(-/-) mice and were qualitatively altered in Agtr1A(+/-) heterozygotes. Compared with wild-type controls, systolic blood pressure measured by tail cuff sphygmomanometer was reduced by 12 mmHg (1 mmHg = 133 Pa) in Agtr1A(+/-) mice and by 24 mmHg in Agtr1A(-/-) mice. Similar differences in blood pressure between the groups were seen when intraarterial pressures were measured by carotid cannulation. These studies demonstrate that type 1A angiotensin II receptor function is required for vascular and hemodynamic responses to angiotensin II and that altered expression of the Agtr1A gene has marked effects on blood pressures.

School of Nursing Class of 1992

Top Row: Lisa M. Badalament, Heidi S. Bailey, Bonita Ballard, Betsy M. Bateman, Virginia Blackmer, Andrea L. Bonfield, Michelle L. Brown, Jane M. Christie, Gina M. Connolly, Matthew Cornell

Row 2: Mary M. Daugherty, Nancy L. Dewey, Linnette Drzewiecki, Jennifer Farah, Kelly S. Fonger, Yolanda Gardner, Kimberly A. Germain, Kelley Goetz, Laura M. Gonzalez, Melissa Gorr, Julie A. Hale, Jennifer Henstock

Row 3: Charles Houghtby III, Jennifer Hughes, Jill C. Jennings, Renee Manshardt, Jill A. Holquist, Paula R. Cowall, Kristen A. George, Michelle Ingram, Amy Jacobs

Row 4: Tara James, David Jansma, Debra A. Jorgenson, Sherry Keener

Row 5: Karen L. Kelley, Sunnah Kim, Tina Koonter-Banks, Jennifer Kratt

Row 6: Cynthia L. Lazaros, Christine Morelli, Charlotte Murphy, Sharon K. Norton

Row 7: Deborah Oliverio, Karla J. Pontier, Nicole Pruett, Laura Rankin, Jill E. Read, Diane Rosati

Row 8: Katherine E. Ross, Lisa Rubin, Lorie K. Sandberg, Violet Barkauskas, Janice Lindberg, Shake Ketefian, Elisabeth Pennington, Beverly Jones, Donita M. Shaum, Marcie S. Skinner, Julie M. Smallegan

Row 9: K. Christy Spencer, Danette L. Starr, Pamela S. Steele, Dena Stempien-Runyon, Jennifer J. Treacy, Patrica Van Maanen, Roberta Wahl, Marie A. White, Kim Wiersma, Wendy Williams, Dana Wilson

School of Nursing Class of 1993

Top Row: Kristen Clark, Katherine Grinenko, Shinyi Tang, Troy Tann, Kelly Pasanen, Barbara Loson, Dennis Lake, Lisa Mancuso, Elizabeth Kim, Linda Dengate, Linda Morse, Stacey Horner, Juliet McKeone, Laura Schenk, Corrie Boguth

Row 2: Valerie Straka, Jamie T. Mose, Robert VanCamp, Cary Johnson, Laura Chamberlain, Kenyatta A. Paige, Kevin T. Sprecher, Jean L. Novak, Amanda Sue Niskar, Lisa Oliverio, Rosalyn Baumann, Elaine Schultz, Jennifer Lee Bastress, Kristen Hedge

Row 3: Jennifer Joh, Jennifer Monroe, Marion Tauriainen, Anne Chesky, Michael Fournier, Amy Sebright, Brian Simmons, Ann Luciano, Robin Van Eck, Beth Hart

Row 4: Jacqueline weibel, Dawn Garrett, Vicki McWalters, Malina Rocoff, Holly Medley, Ann Kosky, Tina L. Kessey, Caesanea A. Smith, Michelle Koch, Julie C. Wolf

Row 5: Robin Wygant, Cynthia Nichols, Susan Worek, Sandi Sassack, Timothy Wright, Bridgette Nichols, Kelly Sheridan, Kristin Sirosky, Kathy Kentala, Susan Oslund, Zaleha Williams, Heidi C. Goiz

Row 6: Kathryn Erdmann, Karen Crandall, Darryl Anderson, Karla Stoermer, Janice Lindberg, Beverly Jones, Rhetaugh G. Duman, Elisabeth Pennington, Violet Barkauskas, Laura Stock, Jacqueline Mickle, Catharine Quinn, Laura Nourse

Row 7: Christopher Kelly, Deborah Zolinski, Victoria Buckles, Pamela Brown, Stephanie Macey, Meredith Muncy, Susan, M. Smashey, Laura Welch, Rene Thompson, Sarah Scott, Juliette Lovell, Diane Ferguson, Deborah Ann Dolasinski, Cynthia Zammit, Lorie Malarney

Row 8: Janet Ingram, Rosemary Stafford, Diane Mayernik, Thea Picklesimer, Hannah Clark, JoyMarie Bruhowzki, Jennifer Beckert, Elizabeth Bryant, Jennifer Voeffray, Jane Perrin, Sophia Jan, Diana apostolou, Deborah Ruzicka, Liesel Culver

Row 9: Lori Wessman, Nicole Kerridge, Julia Oman, Melissa Naser, Jennifer Cole, Elizabeth Brickman, Detria Williams, Kris Haaksma, Alison Flaskamp, Nela L. Humm, Carol Taylor, Dena Mitchell, Karen L. Domke

School of Nursing Class of 2003

Top Row: Melissa Alfaro, Dana Alguire, Jessica Ault, Joanna Bancroft, Lara Bankowski, Sarah Bauer, Andrew Bauman, Samantha Becker, Erin Blazo, Courtney Braddock, Alethea Brancheau, Anna Carr

Row 2: Jennifer Grady, Julie Humphries, Lindsey Jack, Kristin Kirby, Laura Marten, Cathy Fanone, Elizabeth Van Hall, Ewurabena Menyah, Veronica McGraw, Kierste Mundinger, Kortney Stewart, Elizabeth Walkowiak, Erin Wilson

Row 3: Rebekah Chamberlain, Jason T. Chambers, Julie Ciaravino, Amanda Corwin, Sarah Debri, Heidi DenBesten, Harmony Dickerson, Elise Erickson

Row 4: Elissa Erman, Stacey Falconer, Julia Feczko, Sarah Fedewa, Angela Fisher, Lisa Flaskamp-Shaft, Leigh Frinkle, Joy Garrett, Theresa Giachino, Laura Heilig

Row 5: Amy Henderiksma, Aimee Hermes, Ann Johnson, Margaret Calarco, Patricia Coleman-Burns, Jan lee, Ada Sue Hinshaw, Carol Loveland-Cherry, Judy Lynch-Sauer, Joanne Pohl, Carolyn Sampselle, Shelly Jones, Sandra Kelly, Lindsay Klein

Row 6: Krystal Kobasic, Bryan Krehnbrink, Kelly Krueger, Donna Lehnert, Nicole Leith, Rachel Luria, Phuong Ly, Sara Maksym, Ivana Malusev, Jennifer Matousek, sara Genova McCrea, Melissa Meier, Maria Mendoza, Joshua Miller, Jennifer Moran, Amanda Muiter, Danielle Oliverio, Cindy Overholser, Karen Parsons, Kelly Patrick, Amanda Star Phebus, Magdalena Pilarski, Natascha Pocsatko, Alexis Punches, Ella Rakitin, Susan Ramlow

Row 7: Yvette Reed, Bethena Ridley, Lori Riley, Megan Rooney, Rebecca Rubin, Kami Shelton, Renee Sliker, Kristine Snyder, Robyn Sorensen, Deborah Sorgen, Lauren Stringi, Cynthia Thelen

Row 8: Judy Tigay, Giosi Toldeo, Kristie Vanwieren, Kate Warner, Carolyn Washnock, Carla Watts, Sonya Weber, Christine Wiles, Vanessa Williams, Holly Wilson, Jordan Woltersom

GOVERNO ABERTO: TRANSPARÊNCIA, COLABORAÇÃO E PARTICIPAÇÃO NA COMUNICAÇÃO ENTRE GOVERNO E CIDADÃO

O conceito de Governo aberto está diretamente ligado a questões culturais do cidadão e do governo. Entretanto, há divergências conceituais com relação ao significado de Governo aberto, já que para alguns teóricos a abertura de governo está ligada somente à transparência ou à abertura dos dados governamentais, para outros, além da transparência, mais fatores são considerados essenciais para Governo aberto. O presente estudo está dividido em duas partes fundamentais. A primeira vista compreender o conceito de democracia e de Governo aberto, para isso se baseia em literatura especializada sobre o tema. Na segunda parte, a partir de uma pesquisa nos 39 municípios da região metropolitana de São Paulo, identifica nas iniciativas de Governo aberto a possível presença de condições causais comuns. A questão de fundo, quais as condições causais podem influenciar nas indicações de abertura de governo, enquanto processo comunicativo de promoção para participação, colaboração e transparência, nas administrações municipais da região metropolitana de São Paulo. As soluções encontradas indicam diferentes rotas para chegar às condições de governo aberto analisadas. Verificando os resultados é possível afirmar que duas condições têm potencial para incentivar uma possível abertura de governo em um município, o IDH e a condição de acesso.

Transglutaminase 2 is involved in autophagosome maturation

Autophagy is a highly conserved cellular process responsible for the degradation of long-lived proteins and organelles. Autophagy occurs at low levels under normal conditions, but it is enhanced in response to stress, e.g. nutrient deprivation, hypoxia, mitochondrial dysfunction and infection. "Tissue" transglutaminase (TG2) accumulates, both in vivo and in vitro, to high levels in cells under stressful conditions. Therefore, in this study, we investigated whether TG2 could also play a role in the autophagic process. To this end, we used TG2 knockout mice and cell lines in which the enzyme was either absent or overexpressed. The ablation of TG2 protein both in vivo and in vitro, resulted in an evident accumulation of microtubule-associated protein 1 light chain 3 cleaved isoform II (LC3 II) on pre-autophagic vesicles, suggesting a marked induction of autophagy. By contrast, the formation of the acidic vesicular organelles in the same cells was very limited, indicating an impairment of the final maturation of autophagolysosomes. In fact, the treatment of TG2 proficient cells with NH4Cl, to inhibit lysosomal activity, led to a marked accumulation of LC3 II and damaged mitochondria similar to what we observed in TG2-deficient cells. These data indicate a role for TG2-mediated post-translational modifications of proteins in the maturation of autophagosomes accompanied by the accumulation of many damaged mitochondria.