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Eric N. Olson

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https://www.readbyqxmd.com/read/28724790/med12-regulates-a-transcriptional-network-of-calcium-handling-genes-in-the-heart
#1
Kedryn K Baskin, Catherine A Makarewich, Susan M DeLeon, Wenduo Ye, Beibei Chen, Nadine Beetz, Heinrich Schrewe, Rhonda Bassel-Duby, Eric N Olson
The Mediator complex regulates gene transcription by linking basal transcriptional machinery with DNA-bound transcription factors. The activity of the Mediator complex is mainly controlled by a kinase submodule that is composed of 4 proteins, including MED12. Although ubiquitously expressed, Mediator subunits can differentially regulate gene expression in a tissue-specific manner. Here, we report that MED12 is required for normal cardiac function, such that mice with conditional cardiac-specific deletion of MED12 display progressive dilated cardiomyopathy...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28681861/a-defect-in-myoblast-fusion-underlies-carey-fineman-ziter-syndrome
#2
Silvio Alessandro Di Gioia, Samantha Connors, Norisada Matsunami, Jessica Cannavino, Matthew F Rose, Nicole M Gilette, Pietro Artoni, Nara Lygia de Macena Sobreira, Wai-Man Chan, Bryn D Webb, Caroline D Robson, Long Cheng, Carol Van Ryzin, Andres Ramirez-Martinez, Payam Mohassel, Mark Leppert, Mary Beth Scholand, Christopher Grunseich, Carlos R Ferreira, Tyler Hartman, Ian M Hayes, Tim Morgan, David M Markie, Michela Fagiolini, Amy Swift, Peter S Chines, Carlos E Speck-Martins, Francis S Collins, Ethylin Wang Jabs, Carsten G Bönnemann, Eric N Olson, John C Carey, Stephen P Robertson, Irini Manoli, Elizabeth C Engle
Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes...
July 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28667019/retrotransposons-are-the-major-contributors-to-the-expansion-of-the-drosophila-ananassae-muller-f-element
#3
Wilson Leung, Christopher D Shaffer, Elizabeth J Chen, Thomas J Quisenberry, Kevin Ko, John M Braverman, Thomas C Giarla, Nathan T Mortimer, Laura K Reed, Sheryl T Smith, Srebrenka Robic, Shannon R McCartha, Danielle R Perry, Lindsay M Prescod, Zenyth A Sheppard, Ken J Saville, Allison McClish, Emily A Morlock, Victoria R Sochor, Brittney Stanton, Isaac C Veysey-White, Dennis Revie, Luis A Jimenez, Jennifer J Palomino, Melissa D Patao, Shane M Patao, Edward T Himelblau, Jaclyn D Campbell, Alexandra L Hertz, Maddison F McEvilly, Allison R Wagner, James Youngblom, Baljit Bedi, Jeffery Bettincourt, Erin Duso, Maiye Her, William Hilton, Samantha House, Masud Karimi, Kevin Kumimoto, Rebekah Lee, Darryl Lopez, George Odisho, Ricky Prasad, Holly Lyn Robbins, Tanveer Sandhu, Tracy Selfridge, Kara Tsukashima, Hani Yosif, Nighat P Kokan, Latia Britt, Alycia Zoellner, Eric P Spana, Ben T Chlebina, Insun Chong, Harrison Friedman, Danny A Mammo, Chun L Ng, Vinayak S Nikam, Nicholas U Schwartz, Thomas Q Xu, Martin G Burg, Spencer M Batten, Lindsay M Corbeill, Erica Enoch, Jesse J Ensign, Mary E Franks, Breanna Haiker, Judith A Ingles, Lyndsay D Kirkland, Joshua M Lorenz-Guertin, Jordan Matthews, Cody M Mittig, Nicholaus Monsma, Katherine J Olson, Guillermo Perez-Aragon, Alen Ramic, Jordan R Ramirez, Christopher Scheiber, Patrick A Schneider, Devon E Schultz, Matthew Simon, Eric Spencer, Adam C Wernette, Maxine E Wykle, Elizabeth Zavala-Arellano, Mitchell J McDonald, Kristine Ostby, Peter Wendland, Justin R DiAngelo, Alexis M Ceasrine, Amanda H Cox, James E B Docherty, Robert M Gingras, Stephanie M Grieb, Michael J Pavia, Casey L Personius, Grzegorz L Polak, Dale L Beach, Heaven L Cerritos, Edward A Horansky, Karim A Sharif, Ryan Moran, Susan Parrish, Kirsten Bickford, Jennifer Bland, Juliana Broussard, Kerry Campbell, Katelynn E Deibel, Richard Forka, Monika C Lemke, Marlee B Nelson, Catherine O'Keeffe, S Mariel Ramey, Luke Schmidt, Paola Villegas, Christopher J Jones, Stephanie L Christ, Sami Mamari, Adam S Rinaldi, Ghazal Stity, Amy T Hark, Mark Scheuerman, Cathy Silver Key, Briana D McRae, Adam S Haberman, Sam Asinof, Harriette Carrington, Kelly Drumm, Terrance Embry, Richard McGuire, Drew Miller-Foreman, Stella Rosen, Nadia Safa, Darrin Schultz, Matt Segal, Yakov Shevin, Petros Svoronos, Tam Vuong, Gary Skuse, Don W Paetkau, Rachael K Bridgman, Charlotte M Brown, Alicia R Carroll, Francesca M Gifford, Julie Beth Gillespie, Susan E Herman, Krystal L Holtcamp, Misha A Host, Gabrielle Hussey, Danielle M Kramer, Joan Q Lawrence, Madeline M Martin, Ellen N Niemiec, Ashleigh P O'Reilly, Olivia A Pahl, Guadalupe Quintana, Elizabeth A S Rettie, Torie L Richardson, Arianne E Rodriguez, Mona O Rodriguez, Laura Schiraldi, Joanna J Smith, Kelsey F Sugrue, Lindsey J Suriano, Kaitlyn E Takach, Arielle M Vasquez, Ximena Velez, Elizabeth J Villafuerte, Laura T Vives, Victoria R Zellmer, Jeanette Hauke, Charles R Hauser, Karolyn Barker, Laurie Cannon, Perouza Parsamian, Samantha Parsons, Zachariah Wichman, Christopher W Bazinet, Diana E Johnson, Abubakarr Bangura, Jordan A Black, Victoria Chevee, Sarah A Einsteen, Sarah K Hilton, Max Kollmer, Rahul Nadendla, Joyce Stamm, Antoinette E Fafara-Thompson, Amber M Gygi, Emmy E Ogawa, Matt Van Camp, Zuzana Kocsisova, Judith L Leatherman, Cassie M Modahl, Michael R Rubin, Susana S Apiz-Saab, Suzette M Arias-Mejias, Carlos F Carrion-Ortiz, Patricia N Claudio-Vazquez, Debbie M Espada-Green, Marium Feliciano-Camacho, Karina M Gonzalez-Bonilla, Mariela Taboas-Arroyo, Dorianmarie Vargas-Franco, Raquel Montañez-Gonzalez, Joseph Perez-Otero, Myrielis Rivera-Burgos, Francisco J Rivera-Rosario, Heather L Eisler, Jackie Alexander, Samatha K Begley, Deana Gabbard, Robert J Allen, Wint Yan Aung, William D Barshop, Amanda Boozalis, Vanessa P Chu, Jeremy S Davis, Ryan N Duggal, Robert Franklin, Katherine Gavinski, Heran Gebreyesus, Henry Z Gong, Rachel A Greenstein, Averill D Guo, Casey Hanson, Kaitlin E Homa, Simon C Hsu, Yi Huang, Lucy Huo, Sarah Jacobs, Sasha Jia, Kyle L Jung, Sarah Wai-Chee Kong, Matthew R Kroll, Brandon M Lee, Paul F Lee, Kevin M Levine, Amy S Li, Chengyu Liu, Max Mian Liu, Adam P Lousararian, Peter B Lowery, Allyson P Mallya, Joseph E Marcus, Patrick C Ng, Hien P Nguyen, Ruchik Patel, Hashini Precht, Suchita Rastogi, Jonathan M Sarezky, Adam Schefkind, Michael B Schultz, Delia Shen, Tara Skorupa, Nicholas C Spies, Gabriel Stancu, Hiu Man Vivian Tsang, Alice L Turski, Rohit Venkat, Leah E Waldman, Kaidi Wang, Tracy Wang, Jeffrey W Wei, Dennis Y Wu, David D Xiong, Jack Yu, Karen Zhou, Gerard P McNeil, Robert W Fernandez, Patrick Gomez Menzies, Tingting Gu, Jeremy Buhler, Elaine R Mardis, Sarah C R Elgin
The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (~5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in Drosophila ananassae To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4 Mb region of the D. ananassae F element, and a 1.7 Mb region from the D element for comparison...
June 30, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28528987/mining-for-micropeptides
#4
REVIEW
Catherine A Makarewich, Eric N Olson
Advances in computational biology and large-scale transcriptome analyses have revealed that a much larger portion of the genome is transcribed than was previously recognized, resulting in the production of a diverse population of RNA molecules with both protein-coding and noncoding potential. Emerging evidence indicates that several RNA molecules have been mis-annotated as noncoding and in fact harbor short open reading frames (sORFs) that encode functional peptides and that have evaded detection until now due to their small size...
May 18, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28439558/crispr-cpf1-correction-of-muscular-dystrophy-mutations-in-human-cardiomyocytes-and-mice
#5
Yu Zhang, Chengzu Long, Hui Li, John R McAnally, Kedryn K Baskin, John M Shelton, Rhonda Bassel-Duby, Eric N Olson
Duchenne muscular dystrophy (DMD), caused by mutations in the X-linked dystrophin gene (DMD), is characterized by fatal degeneration of striated muscles. Dilated cardiomyopathy is one of the most common lethal features of the disease. We deployed Cpf1, a unique class 2 CRISPR (clustered regularly interspaced short palindromic repeats) effector, to correct DMD mutations in patient-derived induced pluripotent stem cells (iPSCs) and mdx mice, an animal model of DMD. Cpf1-mediated genomic editing of human iPSCs, either by skipping of an out-of-frame DMD exon or by correcting a nonsense mutation, restored dystrophin expression after differentiation to cardiomyocytes and enhanced contractile function...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28432117/control-of-muscle-metabolism-by-the-mediator-complex
#6
Leonela Amoasii, Eric N Olson, Rhonda Bassel-Duby
Exercise represents an energetic challenge to whole-body homeostasis. In skeletal muscle, exercise activates a variety of signaling pathways that culminate in the nucleus to regulate genes involved in metabolism and contractility; however, much remains to be learned about the transcriptional effectors of exercise. Mediator is a multiprotein complex that links signal-dependent transcription factors and other transcriptional regulators with the basal transcriptional machinery, thereby serving as a transcriptional "hub...
April 21, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28415742/androgen-receptor-amplification-is-concordant-between-circulating-tumor-cells-and-biopsies-from-men-undergoing-treatment-for-metastatic-castration-resistant-prostate-cancer
#7
Jennifer Podolak, Kristi Eilers, Timothy Newby, Rachel Slottke, Erin Tucker, Susan B Olson, Hui-Wen Lue, Jack Youngren, Rahul Aggarwal, Eric J Small, Julie N Graff, Joshi J Alumkal, Tomasz M Beer, George V Thomas
Increased AR activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC increase AR activity. To determine whether AR amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed AR amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence in situ hybridization (FISH)...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386024/control-of-muscle-formation-by-the-fusogenic-micropeptide-myomixer
#8
Pengpeng Bi, Andres Ramirez-Martinez, Hui Li, Jessica Cannavino, John R McAnally, John M Shelton, Efrain Sánchez-Ortiz, Rhonda Bassel-Duby, Eric N Olson
Skeletal muscle formation occurs through fusion of myoblasts to form multinucleated myofibers. From a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) loss-of-function screen for genes required for myoblast fusion and myogenesis, we discovered an 84-amino acid muscle-specific peptide that we call Myomixer. Myomixer expression coincides with myoblast differentiation and is essential for fusion and skeletal muscle formation during embryogenesis. Myomixer localizes to the plasma membrane, where it promotes myoblast fusion and associates with Myomaker, a fusogenic membrane protein...
April 21, 2017: Science
https://www.readbyqxmd.com/read/28262548/notch-inhibition-enhances-cardiac-reprogramming-by-increasing-mef2c-transcriptional-activity
#9
Maria Abad, Hisayuki Hashimoto, Huanyu Zhou, Maria Gabriela Morales, Beibei Chen, Rhonda Bassel-Duby, Eric N Olson
Conversion of fibroblasts into functional cardiomyocytes represents a potential means of restoring cardiac function after myocardial infarction, but so far this process remains inefficient and little is known about its molecular mechanisms. Here we show that DAPT, a classical Notch inhibitor, enhances the conversion of mouse fibroblasts into induced cardiac-like myocytes by the transcription factors GATA4, HAND2, MEF2C, and TBX5. DAPT cooperates with AKT kinase to further augment this process, resulting in up to 70% conversion efficiency...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28241208/association-between-telomere-length-and-risk-of-cancer-and-non-neoplastic-diseases-a-mendelian-randomization-study
#10
Philip C Haycock, Stephen Burgess, Aayah Nounu, Jie Zheng, George N Okoli, Jack Bowden, Kaitlin Hazel Wade, Nicholas J Timpson, David M Evans, Peter Willeit, Abraham Aviv, Tom R Gaunt, Gibran Hemani, Massimo Mangino, Hayley Patricia Ellis, Kathreena M Kurian, Karen A Pooley, Rosalind A Eeles, Jeffrey E Lee, Shenying Fang, Wei V Chen, Matthew H Law, Lisa M Bowdler, Mark M Iles, Qiong Yang, Bradford B Worrall, Hugh Stephen Markus, Rayjean J Hung, Chris I Amos, Amanda B Spurdle, Deborah J Thompson, Tracy A O'Mara, Brian Wolpin, Laufey Amundadottir, Rachael Stolzenberg-Solomon, Antonia Trichopoulou, N Charlotte Onland-Moret, Eiliv Lund, Eric J Duell, Federico Canzian, Gianluca Severi, Kim Overvad, Marc J Gunter, Rosario Tumino, Ulrika Svenson, Andre van Rij, Annette F Baas, Matthew J Bown, Nilesh J Samani, Femke N G van t'Hof, Gerard Tromp, Gregory T Jones, Helena Kuivaniemi, James R Elmore, Mattias Johansson, James Mckay, Ghislaine Scelo, Robert Carreras-Torres, Valerie Gaborieau, Paul Brennan, Paige M Bracci, Rachel E Neale, Sara H Olson, Steven Gallinger, Donghui Li, Gloria M Petersen, Harvey A Risch, Alison P Klein, Jiali Han, Christian C Abnet, Neal D Freedman, Philip R Taylor, John M Maris, Katja K Aben, Lambertus A Kiemeney, Sita H Vermeulen, John K Wiencke, Kyle M Walsh, Margaret Wrensch, Terri Rice, Clare Turnbull, Kevin Litchfield, Lavinia Paternoster, Marie Standl, Gonçalo R Abecasis, John Paul SanGiovanni, Yong Li, Vladan Mijatovic, Yadav Sapkota, Siew-Kee Low, Krina T Zondervan, Grant W Montgomery, Dale R Nyholt, David A van Heel, Karen Hunt, Dan E Arking, Foram N Ashar, Nona Sotoodehnia, Daniel Woo, Jonathan Rosand, Mary E Comeau, W Mark Brown, Edwin K Silverman, John E Hokanson, Michael H Cho, Jennie Hui, Manuel A Ferreira, Philip J Thompson, Alanna C Morrison, Janine F Felix, Nicholas L Smith, Angela M Christiano, Lynn Petukhova, Regina C Betz, Xing Fan, Xuejun Zhang, Caihong Zhu, Carl D Langefeld, Susan D Thompson, Feijie Wang, Xu Lin, David A Schwartz, Tasha Fingerlin, Jerome I Rotter, Mary Frances Cotch, Richard A Jensen, Matthias Munz, Henrik Dommisch, Arne S Schaefer, Fang Han, Hanna M Ollila, Ryan P Hillary, Omar Albagha, Stuart H Ralston, Chenjie Zeng, Wei Zheng, Xiao-Ou Shu, Andre Reis, Steffen Uebe, Ulrike Hüffmeier, Yoshiya Kawamura, Takeshi Otowa, Tsukasa Sasaki, Martin Lloyd Hibberd, Sonia Davila, Gang Xie, Katherine Siminovitch, Jin-Xin Bei, Yi-Xin Zeng, Asta Försti, Bowang Chen, Stefano Landi, Andre Franke, Annegret Fischer, David Ellinghaus, Carlos Flores, Imre Noth, Shwu-Fan Ma, Jia Nee Foo, Jianjun Liu, Jong-Won Kim, David G Cox, Olivier Delattre, Olivier Mirabeau, Christine F Skibola, Clara S Tang, Merce Garcia-Barcelo, Kai-Ping Chang, Wen-Hui Su, Yu-Sun Chang, Nicholas G Martin, Scott Gordon, Tracey D Wade, Chaeyoung Lee, Michiaki Kubo, Pei-Chieng Cha, Yusuke Nakamura, Daniel Levy, Masayuki Kimura, Shih-Jen Hwang, Steven Hunt, Tim Spector, Nicole Soranzo, Ani W Manichaikul, R Graham Barr, Bratati Kahali, Elizabeth Speliotes, Laura M Yerges-Armstrong, Ching-Yu Cheng, Jost B Jonas, Tien Yin Wong, Isabella Fogh, Kuang Lin, John F Powell, Kenneth Rice, Caroline L Relton, Richard M Martin, George Davey Smith
Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Data Sources: Genomewide association studies (GWAS) published up to January 15, 2015...
May 1, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28218909/a-twist2-dependent-progenitor-cell-contributes-to-adult-skeletal-muscle
#11
Ning Liu, Glynnis A Garry, Stephen Li, Svetlana Bezprozvannaya, Efrain Sanchez-Ortiz, Beibei Chen, John M Shelton, Priscilla Jaichander, Rhonda Bassel-Duby, Eric N Olson
Skeletal muscle possesses remarkable regenerative potential due to satellite cells, an injury-responsive stem cell population located beneath the muscle basal lamina that expresses Pax7. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a myogenic lineage that resides outside the basal lamina of adult skeletal muscle. Tw2(+) progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro, and can fuse with themselves and with satellite cells...
March 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28181678/safety-and-immunological-efficacy-of-a-dna-vaccine-encoding-the-androgen-receptor-ligand-binding-domain-ar-lbd
#12
Brian M Olson, Eric S Bradley, Thomas Sawicki, Weixiong Zhong, Erik A Ranheim, Jordan E Bloom, Viswa T Colluru, Laura E Johnson, Brian T Rekoske, Jens C Eickhoff, Douglas G McNeel
BACKGROUND: The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR...
May 2017: Prostate
https://www.readbyqxmd.com/read/28143939/blockade-to-pathological-remodeling-of-infarcted-heart-tissue-using-a-porcupine-antagonist
#13
Jesung Moon, Huanyu Zhou, Li-Shu Zhang, Wei Tan, Ying Liu, Shanrong Zhang, Lorraine K Morlock, Xiaoping Bao, Sean P Palecek, Jian Q Feng, Noelle S Williams, James F Amatruda, Eric N Olson, Rhonda Bassel-Duby, Lawrence Lum
The secreted Wnt signaling molecules are essential to the coordination of cell-fate decision making in multicellular organisms. In adult animals, the secreted Wnt proteins are critical for tissue regeneration and frequently contribute to cancer. Small molecules that disable the Wnt acyltransferase Porcupine (Porcn) are candidate anticancer agents in clinical testing. Here we have systematically assessed the effects of the Porcn inhibitor (WNT-974) on the regeneration of several tissue types to identify potentially unwanted chemical effects that could limit the therapeutic utility of such agents...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28133863/genetics-and-genotype-phenotype-correlations-in-early-onset-epileptic-encephalopathy-with-burst-suppression
#14
Heather E Olson, McKenna Kelly, Christopher M LaCoursiere, Rebecca Pinsky, Dimira Tambunan, Catherine Shain, Sriram Ramgopal, Masanori Takeoka, Mark H Libenson, Kristina Julich, Tobias Loddenkemper, Eric D Marsh, Devorah Segal, Susan Koh, Michael S Salman, Alex R Paciorkowski, Edward Yang, Ann M Bergin, Beth Rosen Sheidley, Annapurna Poduri
OBJECTIVE: We sought to identify genetic causes of early onset epileptic encephalopathies with burst suppression (Ohtahara syndrome and early myoclonic encephalopathy) and evaluate genotype-phenotype correlations. METHODS: We enrolled 33 patients with a referral diagnosis of Ohtahara syndrome or early myoclonic encephalopathy without malformations of cortical development. We performed detailed phenotypic assessment including seizure presentation, electroencephalography, and magnetic resonance imaging...
March 2017: Annals of Neurology
https://www.readbyqxmd.com/read/27999108/insulin-regulates-astrocytic-glucose-handling-through-cooperation-with-igf-i
#15
Ana M Fernandez, Edwin Hernandez-Garzón, Paloma Perez-Domper, Alberto Perez-Alvarez, Sara Mederos, Takashi Matsui, Andrea Santi, Angel Trueba-Saiz, Lucía García-Guerra, Julia Pose-Utrilla, Jens Fielitz, Eric N Olson, Ruben Fernandez de la Rosa, Luis Garcia Garcia, Miguel Angel Pozo, Teresa Iglesias, Alfonso Araque, Hideaki Soya, Gertrudis Perea, Eduardo D Martin, Ignacio Torres Aleman
Brain activity requires a flux of glucose to active regions to sustain increased metabolic demands. Insulin, the main regulator of glucose handling in the body, has been traditionally considered not to intervene in this process. However, we now report that insulin modulates brain glucose metabolism by acting on astrocytes in concert with IGF-I. The cooperation of insulin and IGF-I is needed to recover neuronal activity after hypoglycemia. Analysis of underlying mechanisms show that the combined action of IGF-I and insulin synergistically stimulates a mitogen-activated protein kinase/protein kinase D pathway resulting in translocation of GLUT1 to the cell membrane through multiple protein-protein interactions involving the scaffolding protein GAIP-interacting protein C terminus and the GTPase RAC1...
January 2017: Diabetes
https://www.readbyqxmd.com/read/27923914/widespread-control-of-calcium-signaling-by-a-family-of-serca-inhibiting-micropeptides
#16
Douglas M Anderson, Catherine A Makarewich, Kelly M Anderson, John M Shelton, Svetlana Bezprozvannaya, Rhonda Bassel-Duby, Eric N Olson
Micropeptides function as master regulators of calcium-dependent signaling in muscle. Sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA), the membrane pump that promotes muscle relaxation by taking up Ca(2+) into the sarcoplasmic reticulum, is directly inhibited by three muscle-specific micropeptides: myoregulin (MLN), phospholamban (PLN), and sarcolipin (SLN). The widespread and essential function of SERCA across diverse cell types has raised questions as to how SERCA is regulated in cells that lack MLN, PLN, and SLN...
December 6, 2016: Science Signaling
https://www.readbyqxmd.com/read/27783597/transcription-of-the-non-coding-rna-upperhand-controls-hand2-expression-and-heart-development
#17
Kelly M Anderson, Douglas M Anderson, John R McAnally, John M Shelton, Rhonda Bassel-Duby, Eric N Olson
HAND2 is an ancestral regulator of heart development and one of four transcription factors that control the reprogramming of fibroblasts into cardiomyocytes. Deletion of Hand2 in mice results in right ventricle hypoplasia and embryonic lethality. Hand2 expression is tightly regulated by upstream enhancers that reside within a super-enhancer delineated by histone H3 acetyl Lys27 (H3K27ac) modifications. Here we show that transcription of a Hand2-associated long non-coding RNA, which we named upperhand (Uph), is required to maintain the super-enhancer signature and elongation of RNA polymerase II through the Hand2 enhancer locus...
November 17, 2016: Nature
https://www.readbyqxmd.com/read/27716515/mutations-in-the-histone-modifier-prdm6-are-associated-with-isolated-nonsyndromic-patent-ductus-arteriosus
#18
Na Li, Lakshman Subrahmanyan, Emily Smith, Xiaoqing Yu, Samir Zaidi, Murim Choi, Shrikant Mane, Carol Nelson-Williams, Mohaddeseh Behjati, Mohammad Kazemi, Mohammad Hashemi, Mohsen Fathzadeh, Anand Narayanan, Likun Tian, Farhad Montazeri, Mitra Mani, Michael L Begleiter, Brian G Coon, Henry T Lynch, Eric N Olson, Hongyu Zhao, Jürgen Ruland, Richard P Lifton, Arya Mani
No abstract text is available yet for this article.
October 6, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27668807/genome-editing-of-monogenic-neuromuscular-diseases-a-systematic-review
#19
REVIEW
Chengzu Long, Leonela Amoasii, Rhonda Bassel-Duby, Eric N Olson
Importance: Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1...
November 1, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27630169/galectin-3-regulates-inflammasome-activation-in-cholestatic-liver-injury
#20
Jijing Tian, Guoxiang Yang, Huan-Yuan Chen, Daniel K Hsu, Alexey Tomilov, Kristin A Olson, Ali Dehnad, Sarah R Fish, Gino Cortopassi, Bin Zhao, Fu-Tong Liu, M Eric Gershwin, Natalie J Török, Joy X Jiang
Macrophage activation is an important feature of primary biliary cholangitis (PBC) pathogenesis and other cholestatic liver diseases. Galectin-3 (Gal3), a pleiotropic lectin, is produced by monocytic cells and macrophages. However, its role in PBC has not been addressed. We hypothesized that Gal3 is a key to induce NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in macrophages and in turn to propagate proinflammatory IL-17 signaling. In liver tissues from patients with PBC and dnTGF-βRII mice, a model of autoimmune cholangitis, the expression of Gal3, NLRP3, and the adaptor protein adaptor apoptosis-associated speck-like protein was induced, with the downstream activation of caspase-1 and IL-1β...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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