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Amy Wagers

Hannah Pitt, Samantha L Thomas, Amy Bestman
BACKGROUND: Harmful gambling is a significant public health issue. Alongside the rapid diversification of gambling products, are rapid increases in the marketing for specific types of gambling products, such as online wagering. While concern has been raised about the impact of gambling promotions during sporting matches on the gambling beliefs and behaviours of adolescents, very little research has explored adolescents' and parents' attitudes towards the marketing of gambling products within sport...
2016: BMC Public Health
Wei Leong Chew, Mohammadsharif Tabebordbar, Jason K W Cheng, Prashant Mali, Elizabeth Y Wu, Alex H M Ng, Kexian Zhu, Amy J Wagers, George M Church
CRISPR-Cas9 delivery by adeno-associated virus (AAV) holds promise for gene therapy but faces critical barriers on account of its potential immunogenicity and limited payload capacity. Here, we demonstrate genome engineering in postnatal mice using AAV-split-Cas9, a multifunctional platform customizable for genome editing, transcriptional regulation, and other previously impracticable applications of AAV-CRISPR-Cas9. We identify crucial parameters that impact efficacy and clinical translation of our platform, including viral biodistribution, editing efficiencies in various organs, antigenicity, immunological reactions, and physiological outcomes...
October 2016: Nature Methods
Lige Song, Garyfallia Papaioannou, Hengguang Zhao, Hilary F Luderer, Christine Miller, Claudia Dall'Osso, Rosalynn M Nazarian, Amy J Wagers, Marie B Demay
Ligand-dependent actions of the vitamin D receptor (VDR) play a pleiotropic role in the regulation of innate and adaptive immunity. The liganded VDR is required for recruitment of macrophages during the inflammatory phase of cutaneous wound healing. Although the number of macrophages in the granulation tissue 2 days after wounding is markedly reduced in VDR knockout (KO) compared with wild-type mice, VDR ablation does not alter macrophage polarization. Parabiosis studies demonstrate that circulatory chimerism with wild-type mice is unable to rescue the macrophage defect in the wounds of VDR KO mice and reveal that wound macrophages are of local origin, regardless of VDR status...
October 2016: Endocrinology
Hannah Pitt, Samantha L Thomas, Amy Bestman, Melissa Stoneham, Mike Daube
OBJECTIVE: To investigate how children and adults recall the content and promotional channels for sports wagering marketing. METHODS: A mixed methods study of 152 parent/child (8-16 years) dyads was conducted at AFL (Australian Football League), NRL (National Rugby League), and soccer sporting sites in New South Wales and Victoria, Australia. Questions related to the frequency of viewing AFL and NRL matches, sports wagering promotions and perceptions of the normalisation of wagering in sport...
October 2016: Australian and New Zealand Journal of Public Health
R Grant Rowe, Leo D Wang, Silvia Coma, Areum Han, Ronald Mathieu, Daniel S Pearson, Samantha Ross, Patricia Sousa, Phi T Nguyen, Antony Rodriguez, Amy J Wagers, George Q Daley
For appropriate development, tissue and organ system morphogenesis and maturation must occur in synchrony with the overall developmental requirements of the host. Mistiming of such developmental events often results in disease. The hematopoietic system matures from the fetal state, characterized by robust erythrocytic output that supports prenatal growth in the hypoxic intrauterine environment, to the postnatal state wherein granulocytes predominate to provide innate immunity. Regulation of the developmental timing of these myeloerythroid states is not well understood...
July 25, 2016: Journal of Experimental Medicine
Fred H Gage, Leonard P Guarente, Amy J Wagers
No abstract text is available yet for this article.
August 2016: Trends in Molecular Medicine
Leo D Wang, Scott B Ficarro, John N Hutchinson, Roland Csepanyi-Komi, Phi T Nguyen, Eva Wisniewski, Jessica Sullivan, Oliver Hofmann, Erzsebet Ligeti, Jarrod A Marto, Amy J Wagers
Protein phosphorylation is a central mechanism of signal transduction that both positively and negatively regulates protein function. Large-scale studies of the dynamic phosphorylation states of cell signaling systems have been applied extensively in cell lines and whole tissues to reveal critical regulatory networks, and candidate-based evaluations of phosphorylation in rare cell populations have also been informative. However, application of comprehensive profiling technologies to adult stem cell and progenitor populations has been challenging, due in large part to the scarcity of such cells in adult tissues...
September 15, 2016: Blood
Sayaka Katagiri, Kyoungmin Park, Yasutaka Maeda, Tata Nageswara Rao, Mogher Khamaisi, Qian Li, Hisashi Yokomizo, Akira Mima, Luca Lancerotto, Amy Wagers, Dennis P Orgill, George L King
The effect of enhancing insulin's actions in endothelial cells (ECs) to improve angiogenesis and wound healing was studied in obesity and diabetes. Insulin receptor substrate 1 (IRS1) was overexpressed in ECs using the VE-cadherin promoter to create ECIRS1 TG mice, which elevated pAkt activation and expressions of vascular endothelial growth factor (VEGF), Flk1, and VE-cadherin in ECs and granulation tissues (GTs) of full-thickness wounds. Open wound and epithelialization rates and angiogenesis significantly improved in normal mice and high fat (HF) diet-induced diabetic mice with hyperinsulinemia in ECIRS1 TG versus wild type (WT), but not in insulin-deficient diabetic mice...
September 2016: Diabetes
Benjamin A Olenchock, Javid Moslehi, Alan H Baik, Shawn M Davidson, Jeremy Williams, William J Gibson, Abhishek A Chakraborty, Kerry A Pierce, Christine M Miller, Eric A Hanse, Ameeta Kelekar, Lucas B Sullivan, Amy J Wagers, Clary B Clish, Matthew G Vander Heiden, William G Kaelin
No abstract text is available yet for this article.
April 7, 2016: Cell
Ryan G Walker, Tommaso Poggioli, Lida Katsimpardi, Sean M Buchanan, Juhyun Oh, Sam Wattrus, Bettina Heidecker, Yick W Fong, Lee L Rubin, Peter Ganz, Thomas B Thompson, Amy J Wagers, Richard T Lee
Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely related members of the transforming growth factor β superfamily and are often perceived to serve similar or overlapping roles. Yet, despite commonalities in protein sequence, receptor utilization and signaling, accumulating evidence suggests that these 2 ligands can have distinct functions in many situations. GDF11 is essential for mammalian development and has been suggested to regulate aging of multiple tissues, whereas myostatin is a well-described negative regulator of postnatal skeletal and cardiac muscle mass and modulates metabolic processes...
April 1, 2016: Circulation Research
Albert E Almada, Amy J Wagers
Satellite cells are adult myogenic stem cells that repair damaged muscle. The enduring capacity for muscle regeneration requires efficient satellite cell expansion after injury, their differentiation to produce myoblasts that can reconstitute damaged fibres and their self-renewal to replenish the muscle stem cell pool for subsequent rounds of injury and repair. Emerging studies indicate that misregulation of satellite cell fate and function can contribute to age-associated muscle dysfunction and influence the severity of muscle diseases, including Duchenne muscular dystrophy (DMD)...
May 2016: Nature Reviews. Molecular Cell Biology
Benjamin A Olenchock, Javid Moslehi, Alan H Baik, Shawn M Davidson, Jeremy Williams, William J Gibson, Abhishek A Chakraborty, Kerry A Pierce, Christine M Miller, Eric A Hanse, Ameeta Kelekar, Lucas B Sullivan, Amy J Wagers, Clary B Clish, Matthew G Vander Heiden, William G Kaelin
Ischemic preconditioning is the phenomenon whereby brief periods of sublethal ischemia protect against a subsequent, more prolonged, ischemic insult. In remote ischemic preconditioning (RIPC), ischemia to one organ protects others organs at a distance. We created mouse models to ask if inhibition of the alpha-ketoglutarate (αKG)-dependent dioxygenase Egln1, which senses oxygen and regulates the hypoxia-inducible factor (HIF) transcription factor, could suffice to mediate local and remote ischemic preconditioning...
February 25, 2016: Cell
Wilson Kuswanto, Dalia Burzyn, Marisella Panduro, Kathy K Wang, Young Charles Jang, Amy J Wagers, Christophe Benoist, Diane Mathis
Normal repair of skeletal muscle requires local expansion of a special population of Foxp3(+)CD4(+) regulatory T (Treg) cells. Such cells failed to accumulate in acutely injured muscle of old mice, known to undergo ineffectual repair. This defect reflected reduced recruitment of Treg cells to injured muscle, as well as less proliferation and retention therein. Interleukin-33 (IL-33) regulated muscle Treg cell homeostasis in young mice, and its administration to old mice ameliorated their deficits in Treg cell accumulation and muscle regeneration...
February 16, 2016: Immunity
Mogher Khamaisi, Sayaka Katagiri, Hillary Keenan, Kyoungmin Park, Yasutaka Maeda, Qian Li, Weier Qi, Thomas Thomou, Danielle Eschuk, Ana Tellechea, Aris Veves, Chenyu Huang, Dennis Paul Orgill, Amy Wagers, George L King
Abnormal fibroblast function underlies poor wound healing in patients with diabetes; however, the mechanisms that impair wound healing are poorly defined. Here, we evaluated fibroblasts from individuals who had type 1 diabetes (T1D) for 50 years or more (Medalists, n = 26) and from age-matched controls (n = 7). Compared with those from controls, Medalist fibroblasts demonstrated a reduced migration response to insulin, lower VEGF expression, and less phosphorylated AKT (p-AKT), but not p-ERK, activation. Medalist fibroblasts were also functionally less effective at wound closure in nude mice...
March 1, 2016: Journal of Clinical Investigation
Mohammadsharif Tabebordbar, Kexian Zhu, Jason K W Cheng, Wei Leong Chew, Jeffrey J Widrick, Winston X Yan, Claire Maesner, Elizabeth Y Wu, Ru Xiao, F Ann Ran, Le Cong, Feng Zhang, Luk H Vandenberghe, George M Church, Amy J Wagers
Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration in Duchenne muscular dystrophy (DMD). Removing one or more exons from the mutated transcript can produce an in-frame mRNA and a truncated, but still functional, protein. In this study, we developed and tested a direct gene-editing approach to induce exon deletion and recover dystrophin expression in the mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonucleases coupled with paired guide RNAs flanking the mutated Dmd exon23 resulted in excision of intervening DNA and restored the Dmd reading frame in myofibers, cardiomyocytes, and muscle stem cells after local or systemic delivery...
January 22, 2016: Science
Simone Hettmer, Anna C Schinzel, Daria Tchessalova, Michaela Schneider, Christina L Parker, Roderick T Bronson, Nigel Gj Richards, William C Hahn, Amy J Wagers
Current therapies for sarcomas are often inadequate. This study sought to identify actionable gene targets by selective targeting of the molecular networks that support sarcoma cell proliferation. Silencing of asparagine synthetase (ASNS), an amidotransferase that converts aspartate into asparagine, produced the strongest inhibitory effect on sarcoma growth in a functional genomic screen of mouse sarcomas generated by oncogenic Kras and disruption of Cdkn2a. ASNS silencing in mouse and human sarcoma cell lines reduced the percentage of S phase cells and impeded new polypeptide synthesis...
2015: ELife
Tommaso Poggioli, Ana Vujic, Peiguo Yang, Claudio Macias-Trevino, Aysu Uygur, Francesco S Loffredo, James R Pancoast, Miook Cho, Jill Goldstein, Rachel M Tandias, Emilia Gonzalez, Ryan G Walker, Thomas B Thompson, Amy J Wagers, Yick W Fong, Richard T Lee
RATIONALE: Growth differentiation factor 11 (GDF11) and GDF8 are members of the transforming growth factor-β superfamily sharing 89% protein sequence homology. We have previously shown that circulating GDF11 levels decrease with age in mice. However, a recent study by Egerman et al reported that GDF11/8 levels increase with age in mouse serum. OBJECTIVE: Here, we clarify the direction of change of circulating GDF11/8 levels with age and investigate the effects of GDF11 administration on the murine heart...
January 8, 2016: Circulation Research
Simone Hettmer, Michael M Lin, Daria Tchessalova, Sara J Tortorici, Alessandra Castiglioni, Tushar Desai, Junhao Mao, Andrew P McMahon, Amy J Wagers
Hedgehog (Hh) pathway activation in R26-SmoM2;CAGGS-CreER mice, which carry a tamoxifen-inducible activated Smoothened allele (SmoM2), results in numerous microscopic tumor foci in mouse skeletal muscle. These tumors exhibit a highly differentiated myogenic phenotype and resemble human fetal rhabdomyomas. This study sought to apply previously established strategies to isolate lineally distinct populations of normal mouse myofiber-associated cells in order to examine cellular heterogeneity in SmoM2 tumors. We demonstrate that established SmoM2 tumors are composed of cells expressing myogenic, adipocytic and hematopoietic lineage markers and differentiation capacity...
January 1, 2016: Experimental Cell Research
Monika S Kowalczyk, Itay Tirosh, Dirk Heckl, Tata Nageswara Rao, Atray Dixit, Brian J Haas, Rebekka K Schneider, Amy J Wagers, Benjamin L Ebert, Aviv Regev
Both intrinsic cell state changes and variations in the composition of stem cell populations have been implicated as contributors to aging. We used single-cell RNA-seq to dissect variability in hematopoietic stem cell (HSC) and hematopoietic progenitor cell populations from young and old mice from two strains. We found that cell cycle dominates the variability within each population and that there is a lower frequency of cells in the G1 phase among old compared with young long-term HSCs, suggesting that they traverse through G1 faster...
December 2015: Genome Research
Manoj K Gupta, Adrian Kee Keong Teo, Tata Nageswara Rao, Shweta Bhatt, Andre Kleinridders, Jun Shirakawa, Tomozumi Takatani, Jiang Hu, Dario F De Jesus, Rebecca Windmueller, Amy J Wagers, Rohit N Kulkarni
UNLABELLED: The impact of somatic cell proliferation rate on induction of pluripotent stem cells remains controversial. Herein, we report that rapid proliferation of human somatic fibroblasts is detrimental to reprogramming efficiency when reprogrammed using a lentiviral vector expressing OCT4, SOX2, KLF4, and cMYC in insulin-rich defined medium. Human fibroblasts grown in this medium showed higher proliferation, enhanced expression of insulin signaling and cell cycle genes, and a switch from glycolytic to oxidative phosphorylation metabolism, but they displayed poor reprogramming efficiency compared with cells grown in normal medium...
October 2015: Stem Cells Translational Medicine
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