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Hypophosphorylated Prb Knock-In Mice Exhibit Hallmarks Of Aging And Vitamin C-Preventable Diabetes, Zhe Jiang, Huiqin Li, Stephanie A. Schroer, Veronique Voisin, Young Jun Ju, Marek Pacal, Natalie Erdmann, Wei Shi, Philip E.D. Chung, Tao Deng, Nien Jung Chen, Giovanni Ciavarra, Alessandro Datti, Tak W. Mak, Lea Harrington, Frederick A. Dick, Gary D. Bader, Rod Bremner, Minna Woo, Eldad Zacksenhaus
Hypophosphorylated Prb Knock-In Mice Exhibit Hallmarks Of Aging And Vitamin C-Preventable Diabetes, Zhe Jiang, Huiqin Li, Stephanie A. Schroer, Veronique Voisin, Young Jun Ju, Marek Pacal, Natalie Erdmann, Wei Shi, Philip E.D. Chung, Tao Deng, Nien Jung Chen, Giovanni Ciavarra, Alessandro Datti, Tak W. Mak, Lea Harrington, Frederick A. Dick, Gary D. Bader, Rod Bremner, Minna Woo, Eldad Zacksenhaus
Paediatrics Publications
Despite extensive analysis of pRB phosphorylation in vitro, how this modification influences development and homeostasis in vivo is unclear. Here, we show that homozygous Rb∆K4 and Rb∆K7 knock-in mice, in which either four or all seven phosphorylation sites in the C-terminal region of pRb, respectively, have been abolished by Ser/Thr-to-Ala substitutions, undergo normal embryogenesis and early development, notwithstanding suppressed phosphorylation of additional upstream sites. Whereas Rb∆K4 mice exhibit telomere attrition but no other abnormalities, Rb∆K7 mice are smaller and display additional hallmarks of premature aging including infertility, kyphosis, and diabetes, indicating an accumulative effect of blocking pRb phosphorylation. Diabetes in …
Development Of A Standardized Histopathology Scoring System Using Machine Learning Algorithms For Intervertebral Disc Degeneration In The Mouse Model—An Ors Spine Section Initiative, Itzel Paola Melgoza, Srish S. Chenna, Steven Tessier, Yejia Zhang, Simon Y. Tang, Takashi Ohnishi, Emanuel José Novais, Geoffrey J. Kerr, Sarthak Mohanty, Vivian Tam, Wilson C.W. Chan, Chao Ming Zhou, Ying Zhang, Victor Y. Leung, Angela K. Brice, Cheryle A. Séguin, Danny Chan, Nam Vo, Makarand V. Risbud, Chitra L. Dahia
Development Of A Standardized Histopathology Scoring System Using Machine Learning Algorithms For Intervertebral Disc Degeneration In The Mouse Model—An Ors Spine Section Initiative, Itzel Paola Melgoza, Srish S. Chenna, Steven Tessier, Yejia Zhang, Simon Y. Tang, Takashi Ohnishi, Emanuel José Novais, Geoffrey J. Kerr, Sarthak Mohanty, Vivian Tam, Wilson C.W. Chan, Chao Ming Zhou, Ying Zhang, Victor Y. Leung, Angela K. Brice, Cheryle A. Séguin, Danny Chan, Nam Vo, Makarand V. Risbud, Chitra L. Dahia
Paediatrics Publications
Mice have been increasingly used as preclinical model to elucidate mechanisms and test therapeutics for treating intervertebral disc degeneration (IDD). Several intervertebral disc (IVD) histological scoring systems have been proposed, but none exists that reliably quantitate mouse disc pathologies. Here, we report a new robust quantitative mouse IVD histopathological scoring system developed by building consensus from the spine community analyses of previous scoring systems and features noted on different mouse models of IDD. The new scoring system analyzes 14 key histopathological features from nucleus pulposus (NP), annulus fibrosus (AF), endplate (EP), and AF/NP/EP interface regions. Each feature is categorized and …
Lactate Dehydrogenase Expression Modulates Longevity And Neurodegeneration In Drosophila Melanogaster, Dani M. Long, Ariel Frame, Patrick N. Reardon, Robert C. Cumming, David A. Hendrix, Doris Kretzschmar, Jadwiga M. Giebultowicz
Lactate Dehydrogenase Expression Modulates Longevity And Neurodegeneration In Drosophila Melanogaster, Dani M. Long, Ariel Frame, Patrick N. Reardon, Robert C. Cumming, David A. Hendrix, Doris Kretzschmar, Jadwiga M. Giebultowicz
Paediatrics Publications
Lactate dehydrogenase (LDH) catalyzes the conversion of glycolysis-derived pyruvate to lactate. Lactate has been shown to play key roles in brain energetics and memory formation. However, lactate levels are elevated in aging and Alzheimer's disease patients, and it is not clear whether lactate plays protective or detrimental roles in these contexts. Here we show that Ldh transcript levels are elevated and cycle with diurnal rhythm in the heads of aged flies and this is associated with increased LDH protein, enzyme activity, and lactate concentrations. To understand the biological significance of increased Ldh gene expression, we genetically manipulated Ldh levels in …
P62, Ref(2)P And Ubiquitinated Proteins Are Conserved Markers Of Neuronal Aging, Aggregate Formation And Progressive Autophagic Defects, Bryan J. Bartlett, Pauline Isakson, Jan Lewerenz, Heriberto Sanchez, Roxanne W. Kotzebue, Robert Cumming, Greg L. Harris, Ioannis P. Nezis, David Schubert, Anne Simonsen, Kim D. Finley
P62, Ref(2)P And Ubiquitinated Proteins Are Conserved Markers Of Neuronal Aging, Aggregate Formation And Progressive Autophagic Defects, Bryan J. Bartlett, Pauline Isakson, Jan Lewerenz, Heriberto Sanchez, Roxanne W. Kotzebue, Robert Cumming, Greg L. Harris, Ioannis P. Nezis, David Schubert, Anne Simonsen, Kim D. Finley
Paediatrics Publications
Suppression of macroautophagy, due to mutations or through processes linked to aging, results in the accumulation of cytoplasmic substrates that are normally eliminated by the pathway. This is a significant problem in long-lived cells like neurons, where pathway defects can result in the accumulation of aggregates containing ubiquitinated proteins. The p62/Ref(2)P family of proteins is involved in the autophagic clearance of cytoplasmic protein bodies or sequestosomes. These unique structures are closely associated with protein inclusions containing ubiquitin as well as key components of the autophagy pathway. In this study we show that detergent fractionation followed by western blot analysis of …
The Expression Of Ovine Placental Lactogen, Star And Progesterone-Associated Steroidogenic Enzymes In Placentae Of Overnourished Growing Adolescent Ewes., Richard G Lea, Peter Wooding, Ian Stewart, Lisa T Hannah, Stephen Morton, Karen Wallace, Raymond P Aitken, John S Milne, Timothy Regnault, Russell V Anthony, Jacqueline M Wallace
The Expression Of Ovine Placental Lactogen, Star And Progesterone-Associated Steroidogenic Enzymes In Placentae Of Overnourished Growing Adolescent Ewes., Richard G Lea, Peter Wooding, Ian Stewart, Lisa T Hannah, Stephen Morton, Karen Wallace, Raymond P Aitken, John S Milne, Timothy Regnault, Russell V Anthony, Jacqueline M Wallace
Paediatrics Publications
Overnourishing pregnant adolescent sheep promotes maternal growth but reduces placental mass, lamb birth weight and circulating progesterone. This study aimed to determine whether altered progesterone reflected transcript abundance for StAR (cholesterol transporter) and the steroidogenic enzymes (Cyp11A1, Hsd3b and Cyp17). Circulating and placental expression of ovine placental lactogen (oPL) was also investigated. Adolescent ewes with singleton pregnancies were fed high (H) or moderate (M) nutrient intake diets to restrict or support placental growth. Experiment 1: peripheral progesterone and oPL concentrations were measured in H (n=7) and M (n=6) animals across gestation (days 7-140). Experiment 2: progesterone was measured to mid- …