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1,598 results on '"Chandel, A. S."'

8. Mitochondria regulate proliferation in adult cardiac myocytes

Author

Waypa, Gregory B., Smith, Kimberly A., Mungai, Paul T., Dudley, Vincent J., Helmin, Kathryn A., Singer, Benjamin D., Peek, Clara Bien, Bass, Joseph, Nelson, Lauren, Shah, Sanjiv J., Ofman, Gaston, Wasserstrom, J. Andrew, Muller, William A., Misharin, Alexander V., Budinger, G.R. Scott, Abdala-Valencia, Hiam, Chandel, Navdeep S., Dokic, Danijela, Bartom, Elizabeth, Zhang, Shuang, Tatekoshi, Yuki, Mahmoodzadeh, Amir, Ardehali, Hossein, Thorp, Edward B., and Schumacker, Paul T.

Subjects
Oxidative phosphorylation -- Health aspects, RNA sequencing -- Analysis, Ischemia -- Complications and side effects -- Care and treatment, Epigenetic inheritance -- Analysis, Mitochondrial DNA -- Analysis, Health care industry, Care and treatment, Analysis, Complications and side effects, Health aspects
Abstract

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfsl (mitochondrial Rieske iron- sulfur protein, RISP) in hearts of adult mice. As RISP protein decreased, heart mitochondrial function declined, and glucose utilization increased. Simultaneously, the hearts underwent hyperplastic remodeling during which cardiomyocyte number doubled without cellular hypertrophy. Cellular energy supply was preserved, AMPK activation was absent, and mTOR activation was evident. In ischemic hearts with RISP deletion, new cardiomyocytes migrated into the infarcted region, suggesting the potential for therapeutic cardiac regeneration. RNA sequencing revealed upregulation of genes associated with cardiac development and proliferation. Metabolomic analysis revealed a decrease in a-ketoglutarate (required for TET-mediated demethylation) and an increase in 5-adenosylmethionine (required for methyltransferase activity). Analysis revealed an increase in methylated CpGs near gene transcriptional start sites. Genes that were both differentially expressed and differentially methylated were linked to upregulated cardiac developmental pathways. We conclude that decreased mitochondrial function and increased glucose utilization can restore mitotic capacity in adult cardiomyocytes, resulting in the generation of new heart cells, potentially through the modification of substrates that regulate epigenetic modification of genes required for proliferation., Introduction Mitochondria generate ATP through oxidative phosphorylation (OXPHOS), but they also participate in diverse biological functions that include redox signaling (1), metabolite signaling (2), calcium signaling (3), and the generation [...]

Published
2024
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11. NSD2 drives t(4;14) myeloma cell dependence on adenylate kinase 2 by diverting one-carbon metabolism to the epigenome

Author

Sobh, Amin, Encinas, Elena, Patel, Alisha, Surapaneni, Greeshma, Bonilla, Emilie, Kaestner, Charlotte, Poullard, Janai, Clerio, Monica, Vasan, Karthik, Freeman, Tzipporah, Lv, Dongwen, Dupéré-Richer, Daphné, Riva, Alberto, Barwick, Benjamin G., Zhou, Daohong, Boise, Lawrence H., Mitsiades, Constantine S., Kim, Baek, Bennett, Richard L., Chandel, Navdeep S., and Licht, Jonathan D.

Published
2024
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15. Prevention Is Better Than Cure: Experimental Evidence From Milk Fever Incidence in Dairy Animals of Haryana, India

Author

Cariappa, A. G. Adeeth, Chandel, B. S., Sankhala, Gopal, Mani, Veena, R, Sendhil, Dixit, Anil Kumar, and Meena, B. S.

Subjects
Economics - General Economics
Abstract

Calcium deficiency in high yielding bovines during calving causes milk fever which leads to economic losses of around INR 1000 crores (USD 137 million) per annum in Haryana, India. With increasing milk production, the risk of milk fever is continuously rising. In the context, we aim to address the most fundamental research question: What is the effect of a preventive health product (anionic mineral mixture (AMM)) on milk fever incidence, milk productivity and farmers income? In an effort to contribute to the scanty economic literature on effect of preventive measures on nutritional deficiency disorders in dairy animals, specifically, on AMM effects in India, this study uses a randomized controlled design to estimate internally valid estimates. Using data from 200 dairy farms, results indicate that milk fever incidence decreases from 21 per cent at baseline to 2 per cent in treated animals at follow-up. Further, AMM leads to a 12 per cent and 38 per cent increase in milk yield and farmers net income, respectively. Profits earned due to the prevention of milk fever [INR 16000 (USD 218.7)] overweighs the losses from milk fever [INR 4000 (USD 54.7)]; thus, prevention using AMM is better than cure.

Published
2021
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16. T cells sustain antitumor response by mediating crosstalk between adenosine A2A receptor and glutathione/GPX4

Author

Chen, Siqi, Fan, Jie, Xie, Ping, Ahn, Jihae, Fernandez, Michelle, Billingham, Leah K., Miska, Jason, Wu, Jennifer D., Wainwright, Derek A., Fang, Deyu, Sosman, Jeffrey A., Wan, Yong, Zhang, Yi, Chandel, Navdeep S., and Zhang, Bin

Subjects
Oncology, Experimental -- Physiological aspects, Lipid peroxidation -- Physiological aspects, T cells -- Physiological aspects, Cancer -- Care and treatment -- Research, Health care industry
Abstract

Antitumor responses of [CD8.sup.+] T cells are tightly regulated by distinct metabolic fitness. High levels of glutathione (GSH) are observed in the majority of tumors, contributing to cancer progression and treatment resistance in part by preventing glutathione peroxidase 4-dependent (GPX4-dependent) ferroptosis. Here, we show the necessity of adenosine A2A receptor (A2AR) signaling and the GSH/GPX4 axis in orchestrating metabolic fitness and survival of functionally competent [CD8.sup.+] T cells. Activated [CD8.sup.+] T cells treated ex vivo with simultaneous inhibition of A2AR and lipid peroxidation acquire a superior capacity to proliferate and persist in vivo, demonstrating a translatable means to prevent ferroptosis in adoptive cell therapy. Additionally, we identify a particular cluster of intratumoral [CD8.sup.+] T cells expressing a putative gene signature of GSH metabolism (GMGS) in association with clinical response and survival across several human cancers. Our study addresses a key role of GSH/GPX4 and adenosinergic pathways in fine-tuning the metabolic fitness of antitumor [CD8.sup.+] T cells., Introduction Glutathione (GSH) is the most abundant antioxidant that maintains cellular redox homeostasis. De novo synthesis of GSH is coordinated by the sequential actions of glutaminase, [gamma]-glutamate-cysteine ligase, and GSH [...]

Published
2024
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18. Estimation of economic losses due to milk fever and efficiency gains if prevented: evidence from Haryana, India

Author

Cariappa, A. G. A., Chandel, B. S., Sankhala, G., Mani, V., Sendhil, R., Dixit, A. K., and Meena, B. S.

Subjects
Economics - General Economics
Abstract

Calcium (Ca) requirement increases tenfold upon parturition in dairy cows & buffaloes and its deficiency leads to a condition called milk fever (MF). Estimation of losses is necessary to understand the depth of the problem and design preventive measures. How much is the economic loss due to MF? What will be the efficiency gain if MF is prevented at the advent of a technology? We answer these questions using survey data and official statistics employing economic surplus model. MF incidence in sample buffaloes and cows was 19% and 28%, respectively. Total economic losses were calculated as a sum total of losses from milk production, mortality of animals and treatment costs. Yearly economic loss due to MF was estimated to be INR 1000 crores (US$ 137 million) in Haryana. Value of milk lost had the highest share in total economic losses (58%), followed by losses due to mortality (29%) and treatment costs (13%). Despite lower MF incidence, losses were higher in buffaloes due to higher milk prices and market value of animals. The efficiency gain accruing to producers if MF is prevented, resulting from increased milk production at decreased costs was estimated at INR 10990 crores (US$ 1.5 billion). As the potential gain if prevented is around 10 times the economic losses, this study calls for the use of preventive technology against MF.

Published
2021
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20. Smart Agricultural Mechanization in India—Status and Way Forward

Author

Mehta, C. R., Chandel, N. S., Dubey, Kumkum, Kumar, Amit, Series Editor, Suganthan, Ponnuthurai Nagaratnam, Series Editor, Haase, Jan, Series Editor, Senatore, Sabrina, Editorial Board Member, Gao, Xiao-Zhi, Editorial Board Member, Mozar, Stefan, Editorial Board Member, Srivastava, Pradeep Kumar, Editorial Board Member, and Pakeerathan, Kandiah, editor

Published
2023
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21. Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth

Author

Rashidi, Aida, Billingham, Leah K., Zolp, Andrew, Chia, Tzu-yi, Silvers, Caylee, Katz, Joshua L., Park, Cheol H., Delay, Suzi, Boland, Lauren, Geng, Yuheng, Markwell, Steven M., Dmello, Crismita, Arrieta, Victor A., Zilinger, Kaylee, Jacob, Irene M., Lopez-Rosas, Aurora, Hou, David, Castro, Brandyn, Steffens, Alicia M., McCortney, Kathleen, Walshon, Jordain P., Flowers, Mariah S., Lin, Hanchen, Wang, Hanxiang, Zhao, Junfei, Sonabend, Adam, Zhang, Peng, Ahmed, Atique U., Brat, Daniel J., Heiland, Dieter H., Lee-Chang, Catalina, Lesniak, Maciej S., Chandel, Navdeep S., and Miska, Jason

Published
2024
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23. Molecular and cellular mechanisms underlying the failure of mitochondrial metabolism drugs in cancer clinical trials

Author

Vasan, Karthik and Chandel, Navdeep S.

Subjects
Medical colleges -- Physiological aspects, Clinical trials -- Physiological aspects, Cancer -- Drug therapy, Electron transport -- Physiological aspects, Health care industry
Abstract

The majority of cancer cells have a functional mitochondrial electron transport chain (ETC). Mitochondrial complex I is the primary entry point into the ETC, where oxidative phosphorylation occurs, generating ATP [...]

Published
2024
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26. Aging is associated with a systemic length-associated transcriptome imbalance

Author

Stoeger, Thomas, Grant, Rogan A., McQuattie-Pimentel, Alexandra C., Anekalla, Kishore R., Liu, Sophia S., Tejedor-Navarro, Heliodoro, Singer, Benjamin D., Abdala-Valencia, Hiam, Schwake, Michael, Tetreault, Marie-Pier, Perlman, Harris, Balch, William E., Chandel, Navdeep S., Ridge, Karen M., Sznajder, Jacob I., Morimoto, Richard I., Misharin, Alexander V., Budinger, G. R. Scott, and Nunes Amaral, Luis A.

Published
2022
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44. Author Correction: Reduced expression of mitochondrial complex I subunit Ndufs2 does not impact healthspan in mice

Author

McElroy, Gregory S., Chakrabarty, Ram P., D’Alessandro, Karis B., Hu, Yuan-Shih, Vasan, Karthik, Tan, Jerica, Stoolman, Joshua S., Weinberg, Samuel E., Steinert, Elizabeth M., Reyfman, Paul A., Singer, Benjamin D., Ladiges, Warren C., Gao, Lin, Lopéz‑Barneo, José, Ridge, Karen, Budinger, G. R. Scott, and Chandel, Navdeep S.

Published
2022
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