Digital Commons Network^™

Cardiovascular Adverse Events In Oncology Trials: Understanding And Appreciating The Differences Between Clinical Trial Data And Real-World Reports, Michael S Ewer, Jay Herson

Duncan NRI Faculty and Staff Publications

Reports of cardiac adverse events from oncology clinical trials often are at variance with reports derived from clinical observations or data-base reviews. These differences may lead to confusion, as different levels of risks abound in the literature, and the true cardiac risk of using some agents is uncertain. Additionally, such discrepancies may lead to the creation of over-cautious surveillance algorithms. Reasons for these reported differences are complex and often reflect subtleties in the criteria for individual patient evaluation. Both clinical trial data and real-world data have potential flaws that make reconciliation problematic. Importantly, however, both provide crucial information regarding the …

Sox9 Directs Divergent Epigenomic States In Brain Tumor Subtypes, Debosmita Sardar, Hsiao-Chi Chen, Amanda Reyes, Srinidhi Varadharajan, Antrix Jain, Carrie Mohila, Rachel Curry, Brittney Lozzi, Kavitha Rajendran, Alexis Cervantes, Kwanha Yu, Ali Jalali, Ganesh Rao, Stephen C Mack, Benjamin Deneen

Duncan NRI Faculty and Staff Publications

Epigenetic dysregulation is a universal feature of cancer that results in altered patterns of gene expression that drive malignancy. Brain tumors exhibit subtype-specific epigenetic alterations; however, the molecular mechanisms responsible for these diverse epigenetic states remain unclear. Here, we show that the developmental transcription factor Sox9 differentially regulates epigenomic states in high-grade glioma (HGG) and ependymoma (EPN). Using our autochthonous mouse models, we found that Sox9 suppresses HGG growth and expands associated H3K27ac states, while promoting ZFTA-RELA (ZR

Serum And Plasma Levels Of Brain-Derived Neurotrophic Factor In Individuals With Eating Disorders (Eds): A Systematic Review And Meta-Analysis, Parnian Shobeiri, Sara Bagherieh, Parsa Mirzayi, Amirali Kalantari, Omid Mirmosayyeb, Antônio L Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

Background: Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, development, and plasticity. Evidence suggests that fluctuations in peripheral levels (i.e., plasma or serum) of BDNF are associated with eating behaviors. Nevertheless, the findings are inconsistent. The purpose of this study is to determine if serum or plasma levels of BDNF are altered in individuals with eating disorders (EDs) compared to controls.

Methods: We conducted a systematic search of the core electronic medical databases from inception to March 2022 and identified observational studies that compared individuals with EDs to controls without EDs on serum or plasma levels of BDNF. …

A Narrative Review On Yoga: A Potential Intervention For Augmenting Immunomodulation And Mental Health In Covid-19, Indranill Basu-Ray, Kashinath Metri, Dibbendhu Khanra, Rishab Revankar, Kavitha M Chinnaiyan, Nagaratna Raghuram, Mahesh Chandra Mishra, Bhushan Patwardhan, Manjunath Sharma, Ishwar V Basavaraddi, Akshay Anand, Shrinath Reddy, K K Deepak, Marian Levy, Sue Theus, Glenn N Levine, Holger Cramer, Gregory L Fricchione, Nagendra R Hongasandra

Faculty, Staff and Students Publications

BACKGROUND: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has a significant mortality rate of 3-5%. The principal causes of multiorgan failure and death are cytokine release syndrome and immune dysfunction. Stress, anxiety, and depression has been aggravated by the pandemic and its resultant restrictions in day-to-day life which may contribute to immune dysregulation. Thus, immunity strengthening and the prevention of cytokine release syndrome are important for preventing and minimizing mortality in COVID-19 patients. However, despite a few specific remedies that now exist for the SARS-CoV-2virus, the principal modes of prevention include vaccination, masking, and holistic healing methods, such as …

Therapeutic Targeting Of Macrophage Plasticity Remodels The Tumor-Immune Microenvironment, Hee-Jin Jang, Hyun-Sung Lee, Wendong Yu, Maheshwari Ramineni, Cynthia Y Truong, Daniela Ramos, Taylor Splawn, Jong Min Choi, Sung Yun Jung, Ju-Seog Lee, Daniel Y Wang, Joel M Sederstrom, Massimo Pietropaolo, Farrah Kheradmand, Christopher I Amos, Thomas M Wheeler, R Taylor Ripley, Bryan M Burt

Center for Medical Ethics and Health Policy Staff Publications

Although the majority of patients with advanced lung adenocarcinoma (LUAD) are eligible to receive immune checkpoint blockade, approximately 80% of these tumors are resistant to this therapeutic approach. Insights at the single-cell level into mechanisms that drive LUAD tumorigenesis and the relationship of LUAD histologic heterogeneity to response to immune checkpoint blockade could help identify biomarkers and potential combinational approaches to improve immunotherapy efficacy. Here we used a genetically engineered mouse model that replicates the development of human LUAD through a spectrum of pre-invasive to invasive adenocarcinoma histologic subtypes. A systems onco-immunology approach of integrating the analytical power and unique, …

Cranial Base Synchondrosis Lacks Pthrp-Expressing Column-Forming Chondrocytes, Shawn A Hallett, Annabelle Zhou, Curtis Herzog, Ariel Arbiv, Wanida Ono, Noriaki Ono

Faculty, Staff and Student Publications

The cranial base contains a special type of growth plate termed the synchondrosis, which functions as the growth center of the skull. The synchondrosis is composed of bidirectional opposite-facing layers of resting, proliferating, and hypertrophic chondrocytes, and lacks the secondary ossification center. In long bones, the resting zone of the epiphyseal growth plate houses a population of parathyroid hormone-related protein (PTHrP)-expressing chondrocytes that contribute to the formation of columnar chondrocytes. Whether PTHrP+ chondrocytes in the synchondrosis possess similar functions remains undefined. Using Pthrp-mCherry knock-in mice, we found that PTHrP+ chondrocytes predominantly occupied the lateral wedge-shaped area of the synchondrosis, unlike …

Limited Benefit From The Addition Of Immunotherapy To Chemotherapy In Tki-Refractory Egfr-Mutant Lung Adenocarcinoma, Lingzhi Hong, Whitney E Lewis, Monique Nilsson, Sonia Patel, Susan Varghese, Melvin J Rivera, Robyn R Du, Pingjun Chen, Haley N Kemp, Waree Rinsurongkawong, Simon Heeke, Amy R Spelman, Yasir Y Elamin, Marcelo V Negrao, Boris Sepesi, Don L Gibbons, J Jack Lee, Jia Wu, Natalie I Vokes, John V Heymach, Jianjun Zhang, Xiuning Le

Faculty, Staff and Student Publications

Background: The benefit of chemotherapy combined with immunotherapy in EGFR-mutant lung adenocarcinoma (LUAD) patients whose tumor developed resistance to EGFR tyrosine kinase inhibitors (TKIs) is not thoroughly investigated. The goal of this retrospective cohort study is to assess the clinical efficiency of immunotherapy alone or in combination with chemotherapy in a real-world setting.

Methods: This retrospective cohort study enrolled LUAD patients with EGFR sensitive mutations whose tumor had acquired resistance to EGFR TKIs and received systemic treatment with chemotherapy (chemo; n = 84), chemotherapy combined with immunotherapy (chemoIO; n = 30), chemotherapy plus bevacizumab with or without IO (withBev; n …

A Method For Bridging Population-Specific Genotypes To Detect Gene Modules Associated With Alzheimer's Disease, Yulin Dai, Peilin Jia, Zhongming Zhao, Assaf Gottlieb

Faculty, Staff and Student Publications

BACKGROUND: Genome-wide association studies have successfully identified variants associated with multiple conditions. However, generalizing discoveries across diverse populations remains challenging due to large variations in genetic composition. Methods that perform gene expression imputation have attempted to address the transferability of gene discoveries across populations, but with limited success.

METHODS: Here, we introduce a pipeline that combines gene expression imputation with gene module discovery, including a dense gene module search and a gene set variation analysis, to address the transferability issue. Our method feeds association probabilities of imputed gene expression with a selected phenotype into tissue-specific gene-module discovery over protein interaction …

Scintillation Light Detection In The 6-M Drift-Length Protodune Dual Phase Liquid Argon Tpc, A Abed Abud, B Abi, R Acciarri, M A Acero, M R Adames, G Adamov, M Adamowski, D Adams, M Adinolfi, A Aduszkiewicz, J Aguilar, Z Ahmad, J Ahmed, B Aimard, B Ali-Mohammadzadeh, T Alion, K Allison, S Alonso Monsalve, M Alrashed, C Alt, A Alton, R Alvarez, P Amedo, J Anderson, C Andreopoulos, M Andreotti, M Andrews, F Andrianala, S Andringa, N Anfimov, A Ankowski, M Antoniassi, M Antonova, A Antoshkin, S Antusch, A Aranda-Fernandez, L Arellano, L O Arnold, M A Arroyave, J Asaadi, L Asquith, A Aurisano, V Aushev, D Autiero, V Ayala Lara, M Ayala-Torres, F Azfar, A Back, H Back, J J Back, C Backhouse, I Bagaturia, L Bagby, N Balashov, S Balasubramanian, P Baldi, B Baller, B Bambah, F Barao, G Barenboim, P Barham Alzas, G Barker, W Barkhouse, C Barnes, G Barr, J Barranco Monarca, A Barros, N Barros, J L Barrow, A Basharina-Freshville, A Bashyal, V Basque, C Batchelor, E Batista Das Chagas, J B R Battat, F Battisti, F Bay, M C Q Bazetto, J L L Bazo Alba, J F Beacom, E Bechetoille, B Behera, C Beigbeder, L Bellantoni, G Bellettini, V Bellini, O Beltramello, N Benekos, C Benitez Montiel, F Bento Neves, J Berger, S Berkman, P Bernardini, R M Berner, A Bersani, S Bertolucci, M Betancourt, A Betancur Rodríguez, A Bevan, Y Bezawada, T J C Bezerra, A Bhardwaj, V Bhatnagar, M Bhattacharjee, D Bhattarai, S Bhuller, B Bhuyan, S Biagi, J Bian, M Biassoni, K Biery, B Bilki, M Bishai, A Bitadze, A Blake, F Blaszczyk, G C Blazey, E Blucher, J Boissevain, S Bolognesi, T Bolton, L Bomben, M Bonesini, M Bongrand, C Bonilla-Diaz, F Bonini, A Booth, F Boran, S Bordoni, A Borkum, N Bostan, P Bour, C Bourgeois, D Boyden, J Bracinik, D Braga, D Brailsford, A Branca, A Brandt, J Bremer, D Breton, C Brew, S J Brice, C Brizzolari, C Bromberg, J Brooke, A Bross, G Brunetti, M Brunetti, N Buchanan, H Budd, I Butorov, I Cagnoli, T Cai, D Caiulo, R Calabrese, P Calafiura, J Calcutt, M Calin, S Calvez, E Calvo, A Caminata, M Campanelli, D Caratelli, D Carber, J C Carceller, G Carini, B Carlus, M F Carneiro, P Carniti, I Caro Terrazas, H Carranza, T Carroll, J F Castaño Forero, A Castillo, C Castromonte, E Catano-Mur, C Cattadori, F Cavalier, G Cavallaro, F Cavanna, S Centro, G Cerati, A Cervelli, A Cervera Villanueva, M Chalifour, A Chappell, E Chardonnet, N Charitonidis, A Chatterjee, S Chattopadhyay, M S S Chavarry Neyra, H Chen, M Chen, Y Chen, Z Chen, Z Chen-Wishart, Y Cheon, D Cherdack, C Chi, S Childress, R Chirco, A Chiriacescu, G Chisnall, K Cho, S Choate, D Chokheli, P S Chong, A Christensen, D Christian, G Christodoulou, A Chukanov, M Chung, E Church, V Cicero, P Clarke, G Cline, T E Coan, A G Cocco, J A B Coelho, N Colton, E Conley, R Conley, J Conrad, M Convery, S Copello, P Cova, L Cremaldi, L Cremonesi, J I Crespo-Anadón, M Crisler, E Cristaldo, J Crnkovic, R Cross, A Cudd, C Cuesta, Y Cui, D Cussans, O Dalager, H Da Motta, L Da Silva Peres, C David, Q David, G S Davies, S Davini, J Dawson, K De, S De, P Debbins, I De Bonis, M P Decowski, A De Gouvêa, P C De Holanda, I L De Icaza Astiz, A Deisting, P De Jong, A Delbart, D Delepine, M Delgado, A Dell'acqua, N Delmonte, P De Lurgio, J R T De Mello Neto, D M Demuth, S Dennis, C Densham, G W Deptuch, A De Roeck, V De Romeri, G De Souza, R Devi, R Dharmapalan, M Dias, F Diaz, J S Díaz, S Di Domizio, L Di Giulio, P Ding, L Di Noto, G Dirkx, C Distefano, R Diurba, M Diwan, Z Djurcic, D Doering, S Dolan, F Dolek, M Dolinski, L Domine, Y Donon, D Douglas, D Douillet, A Dragone, G Drake, F Drielsma, L Duarte, D Duchesneau, K Duffy, P Dunne, B Dutta, H Duyang, O Dvornikov, D Dwyer, A Dyshkant, M Eads, A Earle, D Edmunds, J Eisch, L Emberger, S Emery, P Englezos, A Ereditato, T Erjavec, C Escobar, G Eurin, J J Evans, E Ewart, A C Ezeribe, K Fahey, A Falcone, M Fani', C Farnese, Y Farzan, D Fedoseev, J Felix, Y Feng, E Fernandez-Martinez, P Fernandez Menendez, M Fernandez Morales, F Ferraro, L Fields, P Filip, F Filthaut, M Fiorini, V Fischer, R S Fitzpatrick, W Flanagan, B Fleming, R Flight, S Fogarty, W Foreman, J Fowler, W Fox, J Franc, K Francis, D Franco, J Freeman, J Freestone, J Fried, A Friedland, F Fuentes Robayo, S Fuess, I K Furic, K Furman, A P Furmanski, A Gabrielli, A Gago, H Gallagher, A Gallas, A Gallego-Ros, N Gallice, V Galymov, E Gamberini, T Gamble, F Ganacim, R Gandhi, R Gandrajula, F Gao, S Gao, D Garcia-Gamez, M Á García-Peris, S Gardiner, D Gastler, J Gauvreau, G Ge, N Geffroy, B Gelli, A Gendotti, S Gent, Z Ghorbani-Moghaddam, P Giammaria, T Giammaria, N Giangiacomi, D Gibin, I Gil-Botella, S Gilligan, C Girerd, A K Giri, D Gnani, O Gogota, M Gold, S Gollapinni, K Gollwitzer, R A Gomes, L V Gomez Bermeo, L S Gomez Fajardo, F Gonnella, D Gonzalez-Diaz, M Gonzalez-Lopez, M C Goodman, O Goodwin, S Goswami, C Gotti, E Goudzovski, C Grace, R Gran, E Granados, P Granger, A Grant, C Grant, D Gratieri, P Green, L Greenler, J Greer, J Grenard, W C Griffith, M Groh, J Grudzinski, K Grzelak, W Gu, E Guardincerri, V Guarino, M Guarise, R Guenette, E Guerard, M Guerzoni, D Guffanti, A Guglielmi, B Guo, A Gupta, V Gupta, K K Guthikonda, R Gutierrez, P Guzowski, M M Guzzo, S Gwon, C Ha, K Haaf, A Habig, H Hadavand, R Haenni, A Hahn, J Haiston, P Hamacher-Baumann, T Hamernik, P Hamilton, J Han, D A Harris, J Hartnell, T Hartnett, J Harton, T Hasegawa, C Hasnip, R Hatcher, K W Hatfield, A Hatzikoutelis, C Hayes, K Hayrapetyan, J Hays, E Hazen, M He, A Heavey, K M Heeger, J Heise, S Henry, M A Hernandez Morquecho, K Herner, J Hewes, C Hilgenberg, T Hill, S J Hillier, A Himmel, E Hinkle, L R Hirsch, J Ho, J Hoff, A Holin, E Hoppe, G A Horton-Smith, M Hostert, A Hourlier, B Howard, R Howell, J Hoyos, I Hristova, M S Hronek, J Huang, Z Hulcher, G Iles, N Ilic, A M Iliescu, R Illingworth, G Ingratta, A Ioannisian, B Irwin, L Isenhower, R Itay, C M Jackson, V Jain, E James, W Jang, B Jargowsky, F Jediny, D Jena, Y S Jeong, C Jesús-Valls, X Ji, L Jiang, S Jiménez, A Jipa, R Johnson, W Johnson, N Johnston, B Jones, S Jones, M Judah, C K Jung, T Junk, Y Jwa, M Kabirnezhad, A Kaboth, I Kadenko, I Kakorin, A Kalitkina, D Kalra, F Kamiya, N Kaneshige, D M Kaplan, G Karagiorgi, G Karaman, A Karcher, M Karolak, Y Karyotakis, S Kasai, S P Kasetti, L Kashur, N Kazaryan, E Kearns, P Keener, K J Kelly, E Kemp, O Kemularia, W Ketchum, S H Kettell, M Khabibullin, A Khotjantsev, A Khvedelidze, D Kim, B King, B Kirby, M Kirby, J Klein, A Klustova, T Kobilarcik, K Koehler, L W Koerner, D H Koh, S Kohn, P P Koller, L Kolupaeva, D Korablev, M Kordosky, T Kosc, U Kose, V A Kostelecký, K Kothekar, R Kralik, L Kreczko, F Krennrich, I Kreslo, W Kropp, T Kroupova, S Kubota, Y Kudenko, V A Kudryavtsev, S Kulagin, J Kumar, P Kumar, P Kunze, N Kurita, C Kuruppu, V Kus, T Kutter, J Kvasnicka, D Kwak, A Lambert, B Land, C E Lane, K Lang, T Langford, M Langstaff, J Larkin, P Lasorak, D Last, A Laundrie, G Laurenti, A Lawrence, I Lazanu, R Lazur, M Lazzaroni, T Le, S Leardini, J Learned, P Lebrun, T Lecompte, C Lee, S Y Lee, G Lehmann Miotto, R Lehnert, M A Leigui De Oliveira, M Leitner, L M Lepin, S W Li, Y Li, H Liao, C S Lin, Q Lin, S Lin, R A Lineros, J Ling, A Lister, B R Littlejohn, J Liu, Y Liu, S Lockwitz, T Loew, M Lokajicek, I Lomidze, K Long, T Lord, J M Losecco, W C Louis, X-G Lu, K B Luk, B Lunday, X Luo, E Luppi, T Lux, V P Luzio, J Maalmi, D Macfarlane, A A Machado, P Machado, C T Macias, J R Macier, A Maddalena, A Madera, P Madigan, S Magill, K Mahn, A Maio, A Major, J A Maloney, G Mandrioli, R C Mandujano, J Maneira, L Manenti, S Manly, A Mann, K Manolopoulos, M Manrique Plata, V N Manyam, L Manzanillas, M Marchan, A Marchionni, W Marciano, D Marfatia, C Mariani, J Maricic, R Marie, F Marinho, A D Marino, D Marsden, M Marshak, C Marshall, J Marshall, J Marteau, J Martín-Albo, N Martinez, D A Martinez Caicedo, P Martínez Miravé, S Martynenko, V Mascagna, K Mason, A Mastbaum, F Matichard, S Matsuno, J Matthews, C Mauger, N Mauri, K Mavrokoridis, I Mawby, R Mazza, A Mazzacane, E Mazzucato, T Mcaskill, E Mccluskey, N Mcconkey, K S Mcfarland, C Mcgrew, A Mcnab, A Mefodiev, P Mehta, P Melas, O Mena, H Mendez, P Mendez, D P Méndez, A Menegolli, G Meng, M D Messier, W Metcalf, T Mettler, M Mewes, H Meyer, T Miao, G Michna, T Miedema, V Mikola, R Milincic, G Miller, W Miller, J Mills, O Mineev, A Minotti, O G Miranda, S Miryala, C S Mishra, S R Mishra, A Mislivec, M Mitchell, D Mladenov, I Mocioiu, K Moffat, N Moggi, R Mohanta, T A Mohayai, N Mokhov, J Molina, L Molina Bueno, E Montagna, A Montanari, C Montanari, D Montanari, L M Montañno Zetina, S H Moon, M Mooney, A F Moor, D Moreno, D Moretti, C Morris, C Mossey, M Mote, E Motuk, C A Moura, J Mousseau, G Mouster, W Mu, L Mualem, J Mueller, M Muether, S Mufson, F Muheim, A Muir, M Mulhearn, D Munford, H Muramatsu, S Murphy, J Musser, J Nachtman, S Nagu, M Nalbandyan, R Nandakumar, D Naples, S Narita, A Nath, A Navrer-Agasson, N Nayak, M Nebot-Guinot, K Negishi, J K Nelson, J Nesbit, M Nessi, D Newbold, M Newcomer, H Newton, R Nichol, F Nicolas-Arnaldos, A Nikolica, E Niner, K Nishimura, A Norman, A Norrick, R Northrop, P Novella, J A Nowak, M Oberling, J Ochoa-Ricoux, A Olivier, A Olshevskiy, Y Onel, Y Onishchuk, J Ott, L Pagani, G Palacio, O Palamara, S Palestini, J M Paley, M Pallavicini, C Palomares, W Panduro Vazquez, E Pantic, V Paolone, V Papadimitriou, R Papaleo, A Papanestis, S Paramesvaran, S Parke, E Parozzi, Z Parsa, M Parvu, S Pascoli, L Pasqualini, J Pasternak, J Pater, C Patrick, L Patrizii, R B Patterson, S J Patton, T Patzak, A Paudel, B Paulos, L Paulucci, Z Pavlovic, G Pawloski, D Payne, V Pec, S J M Peeters, A Pena Perez, E Pennacchio, A Penzo, O L G Peres, J Perry, D Pershey, G Pessina, G Petrillo, C Petta, R Petti, V Pia, F Piastra, L Pickering, F Pietropaolo, V L Pimentel, G Pinaroli, K Plows, R Plunkett, R Poling, F Pompa, X Pons, N Poonthottathil, F Poppi, S Pordes, J Porter, M Potekhin, R Potenza, B V K S Potukuchi, J Pozimski, M Pozzato, S Prakash, T Prakash, M Prest, S Prince, F Psihas, D Pugnere, X Qian, J L Raaf, V Radeka, J Rademacker, B Radics, A Rafique, E Raguzin, M Rai, M Rajaoalisoa, I Rakhno, A Rakotonandrasana, L Rakotondravohitra, R Rameika, M A Ramirez Delgado, B Ramson, A Rappoldi, G Raselli, P Ratoff, S Raut, R F Razakamiandra, E M Rea, J S Real, B Rebel, R Rechenmacher, M Reggiani-Guzzo, J Reichenbacher, S D Reitzner, H Rejeb Sfar, A Renshaw, S Rescia, F Resnati, M Ribas, S Riboldi, C Riccio, G Riccobene, L C J Rice, J S Ricol, A Rigamonti, Y Rigaut, E V Rincón, H Ritchie-Yates, D Rivera, A Robert, L Rochester, M Roda, P Rodrigues, M J Rodriguez Alonso, E Rodriguez Bonilla, J Rodriguez Rondon, S Rosauro-Alcaraz, M Rosenberg, P Rosier, B Roskovec, M Rossella, M Rossi, J Rout, P Roy, A Rubbia, C Rubbia, B Russell, D Ruterbories, A Rybnikov, A Saa-Hernandez, R Saakyan, S Sacerdoti, T Safford, N Sahu, K Sakashita, P Sala, N Samios, O Samoylov, M C Sanchez, V Sandberg, D A Sanders, D Sankey, S Santana, M Santos-Maldonado, N Saoulidou, P Sapienza, C Sarasty, I Sarcevic, G Savage, V Savinov, A Scaramelli, A Scarff, A Scarpelli, T Schefke, H Schellman, S Schifano, P Schlabach, D Schmitz, A W Schneider, K Scholberg, A Schukraft, E Segreto, A Selyunin, C R Senise, J Sensenig, A Sergi, D Sgalaberna, M H Shaevitz, S Shafaq, F Shaker, M Shamma, R Sharankova, H R Sharma, R Sharma, R K Sharma, T Shaw, K Shchablo, C Shepherd-Themistocleous, A Sheshukov, S Shin, I Shoemaker, D Shooltz, R Shrock, H Siegel, L Simard, J Sinclair, G Sinev, J Singh, L Singh, P Singh, V Singh, R Sipos, F W Sippach, G Sirri, A Sitraka, K Siyeon, K Skarpaas, A Smith, E Smith, P Smith, J Smolik, M Smy, E Snider, P Snopok, D Snowden-Ifft, M Soares Nunes, H Sobel, M Soderberg, S Sokolov, C J Solano Salinas, S Söldner-Rembold, S R Soleti, N Solomey, V Solovov, W E Sondheim, M Sorel, A Sotnikov, J Soto-Oton, F A Soto Ugaldi, A Sousa, K Soustruznik, F Spagliardi, M Spanu, J Spitz, N J C Spooner, K Spurgeon, M Stancari, L Stanco, C Stanford, R Stein, H M Steiner, A F Steklain Lisbôa, J Stewart, B Stillwell, J Stock, F Stocker, T Stokes, M Strait, T Strauss, L Strigari, A Stuart, J G Suarez, J M Suárez Sunción, H Sullivan, D Summers, A Surdo, V Susic, L Suter, C M Sutera, R Svoboda, B Szczerbinska, A M Szelc, H Tanaka, S Tang, A Tapia, B Tapia Oregui, A Tapper, S Tariq, E Tarpara, N Tata, E Tatar, R Tayloe, A M Teklu, P Tennessen, M Tenti, K Terao, C A Ternes, F Terranova, G Testera, T Thakore, A Thea, J L Thompson, C Thorn, S C Timm, V Tishchenko, L Tomassetti, A Tonazzo, D Torbunov, M Torti, M Tortola, F Tortorici, N Tosi, D Totani, M Toups, C Touramanis, R Travaglini, J Trevor, S Trilov, W H Trzaska, Y Tsai, Y-T Tsai, Z Tsamalaidze, K V Tsang, N Tsverava, S Tufanli, C Tull, E Tyley, M Tzanov, L Uboldi, M A Uchida, J Urheim, T Usher, S Uzunyan, M R Vagins, P Vahle, S Valder, G D A Valdiviesso, E Valencia, R Valentim, Z Vallari, E Vallazza, J W F Valle, S Vallecorsa, R Van Berg, R G Van De Water, D Vanegas Forero, D Vannerom, F Varanini, D Vargas Oliva, G Varner, J Vasel, S Vasina, G Vasseur, N Vaughan, K Vaziri, S Ventura, A Verdugo, S Vergani, M A Vermeulen, M Verzocchi, M Vicenzi, H Vieira De Souza, C Vignoli, C Vilela, B Viren, T Vrba, T Wachala, A V Waldron, M Wallbank, C Wallis, H Wang, J Wang, L Wang, M H L S Wang, X Wang, Y Wang, K Warburton, D Warner, M O Wascko, D Waters, A Watson, K Wawrowska, P Weatherly, A Weber, M Weber, H Wei, A Weinstein, D Wenman, M Wetstein, A White, L H Whitehead, D Whittington, M J Wilking, A Wilkinson, C Wilkinson, Z Williams, F Wilson, R J Wilson, W Wisniewski, J Wolcott, T Wongjirad, A Wood, K Wood, E Worcester, M Worcester, K Wresilo, C Wret, W Wu, Y Xiao, F Xie, B Yaeggy, E Yandel, G Yang, K Yang, T Yang, A Yankelevich, N Yershov, K Yonehara, Y S Yoon, T Young, B Yu, H Yu, J Yu, Y Yu, W Yuan, R Zaki, J Zalesak, L Zambelli, B Zamorano, A Zani, L Zazueta, G P Zeller, J Zennamo, K Zeug, C Zhang, S Zhang, Y Zhang, M Zhao, E Zhivun, G Zhu, E D Zimmerman, S Zucchelli, J Zuklin, V Zutshi, R Zwaska, Dune Collaboration

Faculty, Staff and Students Publications

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6 × 6 × 6 m3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019–2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the …

Cranial Base Synchondrosis: Chondrocytes At The Hub, Shawn A Hallett, Wanida Ono, Renny T Franceschi, Noriaki Ono

Faculty, Staff and Student Publications

The cranial base is formed by endochondral ossification and functions as a driver of anteroposterior cranial elongation and overall craniofacial growth. The cranial base contains the synchondroses that are composed of opposite-facing layers of resting, proliferating and hypertrophic chondrocytes with unique developmental origins, both in the neural crest and mesoderm. In humans, premature ossification of the synchondroses causes midfacial hypoplasia, which commonly presents in patients with syndromic craniosynostoses and skeletal Class III malocclusion. Major signaling pathways and transcription factors that regulate the long bone growth plate-PTHrP-Ihh, FGF, Wnt, BMP signaling and Runx2-are also involved in the cranial base synchondrosis. Here, …

Neuronal Activity Induces Glucosylceramide That Is Secreted Via Exosomes For Lysosomal Degradation In Glia, Liping Wang, Guang Lin, Zhongyuan Zuo, Yarong Li, Seul Kee Byeon, Akhilesh Pandey, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Recessive variants in GBA1 cause Gaucher disease, a prevalent form of lysosome storage disease. GBA1 encodes a lysosomal enzyme that hydrolyzes glucosylceramide (GlcCer) into glucose and ceramide. Its loss causes lysosomal dysfunction and increased levels of GlcCer. We generated a null allele of the Drosophila ortholog Gba1b by inserting the Gal4 using CRISPR-Cas9. Here, we show that Gba1b is expressed in glia but not in neurons. Glial-specific knockdown recapitulates the defects found in Gba1b mutants, and these can be rescued by glial expression of human GBA1. We show that GlcCer is synthesized upon neuronal activity, and it is transported …

Describing Characteristics Of Adults With And Without Congenital Heart Defects Hospitalized With Covid-19, Perla Diaz, Will Coughlin, Wilson Lam, Peter Ermis, David Aguilar, Cecilia M Ganduglia Cazaban, A J Agopian

Faculty, Staff and Student Publications

BACKGROUND: We sought to describe patient characteristics in adults with and without congenital heart defects (CHDs) during hospitalization for COVID-19.

METHODS: We analyzed data collected by Optum®, a nationally representative database of electronic medical records, for 369 adults with CHDs and 41,578 without CHDs hospitalized for COVID-19 between January 1, 2020, and December 10, 2020. We used Poisson regression to describe and compare epidemiologic characteristics, heart-related conditions, and severe outcomes between these two groups.

RESULTS: The distributions of many epidemiologic characteristics were similar between the two groups, but patients with CHDs were significantly more likely to be current or former …

Infiltration Of Peripheral Immune Cells Into The Olfactory Bulb In A Mouse Model Of Acute Nasal Inflammation, Hinami Asano, Sanae Hasegawa-Ishii, Ken Arae, Aki Obara, Geoffroy Laumet, Robert Dantzer, Atsuyoshi Shimada

Faculty, Staff and Student Publications

Chronic nasal inflammation induces robust olfactory bulb (OB) atrophy in mice. Here we examined initial events that occur in the OB after bilateral intranasal administration of lipopolysaccharide, focusing on the olfactory nerve fibers and meninges. We analyzed the time course of OB and meninges inflammation using histological and biochemical approaches. Within 12 h, we observed increased chemokine expression and transient infiltration of peripheral immune cells into the OB, resulting in the development of pro-inflammatory status in the OB. Meningeal immunity was activated. Resident microglia produced anti-inflammatory cytokines within 24 h. These could be the initial events that lead to OB …

Pneumonitis After Immune Checkpoint Inhibitor Therapies In Patients With Acute Myeloid Leukemia: A Retrospective Cohort Study, Ajay Sheshadri, Alberto A Goizueta, Vickie R Shannon, David London, Guillermo Garcia-Manero, Hagop M Kantarjian, Farhad Ravandi-Kashani, Tapan M Kadia, Marina Y Konopleva, Courtney D Dinardo, Sherry Pierce, Abdulrazzak Zarifa, Aya A Albittar, Linda L Zhong, Fechukwu O Akhmedzhanov, Muhammad H Arain, Mansour Alfayez, Ahmad Alotaibi, Mehmet Altan, Aung Naing, Tito R Mendoza, Myrna C B Godoy, Girish Shroff, Sang T Kim, Saadia A Faiz, Dimitrios P Kontoyiannis, Fareed Khawaja, Kristofer Jennings, Naval G Daver

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICI), combined with hypomethylating agents, can be used to treat acute myeloid leukemia (AML), but this strategy results in a high rate of pneumonitis. The authors sought to determine risk factors for pneumonitis development and whether pneumonitis increased mortality.

Methods: The authors conducted a retrospective review of 258 AML patients who received ICI-containing regimens from 2016 to 2018. A multidisciplinary adjudication committee diagnosed pneumonia and pneumonitis by reviewing symptoms, imaging, microbiology, and response to therapies. To measure risk factors for pneumonitis and mortality, multivariate Cox proportional hazards models were constructed. Pneumonia, pneumonitis, and disease progression were …

The Origin Of Bladder Cancer From Mucosal Field Effects, Jolanta Bondaruk, Roman Jaksik, Ziqiao Wang, David Cogdell, Sangkyou Lee, Yujie Chen, Khanh Ngoc Dinh, Tadeusz Majewski, Li Zhang, Shaolong Cao, Feng Tian, Hui Yao, Paweł Kuś, Huiqin Chen, John N Weinstein, Neema Navai, Colin Dinney, Jianjun Gao, Dan Theodorescu, Christopher Logothetis, Charles C Guo, Wenyi Wang, David Mcconkey, Peng Wei, Marek Kimmel, Bogdan Czerniak

Faculty, Staff and Student Publications

Whole-organ mapping was used to study molecular changes in the evolution of bladder cancer from field effects. We identified more than 100 dysregulated pathways, involving immunity, differentiation, and transformation, as initiators of carcinogenesis. Dysregulation of interleukins signified the involvement of inflammation in the incipient phases of the process. An aberrant methylation/expression of multiple HOX genes signified dysregulation of the differentiation program. We identified three types of mutations based on their geographic distribution. The most common were mutations restricted to individual mucosal samples that targeted uroprogenitor cells. Two types of mutations were associated with clonal expansion and involved large areas of …

Kras Mutations As Essential Promoters Of Lymphangiogenesis Via Extracellular Vesicles In Pancreatic Cancer, Radu Pirlog, George A Calin

Faculty, Staff and Student Publications

Kirsten rat sarcoma virus (KRAS) gene mutations are present in more than 90% of pancreatic ductal adenocarcinomas (PDACs). KRASG12D is the most frequent alteration, promoting preneoplastic lesions and associating with a more aggressive phenotype. These tumors possess increased intratumoral lymphatic networks and frequent lymph node (LN) metastases. In this issue of the JCI, Luo, Li, et al. explored the relationship between the presence of the KRASG12D mutation and lymphangiogenesis in PDAC. The authors used in vitro and in vivo models and an elegant mechanistic approach to describe an alternative pathway for lymphangiogenesis promotion. KRASG12D induced SUMOylation of heterogenous nuclear ribonucleoprotein …

Alphafold2 And Cryoem: Revisiting Cryoem Modeling In Near-Atomic Resolution Density Maps, Corey F Hryc, Matthew L Baker

Faculty, Staff and Student Publications

With the advent of new artificial intelligence and machine learning algorithms, predictive modeling can, in some cases, produce structures on par with experimental methods. The combination of predictive modeling and experimental structure determination by electron cryomicroscopy (cryoEM) offers a tantalizing approach for producing robust atomic models of macromolecular assemblies. Here, we apply AlphaFold2 to a set of community standard data sets and compare the results with the corresponding reference maps and models. Moreover, we present three unique case studies from previously determined cryoEM density maps of viruses. Our results show that AlphaFold2 can not only produce reasonably accurate models for …

Impairing Proliferation Of Glioblastoma Multiforme With Cd44+ Selective Conjugated Polymer Nanoparticles, Dorota Lubanska, Sami Alrashed, Gage T Mason, Fatima Nadeem, Angela Awada, Mitchell Dipasquale, Alexandra Sorge, Aleena Malik, Monika Kojic, Mohamed A R Soliman, Ana C Decarvalho, Abdalla Shamisa, Swati Kulkarni, Drew Marquardt, Lisa A Porter, Simon Rondeau-Gagné

Faculty, Staff and Student Publications

Glioblastoma is one of the most aggressive types of cancer with success of therapy being hampered by the existence of treatment resistant populations of stem-like Tumour Initiating Cells (TICs) and poor blood-brain barrier drug penetration. Therapies capable of effectively targeting the TIC population are in high demand. Here, we synthesize spherical diketopyrrolopyrrole-based Conjugated Polymer Nanoparticles (CPNs) with an average diameter of 109 nm. CPNs were designed to include fluorescein-conjugated Hyaluronic Acid (HA), a ligand for the CD44 receptor present on one population of TICs. We demonstrate blood-brain barrier permeability of this system and concentration and cell cycle phase-dependent selective uptake …

Cd11bhigh B Cells Increase After Stroke And Regulate Microglia: Cd11bhigh B Cells Increase After Stroke And Regulate Mg, Janelle M Korf, Pedram Honarpisheh, Eric C Mohan, Anik Banerjee, Maria P Blasco-Conesa, Parisa Honarpisheh, Gary U Guzman, Romeesa Khan, Bhanu P Ganesh, Amy L Hazen, Juneyoung Lee, Aditya Kumar, Louise D Mccullough, Anjali Chauhan

Faculty, Staff and Student Publications

Recent studies have highlighted the deleterious contributions of B cells to post-stroke recovery and cognitive decline. Different B cell subsets have been proposed based on expression levels of transcription factors (e.g. T-bet) as well as specific surface proteins. CD11b (α-chain of integrin) is expressed by several immune cell types and is involved in regulation of cell motility, phagocytosis, and other essential functions of host immunity. Although B cells express CD11b, the CD11b^high subset of B cells has not been well characterized, especially in immune dysregulation seen with aging and after stroke. Here, we investigate the role of CD11b^{high …}

An Updated Assessment Of 43,110 Patients Enrolled In The Childhood Cancer Research Network: A Children’S Oncology Group Report, Austin L Brown, Pagna Sok, Michael E Scheurer, Karen R Rabin, Erin L Marcotte, Douglas S Hawkins, Logan G Spector, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Background: The Childhood Cancer Research Network (CCRN) was established by the Children's Oncology Group (COG) as a resource for epidemiologic studies of childhood cancer. The objective of this study was to evaluate the representativeness of CCRN and identify factors associated with enrollment.

Method: The number of US childhood patients with cancer diagnosed < 20 years of age enrolled in CCRN (2008-2015) was compared to expected counts, calculated from Surveillance, Epidemiology, and End Results incidence rates and US Census population estimates. Observed-to-expected ratios and corresponding 95% confidence intervals (CI) were estimated across sex, race, diagnosis age, calendar year, and cancer diagnosis groups. Multivariable linear regression models were generated to evaluate the association between open COG phase 3 therapeutic trials and CCRN enrollment rates.

Result: The 43,110 cases enrolled in CCRN represented 36% of the expected childhood cancers diagnosed from 2008 to 2015 (N = 120,118). CCRN enrollment ratios [95% CI] were highest among males (0.38 [95% CI, 0.37-0.38]), non-Hispanics (0.35 [95% CI, 0.35-0.36]), and those diagnosed from 1 to 4 years …

Toward A Standard Formal Semantic Representation Of The Model Card Report, Muhammad Tuan Amith, Licong Cui, Degui Zhi, Kirk Roberts, Xiaoqian Jiang, Fang Li, Evan Yu, Cui Tao

Faculty, Staff and Student Publications

BACKGROUND: Model card reports aim to provide informative and transparent description of machine learning models to stakeholders. This report document is of interest to the National Institutes of Health's Bridge2AI initiative to address the FAIR challenges with artificial intelligence-based machine learning models for biomedical research. We present our early undertaking in developing an ontology for capturing the conceptual-level information embedded in model card reports.

RESULTS: Sourcing from existing ontologies and developing the core framework, we generated the Model Card Report Ontology. Our development efforts yielded an OWL2-based artifact that represents and formalizes model card report information. The current release of …

Toward A Standard Formal Semantic Representation Of The Model Card Report, Muhammad Tuan Amith, Licong Cui, Degui Zhi, Kirk Roberts, Xiaoqian Jiang, Fang Li, Evan Yu, Cui Tao

Faculty, Staff and Student Publications

BACKGROUND: Model card reports aim to provide informative and transparent description of machine learning models to stakeholders. This report document is of interest to the National Institutes of Health's Bridge2AI initiative to address the FAIR challenges with artificial intelligence-based machine learning models for biomedical research. We present our early undertaking in developing an ontology for capturing the conceptual-level information embedded in model card reports.

RESULTS: Sourcing from existing ontologies and developing the core framework, we generated the Model Card Report Ontology. Our development efforts yielded an OWL2-based artifact that represents and formalizes model card report information. The current release of …

Glyoxal Fixation Is Optimal For Immunostaining Of Brain Vessels, Pericytes And Blood-Brain Barrier Proteins, Sithara Thomas, Jayanarayanan Sadanandan, Spiros L Blackburn, Devin W Mcbride, Ari Dienel, Sungha Hong, Hussein A Zeineddine, Peeyush Kumar Thankamani

Faculty, Staff and Student Publications

Brain vascular staining is very important for understanding cerebrovascular pathologies. 4% paraformaldehyde is considered the gold standard fixation technique for immunohistochemistry and it revolutionized the examination of proteins in fixed tissues. However, this fixation technique produces inconsistent immunohistochemical staining results due to antigen masking. Here, we test a new fixation protocol using 3% glyoxal and demonstrate that this method improves the staining of the brain vasculature, pericytes, and tight junction proteins compared to 4% paraformaldehyde. Use of this new fixation technique will provide more detailed information about vascular protein expressions, their distributions, and colocalizations with other proteins at the molecular …

Comparison Of Flash-Free And Conventional Bonding Systems: A Systematic Review And Meta-Analysis, He Wang, Ge Feng, Bo Hu, Haonan Tian, Yunchun Kuang, Tingwei Zhang, Jinlin Song

Faculty, Staff and Student Publications

OBJECTIVES: To review the literature systematically to compare the performance of adhesive precoated flash-free bonding systems with conventional adhesive precoated (APC) and operator-coated (OPC) bonding systems.

MATERIALS AND METHODS: PubMed, Cochrane Library, Web of Science, and Embase were searched for potential eligible studies. Study selection and data collection were conducted independently. Statistical analysis was performed by Review Manager 5.3. The Cochran Q test was used to test heterogeneity in the included studies. Risk of bias was evaluated using Cochrane RoB 2.0 tool for randomized controlled trials.

RESULTS: Six studies were included and the overall risk-of-bias judgment was low risk of …

Differential Susceptibility Of Retinal Neurons To The Loss Of Mitochondrial Biogenesis Factor Nrf1, Takae Kiyama, Ching-Kang Chen, Annie Zhang, Chai-An Mao

Faculty, Staff and Student Publications

The retina, the accessible part of the central nervous system, has served as a model system to study the relationship between energy utilization and metabolite supply. When the metabolite supply cannot match the energy demand, retinal neurons are at risk of death. As the powerhouse of eukaryotic cells, mitochondria play a pivotal role in generating ATP, produce precursors for macromolecules, maintain the redox homeostasis, and function as waste management centers for various types of metabolic intermediates. Mitochondrial dysfunction has been implicated in the pathologies of a number of degenerative retinal diseases. It is well known that photoreceptors are particularly vulnerable …

Antiphospholipid Antibodies And Vitamin D Deficiency In Covid-19 Infection With And Without Venous Or Arterial Thrombosis: A Pilot Case-Control Study, Ruchi Shah, Yaqub Nadeem Mohammed, Tracy J Koehler, Jasmeet Kaur, Margarita Toufeili, Priyanjali Pulipati, Ahmed Alqaysi, Ali Khan, Mahrukh Khalid, Yi Lee, Parveen Dhillon, Anna Thao Dan, Nicholas Kumar, Monica Bowen, Anupam A Sule, Geetha Krishnamoorthy

Faculty, Staff and Student Publications

BACKGROUND: Coronavirus disease-2019 (COVID-19) is associated with thromboembolism. Antiphospholipid antibody (APLa) formation is one of the mechanisms. Vitamin D deficiency has been associated with thrombosis in antiphospholipid antibody syndrome.

OBJECTIVE: Measure APLa and vitamin D in hospitalized COVID-19 patients with and without thrombosis to evaluate if thromboembolism is associated with concomitant APLa and vitamin D deficiency.

METHODS: Case-control study. Hospitalized COVID-19 patients with a thromboembolic event (ischemic stroke, myocardial infarction, deep venous thrombosis/pulmonary embolism, Cases n = 20). Controls (n = 20): Age, sex-matched without thromboembolic events. Patients with autoimmune disorders, antiphospholipid antibody syndrome, thrombophilia, anticoagulation therapy, prior thromboembolism, chronic …

Editorial: Physiologic Signals In Neonatal Intensive Care, Eric W Reynolds

Faculty, Staff and Student Publications

No abstract provided.

Triplet Therapy, Transplantation, And Maintenance Until Progression In Myeloma, Paul G Richardson, Susanna J Jacobus, Edie A Weller, Hani Hassoun, Sagar Lonial, Noopur S Raje, Eva Medvedova, Philip L Mccarthy, Edward N Libby, Peter M Voorhees, Robert Z Orlowski, Larry D Anderson, Jeffrey A Zonder, Carter P Milner, Cristina Gasparetto, Mounzer E Agha, Abdullah M Khan, David D Hurd, Krisstina Gowin, Rammurti T Kamble, Sundar Jagannath, Nitya Nathwani, Melissa Alsina, R Frank Cornell, Hamza Hashmi, Erica L Campagnaro, Astrid C Andreescu, Teresa Gentile, Michaela Liedtke, Kelly N Godby, Adam D Cohen, Thomas H Openshaw, Marcelo C Pasquini, Sergio A Giralt, Jonathan L Kaufman, Andrew J Yee, Emma Scott, Pallawi Torka, Amy Foley, Mariateresa Fulciniti, Kyle Hebert, Mehmet K Samur, Kelly Masone, Michelle E Maglio, Andrea A Zeytoonjian, Omar Nadeem, Robert L Schlossman, Jacob P Laubach, Claudia Paba-Prada, Irene M Ghobrial, Aurore Perrot, Philippe Moreau, Hervé Avet-Loiseau, Michel Attal, Kenneth C Anderson, Nikhil C Munshi, Determination Investigators

Faculty, Staff and Students Publications

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown.

METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received …

Gut Bacterial Isoamylamine Promotes Age-Related Cognitive Dysfunction By Promoting Microglial Cell Death, Yun Teng, Jingyao Mu, Fangyi Xu, Xiangcheng Zhang, Mukesh K Sriwastva, Qiaohong M Liu, Xiaohong Li, Chao Lei, Kumaran Sundaram, Xin Hu, Lifeng Zhang, Juw Won Park, Jae Yeon Hwang, Eric C Rouchka, Xiang Zhang, Jun Yan, Michael L Merchant, Huang-Ge Zhang

Faculty, Staff and Student Publications

The intestinal microbiome releases a plethora of small molecules. Here, we show that the Ruminococcaceae metabolite isoamylamine (IAA) is enriched in aged mice and elderly people, whereas Ruminococcaceae phages, belonging to the Myoviridae family, are reduced. Young mice orally administered IAA show cognitive decline, whereas Myoviridae phage administration reduces IAA levels. Mechanistically, IAA promotes apoptosis of microglial cells by recruiting the transcriptional regulator p53 to the S100A8 promoter region. Specifically, IAA recognizes and binds the S100A8 promoter region to facilitate the unwinding of its self-complementary hairpin structure, thereby subsequently enabling p53 to access the S100A8 promoter and enhance S100A8 expression. …

The Testis-Specific E3 Ubiquitin Ligase Rnf133 Is Required For Fecundity In Mice, Kaori Nozawa, Yoshitaka Fujihara, Darius J Devlin, Ricardo E Deras, Katarzyna Kent, Irina V Larina, Kohei Umezu, Zhifeng Yu, Courtney M Sutton, Qiuji Ye, Laura K Dean, Chihiro Emori, Masahito Ikawa, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

BACKGROUND: Ubiquitination is a post-translational modification required for a number of physiological functions regulating protein homeostasis, such as protein degradation. The endoplasmic reticulum (ER) quality control system recognizes and degrades proteins no longer needed in the ER through the ubiquitin-proteasome pathway. E2 and E3 enzymes containing a transmembrane domain have been shown to function in ER quality control. The ER transmembrane protein UBE2J1 is a E2 ubiquitin-conjugating enzyme reported to be essential for spermiogenesis at the elongating spermatid stage. Spermatids from Ube2j1 KO male mice are believed to have defects in the dislocation step of ER quality control. However, associated …