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4. Causal Image Synthesis of Brain MR in 3D

Author

Li, Yujia, Shi, Jiong, and Zhou, S. Kevin

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Machine Learning
Abstract

Clinical decision making requires counterfactual reasoning based on a factual medical image and thus necessitates causal image synthesis. To this end, we present a novel method for modeling the causality between demographic variables, clinical indices and brain MR images for Alzheimer's Diseases. Specifically, we leverage a structural causal model to depict the causality and a styled generator to synthesize the image. Furthermore, as a crucial step to reduce modeling complexity and make learning tractable, we propose the use of low dimensional latent feature representation of a high-dimensional 3D image, together with exogenous noise, to build causal relationship between the image and non image variables. We experiment the proposed method based on 1586 subjects and 3683 3D images and synthesize counterfactual brain MR images intervened on certain attributes, such as age, brain volume and cognitive test score. Quantitative metrics and qualitative evaluation of counterfactual images demonstrates the superiority of our generated images., Comment: 11 pages

Published
2023

18. Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data

Author

Kaddurah-Daouk, Rima, Kueider-Paisley, Alexandra, Doraiswamy, P. Murali, Blach, Colette, Moseley, Arthur, Thompson, Will, St John-Williams, Lisa, Mahmoudiandehkhordi, Siamak, Tenenbaum, Jessica, Welsh-Balmer, Kathleen, Plassman, Brenda, Saykin, Andrew J., Nho, Kwangsik, Risacher, Shannon L., Kastenmüller, Gabi, Arnold, Matthias, Han, Xianlin, Baillie, Rebecca, Knight, Rob, Dorrestein, Pieter, Brewer, James, Mayer, Emeran, Labus, Jennifer, Baldi, Pierre, Gupta, Arpana, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Rader, Dan, Kling, Mitchel, Shaw, Leslie, Trojanowski, John, van Duijin, Cornelia, Nevado-Holgado, Alejo, Bennett, David, Krishnan, Ranga, Keshavarzian, Ali, Vogt, Robin, Ikram, Arfan, Hankemeier, Thomas, Thiele, Ines, Price, Nathan, Funk, Cory, Baloni, Priyanka, Jia, Wei, Wishart, David, Brinton, Roberta, Chang, Rui, Farrer, Lindsay, Au, Rhoda, Qiu, Wendy, Würtz, Peter, Koal, Therese, Mangravite, Lara, Krumsiek, Jan, Suhre, Karsten, Newman, John, Moreno, Herman, Foroud, Tatania, Sacks, Frank, Jansson, Janet, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Morris, John C., Perrin, Richard J., Shaw, Leslie M., Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, Gonzalez, Hector, Ho, Carole, Hsiao, John K., Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, Perrin, Richard, Ryan, Laurie, Silverberg, Nina, Fleisher, Adam, Sacrey, Diana Truran, Fockler, Juliet, Conti, Cat, Veitch, Dallas, Neuhaus, John, Jin, Chengshi, Nosheny, Rachel, Ashford, Miriam, Flenniken, Derek, Kormos, Adrienne, Montine, Tom, Rafii, Michael, Raman, Rema, Jimenez, Gustavo, Donohue, Michael, Gessert, Devon, Salazar, Jennifer, Zimmerman, Caileigh, Cabrera, Yuliana, Walter, Sarah, Miller, Garrett, Coker, Godfrey, Clanton, Taylor, Hergesheimer, Lindsey, Smith, Stephanie, Adegoke, Olusegun, Mahboubi, Payam, Moore, Shelley, Pizzola, Jeremy, Shaffer, Elizabeth, Sloan, Brittany, Harvey, Danielle, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Schwarz, Christopher, Jones, David, Gunter, Jeff, Kantarci, Kejal, Senjem, Matthew, Vemuri, Prashanthi, Reid, Robert, Fox, Nick C., Malone, Ian, Thompson, Paul, Thomopoulos, Sophia I., Nir, Talia M., Jahanshad, Neda, DeCarli, Charles, Knaack, Alexander, Fletcher, Evan, Tosun-Turgut, Duygu, Chen, Stephanie Rossi, Choe, Mark, Crawford, Karen, Yushkevich, Paul A., Das, Sandhitsu, Koeppe, Robert A., Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Franklin, Erin, Bernhardt, Haley, Taylor-Reinwald, Lisa, Korecka, Magdalena, Figurski, Michal, Neu, Scott, Apostolova, Liana G., Shen, Li, Foroud, Tatiana M., Nudelman, Kelly, Faber, Kelley, Wilmes, Kristi, Thal, Leon, Silbert, Lisa C., Lind, Betty, Crissey, Rachel, Kaye, Jeffrey A., Carter, Raina, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Dagerman, Karen, Spann, Bryan M., Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S., Doody, Rachelle S., Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Mintz, Akiva, Ances, Beau, Winkfield, David, Carroll, Maria, Stobbs-Cucchi, Georgia, Oliver, Angela, Creech, Mary L., Mintun, Mark A., Schneider, Stacy, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Marson, Daniel, Grossman, Hillel, Goldstein, Martin A., Greenberg, Jonathan, Mitsis, Effie, Shah, Raj C., Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T., Rodriguez, Rosemarie, Albert, Marilyn, Onyike, Chiadi, Farrington, Leonie, Rudow, Scott, Brichko, Rottislav, Kielb, Stephanie, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Sadowski, Martin, Wisniewski, Thomas, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Sheikh, Mohammed O., Singleton-Garvin, Jamika, Petrella, JeffreyR., James, Olga, Wong, Terence Z., Borges-Neto, Salvador, Karlawish, Jason H., Wolk, David A., Vaishnavi, Sanjeev, Clark, Christopher M., Arnold, Steven E., Smith, Charles D., Jicha, Gregory A., Raslau, Flavius D., Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Kelley, Brendan, Nguyen, Trung, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Hajjar, Ihab, Cellar, Janet S., Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Silverman, Daniel H.S., Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H., Bartzokis, George, Woo, Ellen, Teng, Edmond, Graff-Radford, Neill R., Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van, Christopher H., Mecca, Adam P., Good, Susan P., MacAvoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunis, Susan, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Heyn, Chris (Chinthaka), Robin Hsiung, Ging-Yuek, Kim, Ellen, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Rogers, John, Grant, Ian, Muse, Brittanie, Rogalski, Emily, Robson, Jordan, Mesulam, M.-Marsel, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Rosen, Howard J., Miller, Bruce L., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, MCCann, Kelly, Poe, Jessica, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad A., Yesavage, Jerome, Taylor, Joy L., Chao, Steven, Coleman, Jaila, White, Jessica D., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Belden, Christine M., Atri, Alireza, Clark, Kelly A., Zamrini, Edward, Sabbagh, Marwan, Killiany, Ronald, Stern, Robert, Mez, Jesse, Kowall, Neil, Budson, Andrew E., Obisesan, Thomas O., Ntekim, Oyonumo E., Wolday, Saba, Khan, Javed I., Nwulia, Evaristus, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Maillard, Pauline, Olichney, John, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T.-Y., Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Perrin, Allison, Burke, Anna, Scharre, Douglas W., Kataki, Maria, Tarawneh, Rawan, Hart, David, Zimmerman, Earl A., Celmins, Dzintra, Miller, Delwyn D., BolesPonto, Laura L., Smith, Karen Ekstam, Koleva, Hristina, Shim, Hyungsub, Nam, Ki Won, Schultz, Susan K., Williamson, Jeff D., Craft, Suzanne, Cleveland, Jo, Yang, Mia, Sink, Kaycee M., Ott, Brian R., Drake, Jonathan, Tremont, Geoffrey, Daiello, Lori A., Drake, Jonathan D., Ritter, Aaron, Bernick, Charles, Munic, Donna, O'Connelll, Abigail, Mintzer, Jacobo, Wiliams, Arthur, Masdeu, Joseph, Shi, Jiong, Garcia, Angelica, Newhouse, Paul, Potkin, Steven, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Kittur, Smita, Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Relkin, Norman, Chiang, Gloria, Lee, Athena, Lin, Michael, Ravdin, Lisa, Petersen, Ron, Neylan, Thomas, Grafman, Jordan, Danowski, Sarah, Nguyen-Barrera, Catherine, Hayes, Jacqueline, Finley, Shannon, Bernstein, Matthew, Senjem, Matt, Foster, Norm, Kim, Sungeun, Sood, Ajay, Blanchard, Kimberly S., Fleischman, Debra, Arfanakis, Konstantinos, Varon, Daniel, Greig, Maria T., Petrella, Jeffrey R., Goldstein, Bonnie, Martin, Kimberly S., Reist, Christopher, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Rosen, Howard, Marshall, Gad, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Mackin, Scott, Jimenez-Maggiora, Gustavo, Drake, Erin, Donohue, Mike, Nelson, Craig, Bickford, David, Butters, Meryl, Zmuda, Michelle, Reyes, Denise, Faber, Kelley M., Nudelman, Kelly N., Au, Yiu Ho, Scherer, Kelly, Catalinotto, Daniel, Stark, Samuel, Ong, Elise, Fernandez, Dariella, Jo, Taeho, Kim, Junpyo, Bice, Paula, Huynh, Kevin, Wang, Tingting, Meikle, Peter J., and Giles, Corey

Published
2023
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30. Elasticity of the HIV-1 core facilitates nuclear entry and infection.

Author

Deshpande, Akshay, Bryer, Alexander J., Andino-Moncada, Jonathan R., Shi, Jiong, Hong, Jun, Torres, Cameron, Harel, Shimon, Francis, Ashwanth C., Perilla, Juan R., Aiken, Christopher, and Rousso, Itay

Subjects
NUCLEAR pore complex, ATOMIC force microscopy, NUCLEAR forces (Physics), HIV, ELASTICITY
Abstract

HIV-1 infection requires passage of the viral core through the nuclear pore of the cell, a process that depends on functions of the viral capsid. Recent studies have shown that HIV-1 cores enter the nucleus prior to capsid disassembly. Interactions of the viral capsid with the nuclear pore complex are necessary but not sufficient for nuclear entry, and the mechanism by which the viral core traverses the comparably sized nuclear pore is unknown. Here we show that the HIV-1 core is highly elastic and that this property is linked to nuclear entry and infectivity. Using atomic force microscopy-based approaches, we found that purified wild type cores rapidly returned to their normal conical morphology following a severe compression. Results from independently performed molecular dynamic simulations of the mature HIV-1 capsid also revealed its elastic property. Analysis of four HIV-1 capsid mutants that exhibit impaired nuclear entry revealed that the mutant viral cores are brittle. Adaptation of two of the mutant viruses in cell culture resulted in additional substitutions that restored elasticity and rescued infectivity and nuclear entry. We also show that capsid-targeting compound PF74 and the antiviral drug Lenacepavir reduce core elasticity and block HIV-1 nuclear entry at concentrations that preserve interactions between the viral core and the nuclear envelope. Our results indicate that elasticity is a fundamental property of the HIV-1 core that enables nuclear entry, thereby facilitating infection. These results provide new insights into the role of the capsid in HIV-1 nuclear entry and the antiviral mechanisms of HIV-1 capsid inhibitors. Author summary: The genetic material of HIV-1 is packaged inside a cone shaped container that is called the viral core. To infect a cell, the viral core must pass through the cell's nuclear pore. Using atomic force microscopy, a technique that uses a tiny needle to feel the surface of things at the microscopic level, and molecular dynamic simulations, we discovered that wild-type HIV-1 cores quickly revert to their normal shape after compression, while capsid mutants with impaired nuclear entry are brittle. Restoring elasticity in these mutants recovered their ability to infect. Treatment with capsid-targeting drugs also reduced core elasticity. These findings suggest that capsid elasticity is essential for HIV-1 nuclear entry and infection, offering new insights into HIV-1 mechanics and potential antiviral strategies. [ABSTRACT FROM AUTHOR]

Published
2024
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31. The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.

Author

Jennings, Jordan, Bracey, Harrison, Hong, Jun, Nguyen, Danny T., Dasgupta, Rishav, Rivera, Alondra Vázquez, Sluis-Cremer, Nicolas, Shi, Jiong, and Aiken, Christopher

Subjects
GENETIC transcription, VIRAL envelopes, VIRAL DNA, T cells, HIV, VIRAL envelope proteins
Abstract

The viral capsid performs critical functions during HIV-1 infection and is a validated target for antiviral therapy. Previous studies have established that the proper structure and stability of the capsid are required for efficient HIV-1 reverse transcription in target cells. Moreover, it has recently been demonstrated that permeabilized virions and purified HIV-1 cores undergo efficient reverse transcription in vitro when the capsid is stabilized by addition of the host cell metabolite inositol hexakisphosphate (IP6). However, the molecular mechanism by which the capsid promotes reverse transcription is undefined. Here we show that wild type HIV-1 virions can undergo efficient reverse transcription in vitro in the absence of a membrane-permeabilizing agent. This activity, originally termed "natural endogenous reverse transcription" (NERT), depends on expression of the viral envelope glycoprotein during virus assembly and its incorporation into virions. Truncation of the gp41 cytoplasmic tail markedly reduced NERT activity, suggesting that gp41 licenses the entry of nucleotides into virions. By contrast to reverse transcription in permeabilized virions, NERT required neither the addition of IP6 nor a mature capsid, indicating that an intact viral membrane can substitute for the function of the viral capsid during reverse transcription in vitro. Collectively, these results demonstrate that the viral capsid functions as a nanoscale container for reverse transcription during HIV-1 infection. Author summary: HIV-1 infection is critically dependent on reverse transcription, or copying of the viral RNA into DNA, following entry of the viral core in target cells. Reverse transcription depends on the stability of the capsid, yet the precise function the capsid serves during the reaction has not been established. Here we show that the viral capsid functions as a container for the reaction. Addition of dNTPs to intact virions in the absence of a permeabilizing agent resulted in efficient reverse transcription (NERT). Analysis of HIV-1 mutants revealed that the reaction depends on the cytoplasmic domain of gp41, confirming an earlier report. By contrast to the reaction in permeabilized virions, NERT required neither a stable nor a mature capsid, nor was it affected by the capsid-destabilizing inhibitor PF74. NERT also occurred in HIV-1 particles produced in various T cell lines and in simian immunodeficiency particles. Our results demonstrate that the capsid serves a container role in HIV-1 reverse transcription and suggest that it remains fully intact during reverse transcription in target cells. They further suggest that the gp41 protein can permeabilize membranes to nucleotides, potentially contributing to viral dissemination and pathogenesis in the infected host. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Geochronology and geochemistry of the Hekoulinchang Sn-Pb-Zn-Ag polymetallic deposit (73240 t) in Heilongjiang Province, China

Author

Yong Zhang, Quan-heng Song, Shi-jiong Han, and Jian-hua Ding

Subjects
Cassiterite U-Pb dating, Zircon U-Pb dating, Nd-Hf isotopes, Porphyry Sn-Pb-Zn-Ag polymetallic deposit, Hekoulinchang, Heilongjiang Province, Engineering (General). Civil engineering (General), TA1-2040, Geology, QE1-996.5
Abstract

The Hekoulinchang Sn-Pb-Zn-Ag polymetallic deposit (20000 t Sn at 0.27%, 236 t Ag at 122.89 g/t, 15000 t Pb at 0.84%, and 38000 t Zn at 1.43%) is located in the Wandashan Terrane of the easternmost segment of the Central Asian Orogenic Belt. The timing of Sn-Pb-Zn-Ag polymetallic mineralization remains unclear due to a lack of precise isotope dating directly conducted on ore minerals. The authors herein report that the LA-ICP-MS U-Pb ages of cassiterite and zircon from the granite porphyry in the Hekoulinchang Sn-Pb-Zn-Ag polymetallic deposit are 101.4±7.9 Ma and 115.4±1.0 Ma, respectively, indicating that Sn mineralization and magmatism occurred during the Early Cretaceous. The granite porphyry belongs to the subalkaline series peraluminous I-type granites that are depleted in Nb, Ta, and Ti and enriched in Rb, Th, U, and Pb. The εHf(t) values of the granite porphyry range from 0.9 to 7.4, with an average of about 5.6 and two-stage model ages (TDM2) of 705–1116 Ma, with an average age of 819 Ma. The εNd(t) values of the apatites are –1.60–0.45, with an average of –0.9, and two-stage model ages (TDM2) of 872–1040 Ma, with an average age of 983 Ma. The Nd-Hf isotope data indicate that the magma may have been derived from the partial melting of juvenile crustal material.© 2022 China Geology Editorial Office.

Published
2022
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35. Flexible Wood-Based Janus Hydrogel for Nasal Infection

Author

He, Lei, primary, Liu, Yongze, additional, Zhu, Haomiao, additional, Chen, Feng, additional, Shi, Jiong, additional, Song, Panpan, additional, Feng, Fuqi, additional, Cui, Juqing, additional, Ma, Xiaofeng, additional, and Zhang, Jun, additional

Published
2024
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40. The Impact of Aging on Brain Pituitary Adenylate Cyclase Activating Polypeptide, Pathology and Cognition in Mice and Rhesus Macaques

Author

Han, Pengcheng, Nielsen, Megan, Song, Melissa, Yin, Junxiang, Permenter, Michele R, Vogt, Julie A, Engle, James R, Dugger, Brittany N, Beach, Thomas G, Barnes, Carol A, and Shi, Jiong

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Acquired Cognitive Impairment, Neurosciences, Neurodegenerative, Alzheimer's Disease, Behavioral and Social Science, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Alzheimer's disease, PACAP, aging, nonhuman primates, Alzheimer’s disease, Biochemistry and Cell Biology, Cognitive Sciences, Biological psychology
Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is associated with Alzheimer's disease (AD), but its age-related effects are unknown. We chose the rhesus macaque due to its closeness to human anatomy and physiology. We examined four variables: aging, cognitive performance, amyloid plaques and PACAP. Delayed nonmatching-to-sample recognition memory scores declined with age and correlated with PACAP levels in the striatum, parietal and temporal lobes. Because amyloid plaques were the only AD pathology in the old rhesus macaque, we further studied human amyloid precursor protein (hAPP) transgenic mice. Aging was associated with decreased performance in the Morris Water Maze (MWM). In wild type (WT) C57BL/6 mice, the performance was decreased at age 24-26 month whereas in hAPP transgenic mice, it was decreased as early as 9-12 month. Neuritic plaques in adult hAPP mice clustered in hippocampus and adjacent cortical regions, but did not propagate further into the frontal cortex. Cerebral PACAP protein levels were reduced in hAPP mice compared to age-matched WT mice, but the genetic predisposition dominated cognitive decline. Taken together, these data suggest an association among PACAP levels, aging, cognitive function and amyloid load in nonhuman primates, with both similarities and differences from human AD brains. Our results suggest caution in choosing animal models and in extrapolating data to human AD studies.

Published
2017

42. Oncogenic Roles of Laminin Subunit Gamma‐2 in Intrahepatic Cholangiocarcinoma via Promoting EGFR Translation.

Author

Zhang, Jianjuan, Ji, Fubo, Tan, Yaqi, Zhao, Lei, Zhao, Yongzhi, Liu, Jiaxin, Shao, Liyuan, Shi, Jiong, Ye, Meihua, He, Xianglei, Jin, Jianping, Zhao, Bin, Huang, Jun, Roessler, Stephanie, Zheng, Xin, and Ji, Junfang

Subjects
INTRAHEPATIC bile ducts, EPIDERMAL growth factor receptors, CHOLANGIOCARCINOMA, PROTEIN-tyrosine kinase inhibitors, LIVER cancer, BILE ducts
Abstract

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal biliary epithelial cancer in the liver. Here, Laminin subunit gamma‐2 (LAMC2) with important oncogenic roles in iCCA is discovered. In a total of 231 cholangiocarcinoma patients (82% of iCCA patients) across four independent cohorts, LAMC2 is significantly more abundant in iCCA tumor tissue compared to normal bile duct and non‐tumor liver. Among 26.3% of iCCA patients, LAMC2 gene is amplified, contributing to its over‐expression. Functionally, silencing LAMC2 significantly blocks tumor formation in orthotopic iCCA mouse models. Mechanistically, it promotes EGFR protein translation via interacting with nascent unglycosylated EGFR in the endoplasmic reticulum (ER), resulting in activated EGFR signaling. LAMC2‐mediated EGFR translation also depends on its interaction with the ER chaperone BiP via their C‐terminus. Together LAMC2 and BiP generate a binding "pocket" of nascent EGFR and facilitate EGFR translation. Consistently, LAMC2‐high iCCA patients have poor prognosis in two iCCA cohorts. LAMC2‐high iCCA cells are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) treatment both in vitro and in vivo. Together, these data demonstrate LAMC2 as an oncogenic player in iCCA by promoting EGFR translation and an indicator to identify iCCA patients who may benefit from available EGFR‐targeted TKIs therapies. [ABSTRACT FROM AUTHOR]

Published
2024
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46. A randomized, double‐blind, placebo‐controlled phase 1b study to evaluate the safety, tolerability, and pharmacodynamics of an anti‐amyloid‐β antibody SHR‐1707 in patients with mild cognitive impairment and mild Alzheimer’s disease

Author

Shi, Jiong, primary, Cheng, Zhaozhao, additional, Lv, Xinyi, additional, Wang, Qiong, additional, Ye, Zi, additional, Qiu, Hongyan, additional, Zhu, Mengyuan, additional, Feng, Sheng, additional, Wang, Yuqi, additional, and Cheng, Gang, additional

Published
2023
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49. Arizona Brain and Body Donation Program

Author

Beach, Thomas G, Adler, Charles H, Sue, Lucia I, Serrano, Geidy, Shill, Holly A, Walker, Douglas G, Lue, LihFen, Roher, Alex E, Dugger, Brittany N, Maarouf, Chera, Birdsill, Alex C, Intorcia, Anthony, Saxon-Labelle, Megan, Pullen, Joel, Scroggins, Alexander, Filon, Jessica, Scott, Sarah, Hoffman, Brittany, Garcia, Angelica, Caviness, John N, Hentz, Joseph G, Driver-Dunckley, Erika, Jacobson, Sandra A, Davis, Kathryn J, Belden, Christine M, Long, Kathy E, Malek-Ahmadi, Michael, Powell, Jessica J, Gale, Lisa D, Nicholson, Lisa R, Caselli, Richard J, Woodruff, Bryan K, Rapscak, Steven Z, Ahern, Geoffrey L, Shi, Jiong, Burke, Anna D, Reiman, Eric M, and Sabbagh, Marwan N

Subjects
Clinical Research, Parkinson's Disease, Brain Disorders, Neurodegenerative, Neurosciences, Aging, Neurological, Aged, 80 and over, Arizona, Autopsy, Biomarkers, Brain, Female, Humans, Male, Neurodegenerative Diseases, Organ Preservation, Postmortem Changes, Tissue Banks, Tissue Donors, Tissue Survival, Tissue and Organ Procurement, aging, Alzheimer's disease, autopsy, biobank, biospecimen, brain bank, cancer, freeze-thaw, Parkinson's disease, pathology, post-mortem interval, RNA, Clinical Sciences, Neurology & Neurosurgery
Abstract

The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain-only donations and currently has banked more than 1600 brains. More than 430 whole-body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer's Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson's Research. The Program has made rapid autopsy a priority, with a 3.0-hour median post-mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200 grant-funded projects.

Published
2015

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