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102. Non‐selective dampening of the host immune response after hepatitis C clearance and its association with circulating chemokine and endotoxin levels

Author

Quinn, Gabriella, primary, Ali, Rabab O., additional, Zhang, Grace Y., additional, Hill, Kareen, additional, Townsend, Elizabeth, additional, Umarova, Regina, additional, Chakraborty, Moumita, additional, Ahmad, Maleeha F., additional, Gewirtz, Meital, additional, Haddad, James, additional, Rosenzweig, Sergio, additional, Rampertaap, Shakuntala, additional, Schoenfeld, Megan, additional, Yang, Shanna, additional, Koh, Christopher, additional, Levy, Elliot, additional, Kleiner, David E., additional, Etzion, Ohad, additional, and Heller, Theo, additional

Published
2023
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108. Methodology

Author

Sabet, Peyman G. P., Zhang, Grace Q., Sabet, Peyman G. P., and Zhang, Grace Q.

Published
2015
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112. Optimized Vitamin D Repletion in Refractory Patients Undergoing Stem Cell Transplant with Oral Thin Film Cholecalciferol

Author

Bartlett, Allison L, primary, Zhang, Grace, additional, Wallace, Gregory, additional, McLean, Stacie, additional, Myers, Kasiani C, additional, Teusink-Cross, Ashley, additional, Taggart, Cynthia, additional, Patel, Bhaumik, additional, Davidson, Robert, additional, Davies, Stella M, additional, and Jodele, Sonata, additional

Published
2023
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115. Introduction

Author

Dunworth, Katie, Zhang, Grace, Kirkpatrick, Andy, Series editor, Adamson, Bob, Series editor, Dunworth, Katie, editor, and Zhang, Grace, editor

Published
2014
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116. An Ontology of Life and the Myth of the Technological Singularity.

Author

Zhang, Grace

Subjects
CHEMICAL laws, ARTIFICIAL intelligence, MYTH
Abstract

The "singularity"--a future moment when artificial intelligence becomes equal to or surpasses human intelligence making them indistinguishable--can be challenged by philosophy. I present an ontology of life, the subject of bona fide intelligence, to interrogate what underlies human intelligence. I argue: 1) internal purposiveness is intrinsic to life, and 2) living beings are the only things not solely explicable by mechanical and chemical laws. I engage Hubert Dreyfus' critique of artificial reason, What Computers Still Can't Do, though his three criteria for human intelligence fall short due to his separating physical and phenomenological explanatory "worlds" arising in absence of an ontology of life. A further question concerns what instantiates human intelligence, which I later introduce as a promising point of departure. [ABSTRACT FROM AUTHOR]

Published
2024

119. Elastic 'I Think': Stretching over L1 and L2

Author

Zhang, Grace Q. and Sabet, Peyman G. P.

Abstract

While there has been insightful research on the commonly used expression "I think" (IT), this study introduces a non-conventional and innovative conception of elasticity (Zhang 2011), bringing together several properties of IT. Drawn on large-scale naturally occurring classroom data with a rare combination of linguistically and culturally contrasting groups of L1 (American English) and L2 (Chinese- and Persian-speaking learners of English), this study shows that the elasticity of IT is manifested through three stretchable, non-discrete, and fluid continua: frequency, position, and cluster. The patterns show that L1 and L2 speakers stretch IT to variable degrees and stop at variable points along the three continua. A striking finding is that L1 speakers are speaker-oriented and assertive, the Persians are listener-centred and less authoritative, and the Chinese tend to take the middle-ground position. The findings imply that some discrepancies between L1 and L2 should not necessarily be labelled as overuse or underuse: they may simply be different focuses and preferences. The awareness of linguistic elasticity is crucial to communicative success.

Published
2016
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121. Introduction

Author

Sabet, Peyman G. P., Zhang, Grace Q., Sabet, Peyman G. P., and Zhang, Grace Q.

Published
2015
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128. Distinct COPD subtypes in former smokers revealed by gene network perturbation analysis

Author

Buschur, Kristina L., Riley, Craig, Saferali, Aabida, Castaldi, Peter, Zhang, Grace, Aguet, Francois, Ardlie, Kristin G., Durda, Peter, Craig Johnson, W., Kasela, Silva, Liu, Yongmei, Manichaikul, Ani, Rich, Stephen S., Rotter, Jerome I., Smith, Josh, Taylor, Kent D., Tracy, Russell P., Lappalainen, Tuuli, Graham Barr, R., Sciurba, Frank, Hersh, Craig P., Benos, Panayiotis V., Buschur, Kristina L., Riley, Craig, Saferali, Aabida, Castaldi, Peter, Zhang, Grace, Aguet, Francois, Ardlie, Kristin G., Durda, Peter, Craig Johnson, W., Kasela, Silva, Liu, Yongmei, Manichaikul, Ani, Rich, Stephen S., Rotter, Jerome I., Smith, Josh, Taylor, Kent D., Tracy, Russell P., Lappalainen, Tuuli, Graham Barr, R., Sciurba, Frank, Hersh, Craig P., and Benos, Panayiotis V.

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) varies significantly in symptomatic and physiologic presentation. Identifying disease subtypes from molecular data, collected from easily accessible blood samples, can help stratify patients and guide disease management and treatment.MethodsBlood gene expression measured by RNA-sequencing in the COPDGene Study was analyzed using a network perturbation analysis method. Each COPD sample was compared against a learned reference gene network to determine the part that is deregulated. Gene deregulation values were used to cluster the disease samples.ResultsThe discovery set included 617 former smokers from COPDGene. Four distinct gene network subtypes are identified with significant differences in symptoms, exercise capacity and mortality. These clusters do not necessarily correspond with the levels of lung function impairment and are independently validated in two external cohorts: 769 former smokers from COPDGene and 431 former smokers in the Multi-Ethnic Study of Atherosclerosis (MESA). Additionally, we identify several genes that are significantly deregulated across these subtypes, including DSP and GSTM1, which have been previously associated with COPD through genome-wide association study (GWAS).ConclusionsThe identified subtypes differ in mortality and in their clinical and functional characteristics, underlining the need for multi-dimensional assessment potentially supplemented by selected markers of gene expression. The subtypes were consistent across cohorts and could be used for new patient stratification and disease prognosis., QC 20230303

Published
2023
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129. Efficient Multi-Task Reinforcement Learning via Selective Behavior Sharing

Author

Zhang, Grace, Jain, Ayush, Hwang, Injune, Sun, Shao-Hua, Lim, Joseph J., Zhang, Grace, Jain, Ayush, Hwang, Injune, Sun, Shao-Hua, and Lim, Joseph J.

Abstract

The ability to leverage shared behaviors between tasks is critical for sample-efficient multi-task reinforcement learning (MTRL). While prior methods have primarily explored parameter and data sharing, direct behavior-sharing has been limited to task families requiring similar behaviors. Our goal is to extend the efficacy of behavior-sharing to more general task families that could require a mix of shareable and conflicting behaviors. Our key insight is an agent's behavior across tasks can be used for mutually beneficial exploration. To this end, we propose a simple MTRL framework for identifying shareable behaviors over tasks and incorporating them to guide exploration. We empirically demonstrate how behavior sharing improves sample efficiency and final performance on manipulation and navigation MTRL tasks and is even complementary to parameter sharing. Result videos are available at https://sites.google.com/view/qmp-mtrl.

Published
2023

130. Computational and Storage Efficient Quadratic Neurons for Deep Neural Networks

Author

Chen, Chuangtao, Zhang, Grace Li, Yin, Xunzhao, Zhuo, Cheng, Schlichtmann, Ulf, Li, Bing, Chen, Chuangtao, Zhang, Grace Li, Yin, Xunzhao, Zhuo, Cheng, Schlichtmann, Ulf, and Li, Bing

Abstract

Deep neural networks (DNNs) have been widely deployed across diverse domains such as computer vision and natural language processing. However, the impressive accomplishments of DNNs have been realized alongside extensive computational demands, thereby impeding their applicability on resource-constrained devices. To address this challenge, many researchers have been focusing on basic neuron structures, the fundamental building blocks of neural networks, to alleviate the computational and storage cost. In this work, an efficient quadratic neuron architecture distinguished by its enhanced utilization of second-order computational information is introduced. By virtue of their better expressivity, DNNs employing the proposed quadratic neurons can attain similar accuracy with fewer neurons and computational cost. Experimental results have demonstrated that the proposed quadratic neuron structure exhibits superior computational and storage efficiency across various tasks when compared with both linear and non-linear neurons in prior work., Comment: Accepted by Design Automation and Test in Europe (DATE) 2024

Published
2023

131. Factors Predicting Visual Acuity Outcome in Intermediate, Posterior, and Panuveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial

Author

Jaffe, Glenn J., Branchaud, Brenda, Hahn, Paul, Koreen, Larry, Lad, Eleonora (Nora) M., Lin, Phoebe, Martel, Joseph Nissim, Serrano, Neha (Shah), Skalak, Cindy, Vajzovic, Lejla, Baer, Claxton, Bryant, Joyce, Chavala, Sai, Cusick, Michael, Day, Shelley, Dayani, Pouya, Ehlers, Justis, Kesen, Muge, Lee, Annie, Melamud, Alex, Qureshi, Jawad A., Scott, Adrienne Williams, See, Robert F., Shuler, Robert K., Wood, Megan, Yeh, Steven, Fernandes, Alcides, Gibbs, Deborah, Leef, Donna, Martin, Daniel F., Srivastava, Sunil, Dunn, James P., Begum, Hosne, Boring, Jeff, Brotherson, Kristen L., Burkholder, Bryn, Butler, Nicholas J., Cain, Dennis, Cook, Mary A., Emmert, David, Graul, Janis R., Herring, Mark, Laing, Ashley, Leung, Theresa G., Mahon, Michael C., Moradi, Ahmafreza, Nwankwo, Antonia, Ostheimer, Trucian L., Reed, Terry, Arnold, Ellen, Barnabie, Patricia M., Belair, Marie-Lynn, Bolton, Stephen G., Brodine, Joseph B., Brown, Diane M., Brune, Lisa M., Galor, Anat, Gan, Theresa, Jacobowitz, Adam, Kapoor, Meera, Kedhar, Sanjay, Kim, Stephen, Leder, Henry A., Livingston, Alison G., Morton, Yavette, Nolan, Kisten, Peters, George B., Soto, Priscilla, Stevenson, Ricardo, Tarver-Carr, Michelle, Wang, Yue, Foster, C. Stephen, Anesi, Stephen D., Bruner, Linda, Ceron, Olga, Hinkle, David M., Persons, Nancy, Wentworth, Bailey, Acevedo, Sarah, Anzaar, Fahd, Cesca, Tom, Contero, Angelica, Fitzpatrick, Kayleigh, Goronga, Faith, Johnson, Jyothir, Lebron, Karina Q., Marvell, Danielle, Morgan, Chandra, Patel, Nita, Pinto, Jennifer, Siddique, Sana S., Sprague, Janet, Yilmaz, Taygan, Sen, H. Nida, Bono, Michael, Cunningham, Denise, Hayes, Darryl, Koutsandreas, Dessie, Nussenblatt, Robert B., Sherry, Patti R., Short, Gregory L., Smith, Wendy, Temple, Alana, Bamji, Allison, Coleman, Hanna, Davuluri, Geetaniali, Faia, Lisa, Gottlieb, Chloe, Jirawuthiworavong, Guy V., Lew, Julie C., Mercer, Richard, Obiyor, Dominic, Perry, Cheryl H., Potapova, Natalia, Weichel, Eric, Wroblewski, Keith J., Latkany, Paul A., Coonan, Corinne, Honda, Andrea, Lorenzo-Latkany, Monica, Masini, Robert, Morell, Susan, Nguyen, Angela, Badamo, Jason, Boyd, Kenneth M., Enos, Matthew, Gallardo, Jenny, Jarczynski, Jacek, Lee, Ji Yun, McGrosky, Mirjana, Nour, Ann, Sanchez, Meredith, Steinberg, Kate, Stawell, Richard J., Breayley, Lisa, D'Sylva, Carly, Glatz, Elizabeth, Hodgson, Lauren, Lim, Lyndell, Ling, Cecilia, McIntosh, Rachel, Morrison (Ewing), Julie, Newton, Andrew, Sanmugasundram, Sutha, Smallwood, Richard, Zamir, Ehud, Hunt, Nicola, Jones, Lisa, Koukouras, Ignatios, Williams, Suzanne, Merrill, Pauline T., Carns, Danielle, Richine, Len, Voskuil-Marre, Denise L., Woo, Kisung, Gaynes, Bruce, Giannoulis, Christina, Hulvey, Pam, Kernbauer, Elaine, Khan, Heena S., Levine, Sarah J., Toennessen, Scott, Tonner, Eileen, Wang, Robert C., Aguado, Hank, Arceneaux, Sally, Duignan, Karen, Fish, Gary E., Hesse, Nick, Jaramillo, Diana, Mackens, Michael, Arnwine, Jean, Callanan, David, Cummings, Kimberly, Gray, Keith, Howden, Susie, Mutz, Karin, Sanchez, Brenda, Lightman, Susan, Ismetova, Filis, Prytherch, Ashley, Seguin-Greenstein, Sophie, Tomkins, Oren, Bar, Asat, Edwards, Kate, Joshi, Lavanish, Moraji, Jiten, Samy, Ahmed, Stubbs, Timothy, Taylor, Simon, Towler, Hamish, Tronnberg, Rebecca, Holland, Gary N., Almanzor, Robert D., Castellanos, Jose, Hubschman, Jean Pierre, Johiro, Ann K., Kukuyev, Alla, Levinson, Ralph D., McCannel, Colin A., Ransome, Susan S., Gonzales, Christine R., Gupta, Anurag, Kalyani, Partho S., Kapamajian, Michael A., Kappel, Peter J., Arcinue, Cheryl, Chuang, Janne, Barteselli, Giulio, Currie, Glenn, Mendoza, Veronica, Powell, Debbie, Clark, Tom, Cochran, Denine E., Freeman, William R., Hedaya, Joshua, Kemper, Tiara, Kozak, Igor, LeMoine, Jacqueline M., Loughran, Megan E., Magana, Luzandra, Mojana, Francesca, Morrison, Victoria, Nguyen, Vivian, Oster, Stephen F., Acharya, Nisha, Clay, David, Lee, Salena, Lew, Mary, Margolis, Todd P., Stewart, Jay, Wong, Ira G., Brown, Debra, Khouri, Claire M., Goldstein, Debra A., Birnbaum, Andrea, Degillio, Andrea, Rosa, Gemma De la, Ramirez, Carmen, Simjanowski, Evica, Skelly, Mariner, Castro-Malek, Anna L., Crooke, Catherine E., Huntley, Melody, Nash, Katrina, Niec, Marcia, Pyatetsky, Dimitry, Ramirez, Misel, Rozenbajgier, Zuzanna, Tessler, Howard H., Davis, Janet L., Albini, Thomas A., Chin, Marie, Castaño, Daniela, Elizondo, Ariana, Ho, Macy, Kovach, Jaclyn L., Lin, Richard C-S., Mandelcorn, Efrem, Nguyen, Jackie K-D., Pacini, Aura, Pineda, Susan, Pinto, David A., Rebimbas, Jose, Stepien, Kimberly E., Teran, Claudia, Elner, Susan G., Bernard, Hillary, Fournier, Linda, Godsey, Lindsay, Goings, Linda, Hackel, Richard, Hesselgrave, Moella, Jayasundera, K. Thiran, Prusak, Robert, Titus, Pamela, Bergeron, Melissa, Blosser, Reneé, Brown, Rebecca, Chrisman-McClure, Carrie, Gothrup, Julie R., Saxe, Stephen J., Sizemore, Deanna, Kempen, John H., Berger, James, Drossner, Sheri, DuPont, Joan C., Maguire, Albert M., Petner, Janice, Engelhard, Stephanie, Hopkins, Tim, Lo, Jonathan, McCall, Dawn, McRay, Monique, Salvo, Rebecca, Will, Daniel, Xu, Wei, Windsor, Elizabeth, Weeney, Laurel, Pavan, Peter R., Albritton, Ken, Leto, JoAnn, Madow, Brian, Mayor, Lori, Pautler, Scott E., Saxon, Wyatt, Soto, Judy, Goldstein, Burton, Klukoff, Amy, Lambright, Lucy, McDonald, Kim, Ortiz, Maria, Scymanky, Susan, Szalay, Dee Dee, Rao, Narsing, Davis, Tamara, Douglass, Jackie, Linton, Judith, Padilla, Margaret, Ramos, Sylvia, Rao, Narsing A., Aguirre, Alexia, Chong, Lawrence, Cisneros, Lupe, Corona, Elizabeth, Eliott, Dean, Fawzi, Amani, Garcia, Jesse, Khurana, Rahul, Lim, Jennifer, Mead, Rachel, Tsai, Julie H., Vitale, Albert, Bernstein, Paul S., Carlstrom, Bonnie, Gilman, James, Hanseen, Sandra, Morris, Paula, Ramirez, Diana, Wegner, Kimberley, Sheppard, John D., Anthony, Brianne, Casper, Amber, Felix-Kent, Lisa, Fernandez, Jeanette, Johnson, Tari, Scoper, Stephen V., Cole, R. Denise, Crawford, Nancy, Franklin, Lisa, Hamelin, Krista, Martin, Jen, Marx, Rebecca, Schultz, Gregory, Webb, Joseph, Yeager, Pamela, Kim, Rosa Y., Benz, Matthew S., Brown, David M., Chen, Eric, Fish, Richard H., Kegley, Eric, Shawver, Laura, Wong, Tien P., De La Garza, Rebecca, Friday (Hay), Shayla, Rao, P. Kumar, Adcock, Eve, Apte, Rajendra S., Baladenski, Amy, Curtis, Rhonda, Gould, Sarah, Hebden, Amanda, Kambarian, Jamie, Meyer, Charla, Pistorius, Sam, Quinn, Melanie, Rathert, Greg, Blinder, Kevin J., Hartz, Ashley, Light, Pam, Shah, Gaurav K., VanGelder, Russell, Jabs, Douglas A., Altaweel, Michael M., Holbrook, Janet T., Kurinij, Natalie, Brown, Diane, Prusakowski, Nancy, Thorne, Jennifer E., Hubbard, Larry, Wittes, Janet, Barlow, William E., Hochberg, Marc, Lyon, Alice T., Palestine, Alan G., Simon, Lee S., Rosenbaum, James T., Smith, Harmon, Davis, Janet, Thorne, Jennifer, Acharya, Nisha R., Vitale, Albert T., Boring, Jeffrey A., Alexander, Judith, Ng, Wai Ping, Friedman, David S., Adler, Anna, Burke, Alyce, Katz, Joanne, Reed, Susan, Ansari, Husam, Cohen, Nicholas, Modak, Sanjukta, Sugar, Elizabeth A., Burke, Alyce E., Drye, Lea T., Van Natta, Mark L., Frick, Kevin, Katz, JoAnn, Louis, Thomas A., Shade, David, Pascual, Karen, Slutsky-Sanon, Jill S., Allen, Amanda, Glomp, Colby, Hilal, Yasmin, Nieves, Melissa A., Stevens, Maria, Abreu, Francis, Casper, Anne Shanklin, Ewing, Cathleen, Hart, Adante, Lears, Andrea, Li, Shirley, Meinert, Jill, Morrison, Vinnette, Nowakowski, Deborah, Reyes, Girlie, Shade, Dave M., Smith, Jacqueline, Steuernagle, Karen, Van Natta, Mark, Venugopal, Vidya, Yu, Tsung, Chen, Paul, Collins, Karen, Dodge, John, Frick, Kevin D., Jackson, Rosetta, Jimenez, Christian, Landers, Ariel, Livingston, Hope, Meinert, Curtis L., Rayapudi, Sobharani, Shen, Weijiang, Shiflett, Charles, Smith, Rochelle, Tieman, Ada, Tonascia, James A., Zheng, Richard, Allan, James, Benz, Wendy K., Domalpally, Amitha, Johnson, Kristine A., Myers, Dawn J., Won Pak, Jeong, Reimers, James L., Chambers, Geoffrey, Christianson, Debra J., Fleischli, Margaret A., Freund, Jacquelyn, Gama, Vonnie, Gangaputra, Sapna, Glander, Kathleen E., Goulding, Anne, Hafford, Dennis, Harris, Susan E., Hubbard, Larry D., Joyce, Jeffrey M., Kruse, Christina N., Nagle, Lauren, Padden-Lechten, Gwyn E., Pohlman, Alyson, Remm, Amy, Shaw, Ruth A., Sivesind, Peggy, Thayer, Dennis, Treichel, Erika, Warren, Kelly J., Watson, Sheila M., Webster, Mary K., White, James K., Wilhelmson, Tara, Zhang, Grace, and Lightman, Susan L.

Published
2015
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132. A 3D Hybrid Optical-Electrical NoC Using Novel Mapping Strategy Based DCNN Dataflow Acceleration

Author

Zhang, Bowen, Gu, Huaxi, Zhang, Grace Li, Yang, Yintang, Ma, Ziteng, and Schlichtmann, Ulf

Abstract

A large number of multiply-accumulate operations and memory accesses required in deep convolutional neural networks (DCNN) leads to high latency and energy consumption (EC), that hinder their further applications. Dataflow-based acceleration schemes reduce memory accesses by leveraging reusable data in DCNNs. Row Stationary (RS) dataflow is a more advanced dataflow. In the convolutional layer acceleration of RS dataflow, the flexibility of mapping from logical processing element (LPE) sets to physical PE sets is relatively poor. The utilization of processing elements (PEs) is low. In this article, a novel mapping strategy based on genetic algorithm (GAMS) with the goal of optimizing EC is proposed. GAMS is designed to address the energy inefficiencies faced when mapping RS dataflow. A 3D hybrid optical-electrical Network-on-Chip (3DHOENoC) is proposed to further improve the communication efficiency, energy efficiency and the processing speed of DCNN. Simulation and evaluation results show that GAMS can achieve better mapping flexibility, higher PEs utilization and 15.9% improvement of execution speed on average. In addition, the execution time (ET) performance of processing the DCNN can be further improved by adopting the 3DHOENoC architecture with better communication parallelism.

Published
2024
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133. Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids

Author

Wang, Shuai, Martins, Rene, Sullivan, Megan C., Friedman, Elliot S., Misic, Ana M., El-Fahmawi, Ayah, De Martinis, Elaine Cristina Pereira, O’Brien, Kevin, Chen, Ying, Bradley, Charles, Zhang, Grace, Berry, Alexander S. F., Hunter, Christopher A., Baldassano, Robert N., Rondeau, Mark P., and Beiting, Daniel P.

Published
2019
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134. A comprehensive analysis of tobacco smoking history as a risk for outcomes after endoscopic transsphenoidal resection of pituitary adenoma

Author

Min, Susie, additional, Zhang, Grace, additional, Hu, Alex, additional, Petito, Gabrielle, additional, Tripathi, Siddhant, additional, Shukla, Geet, additional, Kumar, Adithya, additional, Shah, Sanjit, additional, Phillips, Katie, additional, Forbes, Jonathan A., additional, Zuccarello, Mario, additional, Andaluz, Norberto, additional, and Sedaghat, Ahmad R, additional

Published
2023
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135. A Comprehensive Analysis of Tobacco Smoking History as a Risk for Outcomes after Transsphenoidal Resection of Pituitary Adenoma

Author

Min, Susie, additional, Zhang, Grace, additional, Hu, Alex, additional, Petito, Gabrielle T., additional, Tripathi, Siddhant H., additional, Shukla, Geet, additional, Kumar, Adithya, additional, Shah, Sanjit, additional, Philips, Katie M., additional, Forbes, Jonathan A., additional, Zuccarello, Mario, additional, Andaluz, Norberto O., additional, and Sedaghat, Ahmad R., additional

Published
2023
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139. Assessment of Essential Surgical and Anaesthesia Care Capacity: A Cross-Sectional Study in Five Pacific Island Countries

Author

Qin, Rennie Xinrui, primary, Zhang, Grace, additional, Lim, Meghan Xuxin, additional, Waqainabete, Ifereimi, additional, Tudravu, Jemesa, additional, Turagava, Josese, additional, Patel, Rajeev, additional, Ulufonua, Lisiate K., additional, Herman, Josephine Aumea, additional, May, Yin Yin, additional, Teapa, Deacon, additional, Tarere-Lehi, Margaret, additional, Leodoro, Basil, additional, Mekoll, Ngirachisau, additional, McLeod, Elizabeth, additional, Park, Kee B., additional, Kafoa, Berlin, additional, Maoate, Kiki, additional, and Tangi, Viliami, additional

Published
2023
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142. Longitudinal multi-omics analyses of the gut–liver axis reveals metabolic dysregulation in hepatitis C infection and cirrhosis

Author

Ali, Rabab O., primary, Quinn, Gabriella M., additional, Umarova, Regina, additional, Haddad, James A., additional, Zhang, Grace Y., additional, Townsend, Elizabeth C., additional, Scheuing, Lisa, additional, Hill, Kareen L., additional, Gewirtz, Meital, additional, Rampertaap, Shakuntala, additional, Rosenzweig, Sergio D., additional, Remaley, Alan T., additional, Han, Jung Min, additional, Periwal, Vipul, additional, Cai, Hongyi, additional, Walter, Peter J., additional, Koh, Christopher, additional, Levy, Elliot B., additional, Kleiner, David E., additional, Etzion, Ohad, additional, and Heller, Theo, additional

Published
2022
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150. Chondroitin 4-O-sulfation regulates hippocampal perineuronal nets and social memory.

Author

Huiqian Huang, Joffrin, Amélie M., Yuan Zhao, Miller, Gregory M., Zhang, Grace C., Yuki Oka, and Hsieh-Wilson, Linda C.

Subjects
PERINEURONAL nets, COLLECTIVE memory, CHONDROITIN, CHONDROITIN sulfates, GLYCAN structure
Abstract

Glycan alterations are associated with aging, neuropsychiatric, and neurodegenerative diseases, although the contributions of specific glycan structures to emotion and cognitive functions remain largely unknown. Here, we used a combination of chemistry and neurobiology to show that 4-O-sulfated chondroitin sulfate (CS) polysaccharides are critical regulators of perineuronal nets (PNNs) and synapse development in the mouse hippocampus, thereby affecting anxiety and cognitive abilities such as social memory. Brain-specific deletion of CS 4-O-sulfation in mice increased PNN densities in the area CA2 (cornu ammonis 2), leading to imbalanced excitatory-to-inhibitory synaptic ratios, reduced CREB activation, elevated anxiety, and social memory dysfunction. The impairments in PNN densities, CREB activity, and social memory were recapitulated by selective ablation of CS 4-O-sulfation in the CA2 region during adulthood. Notably, enzymatic pruning of the excess PNNs reduced anxiety levels and restored social memory, while chemical manipulation of CS 4-O-sulfation levels reversibly modulated PNN densities surrounding hippocampal neurons and the balance of excitatory and inhibitory synapses. These findings reveal key roles for CS 4-O-sulfation in adult brain plasticity, social memory, and anxiety regulation, and they suggest that targeting CS 4-O-sulfation may represent a strategy to address neuropsychiatric and neurodegenerative diseases associated with social cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Published
2023
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