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1. Interstitial macrophages are a focus of viral takeover and inflammation in COVID-19 initiation in human lung

Author

Wu, Timothy Ting-Hsuan, Travaglini, Kyle J, Rustagi, Arjun, Xu, Duo, Zhang, Yue, Andronov, Leonid, Jang, SoRi, Gillich, Astrid, Dehghannasiri, Roozbeh, Martínez-Colón, Giovanny J, Beck, Aimee, Liu, Daniel Dan, Wilk, Aaron J, Morri, Maurizio, Trope, Winston L, Bierman, Rob, Weissman, Irving L, Shrager, Joseph B, Quake, Stephen R, Kuo, Christin S, Salzman, Julia, Moerner, WE, Kim, Peter S, Blish, Catherine A, and Krasnow, Mark A

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Lung, Vaccine Related, Emerging Infectious Diseases, Infectious Diseases, Pneumonia, Prevention, Pneumonia & Influenza, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Aetiology, Infection, Respiratory, Good Health and Well Being, Humans, COVID-19, SARS-CoV-2, Macrophages, Inflammation, RNA, Viral, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Early stages of deadly respiratory diseases including COVID-19 are challenging to elucidate in humans. Here, we define cellular tropism and transcriptomic effects of SARS-CoV-2 virus by productively infecting healthy human lung tissue and using scRNA-seq to reconstruct the transcriptional program in "infection pseudotime" for individual lung cell types. SARS-CoV-2 predominantly infected activated interstitial macrophages (IMs), which can accumulate thousands of viral RNA molecules, taking over 60% of the cell transcriptome and forming dense viral RNA bodies while inducing host profibrotic (TGFB1, SPP1) and inflammatory (early interferon response, CCL2/7/8/13, CXCL10, and IL6/10) programs and destroying host cell architecture. Infected alveolar macrophages (AMs) showed none of these extreme responses. Spike-dependent viral entry into AMs used ACE2 and Sialoadhesin/CD169, whereas IM entry used DC-SIGN/CD209. These results identify activated IMs as a prominent site of viral takeover, the focus of inflammation and fibrosis, and suggest targeting CD209 to prevent early pathology in COVID-19 pneumonia. This approach can be generalized to any human lung infection and to evaluate therapeutics.

Published
2024

3. Quality of Life in Patients With Chronic Limb-Threatening Ischemia Treated With Revascularization

Author

Menard, Matthew T., Farber, Alik, Powell, Richard J., Rosenfield, Kenneth, Conte, Michael S., Hamza, Taye H., Kaufman, John A., Cziraky, Mark J., Creager, Mark A., Dake, Michael D., Jaff, Michael R., Reid, Diane, Sopko, George, White, Christopher J., Strong, Michael B., van Over, Max, Chisci, Emiliano, Goodney, Philip P., Gray, Bruce, Kayssi, Ahmed, Siracuse, Jeffrey J., Choudhry, Niteesh K., Maurao, Mick, Muluk, Satish, Belkin, Michael, Lyden, Sean, Shishehbor, Mehdi, Bajakian, Danielle, Duwayri, Yazan, Bowens, Nina, Nypaver, Timothy, Mukherjee, Dipankar, Obrand, Daniel, LaMuraglia, Glenn, Kalra, Manju, Bernardo, Nelson, Barshes, Neal, Lipsitz, Evan, Jenkins, J. Stephen, Gasper, Warren, Owens, Christopher, Pomposelli, Frank, Rogers, Kevin, Vouyouka, Ageliki, Passman, Marc, Pena, Constantino, Ramaiah, Venkatesh, Hoch, John, Bersin, Robert, Hayes, Greg, Ho, Karen, Shah, Aamir, Lum, Ying Wie, Darling, R. Clement, III, Aalami, Oliver, Zhou, Wei, Patel, Parag, Aziz, Abdulhameed, Halloran, Brian, Jung, Enjae, Mitchell, Erica, Turba, Ulku Cenk, Choi, Eric, Hiramoto, Jade, Owens, Christopher, Milner, Ross, Crawford, Robert, Ucuzian, Areck, Henke, Peter, Chaer, Rabih, Lahiri (Adams), Julie, Gelabert, Hugh, Safian, Robert, Mena-Hurtado, Carlos, Ihnat, Daniel, Rowe, Vincent, Kashyap, Vikram, Shaw, Palma, Korngold, Ethan, Lindsay, Thomas, Winkelaar, Gerrit, Mell, Matthew, DuVal, Bruce, Aziz, Faisal, Reed, Amy, Nazzal, Munier, Schanzer, Andres, Hamdan, Allen, Smeds, Matthew, Kalish, Jeffrey, Slaiby, Jeffrey, Androes, Mark, Hanover, Tod, Motaganahalli, Raghu, Chang, Catherine, Hye, Robert, Alexander, Jason, Ansel, Gary, Bohannon, Todd, Desai, Sapan, Hodgson, Kim, Hood, Douglas, Guzman, Randolph Pl, Giles, Kristina, Shah, Samir, Hawkins, Beau, Brothers, Thomas Edward, Azizzadeh, Ali, Charlton-Ouw, Kristofer, Khan, Sophia, Brooke, Benjamin S., Kabutey, Nii-Kabu, Sachar, Ravish, Dosluoglu, Hasan, Berman, Scott, Blebea, John, Taubman, Kevin, Douville, Yvan, Cox, Mitchell W., Davis, Joseph, Caps, Michael, Schneider, Peter, Abou-Zamzam, Ahmed, Feldman, Robert, von Mering, Gregory, Tan, Tze-Woei, Virk, Chiranjiv S., Zhang, Wayne, Bacharach, Michael, Seidman, Craig, Iafrati, Mark, Findeiss, Laura, Bailey, Charles, Shames, Murray, Lane, John, Baril, Donald, Hass, Stephen, Stone, Patrick, Sharma, Aditya, Tracci, Margaret, Mackenzie, Kent, Stoner, Michael, Starr, Jean, McAllister, David, Singh, Niten, Tsai, Shirling, Kinlay, Scott, Macsata, Robyn, Neville, Richard, Rundback, John, McGinigle, Kate, Vallabhaneni, Raghu, Espinoza, Andrey, Azarbal, Amir, Longo, G. Matthew, Kovach, Richard, Soukas, Peter, Metzger, Chris, Artis, Andre, Bachinsky, William, Armstrong, Ehrin, Hattler, Brack, Chandra, Venita, Schor, Jonathan, Bianchi, Christian, Kiang, Sharon, Ben-Arie, Eyal, Verta, Michael, Wilkinson, Julia, Hurie, Justin, Kopriva, David, Molnar, Robert, Chun, Linda Jun, Azene, Ezana, Davis, Clark, Blazick, Elizabeth, Henao, Steve, Proffitt, Trent, Herman, Christine, Nathan, Derek, Chang, Robert, Lane, John, Mureebe, Leila, Chen, Jerry, Semel, Marcus, Fecteau, Scott, Mehta, Manish, Nagpal, Sudhir, Shammas, Nicolas, Kujath, Scott, Beasley, Robert, Vogel, Todd, Hedayati, Nasim, Brooks, James, Nelson, Peter, Parrack, Inkyong, Bernik, Thomas, Dexter, David, Brown, Kellie, Huang, Joe, Wu, Timothy, Hacker, Robert, Garland, Brandon Tyler, Griffin, Joseph, Laskowski, Igor, Pfau, Steven, Duncan, Audra, Trachtenberg, Jeffrey, Gordon, Ian, Tan, Tze-Woei, Aulivola, Bernadette, Zayed, Mohamed, Venermo, Maarit, Hill, Andrew, Wickremesekera, Janaka Kesara, Ketteler, Erika, Michelagnoli, Stefano, Bannazadeh, Mohsen, Sikalas, Nicholas, Khashram, Manar, Vasudevan, Thodur, Simmons, Justin, Osborne, Nicholas, Fox, Charles, and Vallabhaneni, Raghuveer

Published
2024
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4. Cell types of origin of the cell-free transcriptome

Author

Jones, Robert C, Karkanias, Jim, Krasnow, Mark, Pisco, Angela Oliveira, Quake, Stephen R, Salzman, Julia, Yosef, Nir, Bulthaup, Bryan, Brown, Phillip, Harper, William, Hemenez, Marisa, Ponnusamy, Ravikumar, Salehi, Ahmad, Sanagavarapu, Bhavani A, Spallino, Eileen, Aaron, Ksenia A, Concepcion, Waldo, Gardner, James M, Kelly, Burnett, Neidlinger, Nikole, Wang, Zifa, Crasta, Sheela, Kolluru, Saroja, Morri, Maurizio, Tan, Serena Y, Travaglini, Kyle J, Xu, Chenling, Alcántara-Hernández, Marcela, Almanzar, Nicole, Antony, Jane, Beyersdorf, Benjamin, Burhan, Deviana, Calcuttawala, Kruti, Carter, Matthew M, Chan, Charles KF, Chang, Charles A, Chang, Stephen, Colville, Alex, Culver, Rebecca N, Cvijović, Ivana, D’Amato, Gaetano, Ezran, Camille, Galdos, Francisco X, Gillich, Astrid, Goodyer, William R, Hang, Yan, Hayashi, Alyssa, Houshdaran, Sahar, Huang, Xianxi, Irwin, Juan C, Jang, SoRi, Juanico, Julia Vallve, Kershner, Aaron M, Kim, Soochi, Kiss, Bernhard, Kong, William, Kumar, Maya E, Kuo, Angera H, Leylek, Rebecca, Li, Baoxiang, Loeb, Gabriel B, Lu, Wan-Jin, Mantri, Sruthi, Markovic, Maxim, McAlpine, Patrick L, de Morree, Antoine, Mrouj, Karim, Mukherjee, Shravani, Muser, Tyler, Neuhöfer, Patrick, Nguyen, Thi D, Perez, Kimberly, Phansalkar, Ragini, Puluca, Nazan, Qi, Zhen, Rao, Poorvi, Raquer-McKay, Hayley, Schaum, Nicholas, Scott, Bronwyn, Seddighzadeh, Bobak, Segal, Joe, Sen, Sushmita, Sikandar, Shaheen, Spencer, Sean P, Steffes, Lea, Subramaniam, Varun R, Swarup, Aditi, Swift, Michael, Van Treuren, Will, Trimm, Emily, Veizades, Stefan, Vijayakumar, Sivakamasundari, Vo, Kim Chi, Vorperian, Sevahn K, Wang, Wanxin, Weinstein, Hannah NW, Winkler, Juliane, Wu, Timothy TH, Xie, Jamie, and Yung, Andrea R

Subjects
Human Genome, Genetics, Cell-Free Nucleic Acids, Humans, Transcriptome, Tabula Sapiens Consortium
Abstract

Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. We extend this concept to identify cell types of origin using the Tabula Sapiens transcriptomic cell atlas as well as individual tissue transcriptomic cell atlases in combination with the Human Protein Atlas RNA consensus dataset. We define cell type signature scores, which allow the inference of cell types that contribute to cell-free RNA for a variety of diseases.

Published
2022

5. The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans

Author

Jones, Robert C, Karkanias, Jim, Krasnow, Mark A, Pisco, Angela Oliveira, Quake, Stephen R, Salzman, Julia, Yosef, Nir, Bulthaup, Bryan, Brown, Phillip, Harper, William, Hemenez, Marisa, Ponnusamy, Ravikumar, Salehi, Ahmad, Sanagavarapu, Bhavani A, Spallino, Eileen, Aaron, Ksenia A, Concepcion, Waldo, Gardner, James M, Kelly, Burnett, Neidlinger, Nikole, Wang, Zifa, Crasta, Sheela, Kolluru, Saroja, Morri, Maurizio, Tan, Serena Y, Travaglini, Kyle J, Xu, Chenling, Alcántara-Hernández, Marcela, Almanzar, Nicole, Antony, Jane, Beyersdorf, Benjamin, Burhan, Deviana, Calcuttawala, Kruti, Carter, Matthew M, Chan, Charles KF, Chang, Charles A, Chang, Stephen, Colville, Alex, Culver, Rebecca N, Cvijović, Ivana, D'Amato, Gaetano, Ezran, Camille, Galdos, Francisco X, Gillich, Astrid, Goodyer, William R, Hang, Yan, Hayashi, Alyssa, Houshdaran, Sahar, Huang, Xianxi, Irwin, Juan C, Jang, SoRi, Juanico, Julia Vallve, Kershner, Aaron M, Kim, Soochi, Kiss, Bernhard, Kong, William, Kumar, Maya E, Kuo, Angera H, Li, Baoxiang, Loeb, Gabriel B, Lu, Wan-Jin, Mantri, Sruthi, Markovic, Maxim, McAlpine, Patrick L, de Morree, Antoine, Mrouj, Karim, Mukherjee, Shravani, Muser, Tyler, Neuhöfer, Patrick, Nguyen, Thi D, Perez, Kimberly, Puluca, Nazan, Qi, Zhen, Rao, Poorvi, Raquer-McKay, Hayley, Schaum, Nicholas, Scott, Bronwyn, Seddighzadeh, Bobak, Segal, Joe, Sen, Sushmita, Sikandar, Shaheen, Spencer, Sean P, Steffes, Lea C, Subramaniam, Varun R, Swarup, Aditi, Swift, Michael, Van Treuren, Will, Trimm, Emily, Veizades, Stefan, Vijayakumar, Sivakamasundari, Vo, Kim Chi, Vorperian, Sevahn K, Wang, Wanxin, Weinstein, Hannah NW, Winkler, Juliane, Wu, Timothy TH, Xie, Jamie, Yung, Andrea R, Zhang, Yue, and Detweiler, Angela M

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Generic health relevance, Atlases as Topic, B-Lymphocytes, Cells, Humans, Organ Specificity, RNA Splicing, Single-Cell Analysis, T-Lymphocytes, Transcriptome, Tabula Sapiens Consortium*, General Science & Technology
Abstract

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.

Published
2022

10. NTIRE 2020 Challenge on Real-World Image Super-Resolution: Methods and Results

Author

Lugmayr, Andreas, Danelljan, Martin, Timofte, Radu, Ahn, Namhyuk, Bai, Dongwoon, Cai, Jie, Cao, Yun, Chen, Junyang, Cheng, Kaihua, Chun, SeYoung, Deng, Wei, El-Khamy, Mostafa, Ho, Chiu Man, Ji, Xiaozhong, Kheradmand, Amin, Kim, Gwantae, Ko, Hanseok, Lee, Kanghyu, Lee, Jungwon, Li, Hao, Liu, Ziluan, Liu, Zhi-Song, Liu, Shuai, Lu, Yunhua, Meng, Zibo, Michelini, Pablo Navarrete, Micheloni, Christian, Prajapati, Kalpesh, Ren, Haoyu, Seo, Yong Hyeok, Siu, Wan-Chi, Sohn, Kyung-Ah, Tai, Ying, Umer, Rao Muhammad, Wang, Shuangquan, Wang, Huibing, Wu, Timothy Haoning, Wu, Haoning, Yang, Biao, Yang, Fuzhi, Yoo, Jaejun, Zhao, Tongtong, Zhou, Yuanbo, Zhuo, Haijie, Zong, Ziyao, and Zou, Xueyi

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

This paper reviews the NTIRE 2020 challenge on real world super-resolution. It focuses on the participating methods and final results. The challenge addresses the real world setting, where paired true high and low-resolution images are unavailable. For training, only one set of source input images is therefore provided along with a set of unpaired high-quality target images. In Track 1: Image Processing artifacts, the aim is to super-resolve images with synthetically generated image processing artifacts. This allows for quantitative benchmarking of the approaches \wrt a ground-truth image. In Track 2: Smartphone Images, real low-quality smart phone images have to be super-resolved. In both tracks, the ultimate goal is to achieve the best perceptual quality, evaluated using a human study. This is the second challenge on the subject, following AIM 2019, targeting to advance the state-of-the-art in super-resolution. To measure the performance we use the benchmark protocol from AIM 2019. In total 22 teams competed in the final testing phase, demonstrating new and innovative solutions to the problem.

Published
2020

18. The Alkaline Phosphatase (ALPL) Locus Is Associated with B6 Vitamer Levels in CSF and Plasma

Author

Loohuis, Loes M Olde, Albersen, Monique, de Jong, Simone, Wu, Timothy, Luykx, Jurjen J, Jans, Judith JM, Verhoeven-Duif, Nanda M, and Ophoff, Roel A

Subjects
Biological Sciences, Genetics, Nutrition, Human Genome, 1.1 Normal biological development and functioning, Underpinning research, Aetiology, 2.1 Biological and endogenous factors, genome wide association study, vitamin B6, cerebrospinal fluid, plasma
Abstract

The active form of vitamin B6, pyridoxal phosphate (PLP), is essential for human metabolism. The brain is dependent on vitamin B6 for its neurotransmitter balance. To obtain insight into the genetic determinants of vitamin B6 homeostasis, we conducted a genome-wide association study (GWAS) of the B6 vitamers pyridoxal (PL), PLP and the degradation product of vitamin B6, pyridoxic acid (PA). We collected a unique sample set of cerebrospinal fluid (CSF) and plasma from the same healthy human subjects of Dutch ancestry (n = 493) and included concentrations and ratios in and between these body fluids in our analysis. Based on a multivariate joint analysis of all B6 vitamers and their ratios, we identified a genome-wide significant association at a locus on chromosome 1 containing the ALPL (alkaline phosphatase) gene (minimal p = 7.89 × 10-10, rs1106357, minor allele frequency (MAF) = 0.46), previously associated with vitamin B6 levels in blood. Subjects homozygous for the minor allele showed a 1.4-times-higher ratio between PLP and PL in plasma, and even a 1.6-times-higher ratio between PLP and PL in CSF than subjects homozygous for the major allele. In addition, we observed a suggestive association with the CSF:plasma ratio of PLP on chromosome 15 (minimal p = 7.93 × 10-7, and MAF = 0.06 for rs28789220). Even though this finding is not reaching genome-wide significance, it highlights the potential of our experimental setup for studying transport and metabolism across the blood⁻CSF barrier. This GWAS of B6 vitamers identifies alkaline phosphatase as a key regulator in human vitamin B6 metabolism in CSF as well as plasma. Furthermore, our results demonstrate the potential of genetic studies of metabolites in plasma and CSF to elucidate biological aspects underlying metabolite generation, transport and degradation.

Published
2019

19. The Alkaline Phosphatase (ALPL) Locus Is Associated with B6 Vitamer Levels in CSF and Plasma.

Author

Loohuis, Loes M, Albersen, Monique, de Jong, Simone, Wu, Timothy, Luykx, Jurjen J, Jans, Judith JM, Verhoeven-Duif, Nanda M, and Ophoff, Roel A

Subjects
cerebrospinal fluid, genome wide association study, plasma, vitamin B6, Genetics
Abstract

The active form of vitamin B6, pyridoxal phosphate (PLP), is essential for human metabolism. The brain is dependent on vitamin B6 for its neurotransmitter balance. To obtain insight into the genetic determinants of vitamin B6 homeostasis, we conducted a genome-wide association study (GWAS) of the B6 vitamers pyridoxal (PL), PLP and the degradation product of vitamin B6, pyridoxic acid (PA). We collected a unique sample set of cerebrospinal fluid (CSF) and plasma from the same healthy human subjects of Dutch ancestry (n = 493) and included concentrations and ratios in and between these body fluids in our analysis. Based on a multivariate joint analysis of all B6 vitamers and their ratios, we identified a genome-wide significant association at a locus on chromosome 1 containing the ALPL (alkaline phosphatase) gene (minimal p = 7.89 × 10-10, rs1106357, minor allele frequency (MAF) = 0.46), previously associated with vitamin B6 levels in blood. Subjects homozygous for the minor allele showed a 1.4-times-higher ratio between PLP and PL in plasma, and even a 1.6-times-higher ratio between PLP and PL in CSF than subjects homozygous for the major allele. In addition, we observed a suggestive association with the CSF:plasma ratio of PLP on chromosome 15 (minimal p = 7.93 × 10-7, and MAF = 0.06 for rs28789220). Even though this finding is not reaching genome-wide significance, it highlights the potential of our experimental setup for studying transport and metabolism across the blood⁻CSF barrier. This GWAS of B6 vitamers identifies alkaline phosphatase as a key regulator in human vitamin B6 metabolism in CSF as well as plasma. Furthermore, our results demonstrate the potential of genetic studies of metabolites in plasma and CSF to elucidate biological aspects underlying metabolite generation, transport and degradation.

Published
2018

22. Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia.

Author

Olde Loohuis, Loes M, Mangul, Serghei, Ori, Anil PS, Jospin, Guillaume, Koslicki, David, Yang, Harry Taegyun, Wu, Timothy, Boks, Marco P, Lomen-Hoerth, Catherine, Wiedau-Pazos, Martina, Cantor, Rita M, de Vos, Willem M, Kahn, René S, Eskin, Eleazar, and Ophoff, Roel A

Subjects
Humans, Amyotrophic Lateral Sclerosis, Gene Expression Profiling, Sequence Analysis, RNA, Bipolar Disorder, Schizophrenia, Adult, Middle Aged, Female, Male, Young Adult, Microbiota, Sequence Analysis, RNA, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

The role of the human microbiome in health and disease is increasingly appreciated. We studied the composition of microbial communities present in blood across 192 individuals, including healthy controls and patients with three disorders affecting the brain: schizophrenia, amyotrophic lateral sclerosis, and bipolar disorder. By using high-quality unmapped RNA sequencing reads as candidate microbial reads, we performed profiling of microbial transcripts detected in whole blood. We were able to detect a wide range of bacterial and archaeal phyla in blood. Interestingly, we observed an increased microbial diversity in schizophrenia patients compared to the three other groups. We replicated this finding in an independent schizophrenia case-control cohort. This increased diversity is inversely correlated with estimated cell abundance of a subpopulation of CD8+ memory T cells in healthy controls, supporting a link between microbial products found in blood, immunity and schizophrenia.

Published
2018

23. Cestodiasis in 2 Puerto Rican crested anoles

Author

Wu, Timothy K., primary, Kaneko, Stacy, additional, Lucio-Forster, Araceli, additional, Spagnoli, Sean, additional, Schultz-Powell, Latoya, additional, Liotta, Janice, additional, and Bowman, Dwight, additional

Published
2024
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27. Contemporary Outcomes After Partial Resection of Infected Aortic Grafts

Author

Janko, Matthew, Hubbard, Grant, Woo, Karen, Kashyap, Vikram S., Mitchell, Megan, Murugesan, Arun, Chen, Lin, Gardner, Rachel, Baril, Donald, Hacker, Robert I., Szeberin, Zoltan, ElSayed, Ramsey, Magee, Gregory A., Motta, Fernando, Zhou, Wei, Lemmon, Gary, Coleman, Dawn, Behrendt, Christian-Alexander, Aziz, Faisal, Black, James H., Tran, Kimberly, Dao, Allen, Shutze, William, Garrett, H. Edward, De Caridi, Giovanni, Patel, Rhusheet, Liapis, Christos D., Geroulakos, George, Kakisis, John, Moulakakis, Konstantinos, Kakkos, Starvos K., Obara, Hideaki, Wang, Grace, Stoecker, Jordan, Rhéaume, Pascal, Davila, Victor, Ravin, Reid, DeMartino, Randall, Milner, Ross, Shalhub, Sherene, Jim, Jeffrey, Lee, Jason, Dubuis, Celine, Ricco, Jean-Baptiste, Coselli, Joseph, Lemaire, Scott, Fatima, Javairiah, Sanford, Jennifer, Yoshida, Winston, Schermerhorn, Marc L, Menard, Matthew, Belkin, Michael, Blackwood, Stuart, Conrad, Mark, Wang, Linda, Crofts, Sara, Nixon, Thomas, Wu, Timothy, Chiesa, Roberto, Bose, Saideep, Turner, Jason, Moore, Ryan, Smith, Justin, Irshad, Ali, Hsu, Jeffrey, Czerny, Martin, Cullen, Jonathan, Kahlberg, Andrea, Setacci, Carlo, Joh, Jin Hyun, Senneville, Eric, Garrido, Pedro, Sarac, Timur P., Rizzo, Anthony, Go, Michael R., Bjorck, Martin, Gavali, Hamid, Wanhainen, Anders, D'Oria, Mario, Lepidi, Sandro, Mastrorilli, Davide, Veraldi, Gianfranco, Piazza, Michele, Squizzato, Francesco, Beck, Adam, St. John, Rebecca, Wishy, Andrew, Humphries, Misty, Shah, Samir K., Back, Martin, Chung, Jayer, Lawrence, Peter F, Bath, Jonathan, and Smeds, Matthew R.

Published
2021
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28. In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas

Author

Janko, Matthew R., Woo, Karen, Hacker, Robert I., Baril, Donald, Bath, Jonathan, Smeds, Matthew R., Kashyap, Vikram S., Szeberin, Zoltan, Magee, Gregory A., Elsayed, Ramsey, Wishy, Andrew, St. John, Rebecca, Beck, Adam, Farber, Mark, Motta, Fernando, Zhou, Wei, Lemmon, Gary, Coleman, Dawn, Behrendt, Christian-Alexander, Aziz, Faisal, Black, James, Shutze, William, Garrett, H. Edward, Jr., De Caridi, Giovanni, Liapis, Christos D., Geroulakos, George, Kakisis, John, Moulakakis, Konstantinos, Kakkos, Stavros K., Obara, Hideaki, Wang, Grace, Rhéaume, Pascal, Davila, Victor, Ravin, Reid, DeMartino, Randall, Milner, Ross, Shalhub, Sherene, Jim, Jeffrey, Lee, Jason, Dubuis, Celine, Ricco, Jean-Baptiste, Coselli, Joseph, Lemaire, Scott, Fatima, Javairiah, Sanford, Jennifer, Yoshida, Winston, Schermerhorn, Marc L., Menard, Matthew, Belkin, Michael, Blackwood, Stuart, Conrad, Mark, Wang, Linda, Crofts, Sara, Nixon, Thomas, Wu, Timothy, Chiesa, Roberto, Bose, Saideep, Turner, Jason, Moore, Ryan, Smith, Justin, Ciocca, Rocco, Hsu, Jeffrey, Czerny, Martin, Cullen, Jonathan, Kahlberg, Andrea, Setacci, Carlo, Joh, Jin Hyun, Senneville, Eric, Garrido, Pedro, Sarac, Timur P., Rizzo, Anthony, Go, Michael R., Bjorck, Martin, Gavali, Hamid, Wanhainen, Anders, Lawrence, Peter F., and Chung, Jayer

Published
2021
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30. Epigenetic age analysis of children who seem to evade aging.

Author

Walker, Richard F, Liu, Jia Sophie, Peters, Brock A, Ritz, Beate R, Wu, Timothy, Ophoff, Roel A, and Horvath, Steve

Subjects
Humans, Abnormalities, Multiple, DNA Methylation, Epigenesis, Genetic, Aging, Adolescent, Child, Child, Preschool, Female, Young Adult, DNA methylation, biomarker of aging, epigenetic clock, slow aging, syndrome X, Abnormalities, Multiple, Epigenesis, Genetic, Preschool, Pediatric, Genetics, Developmental Biology, Biochemistry and Cell Biology, Physiology, Oncology and Carcinogenesis
Abstract

We previously reported the unusual case of a teenage girl stricken with multifocal developmental dysfunctions whose physical development was dramatically delayed resulting in her appearing to be a toddler or at best a preschooler, even unto the occasion of her death at the age of 20 years. Her life-long physician felt that the disorder was unique in the world and that future treatments for age-related diseases might emerge from its study. The objectives of our research were to determine if other such cases exist, and if so, whether aging is actually slowed. Of seven children characterized by dramatically slow developmental rates, five also had associated disorders displayed by the first case. All of the identified subjects were female. To objectively measure the age of blood tissue from these subjects, we used a highly accurate biomarker of aging known as "epigenetic clock" based on DNA methylation levels. No statistically significant differences in chronological and epigenetic ages were detected in any of the newly discovered cases.

Published
2015

31. Worn down nails after acrylic nail removal

Author

Wu, Timothy P, Morrison, Brian W, and Tosti, Antonella

Abstract

Worn-down nail syndrome is a nail disorder characterized by thinning of the distal nail plate caused by repetitive chemical or mechanical trauma. We present a previously undescribed source of worn-down nail syndrome caused by trauma from nail filing after acrylic nail removal.

Published
2015

34. Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia

Author

de Vrij, Femke M., Bouwkamp, Christian G., Gunhanlar, Nilhan, Shpak, Guy, Lendemeijer, Bas, Baghdadi, Maarouf, Gopalakrishna, Shreekara, Ghazvini, Mehrnaz, Li, Tracy M., Quadri, Marialuisa, Olgiati, Simone, Breedveld, Guido J., Coesmans, Michiel, Mientjes, Edwin, de Wit, Ton, Verheijen, Frans W., Beverloo, H. Berna, Cohen, Dan, Kok, Rob M., Bakker, P. Roberto, Nijburg, Aviva, Spijker, Annet T., Haffmans, P. M. Judith, Hoencamp, Erik, Bergink, Veerle, GROUP Study Consortium, Vorstman, Jacob A., Wu, Timothy, Olde Loohuis, Loes M., Amin, Najaf, Langen, Carolyn D., Hofman, Albert, Hoogendijk, Witte J., van Duijn, Cornelia M., Ikram, M. Arfan, Vernooij, Meike W., Tiemeier, Henning, Uitterlinden, André G., Elgersma, Ype, Distel, Ben, Gribnau, Joost, White, Tonya, Bonifati, Vincenzo, and Kushner, Steven A.

Published
2019
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36. Abnormal lymphatic S1P signaling aggravates lymphatic dysfunction and tissue inflammation

Author

Kim, Dongeon, primary, Tian, Wen, additional, Wu, Timothy Ting-Hsuan, additional, Xiang, Menglan, additional, Vinh, Ryan, additional, Chang, Jason, additional, Gu, Shenbiao, additional, Lee, Seunghee, additional, Zhu, Yu, additional, Guan, Torrey, additional, Schneider, Emilie Claire, additional, Bao, Evan, additional, Dixon, J. Brandon, additional, Kao, Peter, additional, Pan, Junliang, additional, Rockson, Stanley G., additional, Jiang, Xinguo, additional, and Nicolls, Mark Robert, additional

Published
2023
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38. Functional screening of lysosomal storage disorder genes identifies modifiers of alpha-synuclein neurotoxicity

Author

Yu, Meigen, primary, Ye, Hui, additional, De-Paula, Ruth B., additional, Mangleburg, Carl Grant, additional, Wu, Timothy, additional, Lee, Tom V., additional, Li, Yarong, additional, Duong, Duc, additional, Phillips, Bridget, additional, Cruchaga, Carlos, additional, Allen, Genevera I., additional, Seyfried, Nicholas T., additional, Al-Ramahi, Ismael, additional, Botas, Juan, additional, and Shulman, Joshua M., additional

Published
2023
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39. Corrigendum to “First paleoparasitological evidence of Muellerius sp. in sheep or goat dated to the Sasanian Empire (500 CE) in ancient Iran” [Veterinary Parasitology: Regional Studies and Reports Volume 34, September 2022, 100758]

Author

Wu, Timothy K., primary, Heidari, Zahra, additional, Makki, Mahsa Sadat, additional, Yazdi, Bayan, additional, Aali, Abolfazl, additional, Stöllner, Thomas, additional, Boenke, Nicole, additional, Bowman, Dwight D., additional, and Mowlavi, Gholamreza, additional

Published
2023
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42. Abnormal lymphatic S1P signaling aggravates lymphatic dysfunction and tissue inflammation

Author

Kim, Dongeon, Tian, Wen, Wu, Timothy Ting-Hsuan, Xiang, Menglan, Vinh, Ryan, Chang, Jason, Gu, Shenbiao, Lee, Seunghee, Zhu, Yu, Guan, Torrey, Schneider, Emilie Claire, Bao, Evan, Dixon, J. Brandon, Kao, Peter, Pan, Junliang, Rockson, Stanley G., Jiang, Xinguo, and Nicolls, Mark Robert

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Article
Abstract

BACKGROUND: Lymphedema is a global health problem with no effective drug treatment. Enhanced T cell immunity and abnormal lymphatic endothelial cell (LEC) signaling are promising therapeutic targets for this condition. Sphingosine-1-phosphate (S1P) mediates a key signaling pathway required for normal LEC function, and altered S1P signaling in LECs could lead to lymphatic disease and pathogenic T cell activation. Characterizing this biology is relevant for developing much-needed therapies. METHODS: Human and mouse lymphedema was studied. Lymphedema was induced in mice by surgically ligating the tail lymphatics. Lymphedematous dermal tissue was assessed for S1P signaling. To verify the role of altered S1P signaling effects in lymphatic cells, LEC-specific S1pr1-deficient (S1pr1(LECKO)) mice were generated. Disease progression was quantified by tail-volumetric and -histopathological measurements over time. LECs from mice and humans, with S1P signaling inhibition, were then co-cultured with CD4 T cells, followed by an analysis of CD4 T cell activation and pathway signaling. Finally, animals were treated with a monoclonal antibody specific to P-selectin to assess its efficacy in reducing lymphedema and T cell activation. RESULTS: Human and experimental lymphedema tissues exhibited decreased LEC S1P signaling through S1PR1. LEC S1pr1 loss-of-function exacerbated lymphatic vascular insufficiency, tail swelling, and increased CD4 T cell infiltration in mouse lymphedema. LECs, isolated from S1pr1(LECKO) mice and co-cultured with CD4 T cells, resulted in augmented lymphocyte differentiation. Inhibiting S1PR1 signaling in human dermal LECs (HDLECs) promoted T helper type 1 and 2 (Th1 and Th2) cell differentiation through direct cell contact with lymphocytes. HDLECs with dampened S1P signaling exhibited enhanced P-selectin, an important cell adhesion molecule expressed on activated vascular cells. In vitro, P-selectin blockade reduced the activation and differentiation of Th cells co-cultured with shS1PR1-treated HDLECs. P-selectin-directed antibody treatment improved tail swelling and reduced Th1/Th2 immune responses in mouse lymphedema CONCLUSION: This study suggests that reduction of the LEC S1P signaling aggravates lymphedema by enhancing LEC adhesion and amplifying pathogenic CD4 T cell responses. P-selectin inhibitors are suggested as a possible treatment for this pervasive condition.

Published
2023

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