816 results on '"Martin, Maureen"'
Search Results
2. From Jack Tar to Union Jack: Representing Naval Manhood in the British Empire, 1870-1918 (review)
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Martin, Maureen M.
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- 2011
3. HIV post-treatment controllers have distinct immunological and virological features
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Etemad, Behzad, Sun, Xiaoming, Li, Yijia, Melberg, Meghan, Moisi, Daniela, Gottlieb, Rachel, Ahmed, Hayat, Aga, Evgenia, Bosch, Ronald J, Acosta, Edward P, Yuki, Yuko, Martin, Maureen P, Carrington, Mary, Gandhi, Rajesh T, Jacobson, Jeffrey M, Volberding, Paul, Connick, Elizabeth, Mitsuyasu, Ronald, Frank, Ian, Saag, Michael, Eron, Joseph J, Skiest, Daniel, Margolis, David M, Havlir, Diane, Schooley, Robert T, Lederman, Michael M, Yu, Xu G, and Li, Jonathan Z
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Infectious Diseases ,Infection ,Good Health and Well Being ,Humans ,CD8-Positive T-Lymphocytes ,Killer Cells ,Natural ,Lymphocyte Activation ,RNA ,HIV Infections ,Viremia ,HIV ,analytical treatment interruption ,post-treatment controller ,reservoir ,T cell - Abstract
HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms of HIV post-treatment control will inform development of strategies aiming at achieving HIV functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies who maintained viral loads ≤400 copies/mL for ≥24 wk. There were no significant differences in demographics or frequency of protective and susceptible human leukocyte antigen (HLA) alleles between PTCs and post-treatment noncontrollers (NCs, n = 37). Unlike NCs, PTCs demonstrated a stable HIV reservoir measured by cell-associated RNA (CA-RNA) and intact proviral DNA assay (IPDA) during analytical treatment interruption (ATI). Immunologically, PTCs demonstrated significantly lower CD4+ and CD8+ T cell activation, lower CD4+ T cell exhaustion, and more robust Gag-specific CD4+ T cell responses and natural killer (NK) cell responses. Sparse partial least squares discriminant analysis (sPLS-DA) identified a set of features enriched in PTCs, including a higher CD4+ T cell% and CD4+/CD8+ ratio, more functional NK cells, and a lower CD4+ T cell exhaustion level. These results provide insights into the key viral reservoir features and immunological profiles for HIV PTCs and have implications for future studies evaluating interventions to achieve an HIV functional cure.
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- 2023
4. Host variation in type I interferon signaling genes (MX1), C-C chemokine receptor type 5 gene, and major histocompatibility complex class I alleles in treated HIV+ noncontrollers predict viral reservoir size.
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Siegel, David A, Thanh, Cassandra, Wan, Eunice, Hoh, Rebecca, Hobbs, Kristen, Pan, Tony, Gibson, Erica A, Kroetz, Deanna L, Martin, Jeffrey, Hecht, Frederick, Pilcher, Christopher, Martin, Maureen, Carrington, Mary, Pillai, Satish, Busch, Michael P, Stone, Mars, Levy, Claire N, Huang, Meei-Li, Roychoudhury, Pavitra, Hladik, Florian, Jerome, Keith R, Kiem, Hans-Peter, Henrich, Timothy J, Deeks, Steven G, and Lee, Sulggi A
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CD8-Positive T-Lymphocytes ,Humans ,HIV-1 ,HIV Infections ,Interferon Type I ,Histocompatibility Antigens Class I ,HLA Antigens ,Cross-Sectional Studies ,Alleles ,Myxovirus Resistance Proteins ,Major Histocompatibility Complex ,Receptors ,Chemokine ,RNA ,Viral Load ,Genetics ,Infectious Diseases ,Human Genome ,HIV/AIDS ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,C-C chemokine receptor type 5 gene ,HIV reservoir ,host genetics ,major histocompatibility complex class I ,type I interferon ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology - Abstract
ObjectivePrior genomewide association studies have identified variation in major histocompatibility complex (MHC) class I alleles and C-C chemokine receptor type 5 gene (CCR5Δ32) as genetic predictors of viral control, especially in 'elite' controllers, individuals who remain virally suppressed in the absence of therapy.DesignCross-sectional genomewide association study.MethodsWe analyzed custom whole exome sequencing and direct human leukocyte antigen (HLA) typing from 202 antiretroviral therapy (ART)-suppressed HIV+ noncontrollers in relation to four measures of the peripheral CD4+ T-cell reservoir: HIV intact DNA, total (t)DNA, unspliced (us)RNA, and RNA/DNA. Linear mixed models were adjusted for potential covariates including age, sex, nadir CD4+ T-cell count, pre-ART HIV RNA, timing of ART initiation, and duration of ART suppression.ResultsPreviously reported 'protective' host genetic mutations related to viral setpoint (e.g. among elite controllers) were found to predict smaller HIV reservoir size. The HLA 'protective' B∗57:01 was associated with significantly lower HIV usRNA (q = 3.3 × 10-3), and among the largest subgroup, European ancestry individuals, the CCR5Δ32 deletion was associated with smaller HIV tDNA (P = 4.3 × 10-3) and usRNA (P = 8.7 × 10-3). In addition, genomewide analysis identified several single nucleotide polymorphisms in MX1 (an interferon stimulated gene) that were significantly associated with HIV tDNA (q = 0.02), and the direction of these associations paralleled MX1 gene eQTL expression.ConclusionsWe observed a significant association between previously reported 'protective' MHC class I alleles and CCR5Δ32 with the HIV reservoir size in noncontrollers. We also found a novel association between MX1 and HIV total DNA (in addition to other interferon signaling relevant genes, PPP1CB, DDX3X). These findings warrant further investigation in future validation studies.
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- 2023
5. Painting the Nation: Identity and Nationalism in Scottish Painting, 1800-1920 (review)
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Martin, Maureen M
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- 2007
6. Genetic variation that determines TAPBP expression levels associates with the course of malaria in an HLA allotype-dependent manner
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Walker-Sperling, Victoria, Digitale, Jean C, Viard, Mathias, Martin, Maureen P, Bashirova, Arman, Yuki, Yuko, Ramsuran, Veron, Kulkarni, Smita, Naranbhai, Vivek, Li, Hongchuan, Anderson, Stephen K, Yum, Lauren, Clifford, Robert, Kibuuka, Hannah, Ake, Julie, Thomas, Rasmi, Rowland-Jones, Sarah, Rek, John, Arinaitwe, Emmanuel, Kamya, Moses, Rodriguez-Barraquer, Isabel, Feeney, Margaret E, and Carrington, Mary
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Malaria ,Biotechnology ,Vector-Borne Diseases ,Rare Diseases ,Vaccine Related ,Genetics ,Immunization ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Binding Sites ,Genetic Variation ,Histocompatibility Antigens Class I ,Humans ,Malaria ,Falciparum ,Membrane Transport Proteins ,MicroRNAs ,Peptides ,Plasmodium falciparum ,RNA ,Messenger ,Transcription Factor AP-2 ,malaria ,tapasin ,HLA - Abstract
HLA class I (HLA-I) allotypes vary widely in their dependence on tapasin (TAPBP), an integral component of the peptide-loading complex, to present peptides on the cell surface. We identified two single-nucleotide polymorphisms that regulate TAPBP messenger RNA (mRNA) expression in Africans, rs111686073 (G/C) and rs59097151 (A/G), located in an AP-2α transcription factor binding site and a microRNA (miR)-4486 binding site, respectively. rs111686073G and rs59097151A induced significantly higher TAPBP mRNA expression relative to the alternative alleles due to higher affinity for AP-2α and abrogation of miR-4486 binding, respectively. These variants associated with lower Plasmodium falciparum parasite prevalence and lower incidence of clinical malaria specifically among individuals carrying tapasin-dependent HLA-I allotypes, presumably by augmenting peptide loading, whereas tapasin-independent allotypes associated with relative protection, regardless of imputed TAPBP mRNA expression levels. Thus, an attenuated course of malaria may occur through enhanced breadth and/or magnitude of antigen presentation, an important consideration when evaluating vaccine efficacy.
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- 2022
7. NKp44/HLA-DP-dependent regulation of CD8 effector T cells by NK cells
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Padoan, Benedetta, Casar, Christian, Krause, Jenny, Schultheiss, Christoph, Baumdick, Martin E., Niehrs, Annika, Zecher, Britta F., Pujantell, Maria, Yuki, Yuko, Martin, Maureen, Remmerswaal, Ester B.M., Dekker, Tamara, van der Bom-Baylon, Nelly D., Noble, Janelle A., Carrington, Mary, Bemelman, Frederike J., van Lier, Rene A.W., Binder, Mascha, Gagliani, Nicola, Bunders, Madeleine J., and Altfeld, Marcus
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- 2024
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8. Comparison between qPCR and RNA-seq reveals challenges of quantifying HLA expression
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Aguiar, Vitor R. C., Castelli, Erick C., Single, Richard M., Bashirova, Arman, Ramsuran, Veron, Kulkarni, Smita, Augusto, Danillo G., Martin, Maureen P., Gutierrez-Arcelus, Maria, Carrington, Mary, and Meyer, Diogo
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- 2023
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9. Signatures of immune selection in intact and defective proviruses distinguish HIV-1 elite controllers
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Lian, Xiaodong, Gao, Ce, Sun, Xiaoming, Jiang, Chenyang, Einkauf, Kevin B, Seiger, Kyra W, Chevalier, Joshua M, Yuki, Yuko, Martin, Maureen, Hoh, Rebecca, Peluso, Michael J, Carrington, Mary, Ruiz-Mateos, Ezequiel, Deeks, Steven G, Rosenberg, Eric S, Walker, Bruce D, Lichterfeld, Mathias, and Yu, Xu G
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Women's Health ,Immunization ,Infectious Diseases ,Genetics ,HIV/AIDS ,Clinical Research ,Sexually Transmitted Infections ,Infection ,CD4-Positive T-Lymphocytes ,Elite Controllers ,Epitopes ,T-Lymphocyte ,HIV Infections ,HIV-1 ,Humans ,Proviruses ,Viral Load ,Biological Sciences ,Medical and Health Sciences ,Medical biotechnology ,Biomedical engineering - Abstract
Increasing evidence suggests that durable drug-free control of HIV-1 replication is enabled by effective cellular immune responses that may induce an attenuated viral reservoir configuration with a weaker ability to drive viral rebound. Here, we comprehensively tracked effects of antiviral immune responses on intact and defective proviral sequences from elite controllers (ECs), analyzing both classical escape mutations and HIV-1 chromosomal integration sites as biomarkers of antiviral immune selection pressure. We observed that, within ECs, defective proviruses were commonly located in permissive genic euchromatin positions, which represented an apparent contrast to autologous intact proviruses that were frequently located in heterochromatin regions; this suggests differential immune selection pressure on intact versus defective proviruses in ECs. In comparison to individuals receiving antiretroviral therapy, intact and defective proviruses from ECs showed reduced frequencies of escape mutations in cytotoxic T cell epitopes and antibody contact regions, possibly due to the small and poorly inducible reservoir that may be insufficient to drive effective viral escape in ECs. About 15% of ECs harbored nef deletions in intact proviruses, consistent with increased viral vulnerability to host immunity in the setting of nef dysfunction. Together, these results suggest a distinct signature of immune footprints in proviral sequences from ECs.
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- 2021
10. Association of Inhibitory Killer Cell Immunoglobulin-like Receptor Ligands With Higher Plasmodium falciparum Parasite Prevalence
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Digitale, Jean C, Callaway, Perri C, Martin, Maureen, Nelson, George, Viard, Mathias, Rek, John, Arinaitwe, Emmanuel, Dorsey, Grant, Kamya, Moses, Carrington, Mary, Rodriguez-Barraquer, Isabel, and Feeney, Margaret E
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Medical Microbiology ,Biomedical and Clinical Sciences ,Vector-Borne Diseases ,Infectious Diseases ,Clinical Research ,Malaria ,Rare Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Infection ,Good Health and Well Being ,Adult ,Child ,Child ,Preschool ,Genotype ,HLA-C Antigens ,Humans ,Infant ,Ligands ,Malaria ,Falciparum ,Parasitemia ,Plasmodium falciparum ,Receptors ,KIR ,KIR ,HLA ,malaria ,NK cells ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands influence the outcome of many infectious diseases. We analyzed the relationship of compound KIR-HLA genotypes with risk of Plasmodium falciparum infection in a longitudinal cohort of 890 Ugandan individuals. We found that presence of HLA-C2 and HLA-Bw4, ligands for inhibitory KIR2DL1 and KIR3DL1, respectively, increased the likelihood of P. falciparum parasitemia in an additive manner. Individuals homozygous for HLA-C2, which mediates strong inhibition via KIR2DL1, had the highest odds of parasitemia, HLA-C1/C2 heterozygotes had intermediate odds, and individuals homozygous for HLA-C1, which mediates weaker inhibition through KIR2DL2/3, had the lowest odds of parasitemia. In addition, higher surface expression of HLA-C, the ligand for inhibitory KIR2DL1/2/3, was associated with a higher likelihood of parasitemia. Together these data indicate that stronger KIR-mediated inhibition confers a higher risk of P. falciparum parasitemia and suggest that KIR-expressing effector cells play a role in mediating antiparasite immunity.
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- 2021
11. Chronic antipsychotic treatment exerts limited effects on the mania-like behavior of dopamine transporter knockdown mice.
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Cope, Zackary, Kenton, Johnny, Minassian, Arpi, Martin, Maureen, Perry, William, Bundgaard, Christoffer, Arnt, Jørn, van Enkhuizen, Jordy, Geyer, Mark, and Young, Jared
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Antipsychotic ,Behavioral pattern monitor ,Bipolar disorder ,Dopamine transporter ,Mania ,Mice ,Animals ,Antipsychotic Agents ,Behavior ,Animal ,Bipolar Disorder ,Dibenzocycloheptenes ,Disease Models ,Animal ,Dopamine D2 Receptor Antagonists ,Dopamine Plasma Membrane Transport Proteins ,Female ,Male ,Mania ,Mice ,129 Strain ,Mice ,Inbred C57BL ,Mice ,Transgenic ,Risperidone - Abstract
BACKGROUND: Bipolar disorder is a life-threatening disorder linked to dopamine transporter (DAT) polymorphisms, with reduced DAT levels seen in positron emission tomography and postmortem brains. AIMS: The purpose of this study was to examine the effects of approved antipsychotics on DAT dysfunction-mediated mania behavior in mice. METHODS: DAT knockdown mice received either D2-family receptor antagonist risperidone or asenapine and mania-related behaviors were assessed in the clinically-relevant behavioral pattern monitor to assess spontaneous exploration. RESULTS: Chronic risperidone did not reverse mania-like behavior in DAT knockdown mice. Chronic asenapine reduced mania behavior but this effect was more pronounced in wild-type littermates than in DAT knockdown mice. CONCLUSION: Taken together, these findings suggest that while acute antipsychotic treatment may be beneficial in management of bipolar mania, more targeted therapeutics may be necessary for long-term treatment. Specific investigation into DAT-targeting drugs could improve future treatment of bipolar mania.
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- 2021
12. HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis
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Akar, Alaa, Flemming, Cornelius, Felix, Flomm, Flosbach, Markus, Jäger, Julia, Jeromin, Niklas, Jung, Johannes, Ohms, Mareike, Reinshagen, Konrad, Rische, Johann, Sagebiel, Adrian, Sandfort, Deborah, Steinert, Fenja, Tomuschat, Christian, Wesche, Jasmin, Shifteh Abedian, Abraham, Clara, Achkar, Jean-Paul, Ahmad, Tariq, Alberts, Rudi, Alizadeh, Behrooz, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Anderson, Carl A., Andrews, Jane M., Annese, Vito, Aumais, Guy, Baidoo, Leonard, Baldassano, Robert N., Bampton, Peter A., Barclay, Murray, Barrett, Jeffrey C., Bethge, Johannes, Bewshea, Claire, Bis, Joshua C., Bitton, Alain, BK, Thelma, Boucher, Gabrielle, Brain, Oliver, Brand, Stephan, Brant, Steven R., Cheon, Jae Hee, Chew, Angela, Cho, Judy H., Cleynen, Isabelle, Cohain, Ariella, Cooney, Rachel, Croft, Anthony, Daly, Mark J., D'Amato, Mauro, Danese, Silvio, Daryani, Naser Ebrahim, Datta, Lisa Wu, Degenhardt, Frauke, Denapiene, Goda, Denson, Lee A., Devaney, Kathy L., Dewit, Olivier, D'Inca, Renata, Drummond, Hazel E., Dubinsky, Marla, Duerr, Richard H., Edwards, Cathryn, Ellinghaus, David, Ellul, Pierre, Esaki, Motohiro, Essers, Jonah, Ferguson, Lynnette R., Festen, Eleonora A., Fleshner, Philip, Florin, Tim, Franchimont, Denis, Franke, Andre, Fuyuno, Yuta, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Goyette, Philippe, Green, Todd, Griffiths, Anne M., Guthery, Stephen L., Hakonarson, Hakon, Halfvarson, Jonas, Hanigan, Katherine, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hayward, Nicholas K., Hedl, Matija, Henderson, Paul, Hold, Georgina L., Hong, Myhunghee, Hu, Xinli, Huang, Hailiang, Hugot, Jean-Pierre, Hui, Ken Y., Imielinski, Marcin, Jazayeri, Omid, Jonaitis, Laimas, Jostins, Luke, Juyal, Garima, Chandra Juyal, Ramesh, Kalla, Rahul, Karlsen, Tom H., Kennedy, Nicholas A., Khan, Mohammed Azam, Kim, Won Ho, Kitazono, Takanari, Kiudelis, Gediminas, Kubo, Michiaki, Kugathasan, Subra, Kupcinskas, Limas, Lamb, Christopher A., de Lange, Katrina M., Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lee, James C., Lees, Charlie W., Leja, Marcis, Lewis, Nina, Van Limbergen, Johan, Lionetti, Paolo, Liu, Jimmy Z., Louis, Edouard, Luo, Yang, Mahy, Gillian, Malekzadeh, Masoud Mohammad, Malekzadeh, Reza, Mansfield, John, Marriott, Suzie, Massey, Dunecan, Mathew, Christopher G., Matsui, Toshiyuki, McGovern, Dermot P.B., van der Meulen, Andrea, Midha, Vandana, Milgrom, Raquel, Mirzaei, Samaneh, Mitrovic, Mitja, Montgomery, Grant W., Mowat, Craig, Müller, Christoph, Newman, William G., Ng, Aylwin, Ng, Siew C., Evelyn Ng, Sok Meng, Nikolaus, Susanna, Ning, Kaida, Nöthen, Markus, Oikonomou, Ioannis, Okou, David, Orchard, Timothy R., Palmieri, Orazio, Parkes, Miles, Phillips, Anne, Ponsioen, Cyriel Y., Potocnik, Urõs, Poustchi, Hossein, Prescott, Natalie J., Proctor, Deborah D., Radford-Smith, Graham, Rahier, Jean- Francois, Regueiro, Miguel, Reinisch, Walter, Rieder, Florian, Rioux, John D., Roberts, Rebecca, Rogler, Gerhard, Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schadt, Eric E., Scharl, Michael, Schembri, John, Schreiber, Stefan, Schumm, L. Philip, Scott, Regan, Seielstad, Mark, Shah, Tejas, Sharma, Yashoda, Silverberg, Mark S., Simmons, Alison, Simms, Lisa A., Singh, Abhey, Skieceviciene, Jurgita, van Sommeren, Suzanne, Song, Kyuyoung, Sood, Ajit, Spain, Sarah L., Steinhart, A. Hillary, Stempak, Joanne M., Stronati, Laura, Sung, Joseph J.Y., Targan, Stephan R., Taylor, Kirstin M., Theatre, Emilie, Torkvist, Leif, Torres, Esther A., Tremelling, Mark, Uhlig, Holm H., Umeno, Junji, Vahedi, Homayon, Vasiliauskas, Eric, Velde, Anje ter, Ventham, Nicholas T., Vermeire, Severine, Verspaget, Hein W., De Vos, Martine, Walters, Thomas, Wang, Kai, Wang, Ming-Hsi, Weersma, Rinse K., Wei, Zhi, Whiteman, David, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Wong, Sunny H., Xavier, Ramnik J., Yamazaki, Keiko, Yang, Suk-Kyun, Ye, Byong Duk, Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhang, Hu, Zhang, Wei, Zhao, Hongyu, Zhao, Zhen Z., Baumdick, Martin E., Niehrs, Annika, Schwerk, Maria, Hinrichs, Ole, Jordan-Paiz, Ana, Padoan, Benedetta, Wegner, Lucy H.M., Schloer, Sebastian, Zecher, Britta F., Malsy, Jakob, Joshi, Vinita R., Illig, Christin, Schröder-Schwarz, Jennifer, Möller, Kimberly J., Martin, Maureen P., Yuki, Yuko, Ozawa, Mikki, Sauter, Jürgen, Schmidt, Alexander H., Perez, Daniel, Giannou, Anastasios D., Carrington, Mary, Davis, Randall S., Schumacher, Udo, Sauter, Guido, Huber, Samuel, Puelles, Victor G., Melling, Nathaniel, Altfeld, Marcus, and Bunders, Madeleine J.
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- 2023
- Full Text
- View/download PDF
13. HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda
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Digitale, Jean C, Callaway, Perri C, Martin, Maureen, Nelson, George, Viard, Mathias, Rek, John, Arinaitwe, Emmanuel, Dorsey, Grant, Kamya, Moses, Carrington, Mary, Rodriguez-Barraquer, Isabel, and Feeney, Margaret E
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- 2021
14. Value-Added Model (VAM) Component of Teacher Evaluation and Job Satisfaction, Efficacy, and Retention: Perspectives of Secondary Teachers of Historically Low-Scoring Students and Recommendations for Alternative Student Performance Measurements
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Martin, Maureen A.
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This qualitative study aimed to research the perspectives of four teachers who teach low-scoring populations of students traditionally. The research questions focused on job satisfaction, self-efficacy, and retention in education about Value-Added Model scores in their evaluations. The secondary purpose was for the teachers to recommend authentic assessment of student growth which is weighted 33% of teacher evaluations. I conducted a series of three open-ended interviews with each of the four participants. The interviews were designed to allow rich data to be collected. The significant findings have been discovered using the constant comparative method. The analysis revealed that the teacher's perceptions of VAM scores were not in their control, nor did the teachers understand how the score is calculated; however, it was a stress point in the teaching environment. The recommendations for alternative measurement of student achievement had a common thread of a baseline assessment and a learning gain assessment of the students the teachers directly taught. The emerging themes concluded that the evaluating administrator had more impact on job satisfaction and self-efficacy than VAM scores. The research questions drove the study, and the analysis discovered trends and emerging themes. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]
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- 2021
15. CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome
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Kulkarni, Smita, Lied, Alexandra, Kulkarni, Viraj, Rucevic, Marijana, Martin, Maureen P, Walker-Sperling, Victoria, Anderson, Stephen K, Ewy, Rodger, Singh, Sukhvinder, Nguyen, Hoang, McLaren, Paul J, Viard, Mathias, Naranbhai, Vivek, Zou, Chengcheng, Lin, Zhansong, Gatanaga, Hiroyuki, Oka, Shinichi, Takiguchi, Masafumi, Thio, Chloe L, Margolick, Joseph, Kirk, Gregory D, Goedert, James J, Hoots, W Keith, Deeks, Steven G, Haas, David W, Michael, Nelson, Walker, Bruce, Le Gall, Sylvie, Chowdhury, Fatema Z, Yu, Xu G, and Carrington, Mary
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Sexually Transmitted Infections ,Genetics ,Human Genome ,Infectious Diseases ,HIV/AIDS ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,3' Untranslated Regions ,Alleles ,Biomarkers ,CD4-Positive T-Lymphocytes ,Cell Membrane ,Gene Expression Regulation ,Genes ,Reporter ,Genetic Variation ,Genotype ,HIV Infections ,HIV-1 ,Humans ,Linkage Disequilibrium ,Polymorphism ,Single Nucleotide ,Population Groups ,Prognosis ,RNA Stability ,RNA ,Antisense ,RNA ,Long Noncoding ,RNA ,Messenger ,Receptors ,CCR5 ,Viral Load ,Biochemistry and cell biology - Abstract
Multiple genome-wide studies have identified associations between outcome of human immunodeficiency virus (HIV) infection and polymorphisms in and around the gene encoding the HIV co-receptor CCR5, but the functional basis for the strongest of these associations, rs1015164A/G, is unknown. We found that rs1015164 marks variation in an activating transcription factor 1 binding site that controls expression of the antisense long noncoding RNA (lncRNA) CCR5AS. Knockdown or enhancement of CCR5AS expression resulted in a corresponding change in CCR5 expression on CD4+ T cells. CCR5AS interfered with interactions between the RNA-binding protein Raly and the CCR5 3' untranslated region, protecting CCR5 messenger RNA from Raly-mediated degradation. Reduction in CCR5 expression through inhibition of CCR5AS diminished infection of CD4+ T cells with CCR5-tropic HIV in vitro. These data represent a rare determination of the functional importance of a genome-wide disease association where expression of a lncRNA affects HIV infection and disease progression.
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- 2019
16. Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1
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Martin, Maureen P, Naranbhai, Vivek, Shea, Patrick R, Qi, Ying, Ramsuran, Veron, Vince, Nicolas, Gao, Xiaojiang, Thomas, Rasmi, Brumme, Zabrina L, Carlson, Jonathan M, Wolinsky, Steven M, Goedert, James J, Walker, Bruce D, Segal, Florencia P, Deeks, Steven G, Haas, David W, Migueles, Stephen A, Connors, Mark, Michael, Nelson, Fellay, Jacques, Gostick, Emma, Llewellyn-Lacey, Sian, Price, David A, Lafont, Bernard A, Pymm, Phillip, Saunders, Philippa M, Widjaja, Jacqueline, Wong, Shu Cheng, Vivian, Julian P, Rossjohn, Jamie, Brooks, Andrew G, and Carrington, Mary
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,Genetics ,HIV/AIDS ,Human Genome ,Clinical Research ,Sexually Transmitted Infections ,2.1 Biological and endogenous factors ,Aetiology ,Infection ,Good Health and Well Being ,Adult ,Cohort Studies ,Female ,Genetic Variation ,HIV Infections ,HIV-1 ,HLA-B Antigens ,Humans ,Male ,Middle Aged ,Receptors ,KIR3DL1 ,AIDS/HIV ,Innate immunity ,MHC class 1 ,NK cells ,Medical and Health Sciences ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
HLA-B*57 control of HIV involves enhanced CD8+ T cell responses against infected cells, but extensive heterogeneity exists in the level of HIV control among B*57+ individuals. Using whole-genome sequencing of untreated B*57+ HIV-1-infected controllers and noncontrollers, we identified a single variant (rs643347A/G) encoding an isoleucine-to-valine substitution at position 47 (I47V) of the inhibitory killer cell immunoglobulin-like receptor KIR3DL1 as the only significant modifier of B*57 protection. The association was replicated in an independent cohort and across multiple outcomes. The modifying effect of I47V was confined to B*57:01 and was not observed for the closely related B*57:03. Positions 2, 47, and 54 tracked one another nearly perfectly, and 2 KIR3DL1 allotypes differing only at these 3 positions showed significant differences in binding B*57:01 tetramers, whereas the protective allotype showed lower binding. Thus, variation in an immune NK cell receptor that binds B*57:01 modifies its protection. These data highlight the exquisite specificity of KIR-HLA interactions in human health and disease.
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- 2018
17. Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells
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Ramsuran, Veron, Naranbhai, Vivek, Horowitz, Amir, Qi, Ying, Martin, Maureen P, Yuki, Yuko, Gao, Xiaojiang, Walker-Sperling, Victoria, Del Prete, Gregory Q, Schneider, Douglas K, Lifson, Jeffrey D, Fellay, Jacques, Deeks, Steven G, Martin, Jeffrey N, Goedert, James J, Wolinsky, Steven M, Michael, Nelson L, Kirk, Gregory D, Buchbinder, Susan, Haas, David, Ndung’u, Thumbi, Goulder, Philip, Parham, Peter, Walker, Bruce D, Carlson, Jonathan M, and Carrington, Mary
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Sexually Transmitted Infections ,HIV/AIDS ,Women's Health ,Infectious Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Infection ,Alleles ,CD4 Lymphocyte Count ,Cohort Studies ,HIV ,HIV Infections ,HLA Antigens ,Humans ,Killer Cells ,Natural ,Ligands ,NK Cell Lectin-Like Receptor Subfamily C ,Protein Sorting Signals ,Viremia ,General Science & Technology - Abstract
The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A-derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor. HLA-B haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease.
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- 2018
18. HLA-B*14:02-Restricted Env-Specific CD8+ T-Cell Activity Has Highly Potent Antiviral Efficacy Associated with Immune Control of HIV Infection
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Leitman, Ellen M, Willberg, Christian B, Tsai, Ming-Han, Chen, Huabiao, Buus, Søren, Chen, Fabian, Riddell, Lynn, Haas, David, Fellay, Jacques, Goedert, James J, Piechocka-Trocha, Alicja, Walker, Bruce D, Martin, Jeffrey, Deeks, Steven, Wolinsky, Steven M, Martinson, Jeremy, Martin, Maureen, Qi, Ying, Sáez-Cirión, Asier, Yang, Otto O, Matthews, Philippa C, Carrington, Mary, and Goulder, Philip JR
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,Immunization ,Vaccine Related ,HIV/AIDS ,Sexually Transmitted Infections ,Clinical Research ,Prevention ,Vaccine Related (AIDS) ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Infection ,Good Health and Well Being ,Adult ,CD8-Positive T-Lymphocytes ,HIV Envelope Protein gp160 ,HIV Infections ,HIV-1 ,HLA-B14 Antigen ,Humans ,Immunity ,Cellular ,Peptides ,gag Gene Products ,Human Immunodeficiency Virus ,CD8(+) T cells ,HIV ,HLA-B*14 ,immune control ,CD8+ T cells ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology ,Agricultural ,veterinary and food sciences ,Biological sciences ,Biomedical and clinical sciences - Abstract
Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8+ T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, HLA-B*14-DA9). Using HLA-B*14/peptide-saporin-conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9. HLA-B*14-EL9 also has significantly higher functional avidity (P < 0.0001) and drives stronger selection pressure on the virus than HLA-B*14-DA9. However, these differences were HLA-B*14 subtype specific, applying only to HLA-B*14:02 and not to HLA-B*14:01. Furthermore, the HLA-B*14-associated protection against HIV disease progression is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response. Thus, although Gag-specific CD8+ T-cell responses may usually have greater anti-HIV efficacy, factors independent of protein specificity, including functional avidity of individual responses, are also critically important to immune control of HIV.IMPORTANCE In HIV infection, although cytotoxic T lymphocytes (CTL) play a potentially critical role in eradication of viral reservoirs, the features that constitute an effective response remain poorly defined. We focus on HLA-B*14, unique among HLAs associated with control of HIV in that the dominant CTL response is Env specific, not Gag specific. We demonstrate that Env-specific HLA-B*14-restricted activity is substantially more efficacious than the subdominant HLA-B*14-restricted Gag response. Env immunodominance over Gag and strong Env-mediated selection pressure on HIV are observed only in subjects expressing HLA-B*14:02, and not HLA-B*14:01. This reflects the increased functional avidity of the Env response over Gag, substantially more marked for HLA-B*14:02. Finally, we show that HLA-B*14:02 is significantly more strongly associated with viremic control than HLA-B*14:01. These findings indicate that, although Gag-specific CTL may usually have greater anti-HIV efficacy than Env responses, factors independent of protein specificity, including functional avidity, may carry greater weight in mediating effective control of HIV.
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- 2017
19. KIR Locus Variation
- Author
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Martin, Maureen P., Bashirova, Arman, Carrington, Mary, Hope, Thomas J., editor, Richman, Douglas D., editor, and Stevenson, Mario, editor
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- 2018
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20. HLA-DPA1* 02:01~B1*01:01 is a risk haplotype for primary sclerosing cholangitis mediating activation of NKp44+ NK cells.
- Author
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Zecher, Britta F., Ellinghaus, David, Schloer, Sebastian, Niehrs, Annika, Padoan, Benedetta, Baumdick, Martin E., Yuko Yuki, Martin, Maureen P., Glow, Dawid, Schröder-Schwarz, Jennifer, Niersch, Jennifer, Brias, Sébastien, Müller, Luisa M., Habermann, Robin, Kretschmer, Paul, Früh, Tristan, Dänekas, Janis, Wehmeyer, Malte H., Poch, Tobias, and Sebode, Marcial
- Subjects
CHOLANGITIS ,KILLER cells ,HAPLOTYPES ,INTRAHEPATIC bile ducts ,MOLECULAR biology - Published
- 2024
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21. Understanding the heterogeneity of alloreactive natural killer cell function in kidney transplantation
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Ruan, Dan Fu, primary, Fribourg, Miguel, additional, Yuki, Yuko, additional, Park, Yeon-Hwa, additional, Martin, Maureen, additional, Kelly, Geoffrey, additional, Lee, Brian, additional, de Real, Ronaldo Miguel, additional, Lee, Rachel, additional, Geanon, Daniel, additional, Kim-Schulze, Seunghee, additional, McCarthy, Melissa, additional, Chun, Nicholas, additional, Cravedi, Paolo, additional, Carrington, Mary, additional, Heeger, Peter S., additional, and Horowitz, Amir, additional
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- 2023
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22. Children with Developmental Verbal Dyspraxia: Changes in Articulation and Perceived Resilience with Intensive Multimodal Intervention
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Martin, Maureen K, Wright, Lindsay Elizabeth, Perry, Susan, Cornett, Daphne, Schraeder, Missy, and Johnson, James T.
- Abstract
Research into intervention strategies for developmental verbal dyspraxia (DVD) clearly demonstrates the need to identify effective interventions. The goals of this study were to examine changes in articulation skills following the use of phonetic, multimodal intervention and to consider the relationship between these improved articulation skills and perceptions of resilience behaviors. These changes were related to components of the World Health Organization (WHO) International Classification of Functioning, Disability, and Health, Children and Youth version (ICF-CY). The intervention was implemented daily for 12 children diagnosed with DVD, ages 3 to 10 years, enrolled in a school for children with speech, language, and hearing impairments on a university campus in the southeast of the USA. Eleven children presented with significant comorbid conditions. Changes in articulation, along with changes in parents' and speech-language therapists' (SLTs') perceptions of resilience behaviors were measured. At the end of a 2-year period, statistically significant gains in articulation and parents' and SLTs' perceptions of resilience behaviors were noted. The relationship between improved articulation skills and increased resilience behaviors is discussed.
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- 2016
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23. Coding and Noncoding Gene Expression Biomarkers in Mood Disorders and Schizophrenia
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Mamdani, Firoza, Martin, Maureen V, Lencz, Todd, Rollins, Brandi, Robinson, Delbert G, Moon, Emily A, Malhotra, Anil K, and Vawter, Marquis P
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Peripheral-Blood Lymphocytes ,Lymphoblastoid Cell-Lines ,Transporter Messenger-Rna ,Major Depression ,Bipolar Disorder ,Serotonin Transporter ,Neoadjuvant Chemotherapy ,Antidepressant Response ,Therapeutic Response ,Altered Expression - Published
- 2013
24. Impact of protective killer inhibitory receptor/human leukocyte antigen genotypes on natural killer cell and T-cell function in HIV-1-infected controllers
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Tomescu, Costin, Duh, Fuh-Mei, Hoh, Rebecca, Viviani, Anne, Harvill, Kara, Martin, Maureen P, Carrington, Mary, Deeks, Steven G, and Montaner, Luis J
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,Sexually Transmitted Infections ,HIV/AIDS ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Infection ,Inflammatory and immune system ,Good Health and Well Being ,Acquired Immunodeficiency Syndrome ,Adaptive Immunity ,Adult ,CD4-Positive T-Lymphocytes ,CD8-Positive T-Lymphocytes ,California ,Disease Progression ,Female ,Genotype ,HIV Seropositivity ,HIV-1 ,Humans ,Immunity ,Innate ,Killer Cells ,Natural ,Male ,RNA ,Viral ,Receptors ,KIR ,Receptors ,KIR3DL1 ,Virus Replication ,AIDS ,elite controllers ,human leukocyte antigen ,killer inhibitory receptor ,natural killer cells ,T cells ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveBoth protective T-cell genotypes and natural killer (NK) cell genotypes have been associated with delayed progression to AIDS and shown to be co-inherited in HIV-1-infected individuals who limit viral replication in absence of antiretroviral therapy ('controllers'). However, a comparative analysis of the genotype and function of the innate and adaptive immune compartments in HIV-1-infected controller individuals has been understudied to date.DesignHere, we simultaneously tested NK and T-cell function in controllers to investigate the mechanism(s) that might account for host immune control over viral replication.MethodsWe measured CD8 T-cell responses against HIV-1 utilizing overlapping 15-mer peptides spanning the HIV-1 consensus clade B Gag protein and tested NK cell degranulation and cytokine secretion against tumor target cells following interferon-α (IFNα) stimulation.ResultsAmong a cohort of 37 controllers, the presence of protective major histocompatibility complex class I human leukocyte antigen (HLA) alleles (such as HLA-B*57) was not correlated with HIV-specific CD8 responses. In contrast, the inheritance of a protective killer inhibitory receptor KIR3DL1*h/*y receptor genotype along with the corresponding HLA-Bw4*80I ligand was associated with significantly heightened target cell-induced NK degranulation and cytokine secretion following IFNα stimulation (P = 0.0201, n = 13). Interestingly, we observed a significant inverse association between the IFNα stimulated NK response to K562 cells and the HIV-specific CD8 T-cell response to Gag among elite controllers (rho = -0.8321, P = 0.0010, n = 12).ConclusionTogether, these results suggest that heightened NK responses can be evidenced independently of HIV-specific T-cell responses in HIV-1-infected elite controllers.
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- 2012
25. Psoriasis patients are enriched for genetic variants that protect against HIV-1 disease.
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Chen, Haoyan, Hayashi, Genki, Lai, Olivia Y, Dilthey, Alexander, Kuebler, Peter J, Wong, Tami V, Martin, Maureen P, Fernandez Vina, Marcelo A, McVean, Gil, Wabl, Matthias, Leslie, Kieron S, Maurer, Toby, Martin, Jeffrey N, Deeks, Steven G, Carrington, Mary, Bowcock, Anne M, Nixon, Douglas F, and Liao, Wilson
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Killer Cells ,Natural ,Humans ,HIV-1 ,HIV Infections ,Psoriasis ,Genetic Predisposition to Disease ,HLA-B Antigens ,HLA-C Antigens ,Genes ,MHC Class I ,Genes ,MHC Class II ,Protein Binding ,Polymorphism ,Genetic ,Receptors ,KIR3DS1 ,Genetic Association Studies ,Killer Cells ,Natural ,Genes ,MHC Class I ,MHC Class II ,Polymorphism ,Genetic ,Receptors ,KIR3DS1 ,Genetics ,Developmental Biology - Abstract
An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immune-mediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw4-80I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis.
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- 2012
26. Mitochondrial mutations and polymorphisms in psychiatric disorders.
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Sequeira, Adolfo, Martin, Maureen V, Rollins, Brandi, Moon, Emily A, Bunney, William E, Macciardi, Fabio, Lupoli, Sara, Smith, Erin N, Kelsoe, John, Magnan, Christophe N, van Oven, Mannis, Baldi, Pierre, Wallace, Douglas C, and Vawter, Marquis P
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bipolar disorder ,common deletion ,homoplasmy ,mitochondria ,novel mutations ,schizophrenia ,Brain Disorders ,Neurosciences ,Depression ,Serious Mental Illness ,Schizophrenia ,Genetics ,Mental Health ,Clinical Research ,Human Genome ,Aetiology ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Underpinning research ,Mental health ,Clinical Sciences ,Law - Abstract
Mitochondrial deficiencies with unknown causes have been observed in schizophrenia (SZ) and bipolar disorder (BD) in imaging and postmortem studies. Polymorphisms and somatic mutations in mitochondrial DNA (mtDNA) were investigated as potential causes with next generation sequencing of mtDNA (mtDNA-Seq) and genotyping arrays in subjects with SZ, BD, major depressive disorder (MDD), and controls. The common deletion of 4,977 bp in mtDNA was compared between SZ and controls in 11 different vulnerable brain regions and in blood samples, and in dorsolateral prefrontal cortex (DLPFC) of BD, SZ, and controls. In a separate analysis, association of mitochondria SNPs (mtSNPs) with SZ and BD in European ancestry individuals (n = 6,040) was tested using Genetic Association Information Network (GAIN) and Wellcome Trust Case Control Consortium 2 (WTCCC2) datasets. The common deletion levels were highly variable across brain regions, with a 40-fold increase in some regions (nucleus accumbens, caudate nucleus and amygdala), increased with age, and showed little change in blood samples from the same subjects. The common deletion levels were increased in the DLPFC for BD compared to controls, but not in SZ. Full mtDNA genome resequencing of 23 subjects, showed seven novel homoplasmic mutations, five were novel synonymous coding mutations. By logistic regression analysis there were no significant mtSNPs associated with BD or SZ after genome wide correction. However, nominal association of mtSNPs (p
- Published
- 2012
27. Differential microRNA regulation of HLA-C expression and its association with HIV control.
- Author
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Kulkarni, Smita, Savan, Ram, Qi, Ying, Gao, Xiaojiang, Yuki, Yuko, Bass, Sara E, Martin, Maureen P, Hunt, Peter, Deeks, Steven G, Telenti, Amalio, Pereyra, Florencia, Goldstein, David, Wolinsky, Steven, Walker, Bruce, Young, Howard A, and Carrington, Mary
- Subjects
Cell Line ,Humans ,HIV ,HIV Infections ,MicroRNAs ,3' Untranslated Regions ,HLA-C Antigens ,Viral Load ,Gene Expression Regulation ,Base Sequence ,Polymorphism ,Single Nucleotide ,Alleles ,Genes ,Reporter ,Polymorphism ,Single Nucleotide ,Genes ,Reporter ,Untranslated Regions ,General Science & Technology - Abstract
The HLA-C locus is distinct relative to the other classical HLA class I loci in that it has relatively limited polymorphism, lower expression on the cell surface, and more extensive ligand-receptor interactions with killer-cell immunoglobulin-like receptors. A single nucleotide polymorphism (SNP) 35 kb upstream of HLA-C (rs9264942; termed -35) associates with control of HIV, and with levels of HLA-C messenger RNA transcripts and cell-surface expression, but the mechanism underlying its varied expression is unknown. We proposed that the -35 SNP is not the causal variant for differential HLA-C expression, but rather is marking another polymorphism that directly affects levels of HLA-C. Here we show that variation within the 3' untranslated region (UTR) of HLA-C regulates binding of the microRNA hsa-miR-148 to its target site, resulting in relatively low surface expression of alleles that bind this microRNA and high expression of HLA-C alleles that escape post-transcriptional regulation. The 3' UTR variant associates strongly with control of HIV, potentially adding to the effects of genetic variation encoding the peptide-binding region of the HLA class I loci. Variation in HLA-C expression adds another layer of diversity to this highly polymorphic locus that must be considered when deciphering the function of these molecules in health and disease.
- Published
- 2011
28. Left Atrial Strain May Predict Thrombus Formation in Patients With Transthyretin Cardiac Amyloidosis
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Donnellan, Eoin, primary, Hussain, Muzna, additional, Marrouche, Nassir, additional, Park, Margaret, additional, Martin, Maureen, additional, Hanna, Mazen, additional, Wazni, Oussama, additional, Collier, Patrick, additional, and Jaber, Wael, additional
- Published
- 2023
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29. Mitochondrial Variants in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder
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Rollins, Brandi, Martin, Maureen V., Sequeira, P. Adolfo, Moon, Emily A., Morgan, Ling Z., Watson, Stanley J., Schatzberg, Alan, Akil, Huda, Myers, Richard M., Jones, Edward G., Wallace, Douglas C., Bunney, William E., and Vawter, Marquis P.
- Subjects
magnetic-resonance-spectroscopy ,postmortem human-brain ,mtdna point mutations ,subunit gene ndufv2 ,dna deletion levels ,complex-i ,oxidative stress ,parental transmission ,maternal inheritance ,rapid identification - Abstract
BackgroundMitochondria provide most of the energy for brain cells by the process of oxidative phosphorylation. Mitochondrial abnormalities and deficiencies in oxidative phosphorylation have been reported in individuals with schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) in transcriptomic, proteomic, and metabolomic studies. Several mutations in mitochondrial DNA (mtDNA) sequence have been reported in SZ and BD patients.Methodology/Principal FindingsDorsolateral prefrontal cortex (DLPFC) from a cohort of 77 SZ, BD, and MDD subjects and age-matched controls (C) was studied for mtDNA sequence variations and heteroplasmy levels using Affymetrix mtDNA resequencing arrays. Heteroplasmy levels by microarray were compared to levels obtained with SNaPshot and allele specific real-time PCR. This study examined the association between brain pH and mtDNA alleles. The microarray resequencing of mtDNA was 100% concordant with conventional sequencing results for 103 mtDNA variants. The rate of synonymous base pair substitutions in the coding regions of the mtDNA genome was 22% higher (p = 0.0017) in DLPFC of individuals with SZ compared to controls. The association of brain pH and super haplogroup (U, K, UK) was significant (p = 0.004) and independent of postmortem interval time.ConclusionsFocusing on haplogroup and individual susceptibility factors in psychiatric disorders by considering mtDNA variants may lead to innovative treatments to improve mitochondrial health and brain function.
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- 2009
30. Exon expression in lymphoblastoid cell lines from subjects with schizophrenia before and after glucose deprivation
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Martin, Maureen V, Rollins, Brandi, Sequeira, P Adolfo, Mesen, Andrea, Byerley, William, Stein, Richard, Moon, Emily A, Akil, Huda, Jones, Edward G, Watson, Stanley J, Barchas, Jack, DeLisi, Lynn E, Myers, Richard M, Schatzberg, Alan, Bunney, William E, and Vawter, Marquis P
- Subjects
global gene-expression ,bipolar disorder ,prefrontal-cortex ,psychiatric-disorders ,brain disorders ,messenger-rna ,blood ,disease ,microarrays ,stress - Abstract
Background: The purpose of this study was to examine the effects of glucose reduction stress on lymphoblastic cell line (LCL) gene expression in subjects with schizophrenia compared to non-psychotic relatives. Methods: LCLs were grown under two glucose conditions to measure the effects of glucose reduction stress on exon expression in subjects with schizophrenia compared to unaffected family member controls. A second aim of this project was to identify cis-regulated transcripts associated with diagnosis. Results: There were a total of 122 transcripts with significant diagnosis by probeset interaction effects and 328 transcripts with glucose deprivation by probeset interaction probeset effects after corrections for multiple comparisons. There were 8 transcripts with expression significantly affected by the interaction between diagnosis and glucose deprivation and probeset after correction for multiple comparisons. The overall validation rate by qPCR of 13 diagnosis effect genes identified through microarray was 62%, and all genes tested by qPCR showed concordant up- or down-regulation by qPCR and microarray. We assessed brain gene expression of five genes found to be altered by diagnosis and glucose deprivation in LCLs and found a significant decrease in expression of one gene, glutaminase, in the dorsolateral prefrontal cortex (DLPFC). One SNP with previously identified regulation by a 3' UTR SNP was found to influence IRF5 expression in both brain and lymphocytes. The relationship between the 3' UTR rs10954213 genotype and IRF5 expression was significant in LCLs (p = 0.0001), DLPFC (p = 0.007), and anterior cingulate cortex (p = 0.002). Conclusion: Experimental manipulation of cells lines from subjects with schizophrenia may be a useful approach to explore stress related gene expression alterations in schizophrenia and to identify SNP variants associated with gene expression.
- Published
- 2009
31. HLA-DPA1*02:01~B1*01:01is a risk haplotype for primary sclerosing cholangitis mediating activation of NKp44+ NK cells
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Zecher, Britta F, Ellinghaus, David, Schloer, Sebastian, Niehrs, Annika, Padoan, Benedetta, Baumdick, Martin E, Yuki, Yuko, Martin, Maureen P, Glow, Dawid, Schro¨der-Schwarz, Jennifer, Niersch, Jennifer, Brias, Sébastien, Mu¨ller, Luisa M, Habermann, Robin, Kretschmer, Paul, Fru¨h, Tristan, Da¨nekas, Janis, Wehmeyer, Malte H, Poch, Tobias, Sebode, Marcial, Ellinghaus, Eva, Degenhardt, Frauke, Ko¨rner, Christian, Hoelzemer, Angelique, Fehse, Boris, Oldhafer, Karl J, Schumacher, Udo, Sauter, Guido, Carrington, Mary, Franke, Andre, Bunders, Madeleine J, Schramm, Christoph, and Altfeld, Marcus
- Abstract
ObjectivePrimary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring liver transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind the activating NK-cell receptor NKp44, we investigated the role of HLA-DP/NKp44-interactions in PSC.DesignLiver tissue, intrahepatic and peripheral blood lymphocytes of individuals with PSC and control individuals were characterised using flow cytometry, immunohistochemical and immunofluorescence analyses. HLA-DPA1 and HLA-DPB1 imputation and association analyses were performed in 3408 individuals with PSC and 34 213 controls. NK cell activation on NKp44/HLA-DP interactions was assessed in vitro using plate-bound HLA-DP molecules and HLA-DPB wildtype versus knock-out human cholangiocyte organoids.ResultsNKp44+NK cells were enriched in livers, and intrahepatic bile ducts of individuals with PSC showed higher expression of HLA-DP. HLA-DP haplotype analysis revealed a highly elevated PSC risk for HLA-DPA1*02:01~B1*01:01(OR 1.99, p=6.7×10−50). Primary NKp44+NK cells exhibited significantly higher degranulation in response to plate-bound HLA-DPA1*02:01-DPB1*01:01 compared with control HLA-DP molecules, which were inhibited by anti-NKp44-blocking. Human cholangiocyte organoids expressing HLA-DPA1*02:01-DPB1*01:01 after IFN-γ-exposure demonstrated significantly increased binding to NKp44-Fc constructs compared with unstimulated controls. Importantly, HLA-DPA1*02:01-DPB1*01:01-expressing organoids increased degranulation of NKp44+NK cells compared with HLA-DPB1-KO organoids.ConclusionOur studies identify a novel PSC risk haplotype HLA-DP A1*02:01~DPB1*01:01and provide clinical and functional data implicating NKp44+NK cells that recognise HLA-DPA1*02:01-DPB1*01:01 expressed on cholangiocytes in PSC pathogenesis.
- Published
- 2024
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32. The Role of Human Genetics in HIV-1 Infection
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Martin, Maureen P., primary and Carrington, Mary, additional
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- 2019
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33. Chlorophyll and Suspended Sediment Exchange between Central San Francisco Bay and the Coastal Pacific Ocean
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Martin, Maureen A.
- Subjects
chlorophyll-a ,San Francisco Bay ,tidal pumping ,chlorophyll flux ,transport rates - Abstract
We measured suspended sediment and chlorophyll-a fluxes between San Francisco Bay and the coastal ocean for two days in March 2002, October/November 2002, and June 2003, one day during neap tide and one during spring tide. We applied a harmonic analysis to velocity and chlorophyll-a data to model scalar and velocity fields during a spring-neap cycle. We then integrated these modeled data over the fortnightly period to calculate net dispersive fluxes. The net flux consisted of an advective and a dispersive component. Dispersive flux was decomposed into physical mechanisms such as tidal pumping, steady circulation and unsteady circulation.Net flux of both sediment and chlorophyll changed seasonally. The net chlorophyll flux was out of the bay during spring and fall, but in during summer. The net flux of suspended sediment was large and in during the fall and out during spring and summer. The direction of advective flux was always out of the estuary and the magnitude depended on advective speed and mean scalar concentration. Dispersive flux was of similar magnitude as advective flux each season and changed direction seasonally. The dispersive flux was larger than the advective flux, contributing over 63% to the net flux of both scalars across season. Tidal pumping was the dominant dispersive process year round.The dominance of tidal pumping implies that seasonal variability of ocean-estuary exchange is set almost entirely by variation in the east-west gradient of scalar concentrations between the ocean and the estuary. If concentrations are higher during flood tide compared to ebb tide, the tidal pumping flux will be into the estuary, whereas the converse is true if the concentration is higher on ebb tide.The average chlorophyll and sediment concentrations are governed by different processes. During the summer while coastal upwelling occurs, chlorophyll concentration is higher in the ocean than in the estuary creating a gradient driven dispersive flux of coastal phytoplankton into the estuary. The opposite is true during spring when estuarine concentration is higher and the dispersive flux is driven out of the estuary. During fall there were relatively low gradients and the net dispersive chlorophyll flux was relatively small. The seasonal direction of chlorophyll fluxes measured in this study are consistent with physical and biological processes of a typical year, though, the magnitude and timing of these fluxes may change annually or inter-annually depending on the specific physical and biological conditions.While the spatial and temporal distribution of favorable growth conditions determines the direction of the chlorophyll flux, growth within Central Bay plays a relatively small role in the local chlorophyll balance. Blooms or the accumulation of phytoplankton within Central Bay are limited by the large dispersive transport rates.
- Published
- 2006
34. HLA and HIV-1: Heterozygote Advantage and B$^*$35-Cw$^*$04 Disadvantage
- Author
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Carrington, Mary, Nelson, George W., Martin, Maureen P., Kissner, Teri, Vlahov, David, Goedert, James J., Kaslow, Richard, Buchbinder, Susan, Hoots, Keith, and O'Brien, Stephen J.
- Published
- 1999
35. Genetic Acceleration of AIDS Progression by a Promoter Variant of CCR5
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Martin, Maureen P., Dean, Michael, Smith, Michael W., Winkler, Cheryl, Gerrard, Bernard, Michael, Nelson L., Lee, Benhur, Doms, Robert W., Margolick, Joseph, Buchbinder, Susan, Goedert, James J., O'Brien, Thomas R., Hilgartner, Margaret W., Vlahov, David, O'Brien, Stephen J., and Carrington, Mary
- Published
- 1998
36. Post project appraisal of Green Valley Creek, Solano County, California : design and management review
- Author
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Martin, Maureen and Fortin, Alex
- Abstract
We assessed the success of Green Valley River Restoration Project, specifically assessing sedimentation and channel stability. The major objectives of the restoration were to provide flood control by constructing a two terraced channel, re-plant riparian corridor with native species, and mitigate for 1.89 acres of seasonal wetland lost to development. We attempted to compare project conditions after a major flow event in 1995 (second year after project completion) with those of the most recent (2002) surveys. Surveying methods were inconsistent from year to year making direct comparison of surveys difficult. In general, the two-terrace channel has remained relatively stable and successfully conveyed flood waters downstream. Erosion and deposition within the channel are less stable because of excessive sediment loading from upper watershed. Severe sedimentation along Hennessey Creek, a tributary to Green Valley Creek, caused damage to private property within the project reach during flood events. Litigation ensued and one of the outcomes was the development of new watershed scale management strategies. Some of these new strategies included improving farming techniques in the upper watershed to minimize sedimentation, conducting more scientific studies to assess sources of sediment, continuing monitoring creeks throughout the watershed, and consistently revising requirements developers must meet to build within the river corridor. Overall we see Greek Valley Creek as a successful project, one where the shortcomings of the project (sediment transport considerations) will provide useful learning tools for future management.
- Published
- 2003
37. Risk of Classic Kaposi Sarcoma With Combinations of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A Population-Based Case-control Study
- Author
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Goedert, James J., Martin, Maureen P., Vitale, Francesco, Lauria, Carmela, Whitby, Denise, Qi, Ying, Gao, Xiaojiang, and Carrington, Mary
- Published
- 2016
38. Host variation in type I interferon signaling genes (MX1), C–C chemokine receptor type 5 gene, and major histocompatibility complex class I alleles in treated HIV+ noncontrollers predict viral reservoir size
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Siegel, David A., primary, Thanh, Cassandra, additional, Wan, Eunice, additional, Hoh, Rebecca, additional, Hobbs, Kristen, additional, Pan, Tony, additional, Gibson, Erica A., additional, Kroetz, Deanna L., additional, Martin, Jeffrey, additional, Hecht, Frederick, additional, Pilcher, Christopher, additional, Martin, Maureen, additional, Carrington, Mary, additional, Pillai, Satish, additional, Busch, Michael P., additional, Stone, Mars, additional, Levy, Claire N., additional, Huang, Meei-Li, additional, Roychoudhury, Pavitra, additional, Hladik, Florian, additional, Jerome, Keith R., additional, Kiem, Hans-Peter, additional, Henrich, Timothy J., additional, Deeks, Steven G., additional, and Lee, Sulggi A., additional
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- 2022
- Full Text
- View/download PDF
39. HLA and NK Cell Inhibitory Receptor Genes in Resolving Hepatitis C Virus Infection
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Khakoo, Salim I., Thio, Chloe L., Martin, Maureen P., Brooks, Collin R., Gao, Xiaojiang, Astemborski, Jacquie, Cheng, Jie, Goedert, James J., Vlahov, David, Hilgartner, Margaret, Cox, Steven, Little, Ann-Margeret, Alexander, Graeme J., Cramp, Matthew E., O'Brien, Stephen J., Thomas, David L., and Carrington, Mary
- Published
- 2004
40. Author Correction: CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome
- Author
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Kulkarni, Smita, Lied, Alexandra, Kulkarni, Viraj, Rucevic, Marijana, Martin, Maureen P., Walker-Sperling, Victoria, Anderson, Stephen K., Ewy, Rodger, Singh, Sukhvinder, Nguyen, Hoang, McLaren, Paul J., Viard, Mathias, Naranbhai, Vivek, Zou, Chengcheng, Lin, Zhansong, Gatanaga, Hiroyuki, Oka, Shinichi, Takiguchi, Masafumi, Thio, Chloe L., Margolick, Joseph, Kirk, Gregory D., Goedert, James J., Hoots, W. Keith, Deeks, Steven G., Haas, David W., Michael, Nelson, Walker, Bruce, Le Gall, Sylvie, Chowdhury, Fatema Z., Yu, Xu G., and Carrington, Mary
- Published
- 2019
- Full Text
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41. NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer
- Author
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Salomé, Bérengère, primary, Sfakianos, John P., additional, Ranti, Daniel, additional, Daza, Jorge, additional, Bieber, Christine, additional, Charap, Andrew, additional, Hammer, Christian, additional, Banchereau, Romain, additional, Farkas, Adam M., additional, Ruan, Dan Fu, additional, Izadmehr, Sudeh, additional, Geanon, Daniel, additional, Kelly, Geoffrey, additional, de Real, Ronaldo M., additional, Lee, Brian, additional, Beaumont, Kristin G., additional, Shroff, Sanjana, additional, Wang, Yuanshuo A., additional, Wang, Ying-chih, additional, Thin, Tin Htwe, additional, Garcia-Barros, Monica, additional, Hegewisch-Solloa, Everardo, additional, Mace, Emily M., additional, Wang, Li, additional, O’Donnell, Timothy, additional, Chowell, Diego, additional, Fernandez-Rodriguez, Ruben, additional, Skobe, Mihaela, additional, Taylor, Nicole, additional, Kim-Schulze, Seunghee, additional, Sebra, Robert P., additional, Palmer, Doug, additional, Clancy-Thompson, Eleanor, additional, Hammond, Scott, additional, Kamphorst, Alice O., additional, Malmberg, Karl-Johan, additional, Marcenaro, Emanuela, additional, Romero, Pedro, additional, Brody, Rachel, additional, Viard, Mathias, additional, Yuki, Yuko, additional, Martin, Maureen, additional, Carrington, Mary, additional, Mehrazin, Reza, additional, Wiklund, Peter, additional, Mellman, Ira, additional, Mariathasan, Sanjeev, additional, Zhu, Jun, additional, Galsky, Matthew D., additional, Bhardwaj, Nina, additional, and Horowitz, Amir, additional
- Published
- 2022
- Full Text
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42. Genetic variation that determinesTAPBPexpression levels associates with the course of malaria in an HLA allotype-dependent manner
- Author
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Walker-Sperling, Victoria, primary, Digitale, Jean C., additional, Viard, Mathias, additional, Martin, Maureen P., additional, Bashirova, Arman, additional, Yuki, Yuko, additional, Ramsuran, Veron, additional, Kulkarni, Smita, additional, Naranbhai, Vivek, additional, Li, Hongchuan, additional, Anderson, Stephen K., additional, Yum, Lauren, additional, Clifford, Robert, additional, Kibuuka, Hannah, additional, Ake, Julie, additional, Thomas, Rasmi, additional, Rowland-Jones, Sarah, additional, Rek, John, additional, Arinaitwe, Emmanuel, additional, Kamya, Moses, additional, Rodriguez-Barraquer, Isabel, additional, Feeney, Margaret E., additional, and Carrington, Mary, additional
- Published
- 2022
- Full Text
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43. Immune correlates of HIV-1 reservoir cell decline in early-treated infants
- Author
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Hartana, Ciputra Adijaya, primary, Garcia-Broncano, Pilar, additional, Rassadkina, Yelizaveta, additional, Lian, Xiaodong, additional, Jiang, Chenyang, additional, Einkauf, Kevin B., additional, Maswabi, Kenneth, additional, Ajibola, Gbolahan, additional, Moyo, Sikhulile, additional, Mohammed, Terence, additional, Maphorisa, Comfort, additional, Makhema, Joseph, additional, Yuki, Yuko, additional, Martin, Maureen, additional, Bennett, Kara, additional, Jean-Philippe, Patrick, additional, Viard, Mathias, additional, Hughes, Michael D., additional, Powis, Kathleen M., additional, Carrington, Mary, additional, Lockman, Shahin, additional, Gao, Ce, additional, Yu, Xu G., additional, Kuritzkes, Daniel R., additional, Shapiro, Roger, additional, and Lichterfeld, Mathias, additional
- Published
- 2022
- Full Text
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44. UK: Developing the Strategy for Sustainable Development in TVET
- Author
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Martin, Stephen, Martin, Maureen, Cohen, Judith, Maclean, Rupert, editor, Fien, John, editor, and Park, Man-Gon, editor
- Published
- 2009
- Full Text
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45. Associations Between Human Leukocyte Antigen Class I Variants and the Mycobacterium tuberculosis Subtypes Causing Disease
- Author
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Salie, Muneeb, van der Merwe, Lize, Möller, Marlo, Daya, Michelle, van der Spuy, Gian D., van Helden, Paul D., Martin, Maureen P., Gao, Xiao-jiang, Warren, Robin M., Carrington, Mary, and Hoal, Eileen G.
- Published
- 2014
46. Specimen mammography distorts margin status in patients undergoing breast conserving surgery for early‐stage breast cancer
- Author
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Ota, Kyle, Rivera, Carmen, and Martin, Maureen
- Published
- 2017
- Full Text
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47. Risk Factors for Ebola Virus Persistence in Semen of Survivors – Liberia
- Author
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Dyal, Jonathan, primary, Kofman, Aaron, additional, Kollie, Jomah Z., additional, Fankhauser, John, additional, Orone, Romeo, additional, Soka, Moses J., additional, Glaybo, Uriah, additional, Kiawu, Armah, additional, Freeman, Edna, additional, Giah, Giovanni, additional, Tony, Henry D., additional, Faikai, Mylene, additional, Jawara, Mary, additional, Kamara, Kuku, additional, Kamara, Samuel, additional, Flowers, Benjamin, additional, Kromah, Mohammed L., additional, Desamu-Thorpe, Rodel, additional, Graziano, James, additional, Brown, Shelley, additional, Morales-Betoulle, Maria E., additional, Cannon, Deborah L., additional, Su, Kaihong, additional, Linderman, Susanne L., additional, Plucinski, Mateusz, additional, Rogier, Eric, additional, Bradbury, Richard S., additional, Secor, W. Evan, additional, Bowden, Katherine E., additional, Phillips, Christi, additional, Carrington, Mary N., additional, Park, Yeon-Hwa, additional, Martin, Maureen P., additional, del Pilar Aguinaga, Maria, additional, Mushi, Robert, additional, Haberling, Dana L., additional, Ervin, Elizabeth D., additional, Klena, John D., additional, Massaquoi, Moses, additional, Nyenswah, Tolbert, additional, Nichol, Stuart T., additional, Chiriboga, David E., additional, Williams, Desmond E., additional, Hinrichs, Steven H., additional, Ahmed, Rafi, additional, Vonhm, Benjamin T., additional, Rollin, Pierre E., additional, Purpura, Lawrence J., additional, and Choi, Mary J., additional
- Published
- 2022
- Full Text
- View/download PDF
48. Impact of Left Ventricular Diastolic Function on Left Atrial Mechanics in Systolic Heart Failure
- Author
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Motoki, Hirohiko, Borowski, Allen G., Shrestha, Kevin, Troughton, Richard W., Martin, Maureen G., Tang, W.H. Wilson, and Klein, Allan L.
- Published
- 2013
- Full Text
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49. The first decade and beyond of transcriptional profiling in schizophrenia
- Author
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Sequeira, P. Adolfo, Martin, Maureen V., and Vawter, Marquis P.
- Published
- 2012
- Full Text
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50. NKG2A and HLA-E define a novel alternative immune checkpoint axis in bladder cancer
- Author
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Salomé, Bérengère, primary, Sfakianos, John P., additional, Daza, Jorge, additional, Charap, Andrew, additional, Hammer, Christian, additional, Banchereau, Romain, additional, Farkas, Adam M., additional, Geanon, Daniel, additional, Kelly, Geoffrey, additional, de Real, Ronaldo M., additional, Lee, Brian, additional, Beaumont, Kristin G., additional, Shroff, Sanjana, additional, Wang, Yuan Shuo A., additional, Wang, Ying-chih, additional, Thin, Tin Htwe, additional, Garcia-Barros, Monica, additional, Hegewisch-Solloa, Everardo, additional, Mace, Emily M., additional, Wang, Li, additional, O’Donnell, Timothy, additional, Chowell, Diego, additional, Fernandez-Rodriguez, Ruben, additional, Skobe, Mihaela, additional, Taylor, Nicole, additional, Kim-Schulze, Seunghee, additional, Sebra, Robert P., additional, Palmer, Doug, additional, Clancy-Thompson, Eleanor, additional, Hammond, Scott, additional, Kamphorst, Alice O., additional, Malmberg, Karl-Johan, additional, Marcenaro, Emanuela, additional, Romero, Pedro, additional, Brody, Rachel, additional, Viard, Mathias, additional, Yuki, Yuko, additional, Martin, Maureen, additional, Carrington, Mary, additional, Mehrazin, Reza, additional, Wiklund, Peter, additional, Mellman, Ira, additional, Mariathasan, Sanjeev, additional, Zhu, Jun, additional, Galsky, Matthew D., additional, Bhardwaj, Nina, additional, and Horowitz, Amir, additional
- Published
- 2022
- Full Text
- View/download PDF
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