1,295 results on '"Ansari, Aftab A."'
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2. Severe disease during both primary and secondary dengue virus infections in pediatric populations
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Aggarwal, Charu, Ahmed, Hasan, Sharma, Pragati, Reddy, Elluri Seetharami, Nayak, Kaustuv, Singla, Mohit, Maheshwari, Deepti, Chawla, Yadya M., Panda, Harekrushna, Rai, Ramesh Chandra, Gunisetty, Sivaram, Priyamvada, Lalita, Bhaumik, Siddhartha Kumar, Ahamed, Syed Fazil, Vivek, Rosario, Bhatnagar, Priya, Singh, Prabhat, Kaur, Manpreet, Dixit, Kritika, Kumar, Sanjeev, Gottimukkala, Kamal, Saini, Keshav, Bajpai, Prashant, Sreekanth, Gopinathan Pillai, Mammen, Shobha, Rajan, Anand, Verghese, Valsan Philip, Abraham, Asha Mary, Shah, Paresh, Alagarasu, Kalichamy, Yu, Tianwei, Davis, Carl W., Wrammert, Jens, Ansari, Aftab, Antia, Rustom, Kabra, Sushil Kumar, Medigeshi, Guruprasad R., Ahmed, Rafi, Lodha, Rakesh, Shet, Anita, Chandele, Anmol, and Murali-Krishna, Kaja
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- 2024
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3. Treatment with a JAK1/2 inhibitor ameliorates murine autoimmune cholangitis induced by IFN overexpression
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Shao, Tihong, Leung, Patrick SC, Zhang, Weici, Tsuneyama, Koichi, Ridgway, William M, Young, Howard A, Shuai, Zongwen, Ansari, Aftab A, and Gershwin, M Eric
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Biomedical and Clinical Sciences ,Immunology ,Autoimmune Disease ,Digestive Diseases ,Liver Disease ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Good Health and Well Being ,Animals ,Autoantibodies ,Autoimmune Diseases ,CD8-Positive T-Lymphocytes ,Cholangitis ,Inflammation ,Interferon-gamma ,Interleukin-6 ,Janus Kinase Inhibitors ,Mice ,Nitriles ,Pyrazoles ,Pyrimidines ,Primary biliary cholangitis ,Autoimmunity ,Interferons ,Ruxolitinib ,Biochemistry and Cell Biology - Abstract
The interferon (IFN) signaling pathways are major immunological checkpoints with clinical significance in the pathogenesis of autoimmunity. We have generated a unique murine model named ARE-Del, with chronic overexpression of IFNγ, by altering IFNγ metabolism. Importantly, these mice develop an immunologic and clinical profile similar to patients with primary biliary cholangitis, including high titers of autoantibodies and portal inflammation. We hypothesized that the downregulation of IFN signaling pathways with a JAK1/2 inhibitor would inhibit the development and progression of cholangitis. To study this hypothesis, ARE-Del+/- mice were treated with the JAK1/2 inhibitor ruxolitinib and serially studied. JAK inhibition resulted in a significant reduction in portal inflammation and bile duct damage, associated with a significant reduction in splenic and hepatic CD4+ T cells and CD8+ T cells. Functionally, ruxolitinib inhibited the secretion of the proinflammatory cytokines IFNγ and TNF from splenic CD4+ T cells. Additionally, ruxolitinib treatment also decreased the frequencies of germinal center B (GC B) cells and T follicular helper (Tfh) cells and led to lower serological AMA levels. Of note, liver and peritoneal macrophages were sharply decreased and polarized from M1 to M2 with a higher level of IRF4 expression after ruxolitinib treatment. Mechanistically, ruxolitinib inhibited the secretion of IL-6, TNF and MCP1 and the expression of STAT1 but promoted the expression of STAT6 in macrophages in vitro, indicating that M1 macrophage polarization to M2 occurred through activation of the STAT6-IRF4 pathway. Our data highlight the significance, both immunologically and clinically, of the JAK/STAT signaling pathway in autoimmune cholangitis.
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- 2022
4. Antigen-specific T cells and autoimmunity
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Rojas, Manuel, Acosta-Ampudia, Yeny, Heuer, Luke S., Zang, Weici, M Monsalve, Diana, Ramírez-Santana, Carolina, Anaya, Juan-Manuel, M Ridgway, William, A Ansari, Aftab, and Gershwin, M. Eric
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- 2024
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5. State of Art and Comprehensive Study on Smart Meter Networking
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Ansari, Aftab Ahmed, Giribabu, Dyanamina, Angrisani, Leopoldo, Series Editor, Arteaga, Marco, Series Editor, Panigrahi, Bijaya Ketan, Series Editor, Chakraborty, Samarjit, Series Editor, Chen, Jiming, Series Editor, Chen, Shanben, Series Editor, Chen, Tan Kay, Series Editor, Dillmann, Rüdiger, Series Editor, Duan, Haibin, Series Editor, Ferrari, Gianluigi, Series Editor, Ferre, Manuel, Series Editor, Hirche, Sandra, Series Editor, Jabbari, Faryar, Series Editor, Jia, Limin, Series Editor, Kacprzyk, Janusz, Series Editor, Khamis, Alaa, Series Editor, Kroeger, Torsten, Series Editor, Li, Yong, Series Editor, Liang, Qilian, Series Editor, Martín, Ferran, Series Editor, Ming, Tan Cher, Series Editor, Minker, Wolfgang, Series Editor, Misra, Pradeep, Series Editor, Möller, Sebastian, Series Editor, Mukhopadhyay, Subhas, Series Editor, Ning, Cun-Zheng, Series Editor, Nishida, Toyoaki, Series Editor, Pascucci, Federica, Series Editor, Qin, Yong, Series Editor, Seng, Gan Woon, Series Editor, Speidel, Joachim, Series Editor, Veiga, Germano, Series Editor, Wu, Haitao, Series Editor, Zamboni, Walter, Series Editor, Zhang, Junjie James, Series Editor, Dwivedi, Sanjeet, editor, Singh, Sanjeev, editor, Tiwari, Manish, editor, and Shrivastava, Ashish, editor
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- 2023
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6. The gut ecosystem and immune tolerance
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Shao, Tihong, Hsu, Ronald, Rafizadeh, Desiree L., Wang, Li, Bowlus, Christopher L., Kumar, Narendra, Mishra, Jayshree, Timilsina, Suraj, Ridgway, William M., Gershwin, M. Eric, Ansari, Aftab A., Shuai, Zongwen, and Leung, Patrick S.C.
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- 2023
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7. Autoinflammatory and autoimmune conditions at the crossroad of COVID-19
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Rodríguez, Yhojan, Novelli, Lucia, Rojas, Manuel, De Santis, Maria, Acosta-Ampudia, Yeny, Monsalve, Diana M, Ramírez-Santana, Carolina, Costanzo, Antonio, Ridgway, William M, Ansari, Aftab A, Gershwin, M Eric, Selmi, Carlo, and Anaya, Juan-Manuel
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Biomedical and Clinical Sciences ,Clinical Sciences ,Rare Diseases ,Autoimmune Disease ,Adaptive Immunity ,Autoimmune Diseases ,Betacoronavirus ,COVID-19 ,COVID-19 Testing ,Clinical Laboratory Techniques ,Coronavirus Infections ,Critical Illness ,Cytokine Release Syndrome ,Female ,Genetic Predisposition to Disease ,Humans ,Immunity ,Innate ,Immunization ,Passive ,Inflammation Mediators ,Macrophage Activation ,Male ,Pandemics ,Pneumonia ,Viral ,Risk Factors ,SARS-CoV-2 ,Severity of Illness Index ,Sex Factors ,COVID-19 Serotherapy ,Autoimmunity ,Antiphospholipid syndrome ,Cytopenia ,Guillain-Barre syndrome ,Kawasaki disease ,Cytokine storm syndrome ,Vaccines ,Guillain-Barré syndrome ,Immunology - Abstract
Coronavirus disease 2019 (COVID-19) has been categorized as evolving in overlapping phases. First, there is a viral phase that may well be asymptomatic or mild in the majority, perhaps 80% of patients. The pathophysiological mechanisms resulting in minimal disease in this initial phase are not well known. In the remaining 20% of cases, the disease may become severe and/or critical. In most patients of this latter group, there is a phase characterized by the hyperresponsiveness of the immune system. A third phase corresponds to a state of hypercoagulability. Finally, in the fourth stage organ injury and failure occur. Appearance of autoinflammatory/autoimmune phenomena in patients with COVID-19 calls attention for the development of new strategies for the management of life-threatening conditions in critically ill patients. Antiphospholipid syndrome, autoimmune cytopenia, Guillain-Barré syndrome and Kawasaki disease have each been reported in patients with COVID-19. Here we present a scoping review of the relevant immunological findings in COVID-19 as well as the current reports about autoinflammatory/autoimmune conditions associated with the disease. These observations have crucial therapeutic implications since immunomodulatory drugs are at present the most likely best candidates for COVID-19 therapy. Clinicians should be aware of these conditions in patients with COVID-19, and these observations should be considered in the current development of vaccines.
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- 2020
8. Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy
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Ceribelli, Angela, Motta, Francesca, De Santis, Maria, Ansari, Aftab A, Ridgway, William M, Gershwin, M Eric, and Selmi, Carlo
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Infectious Diseases ,Arthritis ,Emerging Infectious Diseases ,Autoimmune Disease ,Prevention ,Vaccine Related ,Lung ,Biodefense ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Infection ,Inflammatory and immune system ,Good Health and Well Being ,Antibodies ,Monoclonal ,Humanized ,Antimalarials ,Antirheumatic Agents ,Azetidines ,Betacoronavirus ,Biological Therapy ,COVID-19 ,Coronavirus Infections ,Cytokines ,Humans ,Immunosuppressive Agents ,Interleukin-1 ,Interleukin-6 ,Pandemics ,Pneumonia ,Viral ,Purines ,Pyrazoles ,Rheumatic Diseases ,SARS-CoV-2 ,Sulfonamides ,Virus Internalization ,COVID-19 Drug Treatment ,CoViD-19 ,SARS-CoV2 ,Rheumatic diseases ,Tocilizumab ,Baricitinib - Abstract
The Coronavirus-associated disease, that was first identified in 2019 in China (CoViD-19), is a pandemic caused by a bat-derived beta-coronavirus, named SARS-CoV2. It shares homology with SARS and MERS-CoV, responsible for past outbreaks in China and in Middle East. SARS-CoV2 spread from China where the first infections were described in December 2019 and is responsible for the respiratory symptoms that can lead to acute respiratory distress syndrome. A cytokine storm has been shown in patients who develop fatal complications, as observed in past coronavirus infections. The management includes ventilatory support and broad-spectrum antiviral drugs, empirically utilized, as a targeted therapy and vaccines have not been developed. Based upon our limited knowledge on the pathogenesis of CoViD-19, a potential role of some anti-rheumatic drugs may be hypothesized, acting as direct antivirals or targeting host immune response. Antimalarial drugs, commonly used in rheumatology, may alter the lysosomal proteases that mediates the viral entry into the cell and have demonstrated efficacy in improving the infection. Anti-IL-1 and anti-IL-6 may interfere with the cytokine storm in severe cases and use of tocilizumab has shown good outcomes in a small cohort. Baricitinib has both antiviral and anti-inflammatory properties. Checkpoints inhibitors such as anti-CD200 and anti-PD1 could have a role in the treatment of CoViD-19. Rheumatic disease patients taking immunosuppressive drugs should be recommended to maintain the chronic therapy, prevent infection by avoiding social contacts and pausing immunosuppressants in case of infection. National and international registries are being created to collect data on rheumatic patients with CoViD-19.
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- 2020
9. Comparative Analysis of Controlling Methods for Doubly Fed Induction Generator Based Wind Energy System
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Ansari, Aftab Ahmed, Dyanamina, Giribabu, Angrisani, Leopoldo, Series Editor, Arteaga, Marco, Series Editor, Panigrahi, Bijaya Ketan, Series Editor, Chakraborty, Samarjit, Series Editor, Chen, Jiming, Series Editor, Chen, Shanben, Series Editor, Chen, Tan Kay, Series Editor, Dillmann, Rüdiger, Series Editor, Duan, Haibin, Series Editor, Ferrari, Gianluigi, Series Editor, Ferre, Manuel, Series Editor, Hirche, Sandra, Series Editor, Jabbari, Faryar, Series Editor, Jia, Limin, Series Editor, Kacprzyk, Janusz, Series Editor, Khamis, Alaa, Series Editor, Kroeger, Torsten, Series Editor, Li, Yong, Series Editor, Liang, Qilian, Series Editor, Martín, Ferran, Series Editor, Ming, Tan Cher, Series Editor, Minker, Wolfgang, Series Editor, Misra, Pradeep, Series Editor, Möller, Sebastian, Series Editor, Mukhopadhyay, Subhas, Series Editor, Ning, Cun-Zheng, Series Editor, Nishida, Toyoaki, Series Editor, Pascucci, Federica, Series Editor, Qin, Yong, Series Editor, Seng, Gan Woon, Series Editor, Speidel, Joachim, Series Editor, Veiga, Germano, Series Editor, Wu, Haitao, Series Editor, Zamboni, Walter, Series Editor, Zhang, Junjie James, Series Editor, Kumar, Shailendra, editor, Singh, Bhim, editor, and Singh, Arun Kumar, editor
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- 2022
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10. State of Art and Comprehensive Study on Smart Meter Networking
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Ansari, Aftab Ahmed, primary and Giribabu, Dyanamina, additional
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- 2022
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11. Structural and XPS studies of polyhedral europium doped gadolinium orthovanadate (Eu3+:GdVO4) nanocatalyst for augmented photodegradation against Congo-red
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Ansari, Aftab and Mohanta, D.
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- 2022
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12. Synthesis of salicylic acid phenylethyl ester (SAPE) and its implication in immunomodulatory and anticancer roles
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Das, Arup Jyoti, Das, Monoj Kumar, Singh, Salam Pradeep, Saikia, Partha Pratim, Singh, Neelu, Islam, Johirul, Ansari, Aftab, Chattopadhyay, Pronobesh, Rajamani, Paulraj, Miyaji, Tatsuro, and Deka, Sankar Chandra
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- 2022
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13. Select gp120 V2 domain specific antibodies derived from HIV and SIV infection and vaccination inhibit gp120 binding to α4β7.
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Lertjuthaporn, Sakaorat, Cicala, Claudia, Van Ryk, Donald, Liu, Matthew, Yolitz, Jason, Wei, Danlan, Nawaz, Fatima, Doyle, Allison, Horowitch, Brooke, Park, Chung, Lu, Shan, Lou, Yang, Wang, Shixia, Pan, Ruimin, Jiang, Xunqing, Villinger, Francois, Byrareddy, Siddappa, Santangelo, Philip, Morris, Lynn, Wibmer, Constantinos, Biris, Kristin, Mason, Rosemarie, Gorman, Jason, Hiatt, Joseph, Martinelli, Elena, Roederer, Mario, Fujikawa, Dai, Gorini, Giacomo, Franchini, Genoveffa, Arakelyan, Anush, Ansari, Aftab, Pattanapanyasat, Kovit, Kong, Xiang-Peng, Fauci, Anthony, and Arthos, James
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AIDS Vaccines ,Animals ,Antibodies ,Monoclonal ,Binding Sites ,Cell Line ,Tumor ,Epitopes ,HIV Antibodies ,HIV Envelope Protein gp120 ,HIV Infections ,HIV-1 ,Integrins ,Macaca ,Protein Binding ,Protein Interaction Domains and Motifs ,SAIDS Vaccines ,Simian Acquired Immunodeficiency Syndrome ,Simian Immunodeficiency Virus ,Vaccination - Abstract
The GI tract is preferentially targeted during acute/early HIV-1 infection. Consequent damage to the gut plays a central role in HIV pathogenesis. The basis for preferential targeting of gut tissues is not well defined. Recombinant proteins and synthetic peptides derived from HIV and SIV gp120 bind directly to integrin α4β7, a gut-homing receptor. Using both cell-surface expressed α4β7 and a soluble α4β7 heterodimer we demonstrate that its specific affinity for gp120 is similar to its affinity for MAdCAM (its natural ligand). The gp120 V2 domain preferentially engages extended forms of α4β7 in a cation -sensitive manner and is inhibited by soluble MAdCAM. Thus, V2 mimics MAdCAM in the way that it binds to α4β7, providing HIV a potential mechanism to discriminate between functionally distinct subsets of lymphocytes, including those with gut-homing potential. Furthermore, α4β7 antagonists developed for the treatment of inflammatory bowel diseases, block V2 binding to α4β7. A 15-amino acid V2 -derived peptide is sufficient to mediate binding to α4β7. It includes the canonical LDV/I α4β7 binding site, a cryptic epitope that lies 7-9 amino acids amino terminal to the LDV/I, and residues K169 and I181. These two residues were identified in a sieve analysis of the RV144 vaccine trial as sites of vaccine -mediated immune pressure. HIV and SIV V2 mAbs elicited by both vaccination and infection that recognize this peptide block V2-α4β7 interactions. These mAbs recognize conformations absent from the β- barrel presented in a stabilized HIV SOSIP gp120/41 trimer. The mimicry of MAdCAM-α4β7 interactions by V2 may influence early events in HIV infection, particularly the rapid seeding of gut tissues, and supports the view that HIV replication in gut tissue is a central feature of HIV pathogenesis.
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- 2018
14. Comparative Analysis of Controlling Methods for Doubly Fed Induction Generator Based Wind Energy System
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Ansari, Aftab Ahmed, primary and Dyanamina, Giribabu, additional
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- 2022
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15. Exploiting valence band mapping and select blue-green and red phosphorescence decay of γ-irradiated nanoscale Eu3+: Gd2O3 below concentration quenching
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Ansari, Aftab, Mohanta, Dambarudhar, and Saha, Abhijit
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- 2021
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16. Design and Development of 3D Printed Shape Memory Triphasic Polymer-Ceramic Bioactive Scaffolds for Bone Tissue Engineering
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Ansari, Aftab Alam, primary, Makwana, Pooja, additional, Dhimmar, Bindiya, additional, Vasita, Rajesh, additional, Jain, Prashant Kumar, additional, and Nanda, Himansu Sekhar, additional
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- 2024
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17. Biogenic nanosized gold particles: Physico-chemical characterization and its anticancer response against breast cancer
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Singh, Neelu, Das, Monoj Kumar, Ansari, Aftab, Mohanta, Dambarudhar, and Rajamani, Paulraj
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- 2021
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18. Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics
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Tanaka, Toshihiro, Zhang, Weici, Sun, Ying, Shuai, Zongwen, Chida, Asiya Seema, Kenny, Thomas P, Yang, Guo‐Xiang, Sanz, Ignacio, Ansari, Aftab, Bowlus, Christopher L, Ippolito, Gregory C, Coppel, Ross L, Okazaki, Kazuichi, He, Xiao‐Song, Leung, Patrick SC, and Gershwin, M Eric
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Biomedical and Clinical Sciences ,Immunology ,Biotechnology ,Liver Disease ,Digestive Diseases ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Antibodies ,Monoclonal ,Autoantigens ,Autoimmunity ,Cholangitis ,Female ,Gene Amplification ,Humans ,Immunoblotting ,Male ,Molecular Mimicry ,Real-Time Polymerase Chain Reaction ,Sensitivity and Specificity ,Thioctic Acid ,Xenobiotics ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
A major problem in autoimmunity has been identification of the earliest events that lead to breach of tolerance. Although there have been major advances in dissecting effector pathways and the multilineage immune responses to mitochondrial self-antigens in primary biliary cholangitis, the critical links between environmental factors and tolerance remain elusive. We hypothesized that environmental xenobiotic modification of the E2 subunit of the pyruvate dehydrogenase (PDC-E2) inner lipoyl domain can lead to loss of tolerance to genetically susceptible hosts. Previously we demonstrated that serum anti-PDC-E2 autoantibodies cross-react with the chemical xenobiotics 2-octynoic acid and 6,8-bis (acetylthio) octanoic acid and further that there is a high frequency of PDC-E2-specific peripheral plasmablasts. Herein we generated 104 recombinant monoclonal antibodies (mAbs) based on paired heavy-chain and light-chain variable regions of individual plasmablasts derived from primary biliary cholangitis patients. We identified 32 mAbs reactive with native PDC-E2, including 20 specific for PDC-E2 and 12 cross-reactive with both PDC-E2 and 2-octynoic acid and 6,8-bis (acetylthio) octanoic acid. A lower frequency of replacement somatic hypermutations, indicating a lower level of affinity maturation, was observed in the complementarity-determining regions of the cross-reactive mAbs in comparison to mAbs exclusively recognizing PDC-E2 or those for irrelevant antigens. In particular, when the highly mutated heavy-chain gene of a cross-reactive mAb was reverted to the germline sequence, the PDC-E2 reactivity was reduced dramatically, whereas the xenobiotic reactivity was retained. Importantly, cross-reactive mAbs also recognized lipoic acid, a mitochondrial fatty acid that is covalently bound to PDC-E2.ConclusionOur data reflect that chemically modified lipoic acid or lipoic acid itself, through molecular mimicry, is the initial target that leads to the development of primary biliary cholangitis. (Hepatology 2017;66:885-895).
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- 2017
19. Simian Immunodeficiency Virus Targeting of CXCR3+ CD4+ T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets
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Fujino, Masayuki, Sato, Hirotaka, Okamura, Tomotaka, Uda, Akihiko, Takeda, Satoshi, Ahmed, Nursarat, Shichino, Shigeyuki, Shiino, Teiichiro, Saito, Yohei, Watanabe, Satoru, Sugimoto, Chie, Kuroda, Marcelo J, Ato, Manabu, Nagai, Yoshiyuki, Izumo, Shuji, Matsushima, Kouji, Miyazawa, Masaaki, Ansari, Aftab A, Villinger, Francois, and Mori, Kazuyasu
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Infectious Diseases ,Sexually Transmitted Infections ,2.1 Biological and endogenous factors ,2.2 Factors relating to the physical environment ,Inflammatory and immune system ,Infection ,Good Health and Well Being ,Animals ,CD4-Positive T-Lymphocytes ,Chemokine CXCL10 ,Gene Expression ,Gene Expression Profiling ,Immunity ,Innate ,Macaca mulatta ,Macrophages ,Male ,Monocytes ,Receptors ,CXCR3 ,Simian Acquired Immunodeficiency Syndrome ,Simian Immunodeficiency Virus ,T-Lymphocyte Subsets ,Simian immunodeficiency virus ,CD4+ T cell ,CXCL10 ,CXCR3 ,SIV ,Th1 ,glycosylation ,innate immunity ,macrophages ,monocytes ,pathogenesis ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology ,Agricultural ,veterinary and food sciences ,Biological sciences ,Biomedical and clinical sciences - Abstract
Glycosylation of Env defines pathogenic properties of simian immunodeficiency virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live-attenuated, quintuple deglycosylated Env mutant (Δ5G) virus target CD4+ T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4+ T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here, we studied the host responses relevant to SIV targeting of CXCR3+ CCR5+ CD4+ T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with robust expression of CXCL10, CXCR3+ T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs was secondary to the induction of CD14+ CD16+ monocytes and MAC387+ macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387+ macrophages, T cells, dendritic cells (DCs), and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239 infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DC lineages.IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Δ5G virus infected distinct CD4+ T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239, but not with Δ5G, deplete CXCR3+ CCR5+ CD4+ T (Th1) cells during the primary infection, thereby compromising the cellular immune response. Thus, we hypothesized that distinct host responses are elicited by the infections with two different viruses. We found that SIVmac239 induced distinctly higher levels of inflammatory Th1 responses than Δ5G. In particular, SIVmac239 infection elicited robust expression of CXCL10, a chemokine for CXCR3+ cells, in CD14+ CD16+ monocytes and MAC387+ macrophages recently infiltrated in SLOs. In contrast, Δ5G infection elicited only modest inflammatory responses. These results suggest that the glycosylation of Env modulates the inflammatory/Th1 responses through the monocyte/macrophage subsets and elicits marked differences in SIV infection and clinical outcomes.
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- 2017
20. The fingerprint of antimitochondrial antibodies and the etiology of primary biliary cholangitis
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Shuai, Zongwen, Wang, Jinjun, Badamagunta, Madhu, Choi, Jinjung, Yang, Guoxiang, Zhang, Weici, Kenny, Thomas P, Guggenheim, Kathryn, Kurth, Mark J, Ansari, Aftab A, Voss, John, Coppel, Ross L, Invernizzi, Pietro, Leung, Patrick SC, and Gershwin, M Eric
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Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Rare Diseases ,Autoimmune Disease ,Antibody Affinity ,Autoantibodies ,Case-Control Studies ,Cholangitis ,Electron Spin Resonance Spectroscopy ,Enzyme-Linked Immunosorbent Assay ,Humans ,Inteins ,Mitochondria ,Pyruvate Dehydrogenase (Lipoamide) ,Xenobiotics ,Medical Biochemistry and Metabolomics ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
The identification of environmental factors that lead to loss of tolerance has been coined the holy grail of autoimmunity. Our work has focused on the reactivity of antimitochondrial autoantibodies (AMA) to chemical xenobiotics and has hypothesized that a modified peptide within PDC-E2, the major mitochondrial autoantigen, will have been immunologically recognized at the time of loss of tolerance. Herein, we successfully applied intein technology to construct a PDC-E2 protein fragment containing amino acid residues 177-314 of PDC-E2 by joining a recombinant peptide spanning residues 177-252 (PDC-228) with a 62-residue synthetic peptide from 253 to 314 (PP), which encompasses PDC-E2 inner lipoyl domain (ILD). We named this intein-constructed fragment PPL. Importantly, PPL, as well as lipoic acid conjugated PPL (LA-PPL) and xenobiotic 2-octynoic acid conjugated PPL (2OA-PPL), are recognized by AMA. Of great importance, AMA has specificity for the 2OA-modified PDC-E2 ILD peptide backbone distinct from antibodies that react with native lipoylated PDC-E2 peptide. Interestingly, this unique AMA subfraction is of the immunoglobulin M isotype and more dominant in early-stage primary biliary cholangitis (PBC), suggesting that exposure to 2OA-PPL-like compounds occurs early in the generation of AMA. To understand the structural basis of this differential recognition, we analyzed PPL, LA-PPL, and 2OA-PPL using electron paramagnetic resonance spectroscopy, with confirmations by enzyme-linked immunosorbent assay, immunoblotting, and affinity antibody analysis. We demonstrate that the conformation of PDC-E2 ILD is altered when conjugated with 2OA, compared to conjugation with lipoic acid.ConclusionA molecular understanding of the conformation of xenobiotic-modified PDC-E2 is critical for understanding xenobiotic modification and loss of tolerance in PBC with widespread implications for a role of environmental chemicals in the induction of autoimmunity. (Hepatology 2017;65:1670-1682).
- Published
- 2017
21. A bridgeless configured asymmetrical alternating current–direct current converter‐based isolated single‐stage electric vehicle battery charger with supply side power factor enhancement.
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Shukla, Tanmay, Baig, Mirza Jawad, Ahirwar, Kaushal Kishor, Raghuwanshi, Anchal, Ansari, Aftab Ahmed, and Adhikari, Apsara
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ELECTRIC vehicle batteries ,ELECTRIC vehicle charging stations ,ELECTRIC vehicles ,SUPPLY & demand ,ALTERNATING currents - Abstract
An approach is presented to employ two different types of converters in bridgeless configuration for supply side power factor enhancement of the system. The isolated single‐stage electric vehicle battery charger uses two different converters in a bridgeless configuration to extract the advantages of both converters for supply‐side power factor enhancement. For the negative and positive semi‐cycles of the supply voltage, the power factor‐enhanced asymmetrical alternating current–direct current converter utilises a fourth order single‐ended primary‐inductor converter and a second order buck‐boost converter, respectively. The use of single‐ended primary‐inductor converter and buck‐boost converter in bridgeless configuration reduces the net order of the system with respect to conventional bridgeless‐single‐ended primary‐inductor converter schemes. The buck‐boost converter also needs the supply‐side filter to eradicate the unwanted harmonics in the supply current which increases the order of the system. The usage of both converters presents many benefits like input inductance of the single‐ended primary‐inductor converter can be utilised as a filtering element with a capacitor for the buck‐boost converter. The anti‐parallel diode conduction operation of both switches facilitates the elimination of extra reverse feed diodes (generally used in bridgeless schemes). The single‐stage charger itself comes with the benefit of elimination of extra stages and thus the losses associated with it. The presented charger also witnesses the elimination of the rectifier due to usage of bridgeless configuration. The isolated single‐stage electric vehicle battery charger is also garnished with electrical isolation which adds to the safety standard of the system. To attain power factor enhancement, the asymmetrical alternating current–direct current converter functions in discontinuous current conduction mode in the present work. The elimination of extra‐stages (with respect to two stage charger), a filter, a rectifier, two extra reverse‐feeding diodes, one voltage sensor, one current sensor (with respect to continuous current conduction mode), and electrical isolation not only makes the system compact and safer but also makes the system cheaper. Elaborated mathematical modelling and stability analysis of the presented alternating current–direct current converter using a pole‐zero map and bode plot have been included in the article. The prototype and MATLAB/Simulink model of isolated single‐stage electric vehicle battery charger system with discontinuous current conduction mode control has been built and results of both prototype and MATLAB/Simulink are deployed to verify isolated single‐stage electric vehicle battery charger system's performance during dynamic and steady‐state conditions. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Significant red-luminescence from citrate-gel and hydrothermally derived nanoscale Eu3+: Gd2O3 with alkali metal ion (Na+, K+) co-doping
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Ansari, Aftab, Dey, Sanchita, and Mohanta, Dambarudhar
- Published
- 2022
- Full Text
- View/download PDF
23. The Zika outbreak of the 21st century
- Author
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Chang, Christopher, Ortiz, Kristina, Ansari, Aftab, and Gershwin, M Eric
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Infectious Diseases ,Pediatric ,Vector-Borne Diseases ,Emerging Infectious Diseases ,Prevention ,Rare Diseases ,Perinatal Period - Conditions Originating in Perinatal Period ,Clinical Research ,Vaccine Related ,2.2 Factors relating to the physical environment ,Aetiology ,Reproductive health and childbirth ,Infection ,Good Health and Well Being ,Animals ,Communicable Disease Control ,Disease Management ,Disease Outbreaks ,Global Health ,History ,21st Century ,Humans ,Population Surveillance ,Zika Virus ,Zika Virus Infection ,Guillain-Barre ,Mosquitoes ,Zika fever ,Pandemic ,Arborvirus ,Sexual transmission ,Aedes aegypti ,Autophagy ,Centrosome ,Dengue ,Glycosylation ,Flavivirus ,Microcephaly ,Immunology - Abstract
The Zika virus outbreak has captivated the attention of the global audience and information has spread rapidly and wildly through the internet and other media channels. This virus was first identified in 1947, when it was isolated from a sentinel rhesus monkey placed by British scientists working at the Yellow Fever Research Laboratory located in the Zika forest area of Uganda, hence its name, and is transmitted primarily by the mosquito vector, Aedes aegypti. The fact that the rhesus macaque is an Asian species being placed in an African forest brings to mind the possibility of rapid adaptation of the virus from an African to Asian species, an issue that has not been considered. Whether such adaptation has played any role in acquiring pathogenicity due to cross species transmission remains to be identified. The first human infection was described in Nigeria in 1954, with only scattered reports of about a dozen human infections identified over a 50-year period. It was not until 2007 that Zika virus raised its ugly head with infections noted in three-quarters of the population on the tiny island of Yap located between the Philippines and Papua New Guinea in the western Pacific Ocean, followed by a major outbreak in French Polynesia in 2013. The virus remained confined to a narrow equatorial band in Africa and Asia until 2014 when it began to spread eastward, first toward Oceania and then to South America. Since then, millions of infected individuals have been identified in Brazil, Colombia, Venezuela, including 25 additional countries in the Americas. While the symptoms associated with Zika virus infection are generally mild, consisting of fever, maculopapular rash, arthralgia and conjunctivitis, there have been reports of more severe reactions that are associated with neurological complications. In pregnant women, fetal neurological complications include brain damage and microcephaly, while in adults there have been several cases of virus-associated Guillain-Barre syndrome. The virus was until recently believed to only be transmitted via mosquitoes. But when the Zika virus was isolated from the semen specimens from a patient in Texas, this provided the basis for the recent report of possible sexual transmission of the Zika virus. Due to the neurological complications, various vectors for infection as well as the rapid spread throughout the globe, it has prompted the World Health Organization to issue a global health emergency. Various governmental organizations have recommended that pregnant women do not travel to countries where the virus is epidemic, and within the countries affected by the virus, recommendations were provided for women of childbearing age to delay pregnancy. The overall public health impact of these above findings highlights the need for a rapid but specific diagnostic test for blood banks worldwide to identify those infected and for the counseling of women who are pregnant or contemplating pregnancy. As of this date, there are neither commercially licensed diagnostic tests nor a vaccine. Because cross-reactivity of the Zika virus with dengue and Chikungunya virus is common, it may pose difficulty in being able to quickly develop such tests and vaccines. So far the most effective public health measures include controlling the mosquito populations via insecticides and preventing humans from direct exposure to mosquitoes.
- Published
- 2016
24. A bridgeless configured asymmetrical alternating current–direct current converter‐based isolated single‐stage electric vehicle battery charger with supply side power factor enhancement
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Shukla, Tanmay, primary, Baig, Mirza Jawad, additional, Ahirwar, Kaushal Kishor, additional, Raghuwanshi, Anchal, additional, Ansari, Aftab Ahmed, additional, and Adhikari, Apsara, additional
- Published
- 2023
- Full Text
- View/download PDF
25. 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention 19–22 July 2015, Vancouver, Canada
- Author
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Pate, Kelly Metcalf, Pohlmeyer, Chris, Walker‐Sperling, Victoria, Foote, Jeremy, Najarro, Kevin, Cryer, Catherine, Salgado, Maria, Gama, Lucio, Engle, Elizabeth, Shirk, Erin, Queen, Suzanne, Chioma, Stanley, Vermillion, Meghan, Bullock, Brandon, Li, Ming, Lyons, Claire, Adams, Robert, Zink, Chris, Clements, Janice, Mankowski, Joseph, Blankson, Joel, Micci, Luca, Ryan, Emily, Fromentin, Rémi, Benne, Clarisse, Chomont, Nicolas, Lifson, Jeffrey, Paiardini, Mirko, Lee, Sulggi, Fromentin, Remi, Silicano, Robert, Silicano, Janet, Richman, Douglas, O'Doherty, Una, Palmer, Sarah, Burbelo, Peter, Deeks, Steven, Ghneim, Khader, Ahlers, Jeff, Fourati, Slim, Shive, Carey, Cameron, Mark, Mukerjee, Pranab, Ghannoum, Mahmoud, Rodriguez, Benigno, Lederman, Michael, Sekaly, Rafick, Frange, Pierre, Faye, Albert, Avettand‐Fenoel, Veronique, Bellaton, Erainna, Deschamps, Diane, Angin, Mathieu, Caillat‐Zucman, Sophie, Peytavin, Gilles, Le Chenadec, Jerome, Warszawski, Josiane, Rouzioux, Christine, Saez‐Cirion, Asier, Cohort, ANRS Epf‐Co10 Pediatric, Chang, Christina, Cameron, Paul, Elliott, Julian, Perelson, Alan, Roche, Michael, Dantanarayana, Ashanti, Solomon, Ajantha, Naranbhai, Vivek, Tenakoon, Surekha, Hoh, Rebecca, McMahon, James, Sikaris, Ken, Hartogensis, Wendy, Bacchetti, Peter, Hecht, Frederick, Deeks, Steve, Lewin, Sharon, Byrareddy, Siddappa, Arthos, James, Cicala, Claudia, Reimann, Keith, Parslow, Tristram, Santangelo, Philip, Villinger, Francois, Fauci, Anthony, Ansari, Aftab, George, Michael, Weiser, Barbara, Burger, Harold, Lewy, Tyler, Anastos, Kathryn, Asmuth, David, Somsouk, Ma, Hunt, Peter, Min, Zhong, Miller, Christopher, and Li, Xiao Dong
- Subjects
Mental Health ,Digestive Diseases ,Infectious Diseases ,Pediatric AIDS ,Bioengineering ,Prevention ,Clinical Research ,Genetics ,Health Services ,Pediatric ,Behavioral and Social Science ,HIV/AIDS ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Reproductive health and childbirth ,Good Health and Well Being ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences - Published
- 2015
26. 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015).
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Pate, Kelly Metcalf, Pohlmeyer, Chris, Walker-Sperling, Victoria, Foote, Jeremy, Najarro, Kevin, Cryer, Catherine, Salgado, Maria, Gama, Lucio, Engle, Elizabeth, Shirk, Erin, Queen, Suzanne, Chioma, Stanley, Vermillion, Meghan, Bullock, Brandon, Li, Ming, Lyons, Claire, Adams, Robert, Zink, Chris, Clements, Janice, Mankowski, Joseph, Blankson, Joel, Micci, Luca, Ryan, Emily, Fromentin, Rémi, Benne, Clarisse, Chomont, Nicolas, Lifson, Jeffrey, Paiardini, Mirko, Lee, Sulggi, Fromentin, Remi, Silicano, Robert, Silicano, Janet, Richman, Douglas, O'Doherty, Una, Palmer, Sarah, Burbelo, Peter, Deeks, Steven, Ghneim, Khader, Ahlers, Jeff, Fourati, Slim, Shive, Carey, Cameron, Mark, Mukerjee, Pranab, Ghannoum, Mahmoud, Rodriguez, Benigno, Lederman, Michael, Sekaly, Rafick, Frange, Pierre, Faye, Albert, Avettand-Fenoel, Veronique, Bellaton, Erainna, Deschamps, Diane, Angin, Mathieu, Caillat-Zucman, Sophie, Peytavin, Gilles, Le Chenadec, Jerome, Warszawski, Josiane, Rouzioux, Christine, Saez-Cirion, Asier, Chang, Christina, Cameron, Paul, Elliott, Julian, Perelson, Alan, Roche, Michael, Dantanarayana, Ashanti, Solomon, Ajantha, Naranbhai, Vivek, Tenakoon, Surekha, Hoh, Rebecca, McMahon, James, Sikaris, Ken, Hartogensis, Wendy, Bacchetti, Peter, Hecht, Frederick, Deeks, Steve, Lewin, Sharon, Byrareddy, Siddappa, Arthos, James, Cicala, Claudia, Reimann, Keith, Parslow, Tristram, Santangelo, Philip, Villinger, Francois, Fauci, Anthony, Ansari, Aftab, George, Michael, Weiser, Barbara, Burger, Harold, Lewy, Tyler, Anastos, Kathryn, Asmuth, David, Somsouk, Ma, Hunt, Peter, Min, Zhong, Miller, Christopher, Li, Xiao Dong, and Hinkle, John
- Subjects
Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences - Published
- 2015
27. Ongoing activation of autoantigen‐specific B cells in primary biliary cirrhosis
- Author
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Zhang, Jun, Zhang, Weici, Leung, Patrick SC, Bowlus, Christopher L, Dhaliwal, Sandeep, Coppel, Ross L, Ansari, Aftab A, Yang, Guo‐Xiang, Wang, Jinjun, Kenny, Thomas P, He, Xiao‐Song, Mackay, Ian R, and Gershwin, M Eric
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Clinical Research ,Rare Diseases ,Liver Disease ,Digestive Diseases ,Autoimmune Disease ,Chronic Liver Disease and Cirrhosis ,2.1 Biological and endogenous factors ,Aetiology ,Adult ,Aged ,Aged ,80 and over ,Antibody Specificity ,Antibody-Producing Cells ,Autoantigens ,B-Lymphocytes ,Case-Control Studies ,Dihydrolipoyllysine-Residue Acetyltransferase ,Female ,Humans ,Liver Cirrhosis ,Biliary ,Male ,Middle Aged ,Receptors ,CCR10 ,Receptors ,CXCR ,Young Adult ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
UnlabelledThe serologic hallmark of primary biliary cirrhosis (PBC), the antimitochondrial response to the E2 component of the pyruvate dehydrogenase complex (PDC-E2), has unique features, including continuous high titers of immunoglobulin M (IgM) and IgG reactivity throughout all stages of disease, capable not only of target enzyme inhibition, but also crossreactive with chemical xenobiotics that share molecular homology with the inner lipoyl domain of PDC-E2; such chemicals have been proposed as potential etiological agents. We used flow cytometry and enzyme-linked immunospot assay (ELISPOT) to examine B-cell subsets in 59 subjects, including 28 with PBC, 13 with primary sclerosing cholangitis (PSC), and 18 healthy controls. Strikingly, in PBC, although there were no significant differences in B-cell phenotype subpopulations, 10% of the total IgG and IgA plasmablast population and 23% of the IgM plasmablast population were uniquely reactive with PDC-E2, detected in the CXCR7+ CCR10low plasmablast population. In contrast, plasmablast reactivity to a control antigen, tetanus toxoid, was minimal and similar in all groups. Additionally, we isolated plasmablast-derived polyclonal antibodies and compared reactivity with plasma-derived antibodies and noted a distinct noncirculating tissue source of xenobiotic crossreacting antibodies. The high levels of autoantigen specific peripheral plasmablasts indicate recent activation of naive or memory B cells and a continuous and robust activation. The presence of CXCR7+ CCR10low PDC-E2-specific ASCs suggests a mechanistic basis for the migration of circulating antigen specific plasmablasts to the mucosal epithelial ligands CXCL12 and CCL28.ConclusionOur findings suggest a sustained rigorous B-cell response in PBC, likely activated and perpetuated by cognate autoantigen.
- Published
- 2014
28. Viremia controls Env-specific antibody-secreting cell responses in simian immunodeficiency virus infected macaques pre and post-antiretroviral therapy
- Author
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Silveira, Eduardo L.V., Hong, Jung Joo, Amancha, Praveen K., Rogers, Kenneth A., Ansari, Aftab A., Byrareddy, Siddappa N., and Villinger, Francois
- Published
- 2021
- Full Text
- View/download PDF
29. IL‐12/Th1 and IL‐23/Th17 biliary microenvironment in primary biliary cirrhosis: Implications for therapy
- Author
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Yang, Chen‐Yen, Ma, Xiong, Tsuneyama, Koichi, Huang, Shanshan, Takahashi, Toru, Chalasani, Naga P, Bowlus, Christopher L, Yang, Guo‐Xiang, Leung, Patrick SC, Ansari, Aftab A, Wu, Linda, Coppel, Ross L, and Gershwin, M Eric
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Liver Disease ,Autoimmune Disease ,Rare Diseases ,Chronic Liver Disease and Cirrhosis ,Digestive Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Oral and gastrointestinal ,Adult ,Aged ,Female ,Humans ,Immunohistochemistry ,Interferon-gamma ,Interleukin-12 ,Interleukin-23 ,Liver Cirrhosis ,Biliary ,Male ,Middle Aged ,Signal Transduction ,Th1 Cells ,Th17 Cells ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
UnlabelledThe interleukin (IL)-12/IL-23-mediated Th1/Th17 signaling pathway has been associated with the etiopathogenesis of primary biliary cirrhosis (PBC). To address the cytokine microenvironment specifically in the liver, we examined the localized expression of cytokine subunits and their corresponding receptors using previously optimized immunohistochemistry with an extensive panel of antibodies directed at IL-12p70, IL-12p35, interferon-gamma (IFN-γ), IL-12RB2, IL-23p40, IL-23p19, IL-17, and IL-23R using liver from PBC (n = 51) and non-PBC (n = 80) control liver disease patients. Multiple portal tracts in each patient were blindly evaluated and individually scored. We report herein that although IL-12/Th1 and IL-23/Th17 staining was detected in all of the liver sections, they were primarily localized around the damaged interlobular bile ducts in PBC. Most important, Th17 skewing was prominent in advanced PBC patients with intensive secretion of IL-23p19 by inflamed hepatocytes around IL-23R, IL-12RB2, and IFN-γ expressing degenerated cholangiocytes. Our novel finding on the direct association of Th17 skewing and disease severity illustrates the significance of the IL-23/Th17 pathway in the perpetuation of IL-12/Th1-mediated immunopathology in PBC. Furthermore, localized IL-23p19 production by hepatocytes may enhance profibrotic Th17 signaling and proinflammatory IFN-γ production that contribute to PBC pathology.ConclusionOur data emphasize the pathogenic relevance of IL-12/Th1 and IL-23/Th17 in the evolution of PBC. Of significance, however, the shift from a Th1 to a Th17 imbalance at advanced stages of the disease suggests the necessity to consider modulation of the IL-23/Th17 pathway as a potential target for therapeutic intervention.
- Published
- 2014
30. A PF Improved LED Drive using Modified Non-bridged Cuk Converter
- Author
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Shukla, Tanmay, primary, Ansari, Aftab Ahmed, additional, and Ansari, Anwar Ahamed, additional
- Published
- 2023
- Full Text
- View/download PDF
31. Antimitochondrial Antibody Recognition and Structural Integrity of the Inner Lipoyl Domain of the E2 Subunit of Pyruvate Dehydrogenase Complex
- Author
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Wang, Jinjun, Budamagunta, Madhu S, Voss, John C, Kurth, Mark J, Lam, Kit S, Lu, Ling, Kenny, Thomas P, Bowlus, Christopher, Kikuchi, Kentaro, Coppel, Ross L, Ansari, Aftab A, Gershwin, M Eric, and Leung, Patrick SC
- Subjects
Digestive Diseases ,Rare Diseases ,Liver Disease ,Amino Acid Sequence ,Antibody Specificity ,Autoantibodies ,Autoantigens ,Dihydrolipoyllysine-Residue Acetyltransferase ,Electron Spin Resonance Spectroscopy ,Humans ,Liver Cirrhosis ,Biliary ,Mitochondria ,Molecular Sequence Data ,Mutagenesis ,Site-Directed ,Protein Structure ,Secondary ,Protein Structure ,Tertiary ,Immunology - Abstract
Antimitochondrial autoantibodies (AMAs), the serological hallmark of primary biliary cirrhosis, are directed against the lipoyl domain of the E2 subunit of pyruvate dehydrogenase (PDC-E2). However, comprehensive analysis of the amino acid residues of PDC-E2 lipoyl β-sheet with AMA specificity is lacking. In this study, we postulated that specific residues within the lipoyl domain are critical to AMA recognition by maintaining conformational integrity. We systematically replaced each of 19 residue peptides of the inner lipoyl domain with alanine and analyzed these mutants for reactivities against 60 primary biliary cirrhosis and 103 control sera. Based on these data, we then constructed mutants with two, three, or four replacements and, in addition, probed the structure of the substituted domains using thiol-specific spin labeling and electron paramagnetic resonance (EPR) of a (5)Ile→Ala and (12)Ile→Ala double mutant. Single alanine replacement at (5)Ile, (12)Ile, and (15)Glu significantly reduced AMA recognition. In addition, mutants with two, three, or four replacements at (5)Ile, (12)Ile, and (15)Glu reduced AMA reactivity even further. Indeed, EPR reveals a highly flexible structure within the (5)Ile and (12)Ile double-alanine mutant. Autoreactivity is largely focused on specific residues in the PDC-E2 lipoyl domain critical in maintaining the lipoyl loop conformation necessary for AMA recognition. Collectively, the AMA binding studies and EPR analysis demonstrate the necessity of the lipoyl β-sheet structural conformation in anti-PDC-E2 recognition.
- Published
- 2013
32. Integrins: Integrating the Biology and Therapy of Cell–cell Interactions
- Author
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Pandolfi, Franco, Franza, Laura, Altamura, Simona, Mandolini, Claudia, Cianci, Rossella, Ansari, Aftab, and Kurnick, James T.
- Published
- 2017
- Full Text
- View/download PDF
33. A Study on the Impact of SDBRs on the Fault Ride-through Capability of DFIG based Wind Farms
- Author
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Ansari, Aftab Ahmed, primary and Dyanamina, Giribabu, additional
- Published
- 2023
- Full Text
- View/download PDF
34. Stability, Control and Protection of Microgrid Technology: A Comprehensive Review and Future Outlook
- Author
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Ansari, Anwar Ahamed, primary, Ahmed Ansari, Aftab, additional, and Dyanamina, Giribabu, additional
- Published
- 2023
- Full Text
- View/download PDF
35. Sustained virologic control in SIV⁺ macaques after antiretroviral and α₄β₇ antibody therapy
- Author
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Byrareddy, Siddappa N., Arthos, James, Cicala, Claudia, Villinger, Francois, Ortiz, Kristina T., Little, Dawn, Sidell, Neil, Kane, Maureen A., Yu, Jianshi, Jones, Jace W., Santangelo, Philip J., Zurla, Chiara, McKinnon, Lyle R., Arnold, Kelly B., Woody, Caroline E., Walter, Lutz, Roos, Christian, Noll, Angela, Van Ryk, Donald, Jelicic, Katija, Cimbro, Raffaello, Gumber, Sanjeev, Reid, Michelle D., Adsay, Volkan, Amancha, Praveen K., Mayne, Ann E., Parslow, Tristram G., Fauci, Anthony S., and Ansari, Aftab A.
- Published
- 2016
36. Nanotechnology-Based Challenges and Scope in the Food Industry: from Production to Packaging
- Author
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Singh, Neelu, primary, Das, Monoj Kumar, additional, Ramteke, Anand, additional, Rajamani, Paulraj, additional, Chandra Deka, Sankar, additional, Ansari, Aftab, additional, Mahanta, Dambarudhar, additional, and Maurya, Anurag, additional
- Published
- 2019
- Full Text
- View/download PDF
37. FDC:TFH Interactions within Cervical Lymph Nodes of SIV-Infected Rhesus Macaques
- Author
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Dave, Rajnish S., Sharma, Ravi K., Muir, Roshell R., Haddad, Elias, Gumber, Sanjeev, Villinger, Francois, Nehra, Artinder P., Khan, Zafar K., Wigdahl, Brian, Ansari, Aftab A., Byrareddy, Siddappa N., and Jain, Pooja
- Published
- 2018
- Full Text
- View/download PDF
38. The Role of Integrin α4β7 in HIV Pathogenesis and Treatment
- Author
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Arthos, James, Cicala, Claudia, Nawaz, Fatima, Byrareddy, Siddappa N., Villinger, Francois, Santangelo, Philip J., Ansari, Aftab A., and Fauci, Anthony S.
- Published
- 2018
- Full Text
- View/download PDF
39. Identification of HLA-A2–restricted CD8+ Cytotoxic T Cell Responses in Primary Biliary Cirrhosis
- Author
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Kita, Hiroto, Lian, Zhe-Xiong, Van de Water, Judy, He, Xiao-Song, Matsumura, Shuji, Kaplan, Marshall, Luketic, Velimir, Coppel, Ross L, Ansari, Aftab A, and Gershwin, M Eric
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Clinical Research ,Immunization ,Autoimmune Disease ,Chronic Liver Disease and Cirrhosis ,Digestive Diseases ,Liver Disease ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Antigen Presentation ,Antigen-Antibody Complex ,Autoimmunity ,Cytokines ,Dendritic Cells ,Dihydrolipoyllysine-Residue Acetyltransferase ,Epitopes ,HLA-A2 Antigen ,Humans ,Lymphocyte Activation ,Oligopeptides ,Pyruvate Dehydrogenase Complex ,T-Lymphocytes ,Cytotoxic ,autoimmunity ,cytotoxic T cells ,cholangitis ,epitopes ,cross-priming ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Primary biliary cirrhosis (PBC) is characterized by an intense biliary inflammatory CD4(+) and CD8(+) T cell response. Very limited information on autoantigen-specific cytotoxic T lymphocyte (CTL) responses is available compared with autoreactive CD4(+) T cell responses. Using peripheral blood mononuclear cells (PBMCs) from PBC, we identified an HLA-A2-restricted CTL epitope of the E2 component of pyruvate dehydrogenase (PDC-E2), the immunodominant mitochondrial autoantigen. This peptide, amino acids 159-167 of PDC-E2, induces specific MHC class I-restricted CD8(+) CTL lines from 10/12 HLA-A2(+) PBC patients, but not controls, after in vitro stimulation with antigen-pulsed dendritic cells (DCs). PDC-E2-specific CTLs could also be generated by pulsing DCs with full-length recombinant PDC-E2 protein. Furthermore, using soluble PDC-E2 complexed with either PDC-E2-specific human monoclonal antibody or affinity-purified autoantibodies against PDC-E2, the generation of PDC-E2-specific CTLs, occurred at 100-fold and 10-fold less concentration, respectively, compared with soluble antigen alone. Collectively, these data demonstrate that autoantibody, helper, and CTL epitopes all contain a shared peptide sequence. The finding that autoantigen-immune complexes can not only cross-present but also that presentation of the autoantigen is of a higher relative efficiency, for the first time defines a unique role for autoantibodies in the pathogenesis of an autoimmune disease.
- Published
- 2002
40. Spontaneous development of an autoimmune hepatitis – primary biliary cholangitis overlap syndrome in dnTGFβRII Aire −/− mice
- Author
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Long, Jie, primary, Yang, Si‐Yu, additional, Huang, Meng‐Xing, additional, Luo, Pan‐Yue, additional, Li, Liang, additional, Tsuneyama, Koichi, additional, Ansari, Aftab A, additional, Lu, Ling, additional, Gershwin, M Eric, additional, Lian, Zhe‐Xiong, additional, and Zhao, Zhi‐Bin, additional
- Published
- 2023
- Full Text
- View/download PDF
41. Decoupled Control of Rotor Side Power Electronic Converter for Grid Connected DFIG Based Wind Energy System
- Author
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Ansari, Aftab Ahmed, primary, Dyanamina, Giribabu, additional, and Ansari, Anwar Ahamed, additional
- Published
- 2023
- Full Text
- View/download PDF
42. Random Phage Mimotopes Recognized by Monoclonal Antibodies against the Pyruvate Dehydrogenase Complex-E2 (PDC-E2)
- Author
-
Cha, Sanghoon, Van De Water, Judy, Tsuneyama, Koichi, Joplin, Ruth E., Ansari, Aftab A., Nakanuma, Yasuni, Schatz, Peter J., Cwirla, Steve, Fabris, Luca E., Neuberger, James M., Gershwin, M. Eric, and Coppel, Ross L.
- Published
- 1996
43. Integrin α4β7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes
- Author
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Sivro, Aida, Schuetz, Alexandra, Sheward, Daniel, Joag, Vineet, Yegorov, Sergey, Liebenberg, Lenine J., Yende-Zuma, Nonhlanhla, Stalker, Andrew, Mwatelah, Ruth S., Selhorst, Philippe, Garrett, Nigel, Samsunder, Natasha, Balgobin, Anisha, Nawaz, Fatima, Cicala, Claudia, Arthos, James, Fauci, Anthony S., Anzala, Aggrey Omu, Kimani, Joshua, Bagaya, Bernard S., Kiwanuka, Noah, Williamson, Carolyn, Kaul, Rupert, Passmore, Jo-Ann S., Phanuphak, Nittaya, Ananworanich, Jintanat, Ansari, Aftab, Abdool Karim, Quarraisha, Abdool Karim, Salim S., and McKinnon, Lyle R.
- Published
- 2018
- Full Text
- View/download PDF
44. Fault Ride-Through Operation Analysis of Doubly Fed Induction Generator-Based Wind Energy Conversion Systems: A Comparative Review
- Author
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Ansari, Aftab Ahmed, primary and Dyanamina, Giribabu, additional
- Published
- 2022
- Full Text
- View/download PDF
45. Incorporation of Innate Immune Effector Mechanisms in the Formulation of a Vaccine Against HIV-1
- Author
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Ansari, Aftab A., Mayne, Ann E., Takahashi, Yoshiaki, Pattanapanyasat, Kovit, Pulendran, Bali, editor, Katsikis, Peter D., editor, and Schoenberger, Stephen P., editor
- Published
- 2011
- Full Text
- View/download PDF
46. Early initiation of antiretroviral treatment post SIV infection does not resolve lymphoid tissue activation
- Author
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Hong, Jung Joo, Silveira, Eduardo L.V., Amancha, Praveen K., Byrareddy, Siddappa N., Gumber, Sanjeev, Chang, Kyu-Tae, Ansari, Aftab A., and Villinger, Francois
- Published
- 2017
- Full Text
- View/download PDF
47. Are Autoimmune Manifestations in Human Dilated Cardiomyopathy Primary or Secondary Events?
- Author
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Pereira, Lara Elizabeth, Ansari, Aftab Ahmed, Shoenfeld, Yehuda, editor, Cervera, Ricard, editor, and Gershwin, M. Eric, editor
- Published
- 2008
- Full Text
- View/download PDF
48. Preliminary studies on the use of pertussis toxin for the modulation of intravaginal SIV transmission in rhesus macaques
- Author
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Ortiz, Kristina, Sampathkumar, Rebecca S., Ansari, Aftab A., and Byrareddy, Siddappa N.
- Published
- 2017
- Full Text
- View/download PDF
49. Immunological Tolerance in Allo- and Xenografts
- Author
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Ansari, Aftab A., Pattanapanyasat, Kovit, Gershwin, M. Eric, editor, Vierling, John M., editor, and Manns, Michael P., editor
- Published
- 2007
- Full Text
- View/download PDF
50. Spontaneous development of an autoimmune hepatitis – primary biliary cholangitis overlap syndrome in dnTGFβRII Aire−/− mice.
- Author
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Long, Jie, Yang, Si‐Yu, Huang, Meng‐Xing, Luo, Pan‐Yue, Li, Liang, Tsuneyama, Koichi, Ansari, Aftab A, Lu, Ling, Gershwin, M Eric, Lian, Zhe‐Xiong, and Zhao, Zhi‐Bin
- Subjects
CHRONIC active hepatitis ,AUTOIMMUNE hepatitis ,CHOLANGITIS ,APOPTOSIS ,ANTINUCLEAR factors ,T cells - Abstract
Autoimmune regulator (Aire) and TGF‐β signaling play important roles in central tolerance and peripheral tolerance, respectively, by eliminating or suppressing the activity of autoreactive T cells. We previously demonstrated that dnTGFβRII mice develop a defect in peripheral tolerance and a primary biliary cholangitis (PBC)‐like disease. We hypothesized that by introducing the Aire gene to this model, we would observe a more severe PBC phenotype. Interestingly, however, we demonstrated that, while dnTGFβRII Aire−/− mice do manifest key histological and serological features of autoimmune cholangitis, they also develop mild to moderate interface hepatitis and show high levels of alanine transaminase (ALT) and antinuclear antibodies (ANA), characteristics of autoimmune hepatitis (AIH). To further understand this unique phenotype, we performed RNA sequencing (RNA‐seq) and flow cytometry to explore the functional pathways and immune cell pathways in the liver of dnTGFβRII Aire−/− mice. Our data revealed enrichments of programmed cell death pathways and predominant CD8+ T cell infiltrates. Depleting CD8+ T cells using an anti‐CD8α antibody significantly alleviated hepatic inflammation and prolonged the life span of these mice. Finally, RNA‐seq data indicated the clonal expansion of hepatic CD8+ T cells. In conclusion, these mice developed an autoreactive CD8+ T‐cell‐mediated autoimmune cholangitis with concurrent hepatitis that exhibited key histological and serological features of the AIH‐PBC overlap syndrome, representing a novel model for the study of tolerance and autoimmune liver disease. © 2023 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
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