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Article ; Online: Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis.

Song, Jing / Schwenzer, Anja / Wong, Alicia / Turcinov, Sara / Rims, Cliff / Martinez, Lorena Rodriguez / Arribas-Layton, David / Gerstner, Christina / Muir, Virginia S / Midwood, Kim S / Malmström, Vivianne / James, Eddie A / Buckner, Jane H

JCI insight

2021 Volume 6, Issue 5

Abstract: Tenascin-C (TNC), an extracellular matrix protein that has proinflammatory properties, is ... our findings raise the possibility that coinciding epitopes recognized by both CD4+ T cells and B cells have ...

Abstract	Tenascin-C (TNC), an extracellular matrix protein that has proinflammatory properties, is a recently described antibody target in rheumatoid arthritis (RA). In this study, we utilized a systematic discovery process and identified 5 potentially novel citrullinated TNC (cit-TNC) T cell epitopes. CD4+ T cells specific for these epitopes were elevated in the peripheral blood of subjects with RA and showed signs of activation. Cit-TNC-specific T cells were also present among synovial fluid T cells and secreted IFN-γ. Two of these cit-TNC T cell epitopes were also recognized by antibodies within the serum and synovial fluid of individuals with RA. Detectable serum levels of cit-TNC-reactive antibodies were prevalent among subjects with RA and positively associated with cyclic citrullinated peptide (CCP) reactivity and the HLA shared epitope. Furthermore, cit-TNC-reactive antibodies were correlated with rheumatoid factor and elevated in subjects with a history of smoking. This work confirms cit-TNC as an autoantigen that is targeted by autoreactive CD4+ T cells and autoantibodies in patients with RA. Furthermore, our findings raise the possibility that coinciding epitopes recognized by both CD4+ T cells and B cells have the potential to amplify autoimmunity and promote the development and progression of RA.
MeSH term(s)	Arthritis, Rheumatoid/immunology ; B-Lymphocytes/cytology ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/immunology ; Epitopes, T-Lymphocyte/immunology ; Humans ; Tenascin/immunology
Chemical Substances	Epitopes, T-Lymphocyte ; TNC protein, human ; Tenascin
Language	English
Publishing date	2021-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.145217
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Article ; Online: Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis

Jing Song / Anja Schwenzer / Alicia Wong / Sara Turcinov / Cliff Rims / Lorena Rodriguez Martinez / David Arribas-Layton / Christina Gerstner / Virginia S. Muir / Kim S. Midwood / Vivianne Malmström / Eddie A. James / Jane H. Buckner

JCI Insight, Vol 6, Iss

2021 Volume 5

Abstract	Tenascin-C (TNC), an extracellular matrix protein that has proinflammatory properties, is a recently described antibody target in rheumatoid arthritis (RA). In this study, we utilized a systematic discovery process and identified 5 potentially novel citrullinated TNC (cit-TNC) T cell epitopes. CD4+ T cells specific for these epitopes were elevated in the peripheral blood of subjects with RA and showed signs of activation. Cit-TNC–specific T cells were also present among synovial fluid T cells and secreted IFN-γ. Two of these cit-TNC T cell epitopes were also recognized by antibodies within the serum and synovial fluid of individuals with RA. Detectable serum levels of cit-TNC–reactive antibodies were prevalent among subjects with RA and positively associated with cyclic citrullinated peptide (CCP) reactivity and the HLA shared epitope. Furthermore, cit-TNC–reactive antibodies were correlated with rheumatoid factor and elevated in subjects with a history of smoking. This work confirms cit-TNC as an autoantigen that is targeted by autoreactive CD4+ T cells and autoantibodies in patients with RA. Furthermore, our findings raise the possibility that coinciding epitopes recognized by both CD4+ T cells and B cells have the potential to amplify autoimmunity and promote the development and progression of RA.
Keywords	Autoimmunity ; Immunology ; Medicine ; R
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
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Article ; Online: Skeletal Muscle Adaptations to High-Load Resistance Training With Pre-Exercise Blood Flow Restriction.

Hammert, William B / Moreno, Enrique N / Martin, Cole C / Jessee, Matthew B / Buckner, Samuel L

Journal of strength and conditioning research

2023 Volume 37, Issue 12, Page(s) 2381–2388

Abstract: ... 4 sets to muscular failure at 70% 1 repetition maximum (1RM)], (b) low repetition high-load ... and (c) low repetition high-load resistance training (LRTRAD); 4 sets of 3 repetitions at 70% 1RM ... Abstract: Hammert, WB, Moreno, EN, Martin, CC, Jessee, MB, and Buckner, SL. Skeletal muscle ...

Abstract	Abstract: Hammert, WB, Moreno, EN, Martin, CC, Jessee, MB, and Buckner, SL. Skeletal muscle adaptations to high-load resistance training with pre-exercise blood flow restriction. J Strength Cond Res 37(12): 2381-2388, 2023-This study aimed to determine if blood flow restriction (BFR) could augment adaptations to a high-load training protocol that was inadequate for muscle growth. Forty nontrained individuals had each arm assigned to 1 of 3 elbow flexion protocols: (a) high-load resistance training [TRAD; 4 sets to muscular failure at 70% 1 repetition maximum (1RM)], (b) low repetition high-load resistance training with pre-exercise BFR (PreBFR; 4 sets of 3 repetitions at 70% 1RM + 3 min of pre-exercise BFR), and (c) low repetition high-load resistance training (LRTRAD); 4 sets of 3 repetitions at 70% 1RM). Muscle thickness (MT), 1RM strength, and local muscular endurance (LME) of the elbow flexors were measured before and after 8 weeks. An alpha level of 0.05 was used for all comparisons. For the 50% site, MT increased for TRAD (0.211 cm, 95% confidence interval [95% CI]: 0.143-0.280), PreBFR (0.105 cm, 95% CI: 0.034-0.175), and LRTRAD (0.073 cm, 95% CI: 0.000-0.146). The change for TRAD was greater than PreBFR and LRTRAD. For the 60% site, MT increased for TRAD (0.235 cm, 95% CI: 0.153-0.317), PreBFR (0.097 cm, 95% CI: 0.014-0.180), and LRTRAD (0.082 cm, 95% CI: 0.000-0.164). The change for TRAD was greater than PreBFR and LRTRAD. For the 70% site MT increased for TRAD (0.308 cm, 95% CI: 0.247-0.369), PreBFR (0.103 cm, 95% CI: 0.041-0.166), and LRTRAD (0.070 cm, 95% CI: 0.004-0.137). The change for TRAD was greater than PreBFR and LRTRAD. One repetition maximum and LME significantly increased for each condition, with no differences between conditions. Collapsed across conditions 1RM strength increased 2.094 kg (95% CI: 1.771-2.416) and LME increased 7.0 repetitions (95% CI: 5.7-8.3). In conclusion, the application of BFR to low-repetition, high-load training did not enhance the adaptative response.
MeSH term(s)	Humans ; Muscle, Skeletal/physiology ; Resistance Training/methods ; Muscle Strength/physiology ; Hemodynamics ; Elbow ; Regional Blood Flow/physiology
Language	English
Publishing date	2023-08-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1156349-7
ISSN	1533-4287 ; 1064-8011
ISSN (online)	1533-4287
ISSN	1064-8011
DOI	10.1519/JSC.0000000000004553
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Article ; Online: Acute muscular and cardiovascular responses to high load training with pre-exercise blood flow restriction.

Moreno, Enrique N / Hammert, William B / Martin, Cole C / Buckner, Samuel L

Clinical physiology and functional imaging

2022 Volume 43, Issue 2, Page(s) 109–119

Abstract: Purpose: The purpose of this study is to examine the acute muscular and cardiovascular responses to applying blood flow restriction (BFR) before high-load training.: Methods: Forty trained individuals visited the lab on three occasions. On Visit 1, ... ...

Abstract	Purpose: The purpose of this study is to examine the acute muscular and cardiovascular responses to applying blood flow restriction (BFR) before high-load training. Methods: Forty trained individuals visited the lab on three occasions. On Visit 1, participants completed paperwork and performed strength assessments. During Visits 2 and 3, participants completed four exercise conditions (one in each arm during each visit) as follows: (1) traditional resistance training (TRAD), (2) low load training with BFR (LLBFR), (3) low repetition high load training with pre-exercise BFR (PreBFR), and (4) low repetition traditional training (LRTRAD). Blood pressure, muscle thickness (MT), and isometric strength (ISO) were measured before and after exercise. Results: Data are displayed as means (SD). Immediately following exercise, MT in TRAD was greater compared with PreBFR (mean difference = 0.18[0.30] cm, p < 0.001) and LRTRAD (mean difference = 0.28[0.30] cm, p < 0.001). In addition, LLBFR demonstrated greater MT compared with PreBFR (mean difference = 0.24[0.30] cm, p < 0.001]. Immediately following exercise, ISO was lower in TRAD compared with PreBFR (mean difference = 33.8[46.9]N, p < 0.001) and the LRTRAD condition (mean difference = 32.8[50.4]N, p < 0.001). In addition, ISO was lower in LLBFR compared with PreBFR (mean difference = 43.9 [47.4]N, p < 0.001) and LRTRAD (mean difference = 42.9 [43.8]N, p < 0.001). Immediately following exercise, systolic blood pressure was greater in TRAD compared with PreBFR and LRTRAD. Conclusion: The application of BFR before engaging in high-load training does not seem to augment the muscular responses to exercise when compared with traditional high loads alone; however, it may pose less demand on the cardiovascular system.
MeSH term(s)	Humans ; Muscle, Skeletal/physiology ; Muscle Strength/physiology ; Regional Blood Flow/physiology ; Hemodynamics ; Cardiovascular System ; Resistance Training
Language	English
Publishing date	2022-11-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2071203-0
ISSN	1475-097X ; 1475-0961
ISSN (online)	1475-097X
ISSN	1475-0961
DOI	10.1111/cpf.12799
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Zs.A 1650: Show issues

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Article ; Online: Organization of the Human Cerebral Cortex Estimated Within Individuals: Networks, Global Topography, and Function.

Du, Jingnan / DiNicola, Lauren M / Angeli, Peter A / Saadon-Grosman, Noam / Sun, Wendy / Kaiser, Stephanie / Ladopoulou, Joanna / Xue, Aihuiping / Yeo, B T Thomas / Eldaief, Mark C / Buckner, Randy L

Journal of neurophysiology

2024

Abstract: The cerebral cortex is populated by specialized regions that are organized into networks. Here we estimated networks from functional MRI (fMRI) data in intensively sampled participants. The procedure was developed in two participants (scanned 31 times) ... ...

Abstract	The cerebral cortex is populated by specialized regions that are organized into networks. Here we estimated networks from functional MRI (fMRI) data in intensively sampled participants. The procedure was developed in two participants (scanned 31 times) and then prospectively applied to 15 participants (scanned 8-11 times). Analysis of the networks revealed a global organization. Locally organized first-order sensory and motor networks were surrounded by spatially adjacent second-order networks that linked to distant regions. Third-order networks possessed regions distributed widely throughout association cortex. Regions of distinct third-order networks displayed side-by-side juxtapositions with a pattern that repeated across multiple cortical zones. We refer to these as Supra-Areal Association Megaclusters (SAAMs). Within each SAAM, two candidate control regions were adjacent to three separate domain-specialized regions. Response properties were explored with task data. The somatomotor and visual networks responded to body movements and visual stimulation, respectively. Second-order networks responded to transients in an oddball detection task, consistent with a role in orienting to salient events. The third-order networks, including distinct regions within each SAAM, showed two levels of functional specialization. Regions linked to candidate control networks responded to working memory load across multiple stimulus domains. The remaining regions dissociated across language, social, and spatial / episodic processing domains. These results suggest progressively higher-order networks nest outwards from primary sensory and motor cortices. Within the apex zones of association cortex, there is specialization that repeatedly divides domain-flexible from domain-specialized regions. We discuss implications of these findings including how repeating organizational motifs may emerge during development.
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00308.2023
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Uc I Zs.224: Show issues

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Article ; Online: The effect of controlled-substance monitoring of ephedrine use and medication waste.

Seman, MitchellT / Craner, Ryan C / Buckner Petty, Skye A / Kraus, Molly B

Journal of clinical anesthesia

2021 Volume 75, Page(s) 110449

MeSH term(s)	Controlled Substances ; Ephedrine/adverse effects ; Humans ; Substance Abuse Detection
Chemical Substances	Controlled Substances ; Ephedrine (GN83C131XS)
Language	English
Publishing date	2021-07-29
Publishing country	United States
Document type	Letter
ZDB-ID	1011618-7
ISSN	1873-4529 ; 0952-8180
ISSN (online)	1873-4529
ISSN	0952-8180
DOI	10.1016/j.jclinane.2021.110449
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Article ; Online: Immunotherapy: Building a bridge to a cure for type 1 diabetes.

Bluestone, Jeffrey A / Buckner, Jane H / Herold, Kevan C

Science (New York, N.Y.)

2021 Volume 373, Issue 6554, Page(s) 510–516

Abstract: Type 1 diabetes (T1D) is an autoimmune disease in which T cells attack and destroy the insulin-producing β cells in the pancreatic islets. Genetic and environmental factors increase T1D risk by compromising immune homeostasis. Although the discovery and ... ...

Abstract	Type 1 diabetes (T1D) is an autoimmune disease in which T cells attack and destroy the insulin-producing β cells in the pancreatic islets. Genetic and environmental factors increase T1D risk by compromising immune homeostasis. Although the discovery and use of insulin have transformed T1D treatment, insulin therapy does not change the underlying disease or fully prevent complications. Over the past two decades, research has identified multiple immune cell types and soluble factors that destroy insulin-producing β cells. These insights into disease pathogenesis have enabled the development of therapies to prevent and modify T1D. In this review, we highlight the key events that initiate and sustain pancreatic islet inflammation in T1D, the current state of the immunological therapies, and their advantages for the treatment of T1D.
MeSH term(s)	Adaptive Immunity ; Animals ; Anti-Inflammatory Agents/therapeutic use ; Autoantibodies/blood ; B-Lymphocytes/immunology ; Cytokines/immunology ; Cytokines/metabolism ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/therapy ; Humans ; Immunity, Innate ; Immunologic Factors/therapeutic use ; Immunotherapy ; Insulin-Secreting Cells/physiology ; Interleukin-2/therapeutic use ; T-Lymphocytes/immunology
Chemical Substances	Anti-Inflammatory Agents ; Autoantibodies ; Cytokines ; Immunologic Factors ; Interleukin-2
Language	English
Publishing date	2021-07-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abh1654
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Article ; Online: Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial.

Nature communications

2024 Volume 15, Issue 1, Page(s) 493

Abstract: ... in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment ... 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well ...

Abstract	Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well tolerated with no dose-limiting toxicity being observed up to the maximum feasible dose (2×10
MeSH term(s)	Humans ; Oncolytic Viruses ; Measles virus/genetics ; Glioblastoma ; Carcinoembryonic Antigen/genetics ; Oncolytic Virotherapy ; Neoplasm Recurrence, Local/therapy ; Measles Vaccine ; Tumor Microenvironment
Chemical Substances	Carcinoembryonic Antigen ; Measles Vaccine
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43076-7
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Book ; Online: HALO

Hayner, Christopher R. / Buckner, Samuel C. / Broyles, Daniel / Madewell, Evelyn / Leung, Karen / Acikmese, Behcet

Hazard-Aware Landing Optimization for Autonomous Systems

2023

Abstract: With autonomous aerial vehicles enacting safety-critical missions, such as the Mars Science Laboratory Curiosity rover's landing on Mars, the tasks of automatically identifying and reasoning about potentially hazardous landing sites is paramount. This ... ...

Abstract	With autonomous aerial vehicles enacting safety-critical missions, such as the Mars Science Laboratory Curiosity rover's landing on Mars, the tasks of automatically identifying and reasoning about potentially hazardous landing sites is paramount. This paper presents a coupled perception-planning solution which addresses the hazard detection, optimal landing trajectory generation, and contingency planning challenges encountered when landing in uncertain environments. Specifically, we develop and combine two novel algorithms, Hazard-Aware Landing Site Selection (HALSS) and Adaptive Deferred-Decision Trajectory Optimization (Adaptive-DDTO), to address the perception and planning challenges, respectively. The HALSS framework processes point cloud information to identify feasible safe landing zones, while Adaptive-DDTO is a multi-target contingency planner that adaptively replans as new perception information is received. We demonstrate the efficacy of our approach using a simulated Martian environment and show that our coupled perception-planning method achieves greater landing success whilst being more fuel efficient compared to a nonadaptive DDTO approach. Comment: The first two authors have contributed equally to this work. This work is to be published in the proceedings of the 2023 IEEE International Conference on Robotics and Automation (ICRA)
Keywords	Computer Science - Robotics ; Computer Science - Computer Vision and Pattern Recognition ; Electrical Engineering and Systems Science - Systems and Control ; Mathematics - Optimization and Control
Subject code	629
Publishing date	2023-04-04
Publishing country	us
Document type	Book ; Online
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Article: Within-Individual Organization of the Human Cerebral Cortex: Networks, Global Topography, and Function.

Du, Jingnan / DiNicola, Lauren M / Angeli, Peter A / Saadon-Grosman, Noam / Sun, Wendy / Kaiser, Stephanie / Ladopoulou, Joanna / Xue, Aihuiping / Yeo, B T Thomas / Eldaief, Mark C / Buckner, Randy L

bioRxiv : the preprint server for biology

2023

Abstract: The human cerebral cortex is populated by specialized regions that are organized into networks. Here we estimated networks using a Multi-Session Hierarchical Bayesian Model (MS-HBM) applied to intensively sampled within-individual functional MRI (fMRI) ... ...

Abstract	The human cerebral cortex is populated by specialized regions that are organized into networks. Here we estimated networks using a Multi-Session Hierarchical Bayesian Model (MS-HBM) applied to intensively sampled within-individual functional MRI (fMRI) data. The network estimation procedure was initially developed and tested in two participants (each scanned 31 times) and then prospectively applied to 15 new participants (each scanned 8 to 11 times). Detailed analysis of the networks revealed a global organization. Locally organized first-order sensory and motor networks were surrounded by spatially adjacent second-order networks that also linked to distant regions. Third-order networks each possessed regions distributed widely throughout association cortex. Moreover, regions of distinct third-order networks displayed side-by-side juxtapositions with a pattern that repeated similarly across multiple cortical zones. We refer to these as Supra-Areal Association Megaclusters (SAAMs). Within each SAAM, two candidate control regions were typically adjacent to three separate domain-specialized regions. Independent task data were analyzed to explore functional response properties. The somatomotor and visual first-order networks responded to body movements and visual stimulation, respectively. A subset of the second-order networks responded to transients in an oddball detection task, consistent with a role in orienting to salient or novel events. The third-order networks, including distinct regions within each SAAM, showed two levels of functional specialization. Regions linked to candidate control networks responded to working memory load across multiple stimulus domains. The remaining regions within each SAAM did not track working memory load but rather dissociated across language, social, and spatial / episodic processing domains. These results support a model of the cerebral cortex in which progressively higher-order networks nest outwards from primary sensory and motor cortices. Within the apex zones of association cortex there is specialization of large-scale networks that divides domain-flexible from domain-specialized regions repeatedly across parietal, temporal, and prefrontal cortices. We discuss implications of these findings including how repeating organizational motifs may emerge during development.
Language	English
Publishing date	2023-08-10
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.08.552437
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