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Article ; Online: Author Correction: Distinct chemical environments in biomolecular condensates.

Kilgore, Henry R / Mikhael, Peter G / Overholt, Kalon J / Boija, Ann / Hannett, Nancy M / Van Dongen, Catherine / Lee, Tong Ihn / Chang, Young-Tae / Barzilay, Regina / Young, Richard A

Nature chemical biology

2023 Volume 19, Issue 12, Page(s) 1561

Language	English
Publishing date	2023-10-26
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2202962-X
ISSN	1552-4469 ; 1552-4450
ISSN (online)	1552-4469
ISSN	1552-4450
DOI	10.1038/s41589-023-01491-3
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Article ; Online: A Mesoscale 3D Culture System for Native and Engineered Biphasic Tissues: Application to the Osteochondral Unit.

Chiesa, Irene / Di Gesù, Roberto / Overholt, Kalon J / Gottardi, Riccardo

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2373, Page(s) 267–281

Abstract: Interface tissues are functionally graded tissues characterized by a complex layered structure, which therefore present a great challenge to be reproduced and cultured in vitro. Here, we describe the design and operation of a 3D printed dual-chamber ... ...

Abstract	Interface tissues are functionally graded tissues characterized by a complex layered structure, which therefore present a great challenge to be reproduced and cultured in vitro. Here, we describe the design and operation of a 3D printed dual-chamber bioreactor as a culturing system for biphasic native or engineered osteochondral tissues. The bioreactor is designed to potentially accommodate a variety of interface tissues and enables the precise study of tissue crosstalk by creating two separate microenvironments while maintaining the tissue compartments in direct contact.
MeSH term(s)	Bioreactors ; Cartilage ; Tissue Engineering ; Tissue Scaffolds
Language	English
Publishing date	2021-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1693-2_16
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution.

Overholt, Kalon J / Krog, Jonathan R / Zanoni, Ivan / Bryson, Bryan D

iScience

2021 Volume 24, Issue 7, Page(s) 102738

Abstract: Severe COVID-19 is accompanied by rampant immune dysregulation in the lung and periphery, with immune cells of both compartments contributing to systemic distress. The extent to which immune cells of the lung and blood enter similar or distinct ... ...

Abstract	Severe COVID-19 is accompanied by rampant immune dysregulation in the lung and periphery, with immune cells of both compartments contributing to systemic distress. The extent to which immune cells of the lung and blood enter similar or distinct pathological states during severe disease remains unknown. Here, we leveraged 96 publicly available single-cell RNA sequencing datasets to elucidate common and compartment-specific features of severe to critical COVID-19 at the levels of transcript expression, biological pathways, and ligand-receptor signaling networks. Comparing severe patients to milder and healthy donors, we identified distinct differential gene expression signatures between compartments and a core set of co-directionally regulated surface markers. A majority of severity-enriched pathways were shared, whereas TNF and interferon responses were polarized. Severity-specific ligand-receptor networks appeared to be differentially active in both compartments. Overall, our results describe a nuanced response during severe COVID-19 where compartment plays a role in dictating the pathological state of immune cells.
Language	English
Publishing date	2021-06-17
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2021.102738
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Distinct chemical environments in biomolecular condensates.

Kilgore, Henry R / Mikhael, Peter G / Overholt, Kalon J / Boija, Ann / Hannett, Nancy M / Van Dongen, Catherine / Lee, Tong Ihn / Chang, Young-Tae / Barzilay, Regina / Young, Richard A

Nature chemical biology

2023 Volume 20, Issue 3, Page(s) 291–301

Abstract: Diverse mechanisms have been described for selective enrichment of biomolecules in membrane-bound organelles, but less is known about mechanisms by which molecules are selectively incorporated into biomolecular assemblies such as condensates that lack ... ...

Abstract	Diverse mechanisms have been described for selective enrichment of biomolecules in membrane-bound organelles, but less is known about mechanisms by which molecules are selectively incorporated into biomolecular assemblies such as condensates that lack surrounding membranes. The chemical environments within condensates may differ from those outside these bodies, and if these differed among various types of condensate, then the different solvation environments would provide a mechanism for selective distribution among these intracellular bodies. Here we use small molecule probes to show that different condensates have distinct chemical solvating properties and that selective partitioning of probes in condensates can be predicted with deep learning approaches. Our results demonstrate that different condensates harbor distinct chemical environments that influence the distribution of molecules, show that clues to condensate chemical grammar can be ascertained by machine learning and suggest approaches to facilitate development of small molecule therapeutics with optimal subcellular distribution and therapeutic benefit.
MeSH term(s)	Biomolecular Condensates ; Machine Learning
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2202962-X
ISSN	1552-4469 ; 1552-4450
ISSN (online)	1552-4469
ISSN	1552-4450
DOI	10.1038/s41589-023-01432-0
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Article ; Online: Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution

Kalon J. Overholt / Jonathan R. Krog / Ivan Zanoni / Bryan D. Bryson

iScience, Vol 24, Iss 7, Pp 102738- (2021)

2021

Abstract: Summary: Severe COVID-19 is accompanied by rampant immune dysregulation in the lung and periphery, with immune cells of both compartments contributing to systemic distress. The extent to which immune cells of the lung and blood enter similar or distinct ... ...

Abstract	Summary: Severe COVID-19 is accompanied by rampant immune dysregulation in the lung and periphery, with immune cells of both compartments contributing to systemic distress. The extent to which immune cells of the lung and blood enter similar or distinct pathological states during severe disease remains unknown. Here, we leveraged 96 publicly available single-cell RNA sequencing datasets to elucidate common and compartment-specific features of severe to critical COVID-19 at the levels of transcript expression, biological pathways, and ligand-receptor signaling networks. Comparing severe patients to milder and healthy donors, we identified distinct differential gene expression signatures between compartments and a core set of co-directionally regulated surface markers. A majority of severity-enriched pathways were shared, whereas TNF and interferon responses were polarized. Severity-specific ligand-receptor networks appeared to be differentially active in both compartments. Overall, our results describe a nuanced response during severe COVID-19 where compartment plays a role in dictating the pathological state of immune cells.
Keywords	Pathophysiology ; Immunology ; Complex system biology ; Transcriptomics ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution

Overholt, Kalon J. / Krog, Jonathan R. / Bryson, Bryan D.

bioRxiv

Abstract: As the global COVID-19 pandemic continues to escalate, no effective treatment has yet been developed for the severe respiratory complications of this disease. This may be due in large part to the unclear immunopathological basis for the development of ... ...

Abstract	As the global COVID-19 pandemic continues to escalate, no effective treatment has yet been developed for the severe respiratory complications of this disease. This may be due in large part to the unclear immunopathological basis for the development of immune dysregulation and acute respiratory distress syndrome (ARDS) in severe and critical patients. Specifically, it remains unknown whether the immunological features of the disease that have been identified so far are compartment-specific responses or general features of COVID-19. Additionally, readily detectable biological markers correlated with strata of disease severity that could be used to triage patients and inform treatment options have not yet been identified. Here, we leveraged publicly available single-cell RNA sequencing data to elucidate the common and compartment-specific immunological features of clinically severe COVID-19. We identified a number of transcriptional programs that are altered across the spectrum of disease severity, few of which are common between the lung and peripheral immune environments. In the lung, comparing severe and moderate patients revealed severity-specific responses of enhanced interferon, A20/IκB, IL-2, and IL-6 pathway signatures along with broad signaling activity of IFNG, SPP1, CCL3, CCL8, and IL18 across cell types. These signatures contrasted with features unique to ARDS observed in the blood compartment, which included depletion of interferon and A20/IκB signatures and a lack of IL-6 response. The cell surface marker S1PR1 was strongly upregulated in patients diagnosed with ARDS compared to non-ARDS patients in γδ T cells of the blood compartment, and we nominate S1PR1 as a potential marker for immunophenotyping ARDS in COVID-19 patients using flow cytometry. HIGHLIGHTS COVID-19 disease severity is associated with a number of compositional shifts in the cellular makeup of the blood and lung environments. Transcriptional data suggest differentially expressed cell surface proteins as markers for COVID-19 immunophenotyping from BALF and PBMC samples. Severity-specific features COVID-19 manifest at the pathway level, suggesting distinct changes to epithelia and differences between local and systemic immune dynamics. Immune-epithelial cellular communication analysis identifies ligands implicated in transcriptional regulation of proto-oncogenes in the lung epithelia of severe COVID-19 patients. Network analysis suggests broadly-acting dysregulatory ligands in the pulmonary microenvironment as candidate therapeutic targets for the treatment of severe COVID-19.
Keywords	covid19
Publisher	BioRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.06.15.147470
Database	COVID19

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Article ; Online: Transcription factors interact with RNA to regulate genes.

Oksuz, Ozgur / Henninger, Jonathan E / Warneford-Thomson, Robert / Zheng, Ming M / Erb, Hailey / Vancura, Adrienne / Overholt, Kalon J / Hawken, Susana Wilson / Banani, Salman F / Lauman, Richard / Reich, Lauren N / Robertson, Anne L / Hannett, Nancy M / Lee, Tong I / Zon, Leonard I / Bonasio, Roberto / Young, Richard A

Molecular cell

2023 Volume 83, Issue 14, Page(s) 2449–2463.e13

Abstract: Transcription factors (TFs) orchestrate the gene expression programs that define each cell's identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or ... ...

Abstract	Transcription factors (TFs) orchestrate the gene expression programs that define each cell's identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or corepressors. We find that at least half of TFs also bind RNA, doing so through a previously unrecognized domain with sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat. RNA binding contributes to TF function by promoting the dynamic association between DNA, RNA, and TF on chromatin. TF-RNA interactions are a conserved feature important for vertebrate development and disrupted in disease. We propose that the ability to bind DNA, RNA, and protein is a general property of many TFs and is fundamental to their gene regulatory function.
MeSH term(s)	Transcription Factors/metabolism ; RNA/metabolism ; Binding Sites ; Protein Binding ; DNA/genetics
Chemical Substances	Transcription Factors ; RNA (63231-63-0) ; DNA (9007-49-2)
Language	English
Publishing date	2023-07-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2023.06.012
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Article ; Online: Transcription factors interact with RNA to regulate genes

Oksuz, Ozgur / Henninger, Jonathan E. / Warneford-Thomson, Robert / Zheng, Ming M. / Erb, Hailey / Vancura, Adrienne / Overholt, Kalon J. / Hawken, Susana Wilson / Banani, Salman F. / Lauman, Richard / Reich, Lauren N. / Robertson, A. L. / Hannett, Nancy M. / Lee, Tong I. / Zon, Leonard I. / Bonasio, Roberto / Young, Richard A.

Molecular Cell. 20232023 July 03, July 03, v. 83, no. 14 p.2449-2463.e13

2023

Abstract: Transcription factors (TFs) orchestrate the gene expression programs that define each cell’s identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or ... ...

Abstract	Transcription factors (TFs) orchestrate the gene expression programs that define each cell’s identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or corepressors. We find that at least half of TFs also bind RNA, doing so through a previously unrecognized domain with sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat. RNA binding contributes to TF function by promoting the dynamic association between DNA, RNA, and TF on chromatin. TF-RNA interactions are a conserved feature important for vertebrate development and disrupted in disease. We propose that the ability to bind DNA, RNA, and protein is a general property of many TFs and is fundamental to their gene regulatory function.
Keywords	DNA ; RNA ; chromatin ; gene expression ; genes ; transactivators ; vertebrates ; transcription factor ; gene regulation ; RNA-binding proteins ; arginine-rich motif ; single-molecule imaging ; development ; zebrafish
Language	English
Dates of publication	2023-0703
Size	p. 2449-2463.e13.
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2023.06.012
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Synthesis and characterization of CaSr-Metal Organic Frameworks for biodegradable orthopedic applications.

Joseph, Naomi / Lawson, Harrison D / Overholt, Kalon J / Damodaran, Krishnan / Gottardi, Riccardo / Acharya, Abhinav P / Little, Steven R

Scientific reports

2019 Volume 9, Issue 1, Page(s) 13024

Abstract: Metal-organic frameworks (MOFs) formed from metals and organic ligands, are crystalline materials that are degradable in aqueous medium, and capable of releasing Ca and Sr ions. In this manuscript, the ability of MOFs to degrade and release osteogenic Ca ...

Abstract	Metal-organic frameworks (MOFs) formed from metals and organic ligands, are crystalline materials that are degradable in aqueous medium, and capable of releasing Ca and Sr ions. In this manuscript, the ability of MOFs to degrade and release osteogenic Ca and Sr ions was investigated. MOFs were generated by choosing osteoinductive Ca and Sr metals, and an organic ligand 1,3,5 tricarboxylicbenzene (H3BTC) as a linker. These MOFs were able to induce in vitro biomineralization from pre-osteoblastic MC3T3 cells and human mesenchymal stem cells (hMSCs). Moreover, these MOFs (when loaded with dimethyloxalylglycine (DMOG)) induced vascular endothelial production from hMSCs. qRT-PCR analysis performed on hMSCs (isolated from femoral heads of patients undergoing joint arthroplasty) treated with MOFs crystals suggested that the CaSr-MOFs by themselves can upregulate osteogenic genes in hMSCs, which is the first time to our knowledge that this has been observed from MOFs.
MeSH term(s)	Animals ; Biomarkers ; Bone Regeneration ; Carbon ; Humans ; Ions/chemistry ; Magnetic Resonance Spectroscopy ; Mesenchymal Stem Cells ; Metal-Organic Frameworks/chemistry ; Metals/chemistry ; Mice ; Orthopedic Procedures
Chemical Substances	Biomarkers ; Ions ; Metal-Organic Frameworks ; Metals ; Carbon (7440-44-0)
Language	English
Publishing date	2019-09-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-49536-9
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Article ; Online: Synthesis and characterization of CaSr-Metal Organic Frameworks for biodegradable orthopedic applications

Naomi Joseph / Harrison D. Lawson / Kalon J. Overholt / Krishnan Damodaran / Riccardo Gottardi / Abhinav P. Acharya / Steven R. Little

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 11

Abstract: Abstract Metal-organic frameworks (MOFs) formed from metals and organic ligands, are crystalline materials that are degradable in aqueous medium, and capable of releasing Ca and Sr ions. In this manuscript, the ability of MOFs to degrade and release ... ...

Abstract	Abstract Metal-organic frameworks (MOFs) formed from metals and organic ligands, are crystalline materials that are degradable in aqueous medium, and capable of releasing Ca and Sr ions. In this manuscript, the ability of MOFs to degrade and release osteogenic Ca and Sr ions was investigated. MOFs were generated by choosing osteoinductive Ca and Sr metals, and an organic ligand 1,3,5 tricarboxylicbenzene (H3BTC) as a linker. These MOFs were able to induce in vitro biomineralization from pre-osteoblastic MC3T3 cells and human mesenchymal stem cells (hMSCs). Moreover, these MOFs (when loaded with dimethyloxalylglycine (DMOG)) induced vascular endothelial production from hMSCs. qRT-PCR analysis performed on hMSCs (isolated from femoral heads of patients undergoing joint arthroplasty) treated with MOFs crystals suggested that the CaSr-MOFs by themselves can upregulate osteogenic genes in hMSCs, which is the first time to our knowledge that this has been observed from MOFs.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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