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Article ; Online: Got Oxygen? Studies on Mesenchymal Cell Hypoxia Inducible Factor-1α in Lung Development.

Stevens, Reece P / Lee, Ji Young / Bauer, Natalie / Stevens, Troy

American journal of respiratory cell and molecular biology

2023 Volume 69, Issue 4, Page(s) 380–382

MeSH term(s)	Oxygen ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Cell Hypoxia ; Organogenesis ; Lung
Chemical Substances	Oxygen (S88TT14065) ; Hypoxia-Inducible Factor 1, alpha Subunit
Language	English
Publishing date	2023-07-21
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	1025960-0
ISSN	1535-4989 ; 1044-1549
ISSN (online)	1535-4989
ISSN	1044-1549
DOI	10.1165/rcmb.2023-0247ED
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Article ; Online: Urban Play as Catalyst for Social Wellbeing Post-Pandemic

Troy Innocent / Quentin Stevens

Frontiers in Computer Science, Vol

2021 Volume 3

Keywords	playable cities ; urban play ; COVID-19 ; urban planning and design ; public art ; Electronic computers. Computer science ; QA75.5-76.95
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Salvaging the endothelium in acute respiratory distress syndrome: a druggable intersection between TLR4 and NAD

Lee, Ji Young / Stevens, Reece P / Migaud, Marie / Stevens, Troy

The European respiratory journal

2021 Volume 57, Issue 5

MeSH term(s)	Endothelium ; Humans ; NAD ; Respiratory Distress Syndrome ; Signal Transduction ; Toll-Like Receptor 4
Chemical Substances	TLR4 protein, human ; Toll-Like Receptor 4 ; NAD (0U46U6E8UK)
Language	English
Publishing date	2021-05-06
Publishing country	England
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.04588-2020
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Zs.A 2322: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 292: Show issues

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Article ; Online: Design and Implementation of a Rat Ex Vivo Lung Perfusion Model.

Cleveland, William J / Hees, Josephine E / Balzer, Claudius / Douglas, Hunter F / Stevens, Troy / Riess, Matthias L

Journal of visualized experiments : JoVE

2023 , Issue 195

Abstract: Ex vivo lung preparations are a useful model that can be translated to many different fields of research, complementing corresponding in vivo and in vitro models. Laboratories wishing to use isolated lungs need to be aware of important steps and inherent ...

Abstract	Ex vivo lung preparations are a useful model that can be translated to many different fields of research, complementing corresponding in vivo and in vitro models. Laboratories wishing to use isolated lungs need to be aware of important steps and inherent challenges to establish a setup that is affordable, reliable, and that can be easily adapted to fit the topic of interest. This paper describes a DIY (do it yourself) model for ex vivo rat lung ventilation and perfusion to study drug and gas effects on pulmonary vascular tone, independent of changes in cardiac output. Creating this model includes a) the design and construction of the apparatus, and b) the lung isolation procedure. This model results in a setup that is more cost-effective than commercial alternatives and yet modular enough to adapt to changes in specific research questions. Various obstacles had to be resolved to ensure a consistent model that is capable of being used for a variety of different research topics. Once established, this model has proven to be highly adaptable to different questions and can easily be altered for different fields of study.
MeSH term(s)	Animals ; Rats ; Extracorporeal Circulation ; Perfusion ; Respiration ; Lung
Language	English
Publishing date	2023-05-26
Publishing country	United States
Document type	Journal Article ; Video-Audio Media ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/64740
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Article ; Online: Substrate stiffness modulates migration and local intercellular membrane motion in pulmonary endothelial cell monolayers.

Paudel, Sunita Subedi / deWeever, Althea / Sayner, Sarah / Stevens, Troy / Tambe, Dhananjay T

American journal of physiology. Cell physiology

2022 Volume 323, Issue 3, Page(s) C936–C949

Abstract: The pulmonary artery endothelium forms a semipermeable barrier that limits macromolecular flux through intercellular junctions. This barrier is maintained by an intrinsic forward protrusion of the interacting membranes between adjacent cells. However, ... ...

Abstract	The pulmonary artery endothelium forms a semipermeable barrier that limits macromolecular flux through intercellular junctions. This barrier is maintained by an intrinsic forward protrusion of the interacting membranes between adjacent cells. However, the dynamic interactions of these membranes have been incompletely quantified. Here, we present a novel technique to quantify the motion of the peripheral membrane of the cells, called paracellular morphological fluctuations (PMFs), and to assess the impact of substrate stiffness on PMFs. Substrate stiffness impacted large-length scale morphological changes such as cell size and motion. Cell size was larger on stiffer substrates, whereas the speed of cell movement was decreased on hydrogels with stiffness either larger or smaller than 1.25 kPa, consistent with cells approaching a jammed state. Pulmonary artery endothelial cells moved fastest on 1.25 kPa hydrogel, a stiffness consistent with a healthy pulmonary artery. Unlike these large-length scale morphological changes, the baseline of PMFs was largely insensitive to the substrate stiffness on which the cells were cultured. Activation of store-operated calcium channels using thapsigargin treatment triggered a transient increase in PMFs beyond the control treatment. However, in hypocalcemic conditions, such an increase in PMFs was absent on 1.25 kPa hydrogel but was present on 30 kPa hydrogel-a stiffness consistent with that of a hypertensive pulmonary artery. These findings indicate that
MeSH term(s)	Calcium/metabolism ; Cells, Cultured ; Endothelial Cells/metabolism ; Hydrogels/metabolism ; Lung/metabolism
Chemical Substances	Hydrogels ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00339.2021
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Article: Dynamics of chromosome organization in a minimal bacterial cell.

Gilbert, Benjamin R / Thornburg, Zane R / Brier, Troy A / Stevens, Jan A / Grünewald, Fabian / Stone, John E / Marrink, Siewert J / Luthey-Schulten, Zaida

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1214962

Abstract: Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial ... ...

Abstract	Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with Brownian dynamics, we investigate changes in chromosome organization during replication and extend the applicability of an existing whole-cell model (WCM) for a genetically minimal bacterium, JCVI-syn3A, to the entire cell-cycle. To achieve cell-scale chromosome structures that are realistic, we model the chromosome as a self-avoiding homopolymer with bending and torsional stiffnesses that capture the essential mechanical properties of dsDNA in Syn3A. In addition, the conformations of the circular DNA must avoid overlapping with ribosomes identitied in cryo-electron tomograms. While Syn3A lacks the complex regulatory systems known to orchestrate chromosome segregation in other bacteria, its minimized genome retains essential loop-extruding structural maintenance of chromosomes (SMC) protein complexes (SMC-scpAB) and topoisomerases. Through implementing the effects of these proteins in our simulations of replicating chromosomes, we find that they alone are sufficient for simultaneous chromosome segregation across all generations within nested theta structures. This supports previous studies suggesting loop-extrusion serves as a near-universal mechanism for chromosome organization within bacterial and eukaryotic cells. Furthermore, we analyze ribosome diffusion under the influence of the chromosome and calculate
Language	English
Publishing date	2023-08-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1214962
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Article ; Online: Lung endothelium, tau, and amyloids in health and disease.

Balczon, Ron / Lin, Mike T / Voth, Sarah / Nelson, Amy R / Schupp, Jonas C / Wagener, Brant M / Pittet, Jean-Francois / Stevens, Troy

Physiological reviews

2023 Volume 104, Issue 2, Page(s) 533–587

Abstract: Lung endothelia in the arteries, capillaries, and veins are heterogeneous in structure and function. Lung capillaries in particular represent a unique vascular niche, with a thin yet highly restrictive alveolar-capillary barrier that optimizes gas ... ...

Abstract	Lung endothelia in the arteries, capillaries, and veins are heterogeneous in structure and function. Lung capillaries in particular represent a unique vascular niche, with a thin yet highly restrictive alveolar-capillary barrier that optimizes gas exchange. Capillary endothelium surveys the blood while simultaneously interpreting cues initiated within the alveolus and communicated via immediately adjacent type I and type II epithelial cells, fibroblasts, and pericytes. This cell-cell communication is necessary to coordinate the immune response to lower respiratory tract infection. Recent discoveries identify an important role for the microtubule-associated protein tau that is expressed in lung capillary endothelia in the host-pathogen interaction. This endothelial tau stabilizes microtubules necessary for barrier integrity, yet infection drives production of cytotoxic tau variants that are released into the airways and circulation, where they contribute to end-organ dysfunction. Similarly, beta-amyloid is produced during infection. Beta-amyloid has antimicrobial activity, but during infection it can acquire cytotoxic activity that is deleterious to the host. The production and function of these cytotoxic tau and amyloid variants are the subject of this review. Lung-derived cytotoxic tau and amyloid variants are a recently discovered mechanism of end-organ dysfunction, including neurocognitive dysfunction, during and in the aftermath of infection.
MeSH term(s)	Humans ; Multiple Organ Failure/metabolism ; Lung/metabolism ; Endothelium, Vascular/metabolism ; Amyloid/chemistry ; Amyloid/metabolism ; Amyloid beta-Peptides/metabolism
Chemical Substances	Amyloid ; Amyloid beta-Peptides
Language	English
Publishing date	2023-08-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	209902-0
ISSN	1522-1210 ; 0031-9333
ISSN (online)	1522-1210
ISSN	0031-9333
DOI	10.1152/physrev.00006.2023
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Article ; Online: Endothelial metabolism in pulmonary vascular homeostasis and acute respiratory distress syndrome.

Stevens, Reece P / Paudel, Sunita S / Johnson, Santina C / Stevens, Troy / Lee, Ji Young

American journal of physiology. Lung cellular and molecular physiology

2021 Volume 321, Issue 2, Page(s) L358–L376

Abstract: Capillary endothelial cells possess a specialized metabolism necessary to adapt to the unique alveolar-capillary environment. Here, we highlight how endothelial metabolism preserves the integrity of the pulmonary circulation by controlling vascular ... ...

Abstract	Capillary endothelial cells possess a specialized metabolism necessary to adapt to the unique alveolar-capillary environment. Here, we highlight how endothelial metabolism preserves the integrity of the pulmonary circulation by controlling vascular permeability, defending against oxidative stress, facilitating rapid migration and angiogenesis in response to injury, and regulating the epigenetic landscape of endothelial cells. Recent reports on single-cell RNA-sequencing reveal subpopulations of pulmonary capillary endothelial cells with distinctive reparative capacities, which potentially offer new insight into their metabolic signature. Lastly, we discuss broad implications of pulmonary vascular metabolism on acute respiratory distress syndrome, touching on emerging findings of endotheliitis in coronavirus disease 2019 (COVID-19) lungs.
MeSH term(s)	COVID-19/complications ; COVID-19/transmission ; COVID-19/virology ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Endothelium, Vascular/virology ; Humans ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/pathology ; Neovascularization, Pathologic/virology ; Pulmonary Circulation ; Respiratory Distress Syndrome/epidemiology ; Respiratory Distress Syndrome/metabolism ; Respiratory Distress Syndrome/pathology ; Respiratory Distress Syndrome/virology ; SARS-CoV-2/isolation & purification
Language	English
Publishing date	2021-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00131.2021
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Zs.A 2749: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Functional and molecular heterogeneity of pulmonary endothelial cells.

Stevens, Troy

Proceedings of the American Thoracic Society

2011 Volume 8, Issue 6, Page(s) 453–457

Abstract: In recent years there has been an increasing appreciation of the functional heterogeneity that exists between extraalveolar and alveolar endothelial cells. One of the most striking features of pulmonary microvascular endothelial cells is that they ... ...

Abstract	In recent years there has been an increasing appreciation of the functional heterogeneity that exists between extraalveolar and alveolar endothelial cells. One of the most striking features of pulmonary microvascular endothelial cells is that they possess a highly impermeable barrier with respect to pulmonary artery or vein endothelial cells. This cellular feature is observed in culture and in the intact microcirculation, prompting a reevaluation of the key physiological principles that control permeability and the fate of fluid (or exudate) once it leaves the circulation. Pulmonary microvascular endothelial cells express calcium channels not found in extraalveolar endothelial cells, including the vanilloid family transient receptor potential 4 channel and the α1G T-type calcium channel. Whereas activation of the TRPV4 channel causes alveolar flooding, activation of the α1G T-type calcium channel promotes P-selectin surface translocation, events specific to the microcirculation. Although endothelium is an attractive therapeutic target in acute lung injury and other vascular disorders, the growing awareness of pulmonary endothelial cell heterogeneity increasingly suggests that a panendothelial cell approach is suboptimal. Rather, development of novel therapeutics based upon anatomically restricted expression of molecular signatures may be developed to better combat vascular disease.
MeSH term(s)	Endothelial Cells/metabolism ; Endothelial Cells/physiology ; Endothelium, Vascular/cytology ; Humans ; Lung/cytology ; Microcirculation ; P-Selectin/metabolism ; Permeability
Chemical Substances	P-Selectin
Language	English
Publishing date	2011-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2132421-9
ISSN	1943-5665 ; 1546-3222
ISSN (online)	1943-5665
ISSN	1546-3222
DOI	10.1513/pats.201101-004MW
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Article: Molecular dynamics simulation of an entire cell.

Stevens, Jan A / Grünewald, Fabian / van Tilburg, P A Marco / König, Melanie / Gilbert, Benjamin R / Brier, Troy A / Thornburg, Zane R / Luthey-Schulten, Zaida / Marrink, Siewert J

Frontiers in chemistry

2023 Volume 11, Page(s) 1106495

Abstract: The ultimate microscope, directed at a cell, would reveal the dynamics of all the cell's components with atomic resolution. In contrast to their real-world counterparts, computational microscopes are currently on the brink of meeting this challenge. In ... ...

Abstract	The ultimate microscope, directed at a cell, would reveal the dynamics of all the cell's components with atomic resolution. In contrast to their real-world counterparts, computational microscopes are currently on the brink of meeting this challenge. In this perspective, we show how an integrative approach can be employed to model an entire cell, the minimal cell, JCVI-syn3A, at full complexity. This step opens the way to interrogate the cell's spatio-temporal evolution with molecular dynamics simulations, an approach that can be extended to other cell types in the near future.
Language	English
Publishing date	2023-01-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711776-5
ISSN	2296-2646
ISSN	2296-2646
DOI	10.3389/fchem.2023.1106495
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