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Article: A team of chaperones play to win in the bacterial periplasm.

Devlin, Taylor / Fleming, Karen G

2024

Abstract: The survival and virulence of Gram-negative bacteria require proper biogenesis and maintenance of the outer membrane (OM), which is densely packed with β-barrel OM proteins (OMPs). Before reaching the OM, precursor unfolded OMPs (uOMPs) must cross the ... ...

Abstract	The survival and virulence of Gram-negative bacteria require proper biogenesis and maintenance of the outer membrane (OM), which is densely packed with β-barrel OM proteins (OMPs). Before reaching the OM, precursor unfolded OMPs (uOMPs) must cross the whole cell envelope. A network of periplasmic chaperones and proteases maintains unfolded but folding-competent conformations of these membrane proteins in the aqueous periplasm while simultaneously preventing off-pathway aggregation. These periplasmic proteins utilize different strategies, including conformational heterogeneity, oligomerization, multivalency, and kinetic partitioning, to perform and regulate their functions. Redundant and unique characteristics of the individual periplasmic players synergize to create a protein quality control team capable responding to changing environmental stresses.
Language	English
Publishing date	2024-04-26
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	194216-5
ISSN	1362-4326 ; 0968-0004 ; 0376-5067
ISSN (online)	1362-4326
ISSN	0968-0004 ; 0376-5067
DOI	10.1016/j.tibs.2024.03.015
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Zs.A 1207: Show issues

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Article ; Online: Generation of unfolded outer membrane protein ensembles defined by hydrodynamic properties.

Devlin, Taylor / Fleming, Patrick J / Loza, Nicole / Fleming, Karen G

European biophysics journal : EBJ

2023 Volume 52, Issue 4-5, Page(s) 415–425

Abstract: Outer membrane proteins (OMPs) must exist as an unfolded ensemble while interacting with a chaperone network in the periplasm of Gram-negative bacteria. Here, we developed a method to model unfolded OMP (uOMP) conformational ensembles using the ... ...

Abstract	Outer membrane proteins (OMPs) must exist as an unfolded ensemble while interacting with a chaperone network in the periplasm of Gram-negative bacteria. Here, we developed a method to model unfolded OMP (uOMP) conformational ensembles using the experimental properties of two well-studied OMPs. The overall sizes and shapes of the unfolded ensembles in the absence of a denaturant were experimentally defined by measuring the sedimentation coefficient as a function of urea concentration. We used these data to model a full range of unfolded conformations by parameterizing a targeted coarse-grained simulation protocol. The ensemble members were further refined by short molecular dynamics simulations to reflect proper torsion angles. The final conformational ensembles have polymer properties different from unfolded soluble and intrinsically disordered proteins and reveal inherent differences in the unfolded states that necessitate further investigation. Building these uOMP ensembles advances the understanding of OMP biogenesis and provides essential information for interpreting structures of uOMP-chaperone complexes.
MeSH term(s)	Hydrodynamics ; Bacterial Outer Membrane Proteins/chemistry ; Bacterial Outer Membrane Proteins/metabolism ; Molecular Chaperones/metabolism ; Periplasm/metabolism ; Cell Membrane/metabolism ; Protein Conformation
Chemical Substances	Bacterial Outer Membrane Proteins ; Molecular Chaperones
Language	English
Publishing date	2023-03-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	283671-3
ISSN	1432-1017 ; 0175-7571
ISSN (online)	1432-1017
ISSN	0175-7571
DOI	10.1007/s00249-023-01639-y
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Zs.A 1121: Show issues

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Article ; Online: A proteome-wide map of chaperone-assisted protein refolding in a cytosol-like milieu.

To, Philip / Xia, Yingzi / Lee, Sea On / Devlin, Taylor / Fleming, Karen G / Fried, Stephen D

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 48, Page(s) e2210536119

Abstract: The journey by which proteins navigate their energy landscapes to their native structures is complex, involving (and sometimes requiring) many cellular factors and processes operating in partnership with a given polypeptide chain's intrinsic energy ... ...

Abstract	The journey by which proteins navigate their energy landscapes to their native structures is complex, involving (and sometimes requiring) many cellular factors and processes operating in partnership with a given polypeptide chain's intrinsic energy landscape. The cytosolic environment and its complement of chaperones play critical roles in granting many proteins safe passage to their native states; however, it is challenging to interrogate the folding process for large numbers of proteins in a complex background with most biophysical techniques. Hence, most chaperone-assisted protein refolding studies are conducted in defined buffers on single purified clients. Here, we develop a limited proteolysis-mass spectrometry approach paired with an isotope-labeling strategy to globally monitor the structures of refolding
MeSH term(s)	Cytosol/metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Heat-Shock Proteins/metabolism ; Molecular Chaperones/genetics ; Molecular Chaperones/metabolism ; Protein Refolding ; Proteome/metabolism
Chemical Substances	Escherichia coli Proteins ; Heat-Shock Proteins ; Molecular Chaperones ; Proteome
Language	English
Publishing date	2022-11-23
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	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2210536119
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Zs.A 1148: Show issues

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Article ; Online: FkpA enhances membrane protein folding using an extensive interaction surface.

Devlin, Taylor / Marx, Dagan C / Roskopf, Michaela A / Bubb, Quenton R / Plummer, Ashlee M / Fleming, Karen G

Protein science : a publication of the Protein Society

2023 Volume 32, Issue 4, Page(s) e4592

Abstract: Outer membrane protein (OMP) biogenesis in gram-negative bacteria is managed by a network of periplasmic chaperones that includes SurA, Skp, and FkpA. These chaperones bind unfolded OMPs (uOMPs) in dynamic conformational ensembles to suppress aggregation, ...

Abstract	Outer membrane protein (OMP) biogenesis in gram-negative bacteria is managed by a network of periplasmic chaperones that includes SurA, Skp, and FkpA. These chaperones bind unfolded OMPs (uOMPs) in dynamic conformational ensembles to suppress aggregation, facilitate diffusion across the periplasm, and enhance folding. FkpA primarily responds to heat-shock stress, but its mechanism is comparatively understudied. To determine FkpA chaperone function in the context of OMP folding, we monitored the folding of three OMPs and found that FkpA, unlike other periplasmic chaperones, increases the folded yield but decreases the folding rate of OMPs. The results indicate that FkpA behaves as a chaperone and not as a folding catalyst to influence the OMP folding trajectory. Consistent with the folding assay results, FkpA binds all three uOMPs as determined by sedimentation velocity (SV) and photo-crosslinking experiments. We determine the binding affinity between FkpA and uOmpA
MeSH term(s)	Humans ; Carrier Proteins/metabolism ; Peptidylprolyl Isomerase ; Escherichia coli Proteins/metabolism ; Escherichia coli/metabolism ; Bacterial Outer Membrane Proteins/chemistry ; Protein Folding ; Molecular Chaperones/metabolism ; Periplasm/metabolism
Chemical Substances	Carrier Proteins ; Peptidylprolyl Isomerase (EC 5.2.1.8) ; Escherichia coli Proteins ; Bacterial Outer Membrane Proteins ; Molecular Chaperones
Language	English
Publishing date	2023-02-08
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	1106283-6
ISSN	1469-896X ; 0961-8368
ISSN (online)	1469-896X
ISSN	0961-8368
DOI	10.1002/pro.4592
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Zs.A 3407: 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: Acoustic localization of terrestrial wildlife: Current practices and future opportunities.

Rhinehart, Tessa A / Chronister, Lauren M / Devlin, Trieste / Kitzes, Justin

Ecology and evolution

2020 Volume 10, Issue 13, Page(s) 6794–6818

Abstract: Autonomous acoustic recorders are an increasingly popular method for low-disturbance, large-scale monitoring of sound-producing animals, such as birds, anurans, bats, and other mammals. A specialized use of autonomous recording units (ARUs) is acoustic ... ...

Abstract	Autonomous acoustic recorders are an increasingly popular method for low-disturbance, large-scale monitoring of sound-producing animals, such as birds, anurans, bats, and other mammals. A specialized use of autonomous recording units (ARUs) is acoustic localization, in which a vocalizing animal is located spatially, usually by quantifying the time delay of arrival of its sound at an array of time-synchronized microphones. To describe trends in the literature, identify considerations for field biologists who wish to use these systems, and suggest advancements that will improve the field of acoustic localization, we comprehensively review published applications of wildlife localization in terrestrial environments. We describe the wide variety of methods used to complete the five steps of acoustic localization: (1) define the research question, (2) obtain or build a time-synchronizing microphone array, (3) deploy the array to record sounds in the field, (4) process recordings captured in the field, and (5) determine animal location using position estimation algorithms. We find eight general purposes in ecology and animal behavior for localization systems: assessing individual animals' positions or movements, localizing multiple individuals simultaneously to study their interactions, determining animals' individual identities, quantifying sound amplitude or directionality, selecting subsets of sounds for further acoustic analysis, calculating species abundance, inferring territory boundaries or habitat use, and separating animal sounds from background noise to improve species classification. We find that the labor-intensive steps of processing recordings and estimating animal positions have not yet been automated. In the near future, we expect that increased availability of recording hardware, development of automated and open-source localization software, and improvement of automated sound classification algorithms will broaden the use of acoustic localization. With these three advances, ecologists will be better able to embrace acoustic localization, enabling low-disturbance, large-scale collection of animal position data.
Language	English
Publishing date	2020-06-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2635675-2
ISSN	2045-7758
ISSN	2045-7758
DOI	10.1002/ece3.6216
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Article: Reverse Triggering: An Introduction to Diagnosis, Management, and Pharmacologic Implications.

Murray, Brian / Sikora, Andrea / Mock, Jason R / Devlin, Thomas / Keats, Kelli / Powell, Rebecca / Bice, Thomas

Frontiers in pharmacology

2022 Volume 13, Page(s) 879011

Abstract: Reverse triggering is an underdiagnosed form of patient-ventilator asynchrony in which a passive ventilator-delivered breath triggers a neural response resulting in involuntary patient effort and diaphragmatic contraction. Reverse triggering may ... ...

Abstract	Reverse triggering is an underdiagnosed form of patient-ventilator asynchrony in which a passive ventilator-delivered breath triggers a neural response resulting in involuntary patient effort and diaphragmatic contraction. Reverse triggering may significantly impact patient outcomes, and the unique physiology underscores critical potential implications for drug-device-patient interactions. The purpose of this review is to summarize what is known of reverse triggering and its pharmacotherapeutic consequences, with a particular focus on describing reported cases, physiology, historical context, epidemiology, and management. The PubMed database was searched for publications that reported patients presenting with reverse triggering. The current body of evidence suggests that deep sedation may predispose patients to episodes of reverse triggering; as such, providers may consider decreasing sedation or modifying ventilator settings in patients exhibiting ventilator asynchrony as an initial measure. Increased clinician awareness and research focus are necessary to understand appropriate management of reverse triggering and its association with patient outcomes.
Language	English
Publishing date	2022-06-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.879011
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Article ; Online: Dose and duration of interferon γ pre-licensing interact with donor characteristics to influence the expression and function of indoleamine-2,3-dioxygenase in mesenchymal stromal cells.

Boyt, Devlin T / Boland, Lauren K / Burand, Anthony J / Brown, Alex J / Ankrum, James A

Journal of the Royal Society, Interface

2020 Volume 17, Issue 167, Page(s) 20190815

Abstract: Human mesenchymal stromal cells (MSCs) are a leading cell therapy candidate for the treatment of immune and inflammatory diseases due to their potent regulation of immune cells. MSC expression of indoleamine-2,3-dioxygenase (IDO) upon interferon γ (IFNγ) ...

Abstract	Human mesenchymal stromal cells (MSCs) are a leading cell therapy candidate for the treatment of immune and inflammatory diseases due to their potent regulation of immune cells. MSC expression of indoleamine-2,3-dioxygenase (IDO) upon interferon γ (IFNγ) exposure has been proposed as both a sentinel marker and key mediator of MSC immunomodulatory potency. Rather than wait for
MeSH term(s)	Cell Proliferation ; Cells, Cultured ; Humans ; Immunomodulation ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Interferon-gamma ; Leukocytes, Mononuclear ; Mesenchymal Stem Cells
Chemical Substances	Indoleamine-Pyrrole 2,3,-Dioxygenase ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2020-06-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2156283-0
ISSN	1742-5662 ; 1742-5689
ISSN (online)	1742-5662
ISSN	1742-5689
DOI	10.1098/rsif.2019.0815
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Article: Sex differences in acute telestroke care: more to the story.

Sevilis, Theresa / Avila, Amanda / McDonald, Mark / Fowler, Mariecken / Chalfin, Renata / Amir, Murtaza / Heath, Gregory / Zaman, Mohammed / Avino, Lorianne / Boyd, Caitlyn / Gao, Lan / Devlin, Thomas

Frontiers in neurology

2023 Volume 14, Page(s) 1203502

Abstract: Background: Previous studies have shown sex differences in stroke care. Female patients have both lower thrombolytic treatment rates with OR reported as low as 0.57 and worse outcomes. With updated standards of care and improved access to care through ... ...

Abstract	Background: Previous studies have shown sex differences in stroke care. Female patients have both lower thrombolytic treatment rates with OR reported as low as 0.57 and worse outcomes. With updated standards of care and improved access to care through telestroke, there is potential to reduce or alleviate these disparities. Methods: Acute stroke consultations seen by TeleSpecialists, LLC physicians in the emergency department in 203 facilities (23 states) from January 1, 2021 to April 30, 2021 were extracted from the Telecare by TeleSpecialists Results: There were 18,783 (10,073 female and 8,710 male) total patients included. Of the total, 6.9% of females received thrombolytics compared to 7.9% of males (OR 0.86, 95% CI 0.75-0.97, Conclusion: While treatment differences between sexes existed in the data and were apparent in univariate analysis, no significant difference was seen in multivariate analysis once stroke risk factors, age, NIHSS score and admitting diagnosis were taken into consideration in the telestroke setting. Differences in rates of thrombolysis between sexes may therefore be reflective of differences in risk factors and symptomatology rather than a healthcare disparity.
Language	English
Publishing date	2023-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2023.1203502
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Article ; Online: Robot-Assisted Transcranial Doppler Versus Transthoracic Echocardiography for Right to Left Shunt Detection.

Rubin, Mark N / Shah, Ruchir / Devlin, Thomas / Youn, Teddy S / Waters, Michael F / Volpi, John J / Stayman, Aaron / Douville, Colleen M / Lowenkopf, Ted / Tsivgoulis, Georgios / Alexandrov, Andrei V

Stroke

2023 Volume 54, Issue 11, Page(s) 2842–2850

Abstract: Background: Right to left shunt (RLS), including patent foramen ovale, is a recognized risk factor for stroke. RLS/patent foramen ovale diagnosis is made by transthoracic echocardiography (TTE), which is insensitive, transesophageal echocardiography, ... ...

Abstract	Background: Right to left shunt (RLS), including patent foramen ovale, is a recognized risk factor for stroke. RLS/patent foramen ovale diagnosis is made by transthoracic echocardiography (TTE), which is insensitive, transesophageal echocardiography, which is invasive, and transcranial Doppler (TCD), which is noninvasive and accurate but scarce. Methods: We conducted a prospective, single-arm device clinical trial of robot-assisted TCD (raTCD) versus TTE for RLS diagnosis at 6 clinical sites in patients who presented with an event suspicious for embolic cerebrovascular ischemia from October 6, 2020 to October 20, 2021. raTCD was performed with standard TCD bubble study technique. TTE bubble study was performed per local standards. The primary outcome was rate of RLS detection by raTCD versus TTE. Results: A total of 154 patients were enrolled, 129 evaluable (intent to scan) and 121 subjects had complete data per protocol. In the intent to scan cohort, mean age was 60±15 years, 47% were women, and all qualifying events were diagnosed as ischemic stroke or transient ischemic attack. raTCD was positive for RLS in 82 subjects (64%) and TTE was positive in 26 (20%; absolute difference 43.4% [95% CI, 35.2%-52.0%]; Conclusions: raTCD was safe and ≈3 times more likely to diagnose RLS than TTE. TTE completely missed or underdiagnosed two thirds of large shunts diagnosed by raTCD. The raTCD device, used by health professionals with no prior TCD training, may allow providers to achieve the known sensitivity of TCD for RLS and patent foramen ovale detection without the need for an experienced operator to perform the test. Pending confirmatory studies, TCD appears to be the superior screen for RLS compared with TTE (funded by NeuraSignal). Registration: URL: https://www. Clinicaltrials: gov; Unique identifier: NCT04604015.
MeSH term(s)	Aged ; Female ; Humans ; Male ; Middle Aged ; Echocardiography ; Echocardiography, Transesophageal ; Foramen Ovale, Patent/complications ; Prospective Studies ; Robotics ; Stroke/etiology ; Ultrasonography, Doppler, Transcranial
Language	English
Publishing date	2023-10-05
Publishing country	United States
Document type	Clinical Trial ; Journal Article
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.123.043380
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Zs.A 448: Show issues

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Article ; Online: The impact of race and ethnicity on acute telestroke care: A multistate experience.

McDonald, Mark / Sevilis, Theresa / Boudreau, Michelle / Chen, Hsiong / Boyd, Caitlyn / Avila, Amanda / Zaman, Mohammed / Heath, Gregory / Gao, Lan / Devlin, Thomas

Journal of telemedicine and telecare

2023 , Page(s) 1357633X231166028

Abstract: Introduction: Previous analyses suggest that ethnic and racial differences exist in acute stroke care including thrombolytic treatment rates. The current study evaluates ethnic or racial differences in acute stroke treatment within a multi-state ... ...

Abstract	Introduction: Previous analyses suggest that ethnic and racial differences exist in acute stroke care including thrombolytic treatment rates. The current study evaluates ethnic or racial differences in acute stroke treatment within a multi-state telestroke program. Methods: Acute telestroke consultations seen in the Emergency Department in 203 facilities and 23 states were extracted from the Telecare by TeleSpecialists Results: The current study included 13,221 acute telestroke consultations consisting of 9890 White, 2048 Black, and 1283 patients classified as Other. A total of 934 patients were Hispanic and 12,287 patients were non-Hispanic. There were no statistically significant differences noted in thrombolytic treatment rates when comparing White (7.9%) patients with non-White patients (7.4%), Conclusions: Contrary to previous reports, we failed to detect any significant differences in thrombolytic treatment rates and DTN times by race or ethnicity among stroke patients in a multistate telestroke program. These findings support the hypothesis that telestroke may mitigate racial and ethnic disparities which may be attributable to local variability in stroke procedures or access to healthcare.
Language	English
Publishing date	2023-04-18
Publishing country	England
Document type	Journal Article
ZDB-ID	1340281-x
ISSN	1758-1109 ; 1357-633X
ISSN (online)	1758-1109
ISSN	1357-633X
DOI	10.1177/1357633X231166028
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