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  1. Article: Watching a signaling protein function: What has been learned over four decades of time-resolved studies of photoactive yellow protein.

    Schotte, Friedrich / Cho, Hyun Sun / Dyda, Fred / Anfinrud, Philip

    Structural dynamics (Melville, N.Y.)

    2024  Volume 11, Issue 2, Page(s) 21303

    Abstract: Photoactive yellow protein (PYP) is a signaling protein whose internal p-coumaric acid chromophore undergoes reversible, light- ... ...

    Abstract Photoactive yellow protein (PYP) is a signaling protein whose internal p-coumaric acid chromophore undergoes reversible, light-induced
    Language English
    Publishing date 2024-04-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2758684-4
    ISSN 2329-7778
    ISSN 2329-7778
    DOI 10.1063/4.0000241
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: From Milliseconds to Minutes: Melittin Self-Assembly from Concerted Non-Equilibrium Pressure-Jump and Equilibrium Relaxation Nuclear Magnetic Resonance.

    Gelenter, Martin D / Yau, Wai-Ming / Anfinrud, Philip A / Bax, Ad

    The journal of physical chemistry letters

    2024  Volume 15, Issue 7, Page(s) 1930–1935

    Abstract: Non-equilibrium kinetics techniques like pressure-jump nuclear magnetic resonance (NMR) are powerful in tracking changes in oligomeric populations and are not limited by relaxation rates for the time scales of exchange that can be probed. However, these ... ...

    Abstract Non-equilibrium kinetics techniques like pressure-jump nuclear magnetic resonance (NMR) are powerful in tracking changes in oligomeric populations and are not limited by relaxation rates for the time scales of exchange that can be probed. However, these techniques are less sensitive to minor, transient populations than are Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments. We integrated non-equilibrium pressure-jump and equilibrium CPMG relaxation dispersion data to fully map the kinetic landscape of melittin tetramerization. While monomeric peptides weakly form dimers (
    MeSH term(s) Melitten ; Nuclear Magnetic Resonance, Biomolecular/methods ; Models, Molecular ; Magnetic Resonance Spectroscopy ; Magnetic Resonance Imaging
    Chemical Substances Melitten (20449-79-0)
    Language English
    Publishing date 2024-02-12
    Publishing country United States
    Document type Journal Article
    ISSN 1948-7185
    ISSN (online) 1948-7185
    DOI 10.1021/acs.jpclett.3c03563
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Proline Peptide Bond Isomerization in Ubiquitin Under Folding and Denaturing Conditions by Pressure-Jump NMR.

    Masoumzadeh, Elahe / Ying, Jinfa / Baber, James L / Anfinrud, Philip / Bax, Ad

    Journal of molecular biology

    2024  Volume 436, Issue 11, Page(s) 168587

    Abstract: Proline isomerization is widely recognized as a kinetic bottleneck in protein folding, amplified for proteins rich in Pro residues. We introduced repeated hydrostatic pressure jumps between native and pressure-denaturing conditions inside an NMR sample ... ...

    Abstract Proline isomerization is widely recognized as a kinetic bottleneck in protein folding, amplified for proteins rich in Pro residues. We introduced repeated hydrostatic pressure jumps between native and pressure-denaturing conditions inside an NMR sample cell to study proline isomerization in the pressure-sensitized L50A ubiquitin mutant. Whereas in two unfolded heptapeptides, X-Pro peptide bonds isomerized ca 1.6-fold faster at 1 bar than at 2.5 kbar, for ubiquitin ca eight-fold faster isomerization was observed for Pro-38 and ca two-fold for Pro-19 and Pro-37 relative to rates measured in the pressure-denatured state. Activation energies for isomerization in pressure-denatured ubiquitin were close to literature values of 20 kcal/mole for denatured polypeptides but showed a substantial drop to 12.7 kcal/mole for Pro-38 at atmospheric pressure. For ubiquitin isomers with a cis E18-P19 peptide bond, the 1-bar NMR spectrum showed sharp resonances with near random coil chemical shifts for the C-terminal half of the protein, characteristic of an unfolded chain, while most of the N-terminal residues were invisible due to exchange broadening, pointing to a metastable partially folded state for this previously recognized 'folding nucleus'. For cis-P37 isomers, a drop in pressure resulted in the rapid loss of nearly all unfolded-state NMR resonances, while the recovery of native state intensity revealed a slow component attributed to cis → trans isomerization of P37. This result implies that the NMR-invisible cis-P37 isomer adopts a molten globule state that encompasses the entire length of the ubiquitin chain, suggestive of a structure that mostly resembles the folded state.
    Language English
    Publishing date 2024-04-23
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2024.168587
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Visualizing endoscopy-generated aerosols with laser light scattering (with videos).

    Passi, Monica / Stadnytskyi, Valentyn / Anfinrud, Philip / Koh, Christopher

    Gastrointestinal endoscopy

    2022  Volume 96, Issue 6, Page(s) 1072–1077

    Abstract: Background and aims: Upper GI endoscopy is speculated to be an aerosol-generating procedure (AGP). Robust evidence exists for aerosol transmission of severe acute respiratory syndrome coronavirus 2. The quality of data available confirming aerosol ... ...

    Abstract Background and aims: Upper GI endoscopy is speculated to be an aerosol-generating procedure (AGP). Robust evidence exists for aerosol transmission of severe acute respiratory syndrome coronavirus 2. The quality of data available confirming aerosol generation during GI endoscopy is limited. We aimed to objectively demonstrate that GI endoscopy is an AGP and illustrate the mechanism by which the greatest risk for aerosolization of droplets during endoscopy may occur.
    Methods: Aerosolized droplets generated during insertion and withdrawal of an endoscope and with passage of various tools through the endoscopic working channel using 2 experimental apparatuses modeling an upper GI tract (ie, a fluid-filled tube and a lamb esophagus) were qualitatively assessed by laser light scattering.
    Results: Insertion and withdrawal of the upper endoscope into the upper GI tract models generated numerous aerosolized particles. A large number of brightly scattering particles were observed at the site of insertion and withdrawal of the endoscope. Passage of a cytology brush, biopsy forceps, and hemostatic clip through the working endoscope channel also generated aerosolized particles but in fewer numbers. There was no significant variation in quantity or brightness of droplets generated on testing different biopsy valve cap models or when suctioning fluid with an open versus closed biopsy valve cap. These results were reproducible over several trials.
    Conclusions: We illustrate in an objective manner that upper GI endoscopy is an AGP. These findings may have implications for transmission of infectious airborne pathogens outside of severe acute respiratory syndrome coronavirus 2 and can help to inform guidance on appropriate personal protective equipment use and other measures for transmission risk mitigation during GI endoscopy.
    MeSH term(s) Animals ; Aerosolized Particles and Droplets/analysis ; Endoscopy, Gastrointestinal ; Lasers ; Light ; Sheep
    Chemical Substances Aerosolized Particles and Droplets
    Language English
    Publishing date 2022-08-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 391583-9
    ISSN 1097-6779 ; 0016-5107
    ISSN (online) 1097-6779
    ISSN 0016-5107
    DOI 10.1016/j.gie.2022.07.030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Hybrid measurement of respiratory aerosol reveals a dominant coarse fraction resulting from speech that remains airborne for minutes.

    Shen, Yang / Courtney, Joseph M / Anfinrud, Philip / Bax, Adriaan

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

    2022  Volume 119, Issue 26, Page(s) e2203086119

    Abstract: Accurate measurements of the size and quantity of aerosols generated by various human activities in different environments are required for efficacious mitigation strategies and accurate modeling of respiratory disease transmission. Previous studies of ... ...

    Abstract Accurate measurements of the size and quantity of aerosols generated by various human activities in different environments are required for efficacious mitigation strategies and accurate modeling of respiratory disease transmission. Previous studies of speech droplets, using standard aerosol instrumentation, reported very few particles larger than 5 μm. This starkly contrasts with the abundance of such particles seen in both historical slide deposition measurements and more recent light scattering observations. We have reconciled this discrepancy by developing an alternative experimental approach that addresses complications arising from nucleated condensation. Measurements reveal that a large volume fraction of speech-generated aerosol has diameters in the 5- to 20-μm range, making them sufficiently small to remain airborne for minutes, not hours. This coarse aerosol is too large to penetrate the lower respiratory tract directly, and its relevance to disease transmission is consistent with the vast majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections initiating in the upper respiratory tract. Our measurements suggest that in the absence of symptoms such as coughing or sneezing, the importance of speech-generated aerosol in the transmission of respiratory diseases is far greater than generally recognized.
    MeSH term(s) COVID-19/transmission ; Humans ; Particle Size ; Respiratory Aerosols and Droplets ; Respiratory Tract Infections/transmission ; SARS-CoV-2 ; Speech ; Time Factors
    Language English
    Publishing date 2022-06-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2203086119
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Time-resolved X-ray scattering studies of proteins.

    Cho, Hyun Sun / Schotte, Friedrich / Stadnytskyi, Valentyn / Anfinrud, Philip

    Current opinion in structural biology

    2021  Volume 70, Page(s) 99–107

    Abstract: Time-resolved small- and wide-angle X-ray scattering studies of proteins in solution based on the pump-probe approach unveil structural information from intermediates over a broad range of length and time scales. In spite of the promise of this ... ...

    Abstract Time-resolved small- and wide-angle X-ray scattering studies of proteins in solution based on the pump-probe approach unveil structural information from intermediates over a broad range of length and time scales. In spite of the promise of this methodology, only a fraction of the wealth of information encoded in scattering data has been extracted in studies performed thus far. Here, we discuss the methodology, summarize results from recent time-resolved X-ray scattering studies, and examine the potential to extract additional information from these scattering curves.
    MeSH term(s) Proteins ; Scattering, Small Angle ; X-Ray Diffraction ; X-Rays
    Chemical Substances Proteins
    Language English
    Publishing date 2021-06-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 1068353-7
    ISSN 1879-033X ; 0959-440X
    ISSN (online) 1879-033X
    ISSN 0959-440X
    DOI 10.1016/j.sbi.2021.05.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Experimental NOE, Chemical Shift, and Proline Isomerization Data Provide Detailed Insights into Amelotin Oligomerization.

    Chiliveri, Sai Chaitanya / Shen, Yang / Baber, James L / Ying, Jinfa / Sagar, Vatsala / Wistow, Graeme / Anfinrud, Philip / Bax, Ad

    Journal of the American Chemical Society

    2023  Volume 145, Issue 32, Page(s) 18063–18074

    Abstract: Amelotin is an intrinsically disordered protein (IDP) rich in Pro residues and is involved in hydroxyapatite mineralization. It rapidly oligomerizes under physiological conditions of pH and pressure but reverts to its monomeric IDP state at elevated ... ...

    Abstract Amelotin is an intrinsically disordered protein (IDP) rich in Pro residues and is involved in hydroxyapatite mineralization. It rapidly oligomerizes under physiological conditions of pH and pressure but reverts to its monomeric IDP state at elevated pressure. We identified a 105-residue segment of the protein that becomes ordered upon oligomerization, and we used pressure-jump NMR spectroscopy to measure long-range NOE contacts that exist exclusively in the oligomeric NMR-invisible state. The kinetics of oligomerization and dissociation were probed at the residue-specific level, revealing that the oligomerization process is initiated in the C-terminal half of the segment. Using pressure-jump NMR, the degree of order in the oligomer at the sites of Pro residues was probed by monitoring changes in
    MeSH term(s) Protein Conformation ; Isomerism ; Proline/chemistry ; Proteins ; Magnetic Resonance Spectroscopy/methods
    Chemical Substances Proline (9DLQ4CIU6V) ; Proteins
    Language English
    Publishing date 2023-08-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.3c05710
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Could SARS-CoV-2 be transmitted via speech droplets?

    Anfinrud, Philip / Bax, Christina E / Stadnytskyi, Valentyn / Bax, Adriaan

    medRxiv : the preprint server for health sciences

    2020  

    Keywords covid19
    Language English
    Publishing date 2020-04-06
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2020.04.02.20051177
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: SARS-CoV-2 transmission via speech-generated respiratory droplets.

    Bax, Adriaan / Bax, Christina E / Stadnytskyi, Valentyn / Anfinrud, Philip

    The Lancet. Infectious diseases

    2020  Volume 21, Issue 3, Page(s) 318

    MeSH term(s) COVID-19 ; Humans ; SARS-CoV-2 ; Speech
    Keywords covid19
    Language English
    Publishing date 2020-09-11
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2061641-7
    ISSN 1474-4457 ; 1473-3099
    ISSN (online) 1474-4457
    ISSN 1473-3099
    DOI 10.1016/S1473-3099(20)30726-X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Audio / Video ; Online: We must learn more about the transmission of COVID-19 via speech droplets

    Christina Bax / Valentyn Stadnytskyi / Philip Anfinrud / Ad Bax

    2020  

    Abstract: Video clips acquired while speaking with and without a face ... ...

    Abstract Video clips acquired while speaking with and without a face mask
    Keywords COVID-19 ; covid19
    Language English
    Publishing date 2020-03-29
    Publishing country eu
    Document type Audio / Video ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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