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  1. Article: Microsecond melting and revitrification of cryo samples with a correlative light-electron microscopy approach.

    Bongiovanni, Gabriele / Harder, Oliver F / Drabbels, Marcel / Lorenz, Ulrich J

    Frontiers in molecular biosciences

    2022  Volume 9, Page(s) 1044509

    Abstract: We have recently introduced a novel approach to time-resolved cryo-electron microscopy (cryo-EM) that affords microsecond time resolution. It involves melting a cryo sample with a laser beam to allow dynamics of the embedded particles to occur. Once the ... ...

    Abstract We have recently introduced a novel approach to time-resolved cryo-electron microscopy (cryo-EM) that affords microsecond time resolution. It involves melting a cryo sample with a laser beam to allow dynamics of the embedded particles to occur. Once the laser beam is switched off, the sample revitrifies within just a few microseconds, trapping the particles in their transient configurations, which can subsequently be imaged to obtain a snap shot of the dynamics at this point in time. While we have previously performed such experiments with a modified transmission electron microscope, we here demonstrate a simpler implementation that uses an optical microscope. We believe that this will make our technique more easily accessible and hope that it will encourage other groups to apply microsecond time-resolved cryo-EM to study the fast dynamics of a variety of proteins.
    Language English
    Publishing date 2022-11-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2022.1044509
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Electron diffraction of deeply supercooled water in no man's land.

    Krüger, Constantin R / Mowry, Nathan J / Bongiovanni, Gabriele / Drabbels, Marcel / Lorenz, Ulrich J

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 2812

    Abstract: A generally accepted understanding of the anomalous properties of water will only emerge if it becomes possible to systematically characterize water in the deeply supercooled regime, from where the anomalies appear to emanate. This has largely remained ... ...

    Abstract A generally accepted understanding of the anomalous properties of water will only emerge if it becomes possible to systematically characterize water in the deeply supercooled regime, from where the anomalies appear to emanate. This has largely remained elusive because water crystallizes rapidly between 160 K and 232 K. Here, we present an experimental approach to rapidly prepare deeply supercooled water at a well-defined temperature and probe it with electron diffraction before crystallization occurs. We show that as water is cooled from room temperature to cryogenic temperature, its structure evolves smoothly, approaching that of amorphous ice just below 200 K. Our experiments narrow down the range of possible explanations for the origin of the water anomalies and open up new avenues for studying supercooled water.
    Language English
    Publishing date 2023-05-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-38520-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Near-atomic resolution reconstructions from in situ revitrified cryo samples.

    Bongiovanni, Gabriele / Harder, Oliver F / Voss, Jonathan M / Drabbels, Marcel / Lorenz, Ulrich J

    Acta crystallographica. Section D, Structural biology

    2023  Volume 79, Issue Pt 6, Page(s) 473–478

    Abstract: A microsecond time-resolved version of cryo-electron microscopy (cryo-EM) has recently been introduced to enable observation of the fast conformational motions of proteins. The technique involves locally melting a cryo sample with a laser beam to allow ... ...

    Abstract A microsecond time-resolved version of cryo-electron microscopy (cryo-EM) has recently been introduced to enable observation of the fast conformational motions of proteins. The technique involves locally melting a cryo sample with a laser beam to allow the proteins to undergo dynamics in the liquid phase. When the laser is switched off, the sample cools within just a few microseconds and revitrifies, trapping particles in their transient configurations, in which they can subsequently be imaged. Two alternative implementations of the technique have previously been described, using either an optical microscope or performing revitrification experiments in situ. Here, it is shown that it is possible to obtain near-atomic resolution reconstructions from in situ revitrified cryo samples. Moreover, the resulting map is indistinguishable from that obtained from a conventional sample within the spatial resolution. Interestingly, it is observed that revitrification leads to a more homogeneous angular distribution of the particles, suggesting that revitrification may potentially be used to overcome issues of preferred particle orientation.
    MeSH term(s) Cryoelectron Microscopy/methods ; Motion
    Language English
    Publishing date 2023-05-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2968623-4
    ISSN 2059-7983 ; 0907-4449
    ISSN (online) 2059-7983
    ISSN 0907-4449
    DOI 10.1107/S2059798323003431
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Advances in Microsecond Time-Resolved Cryo-Electron Microscopy.

    Bongiovanni, Gabriele / Harder, Oliver F / Barrass, Sarah V / Drabbels, Marcel / Lorenz, Ulrich J

    Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada

    2023  Volume 29, Issue Supplement_1, Page(s) 1007

    Language English
    Publishing date 2023-08-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 1385710-1
    ISSN 1435-8115 ; 1431-9276
    ISSN (online) 1435-8115
    ISSN 1431-9276
    DOI 10.1093/micmic/ozad067.506
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Treatable Traits in Systemic Sclerosis.

    Amati, Francesco / Bongiovanni, Gabriele / Tonutti, Antonio / Motta, Francesca / Stainer, Anna / Mangiameli, Giuseppe / Aliberti, Stefano / Selmi, Carlo / De Santis, Maria

    Clinical reviews in allergy & immunology

    2023  Volume 65, Issue 2, Page(s) 251–276

    Abstract: Systemic sclerosis (SSc) is a chronic systemic disease within the spectrum of connective tissue diseases, specifically characterized by vascular abnormalities and inflammatory and fibrotic involvement of the skin and internal organs resulting in high ... ...

    Abstract Systemic sclerosis (SSc) is a chronic systemic disease within the spectrum of connective tissue diseases, specifically characterized by vascular abnormalities and inflammatory and fibrotic involvement of the skin and internal organs resulting in high morbidity and mortality. The clinical phenotype of SSc is heterogeneous, and serum autoantibodies together with the extent of skin involvement have a predictive value in the risk stratification. Current recommendations include an organ-based management according to the predominant involvement with only limited individual factors included in the treatment algorithm. Similar to what has been proposed for other chronic diseases, we hypothesize that a "treatable trait" approach based on relevant phenotypes and endotypes could address the unmet needs in SSc stratification and treatment to maximize the outcomes. We provide herein a comprehensive review and a critical discussion of the literature regarding potential treatable traits in SSc, focusing on established and candidate biomarkers, with the purpose of setting the bases for a precision medicine-based approach. The discussion, structured based on the organ involvement, allows to conjugate the pathogenetic mechanisms of tissue injury with the proposed predictors, particularly autoantibodies and other serum biomarkers. Ultimately, we are convinced that precision medicine is the ideal guide to manage a complex condition such as SSc for which available treatments are largely unsatisfactory.
    Language English
    Publishing date 2023-08-21
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1239045-8
    ISSN 1559-0267 ; 1080-0549
    ISSN (online) 1559-0267
    ISSN 1080-0549
    DOI 10.1007/s12016-023-08969-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Vasoactive drugs for the treatment of pulmonary hypertension associated with interstitial lung diseases: a systematic review.

    Bongiovanni, Gabriele / Tonutti, Antonio / Stainer, Anna / Nigro, Mattia / Kellogg, Dean L / Nambiar, Anoop / Gramegna, Andrea / Mantero, Marco / Voza, Antonio / Blasi, Francesco / Aliberti, Stefano / Amati, Francesco

    BMJ open respiratory research

    2024  Volume 11, Issue 1

    Abstract: Objectives: Vasoactive drugs have exhibited clinical efficacy in addressing pulmonary arterial hypertension, manifesting a significant reduction in morbidity and mortality. Pulmonary hypertension may complicate advanced interstitial lung disease (PH-ILD) ...

    Abstract Objectives: Vasoactive drugs have exhibited clinical efficacy in addressing pulmonary arterial hypertension, manifesting a significant reduction in morbidity and mortality. Pulmonary hypertension may complicate advanced interstitial lung disease (PH-ILD) and is associated with high rates of disability, hospitalisation due to cardiac and respiratory illnesses, and mortality. Prior management hinged on treating the underlying lung disease and comorbidities. However, the INCREASE trial of inhaled treprostinil in PH-ILD has demonstrated that PH-ILD can be effectively treated with vasoactive drugs.
    Methods: This comprehensive systematic review examines the evidence for vasoactive drugs in the management of PH-ILD.
    Results: A total of 1442 pubblications were screened, 11 RCTs were considered for quantitative synthesis. Unfortunately, the salient studies are limited by population heterogeneity, short-term follow-up and the selection of outcomes with uncertain clinical significance.
    Conclusions: This systematic review underscores the necessity of establishing a precision medicine-oriented strategy, directed at uncovering and addressing the intricate cellular and molecular mechanisms that underlie the pathophysiology of PH-ILD.
    Prospero registration number: CRD42023457482.
    MeSH term(s) Humans ; Hypertension, Pulmonary/drug therapy ; Hypertension, Pulmonary/etiology ; Lung Diseases, Interstitial/complications ; Lung Diseases, Interstitial/drug therapy ; Lung Diseases, Interstitial/epidemiology ; Comorbidity
    Language English
    Publishing date 2024-03-13
    Publishing country England
    Document type Systematic Review ; Journal Article
    ZDB-ID 2736454-9
    ISSN 2052-4439 ; 2052-4439
    ISSN (online) 2052-4439
    ISSN 2052-4439
    DOI 10.1136/bmjresp-2023-002161
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  7. Article ; Online: Atomic-Resolution Imaging of Fast Nanoscale Dynamics with Bright Microsecond Electron Pulses.

    Olshin, Pavel K / Bongiovanni, Gabriele / Drabbels, Marcel / Lorenz, Ulrich J

    Nano letters

    2020  Volume 21, Issue 1, Page(s) 612–618

    Abstract: Atomic-resolution electron microscopy is a crucial tool to elucidate the structure of matter. Recently, fast electron cameras have added the time domain to high-resolution imaging, allowing static images to be acquired as movies from which sample drift ... ...

    Abstract Atomic-resolution electron microscopy is a crucial tool to elucidate the structure of matter. Recently, fast electron cameras have added the time domain to high-resolution imaging, allowing static images to be acquired as movies from which sample drift can later be removed computationally and enabling real-time observations of atomic-scale dynamics on the millisecond time scale. Even higher time resolution can be achieved with short electron pulses, yet their potential for atomic-resolution imaging remains unexplored. Here, we generate high-brightness microsecond electron pulses from a Schottky emitter whose current we briefly drive to near its limit. We demonstrate that drift-corrected imaging with such pulses can achieve atomic resolution in the presence of much larger amounts of drift than with a continuous electron beam. Moreover, such pulses enable atomic-resolution observations on the microsecond time scale, which we employ to elucidate the crystallization pathways of individual metal nanoparticles as well as the high-temperature transformation of perovskite nanocrystals.
    Language English
    Publishing date 2020-12-10
    Publishing country United States
    Document type Journal Article
    ISSN 1530-6992
    ISSN (online) 1530-6992
    DOI 10.1021/acs.nanolett.0c04184
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  8. Article ; Online: The fragmentation mechanism of gold nanoparticles in water under femtosecond laser irradiation.

    Bongiovanni, Gabriele / Olshin, Pavel K / Yan, Chengcheng / Voss, Jonathan M / Drabbels, Marcel / Lorenz, Ulrich J

    Nanoscale advances

    2021  Volume 3, Issue 18, Page(s) 5277–5283

    Abstract: Plasmonic nanoparticles in aqueous solution have long been known to fragment under irradiation with intense ultrafast laser pulses, creating progeny particles with diameters of a few nanometers. However, the mechanism of this process is still intensely ... ...

    Abstract Plasmonic nanoparticles in aqueous solution have long been known to fragment under irradiation with intense ultrafast laser pulses, creating progeny particles with diameters of a few nanometers. However, the mechanism of this process is still intensely debated, despite numerous experimental and theoretical studies. Here, we use
    Language English
    Publishing date 2021-08-02
    Publishing country England
    Document type Journal Article
    ISSN 2516-0230
    ISSN (online) 2516-0230
    DOI 10.1039/d1na00406a
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Unmet needs and perspectives in rheumatoid arthritis-associated interstitial lung disease: A critical review.

    Stainer, Anna / Tonutti, Antonio / De Santis, Maria / Amati, Francesco / Ceribelli, Angela / Bongiovanni, Gabriele / Torrisi, Chiara / Iacopino, Antonio / Mangiameli, Giuseppe / Aliberti, Stefano / Selmi, Carlo

    Frontiers in medicine

    2023  Volume 10, Page(s) 1129939

    Abstract: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis as the most common clinical manifestation, and interstitial lung disease (RA-ILD) represents one of the most common and potentially severe extra-articular ... ...

    Abstract Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis as the most common clinical manifestation, and interstitial lung disease (RA-ILD) represents one of the most common and potentially severe extra-articular features. Our current understanding of the mechanisms and predictors of RA-ILD is limited despite the demonstration that an early identification of progressive fibrosing forms is crucial to provide timely treatment with antifibrotic therapies. While high resolution computed tomography is the gold standard technique for the diagnosis and follow-up of RA-ILD, it has been hypothesized that serum biomarkers (including novel and rare autoantibodies), new imaging techniques such as ultrasound of the lung, or the application of innovative radiologic algorithms may help towards predicting and detecting early forms of diseases. Further, while new treatments are becoming available for idiopathic and connective tissue disease-associated forms of lung fibrosis, the treatment of RA-ILD remains anecdotal and largely unexplored. We are convinced that a better understanding of the mechanisms connecting RA with ILD in a subgroup of patients as well as the creation of adequate diagnostic pathways will be mandatory steps for a more effective management of this clinically challenging entity.
    Language English
    Publishing date 2023-03-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1129939
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