| 1. |
- Wiessner, M., et al.
(författare)
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Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia
- 2021
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144:5, s. 1422-1434
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Tidskriftsartikel (refereegranskat)abstract
- Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays. © 2021 The Author(s).
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| 2. |
- Lee, J. W.L., et al.
(författare)
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Time-resolved relaxation and fragmentation of polycyclic aromatic hydrocarbons investigated in the ultrafast XUV-IR regime
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Polycyclic aromatic hydrocarbons (PAHs) play an important role in interstellar chemistry and are subject to high energy photons that can induce excitation, ionization, and fragmentation. Previous studies have demonstrated electronic relaxation of parent PAH monocations over 10-100 femtoseconds as a result of beyond-Born-Oppenheimer coupling between the electronic and nuclear dynamics. Here, we investigate three PAH molecules: fluorene, phenanthrene, and pyrene, using ultrafast XUV and IR laser pulses. Simultaneous measurements of the ion yields, ion momenta, and electron momenta as a function of laser pulse delay allow a detailed insight into the various molecular processes. We report relaxation times for the electronically excited PAH*, PAH(+*) and PAH(2+*) states, and show the time-dependent conversion between fragmentation pathways. Additionally, using recoil-frame covariance analysis between ion images, we demonstrate that the dissociation of the PAH(2+) ions favors reaction pathways involving two-body breakup and/or loss of neutral fragments totaling an even number of carbon atoms. Polycyclic aromatic hydrocarbons play an important role in interstellar chemistry, where interaction with high energy photons can induce ionization and fragmentation reactions. Here the authors, with XUV-IR pump-probe experiments, investigate the ultrafast photoinduced dynamics of fluorene, phenanthrene and pyrene, providing insight into their preferred reaction channels.
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| 3. |
- Lee, J. W. L., et al.
(författare)
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The kinetic energy of PAH dication and trication dissociation determined by recoil-frame covariance map imaging
- 2022
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 24:38, s. 23096-23105
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the dissociation of dications and trications of three polycyclic aromatic hydrocarbons (PAHs), fluorene, phenanthrene, and pyrene. PAHs are a family of molecules ubiquitous in space and involved in much of the chemistry of the interstellar medium. In our experiments, ions are formed by interaction with 30.3 nm extreme ultraviolet (XUV) photons, and their velocity map images are recorded using a PImMS2 multi-mass imaging sensor. Application of recoil-frame covariance analysis allows the total kinetic energy release (TKER) associated with multiple fragmentation channels to be determined to high precision, ranging 1.94-2.60 eV and 2.95-5.29 eV for the dications and trications, respectively. Experimental measurements are supported by Born-Oppenheimer molecular dynamics (BOMD) simulations.
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| 4. |
- Manschwetus, B., et al.
(författare)
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Ultrafast ionization and fragmentation dynamics of polycyclic atomatic hydro-carbons by XUV radiation
- 2020
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Ingår i: Free Electron Laser. - : IOP Publishing. - 1742-6588. ; 1412
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Konferensbidrag (refereegranskat)abstract
- In the interstellar medium polycyclic aromatic hydrocarbon molecules (PAH) are exposed to strong ionizing radation leading to complex organic photochemistry. We investigated these ultrafast fragmentation reac-tions after ionization of the PAHs phenanthrene, fluorene and pyrene at a wavelength of 30.3 nm using pump probe spectroscopy at a free electron laser. We observe double ionization and afterwards hydrogen abstraction and acetylene loss with characteristic time scales for the reaction processes below one hundred femtoseconds.
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| 8. |
- Lodder, Paul, et al.
(författare)
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Type D Personality as a Risk Factor for Adverse Outcome in Patients With Cardiovascular Disease : An Individual Patient-Data Meta-analysis
- 2023
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Ingår i: Psychosomatic Medicine. - : Lippincott Williams & Wilkins. - 0033-3174 .- 1534-7796. ; 85:2, s. 188-202
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveType D personality, a joint tendency toward negative affectivity and social inhibition, has been linked to adverse events in patients with heart disease, although with inconsistent findings. Here, we apply an individual patient-data meta-analysis to data from 19 prospective cohort studies (N = 11,151) to investigate the prediction of adverse outcomes by type D personality in patients with acquired cardiovascular disease.MethodFor each outcome (all-cause mortality, cardiac mortality, myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, major adverse cardiac event, any adverse event), we estimated type D's prognostic influence and the moderation by age, sex, and disease type.ResultsIn patients with cardiovascular disease, evidence for a type D effect in terms of the Bayes factor (BF) was strong for major adverse cardiac event (BF = 42.5; odds ratio [OR] = 1.14) and any adverse event (BF = 129.4; OR = 1.15). Evidence for the null hypothesis was found for all-cause mortality (BF = 45.9; OR = 1.03), cardiac mortality (BF = 23.7; OR = 0.99), and myocardial infarction (BF = 16.9; OR = 1.12), suggesting that type D had no effect on these outcomes. This evidence was similar in the subset of patients with coronary artery disease (CAD), but inconclusive for patients with heart failure (HF). Positive effects were found for negative affectivity on cardiac and all-cause mortality, with the latter being more pronounced in male than female patients.ConclusionAcross 19 prospective cohort studies, type D predicts adverse events in patients with CAD, whereas evidence in patients with HF was inconclusive. In both patients with CAD and HF, we found evidence for a null effect of type D on cardiac and all-cause mortality.
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