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  • 11
    Online Resource
    Online Resource
    Evaluation of lupus anticoagulant, damage, and remission as predictors of pregnancy complications in systemic lupus erythematosus: the French GR2 study
    Oxford University Press (OUP) ; 2022
    In:  Rheumatology Vol. 61, No. 9 ( 2022-08-30), p. 3657-3666
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 61, No. 9 ( 2022-08-30), p. 3657-3666
    Abstract: The specific roles of remission status, lupus low disease activity state (LLDAS), and damage accrual on the prognosis of pregnancies in women with SLE are unknown. We analysed their impact on maternal flares and adverse pregnancy outcomes (APOs). Methods We evaluated all women (≥18 years) with SLE enrolled in the prospective GR2 study with an ongoing singleton pregnancy at 12 weeks (one pregnancy/woman). Several sets of criteria were used to define remission, disease activity and damage. APOs included: foetal/neonatal death, placental insufficiency with preterm delivery and small-for-gestational-age birth weight. First trimester maternal and disease features were tested as predictors of maternal flares and APOs. Results The study included 238 women (98.3% on hydroxychloroquine (HCQ)) with 230 live births. Thirty-five (14.7%) patients had at least one flare during the second/third trimester. At least one APOs occurred in 34 (14.3%) women. Hypocomplementemia in the first trimester was the only factor associated with maternal flares later in pregnancy (P=0.02), while several factors were associated with APOs. In the logistic regression models, damage by SLICC-Damage Index [odds ratio (OR) 1.8, 95% CI: 1.1, 2.9 for model 1 and OR 1.7, 95% CI: 1.1, 2.8 for model 2] and lupus anticoagulant (LA, OR 4.2, 95% CI: 1.8, 9.7 for model 1; OR 3.7, 95% CI: 1.6, 8.7 for model 2) were significantly associated with APOs. Conclusion LA and damage at conception were predictors of APOs, and hypocomplementemia in the first trimester was associated with maternal flares later in pregnancy in this cohort of pregnant patients mostly with well-controlled SLE treated with HCQ. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT02450396.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/keab943
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474143-X
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  • 12
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    Online Resource
    The Effect of Microgravity on Central Aortic Blood Pressure
    Oxford University Press (OUP) ; 2018
    In:  American Journal of Hypertension Vol. 31, No. 11 ( 2018-10-15), p. 1183-1189
    Details
    In: American Journal of Hypertension, Oxford University Press (OUP), Vol. 31, No. 11 ( 2018-10-15), p. 1183-1189
    Abstract: Blood pressure has been traditionally measured at peripheral arteries. In the past decade, evidence has grown that central aortic blood pressure may be a more powerful predictor for cardiovascular events, but data on its regulation are rare. The present work examines the impact of microgravity on central blood pressure for the first time. METHODS We performed 7 parabolic flights with 22 seconds of weightlessness in each parabola. Hemodynamic parameters including central systolic blood pressure were measured noninvasively in a free-floating position in 20 healthy subjects (19–43 years of age). RESULTS Arterial elasticity at rest was normal in all participants (augmentation index 14% (interquartile range (IQR) 10–22), pulse wave velocity 5.2 m/s (IQR 5.0–5.4)). Transition of 1g to 0g led to a significant increase of central systolic blood pressure from 124 (IQR 118–133) to 127 (IQR 119–133) mm Hg (P = 0.017). Cardiac index augmented significantly from 2.5 (IQR 2.2–2.8) to 2.7 (IQR 2.3–3.0) l/min/m2 (P & lt; 0.001), while peripheral vascular resistance showed a decrease from 1.30 (IQR 1.14–1.48) to 1.25 (IQR 1.15–1.40) s × mm Hg/ml (P = 0.037). Peripheral systolic blood pressure did not change significantly (P & gt; 0.05). CONCLUSION Whereas there is a multitude of studies on the effects of microgravity on peripheral blood pressure, this study provides first data on central aortic blood pressure. An acute loss of gravity leads to a central blood volume shift with an augmentation of cardiac output. In healthy subjects with normal arterial stiffness, the compensatory decrease of peripheral resistance does not outweigh this effect resulting in an increase of central blood pressure.
    Type of Medium: Online Resource
    ISSN: 0895-7061 , 1941-7225
    URL: Article
    DOI: 10.1093/ajh/hpy119
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 1479505-X
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  • 13
    Online Resource
    Online Resource
    Adaption of human antibody λ and κ light chain architectures to CDR repertoires
    Oxford University Press (OUP) ; 2019
    In:  Protein Engineering, Design and Selection Vol. 32, No. 3 ( 2019-12-13), p. 109-127
    Details
    In: Protein Engineering, Design and Selection, Oxford University Press (OUP), Vol. 32, No. 3 ( 2019-12-13), p. 109-127
    Abstract: Monoclonal antibodies bind with high specificity to a wide range of diverse antigens, primarily mediated by their hypervariable complementarity determining regions (CDRs). The defined antigen binding loops are supported by the structurally conserved β-sandwich framework of the light chain (LC) and heavy chain (HC) variable regions. The LC genes are encoded by two separate loci, subdividing the entity of antibodies into kappa (LCκ) and lambda (LCλ) isotypes that exhibit distinct sequence and conformational preferences. In this work, a diverse set of techniques were employed including machine learning, force field analysis, statistical coupling analysis and mutual information analysis of a non-redundant antibody structure collection. Thereby, it was revealed how subtle changes between the structures of LCκ and LCλ isotypes increase the diversity of antibodies, extending the predetermined restrictions of the general antibody fold and expanding the diversity of antigen binding. Interestingly, it was found that the characteristic framework scaffolds of κ and λ are stabilized by diverse amino acid clusters that determine the interplay between the respective fold and the embedded CDR loops. In conclusion, this work reveals how antibodies use the remarkable plasticity of the beta-sandwich Ig fold to incorporate a large diversity of CDR loops.
    Type of Medium: Online Resource
    ISSN: 1741-0126 , 1741-0134
    URL: Article
    DOI: 10.1093/protein/gzz012
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1466729-0
    SSG: 12
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  • 14
    Online Resource
    Online Resource
    The impact of aerobic and isometric exercise on different measures of dysfunctional high-density lipoprotein in patients with hypertension
    Oxford University Press (OUP) ; 2019
    In:  European Journal of Preventive Cardiology Vol. 26, No. 12 ( 2019-08), p. 1301-1309
    Details
    In: European Journal of Preventive Cardiology, Oxford University Press (OUP), Vol. 26, No. 12 ( 2019-08), p. 1301-1309
    Abstract: Exercise training increases high-density lipoprotein (HDL) cholesterol, but its effect on HDL function is unclear. In hypertensives, exercise improves endothelial dysfunction, which is related to HDL function. In the present study, we assess for the first time the effects of different exercise modalities on two cell-free assays of HDL function. Design The study was conducted as a prospective randomized controlled trial in 75 hypertensive patients. Methods Patients were randomized in three groups: (a) handgrip isometric training five times weekly; (b) placebo-handgrip; and (c) aerobic exercise training at least three times per week. HDL function was assessed in serum samples at baseline and after 12 weeks of training by two independent assays that determine the proinflammatory phenotype (haptoglobin content) of a specific amount of HDL (Haptoglobin-HDL [HPHDL]) and oxidized HDL (HDLox) as a measure of reduced antioxidant function of HDL. HDL function measures were normalized by the measures of a pooled control of sera from healthy participants and by HDL-C levels (normalized ratio, no units). Results Aerobic exercise led to significant reduction of the HDLox from 0.99 ± 0.27 to 0.90 ± 0.29 (no units, p = 0.03). The HPHDL did not change in any training group. Changes of HDLox correlated with reduction of the systolic blood pressure only after aerobic exercise ( R = 0.64, p = 0.03). Conclusions Aerobic but not isometric exercise improves the antioxidant function of HDL in patients with hypertension. This improvement correlates positively with reductions of blood pressure.
    Type of Medium: Online Resource
    ISSN: 2047-4873 , 2047-4881
    URL: Article
    DOI: 10.1177/2047487319848199
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2646239-4
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  • 15
    Online Resource
    Online Resource
    Flexible-meccano: a tool for the generation of explicit ensemble descriptions of intrinsically disordered proteins and their associated experimental observables
    Oxford University Press (OUP) ; 2012
    In:  Bioinformatics Vol. 28, No. 11 ( 2012-06-01), p. 1463-1470
    Details
    In: Bioinformatics, Oxford University Press (OUP), Vol. 28, No. 11 ( 2012-06-01), p. 1463-1470
    Abstract: Motivation: Intrinsically disordered proteins (IDPs) represent a significant fraction of the human proteome. The classical structure function paradigm that has successfully underpinned our understanding of molecular biology breaks down when considering proteins that have no stable tertiary structure in their functional form. One convenient approach is to describe the protein in terms of an equilibrium of rapidly inter-converting conformers. Currently, tools to generate such ensemble descriptions are extremely rare, and poorly adapted to the prediction of experimental data. Results: We present flexible-meccano—a highly efficient algorithm that generates ensembles of molecules, on the basis of amino acid-specific conformational potentials and volume exclusion. Conformational sampling depends uniquely on the primary sequence, with the possibility of introducing additional local or long-range conformational propensities at an amino acid-specific resolution. The algorithm can also be used to calculate expected values of experimental parameters measured at atomic or molecular resolution, such as nuclear magnetic resonance (NMR) and small angle scattering, respectively. We envisage that flexible-meccano will be useful for researchers who wish to compare experimental data with those expected from a fully disordered protein, researchers who see experimental evidence of deviation from ‘random coil’ behaviour in their protein, or researchers who are interested in working with a broad ensemble of conformers representing the flexibility of the IDP of interest. Availability: A fully documented multi-platform executable is provided, with examples, at http://www.ibs.fr/science-213/scientific-output/software/flexible-meccano/ Contact:  martin.blackledge@ibs.fr
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    URL: Article
    DOI: 10.1093/bioinformatics/bts172
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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