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| 2. |
- Dembele, Vamara, et al.
(författare)
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Correlation properties of a spatially quasi-incoherent imaging interferometer
- 2022
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Ingår i: Applied Optics. - : Optical Society of America. - 1559-128X .- 2155-3165. ; 61:19, s. 5806-5812
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Tidskriftsartikel (refereegranskat)abstract
- The depth-gating capacity of a spatially quasi-incoherent imaging interferometer is investigated in relation to the 3D correlation properties of diffraction field laser speckles. The system exploits a phase-stepped imaging Michelson-type interferometer in which spatially quasi-incoherent illumination is generated by passing an unexpanded laser beam through a rotating diffuser. Numerical simulations and optical experiments both verify that the depth-gating capacity of the imaging interferometer scales as ?/2NA2?λ/2NAp2, where ?λ is the wavelength of the laser and NA?NAp is the numerical aperture of the illumination. For a set depth gate of 150 µm, the depth-gating capacity of the interferometer is demonstrated by scanning a standard USAF target through the measurement volume. The results obtained show that an imaging tool of this kind is expected to provide useful capabilities for imaging through disturbing media and where a single wavelength is required.
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| 3. |
- Dembele, Vamara, et al.
(författare)
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Depth-resolved interferometric imaging utilizing a spatially quasi-incoherent light source
- 2022
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Ingår i: Proceedings Digital Holography and 3-D Imaging 2022. - : Optica Publishing Group.
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Konferensbidrag (refereegranskat)abstract
- An interferometric technique that utilize a spatially quasi-incoherent light source to perform interferometric measurements involving diffusely scattering objects is presented. The proposed technique is demonstrated with settings that give a depth gate of 90 µm.
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| 4. |
- Dembele, Vamara, et al.
(författare)
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Depth-resolved speckle correlation using quasi-incoherent imaging interferometry
- 2021
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Ingår i: Proceedings OSA Imaging and Applied Optics Congress 2021 (3D, COSI, DH, ISA, pcAOP). - : Optical Society of America.
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Konferensbidrag (refereegranskat)abstract
- We described a new concept on a depth-resolved investigation based on imaging interferometry. It exploits a quasi-incoherent imaging interferometry scheme and speckle image correlation techniques. We can spatially resolve a depth-gating capacity of the imaging interferometer with a resolution of around 26 µm.
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| 5. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 6. |
- Giordano, Luca, et al.
(författare)
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Essential Role of Mitochondrial Cytochrome c Oxidase Subunit 4 Isoform 2 (Cox4i2) for Acute Pulmonary Oxygen Sensing
- 2022
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Ingår i: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier. - 0005-2728 .- 1879-2650. ; 1863:Supplement
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial Cytochrome c Oxidase Subunit 4 Isoform 2 (Cox4i2) is essential for acute oxygen sensing and signaling in pulmonary arterial smooth muscle cells (PASMCs) by triggering the production of superoxide during acute hypoxia [1]. However, the molecular mechanism underlying Cox4i2-dependent oxygen sensing remains elusive. We analysed oxygen-dependent respiration by high resolution respirometry, redox changes of the electron transport chain (ETC) by RAMAN spectroscopy, and supercomplex formation by blue native gel analysis of PASMCs isolated from wild type (WT) and Cox4i2-/- mice. To understand the role of Cox4i2-specific cysteine residues we determined hypoxia-induced superoxide production and oxygen affinity in a mouse epithelial cell line (CMT167 cells) overexpressing either Cox4i1, or WT Cox4i2, or Cox4i2 mutants (C41S, C55A, C109S). Respiration and supercomplex formation were similar in WT and Cox4i2-/- PASMCs. Interestingly, hypoxia-induced reduction of ETC components (NADH, ubiquinol, and reduced cytochrome c) was prevented in Cox4i2-/- PASMCs. CMT167 cells expressing either Cox4i1, or Cox4i2 mutants lacked hypoxia-induced superoxide release, which was detected only in cells expressing WT Cox4i2. In contrast, overexpression of Cox4i1, or Cox4i2, or Cox4i2 mutants did not affect oxygen affinity. Our findings suggest that Cox4i2 does not alter superoxide production by rearrangement of supercomplexes, whereas its specific cysteines are needed for the superoxide release. In conclusion, Cox4i2 plays a major role in the hypoxia-induced reduction of ETC components, likely mediated through its redox-active cysteine residues.
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| 7. |
- Knoepp, Fenja, et al.
(författare)
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A Microfluidic System for Simultaneous Raman Spectroscopy, Patch-Clamp Electrophysiology, and Live-Cell Imaging to Study Key Cellular Events of Single Living Cells in Response to Acute Hypoxia
- 2021
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Ingår i: Small Methods. - : John Wiley & Sons. - 2366-9608. ; 5:10
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Tidskriftsartikel (refereegranskat)abstract
- The ability to sense changes in oxygen availability is fundamentally important for the survival of all aerobic organisms. However, cellular oxygen sensing mechanisms and pathologies remain incompletely understood and studies of acute oxygen sensing, in particular, have produced inconsistent results. Current methods cannot simultaneously measure the key cellular events in acute hypoxia (i.e., changes in redox state, electrophysiological properties, and mechanical responses) at controlled partial pressures of oxygen (pO2). The lack of such a comprehensive method essentially contributes to the discrepancies in the field. A sealed microfluidic system that combines i) Raman spectroscopy, ii) patch-clamp electrophysiology, and iii) live-cell imaging under precisely controlled pO2 have therefore been developed. Merging these modalities allows label-free and simultaneous observation of oxygen-dependent alterations in multiple cellular redox couples, membrane potential, and cellular contraction. This technique is adaptable to any cell type and allows in-depth insight into acute oxygen sensing processes underlying various physiologic and pathologic conditions.
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| 8. |
- Knoepp, F., et al.
(författare)
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Development of a Gas-Tight Microfluidic System for Raman Sensing of Single Pulmonary Arterial Smooth Muscle Cells Under Normoxic/Hypoxic Conditions
- 2018
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Ingår i: Sensors. - Basel, Switzerland : MDPI. - 1424-8220. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Acute hypoxia changes the redox-state of pulmonary arterial smooth muscle cells (PASMCs). This might influence the activity of redox-sensitive voltage-gated K⁺-channels (Kv-channels) whose inhibition initiates hypoxic pulmonary vasoconstriction (HPV). However, the molecular mechanism of how hypoxia-or the subsequent change in the cellular redox-state-inhibits Kv-channels remains elusive. For this purpose, a new multifunctional gas-tight microfluidic system was developed enabling simultaneous single-cell Raman spectroscopic studies (to sense the redox-state under normoxic/hypoxic conditions) and patch-clamp experiments (to study the Kv-channel activity). The performance of the system was tested by optically recording the O₂-content and taking Raman spectra on murine PASMCs under normoxic/hypoxic conditions or in the presence of H₂O₂. Oxygen sensing showed that hypoxic levels in the gas-tight microfluidic system were achieved faster, more stable and significantly lower compared to a conventional open system (1.6 ± 0.2%, respectively 6.7 ± 0.7%, n = 6, p < 0.001). Raman spectra revealed that the redistribution of biomarkers (cytochromes, FeS, myoglobin and NADH) under hypoxic/normoxic conditions were improved in the gas-tight microfluidic system (p-values from 0.00% to 16.30%) compared to the open system (p-value from 0.01% to 98.42%). In conclusion, the new redox sensor holds promise for future experiments that may elucidate the role of Kv-channels during HPV.
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