| 1. |
|
|
| 2. |
- Gurgel-Giannetti, J., et al.
(författare)
-
A novel complex neurological phenotype due to a homozygous mutation in FDX2
- 2018
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 141, s. 2289-2298
-
Tidskriftsartikel (refereegranskat)abstract
- Defects in iron-sulphur [Fe-S] cluster biogenesis are increasingly recognized as causing neurological disease. Mutations in a number of genes that encode proteins involved in mitochondrial [Fe-S] protein assembly lead to complex neurological phenotypes. One class of proteins essential in the early cluster assembly are ferredoxins. FDX2 is ubiquitously expressed and is essential in the de novo formation of [2Fe-2S] clusters in humans. We describe and genetically define a novel complex neurological syndrome identified in two Brazilian families, with a novel homozygous mutation in FDX2. Patients were clinically evaluated, underwent MRI, nerve conduction studies, EMG and muscle biopsy. To define the genetic aetiology, a combination of homozygosity mapping and whole exome sequencing was performed. We identified six patients from two apparently unrelated families with autosomal recessive inheritance of a complex neurological phenotype involving optic atrophy and nystagmus developing by age 3, followed by myopathy and recurrent episodes of cramps, myalgia and muscle weakness in the first or second decade of life. Sensory-motor axonal neuropathy led to progressive distal weakness. MRI disclosed a reversible or partially reversible leukoencephalopathy. Muscle biopsy demonstrated an unusual pattern of regional succinate dehydrogenase and cytochrome c oxidase deficiency with iron accumulation. The phenotype was mapped in both families to the same homozygous missense mutation in FDX2 (c. 431C > T, p. P144L). The deleterious effect of the mutation was validated by real-time reverse transcription polymerase chain reaction and western blot analysis, which demonstrated normal expression of FDX2 mRNA but severely reduced expression of FDX2 protein in muscle tissue. This study describes a novel complex neurological phenotype with unusual MRI and muscle biopsy features, conclusively mapped to a mutation in FDX2, which encodes a ubiquitously expressed mitochondrial ferredoxin essential for early [Fe-S] cluster biogenesis.
|
|
| 3. |
- Brahe, C. H., et al.
(författare)
-
Retention and response rates in 14 261 PsA patients starting TNF inhibitor treatment-results from 12 countries in EuroSpA
- 2020
-
Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 59:7, s. 1640-1650
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate TNF inhibitor (TNFi) retention and response rates in European biologic-naive patients with PsA. Methods. Prospectively collected data on PsA patients in routine care from 12 European registries were pooled. Heterogeneity in baseline characteristics between registries were explored (analysis of variance and pairwise comparison). Retention rates (Kaplan-Meier), clinical remission [28-joint count DAS (DAS28) <2.6; 28 joint Disease Activity index for Psoriatic Arthritis 4] and ACR criteria for 20% improvement (ACR20)/ACR50/ACR70 were calculated, including LUNDEX adjustment. Results. Overall, 14 261 patients with PsA initiated a first TNFi. Considerable heterogeneity of baseline characteristics between registries was observed. The median 12-month retention rate (95% CI) was 77% (76, 78%), ranging from 68 to 90% across registries. Overall, DAS28/28 joint Disease Activity index for Psoriatic Arthritis remission rates at 6 months were 56%/27% (LUNDEX: 45%/22%). Six-month ACR20/50/70 responses were 53%/38%/22%, respectively. In patients initiating a first TNFi after 2009 with registered fulfilment of ClASsification for Psoriatic ARthritis (CASPAR) criteria (n = 1980) or registered one or more swollen joint at baseline (n = 5803), the retention rates and response rates were similar to those found overall. Conclusion. Approximately half of >14 000 patients with PsA who initiated first TNFi treatment in routine care were in DAS28 remission after 6 months, and three-quarters were still on the drug after 1 year. Considerable heterogeneity in baseline characteristics and outcomes across registries was observed. The feasibility of creating a large European database of PsA patients treated in routine care was demonstrated, offering unique opportunities for research with real-world data.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- de Oliveira, Raphaela, et al.
(författare)
-
Water Nanochannels in Ultrathin Clinochlore Phyllosilicate Mineral with Ice-like Behavior
-
Ingår i: Journal of Physical Chemistry C. - 1932-7447.
-
Tidskriftsartikel (refereegranskat)abstract
- Water is the matrix of life, and its confinement in nanocavities is a central topic from geophysics to nanotribology. Phyllosilicate layered minerals provide natural nanocavities for water due to their capacity to hydrate by confining water molecules in the interlamellar space. However, the hydration of phyllosilicates at the nanoscale is not a fully understood process and depends on the geological specimens. In this work, we report the formation of aqueous nanochannels in the interlamellar space of ultrathin clinochlore phyllosilicate mineral using infrared scattering-type scanning near-field optical microscopy and Kelvin probe force microscopy. We demonstrate that nanoconfinement of water in clinochlore changes the overall mechanical, optical, and dielectric properties of the system. We propose a capacitive model that describes the dielectric response of the aqueous nanochannels. Our model is endorsed by a robust crystal truncation rod analysis of synchrotron X-ray diffraction data. We found that clinochlore termination combines hydrated structures ordered along the c-axis. We also find evidence of ice-like behavior of the water nanoconfined in clinochlore by Fourier-transform infrared spectroscopy. Notably, our work introduces clinochlore as a natural platform for water confinement in two-dimensional systems that can be engineered for several applications in the frontiers of nanotechnology.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
