| 1. |
- Coppo, Rosanna, et al.
(author)
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Is there long-term value of pathology scoring in immunoglobulin A nephropathy? : A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update
- 2020
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In: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 35:6, s. 1002-1009
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Journal article (peer-reviewed)abstract
- Background: It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up.Methods: In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1-10.8)].Results: In this extended analysis, M1, S1 and T1-T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%).Conclusion: Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.
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| 2. |
- Coppo, Rosanna, et al.
(author)
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Risk factors for progression in children and young adults with IgA nephropathy : an analysis of 261 cases from the VALIGA European cohort
- 2017
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In: Pediatric nephrology (Berlin, West). - : Springer Science and Business Media LLC. - 0931-041X .- 1432-198X. ; 32:1, s. 139-150
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Journal article (peer-reviewed)abstract
- There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. Data on 261 young patients [age < 23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared. In this cohort of 261 subjects aged < 23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged < 18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ae0.4 g/day/1.73 m(2) and an eGFR of < 90 ml/min/1.73 m(2) were determined to be risk factors in subjects with M0. Children aged < 16 years with M0 and well-preserved eGFR (> 90 ml/min/1.73 m(2)) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy. This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.
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| 3. |
- Jardine, Kolby J., et al.
(author)
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Within-plant isoprene oxidation confirmed by direct emissions of oxidation products methyl vinyl ketone and methacrolein
- 2012
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 18:3, s. 973-984
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Journal article (peer-reviewed)abstract
- Isoprene is emitted from many terrestrial plants at high rates, accounting for an estimated 1/3 of annual global volatile organic compound emissions from all anthropogenic and biogenic sources combined. Through rapid photooxidation reactions in the atmosphere, isoprene is converted to a variety of oxidized hydrocarbons, providing higher order reactants for the production of organic nitrates and tropospheric ozone, reducing the availability of oxidants for the breakdown of radiatively active trace gases such as methane, and potentially producing hygroscopic particles that act as effective cloud condensation nuclei. However, the functional basis for plant production of isoprene remains elusive. It has been hypothesized that in the cell isoprene mitigates oxidative damage during the stress-induced accumulation of reactive oxygen species (ROS), but the products of isoprene-ROS reactions in plants have not been detected. Using pyruvate-2-13C leaf and branch feeding and individual branch and whole mesocosm flux studies, we present evidence that isoprene (i) is oxidized to methyl vinyl ketone and methacrolein (iox) in leaves and that iox/i emission ratios increase with temperature, possibly due to an increase in ROS production under high temperature and light stress. In a primary rainforest in Amazonia, we inferred significant in plant isoprene oxidation (despite the strong masking effect of simultaneous atmospheric oxidation), from its influence on the vertical distribution of iox uptake fluxes, which were shifted to low isoprene emitting regions of the canopy. These observations suggest that carbon investment in isoprene production is larger than that inferred from emissions alone and that models of tropospheric chemistry and biotachemistryclimate interactions should incorporate isoprene oxidation within both the biosphere and the atmosphere with potential implications for better understanding both the oxidizing power of the troposphere and forest response to climate change.
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| 4. |
- Sakamoto, K., et al.
(author)
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Resolved Structure of the Arp 220 Nuclei at lambda approximate to 3 mm
- 2017
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 849:1
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Journal article (peer-reviewed)abstract
- We analyze the 3 mm emission of the ultraluminous infrared galaxy Arp 220 for the spatially resolved structure and the spectral properties of the merger nuclei. ALMA archival data at similar to 0.'' 05 resolution are used for extensive visibility fitting and deep imaging of the continuum emission. The data are fitted well by two concentric components for each nucleus, such as two Gaussians or one Gaussian plus one exponential disk. The larger components in the individual nuclei are similar in shape and extent, similar to 100-150 pc, to the centimeter wave emission due to supernovae. They are therefore identified with the known starburst nuclear disks. The smaller components in both nuclei have about a few 10 pc sizes and peak brightness temperatures (Tb) more than twice higher than those in previous single-Gaussian fitting. They correspond to the dust emission that we find centrally concentrated in both nuclei by subtracting the plasma emission measured at 33 GHz. The dust emission in the western nucleus is found to have a peak Tb approximate to 530 K and an FWHM of about 20 pc. This component is estimated to have a bolometric luminosity on the order of 1012.5L& and a 20 pc scale luminosity surface density 1015.5L& kpc-2. A luminous active galactic nucleus is a plausible energy source for these high values while other explanations remain to be explored. Our continuum image also reveals a third structural component of the western nucleus- a pair of faint spurs perpendicular to the disk major axis. We attribute it to a bipolar outflow from the highly inclined (i approximate to 60 degrees) western nuclear disk.
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| 5. |
- Sakamoto, K., et al.
(author)
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Resolved Structure of the Arp 220 Nuclei at λ ≈ 3 mm
- 2017
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 849:1
-
Journal article (peer-reviewed)abstract
- We analyze the 3 mm emission of the ultraluminous infrared galaxy Arp 220 for the spatially resolved structure and the spectral properties of the merger nuclei. ALMA archival data at ∼0.″05 resolution are used for extensive visibility fitting and deep imaging of the continuum emission. The data are fitted well by two concentric components for each nucleus, such as two Gaussians or one Gaussian plus one exponential disk. The larger components in the individual nuclei are similar in shape and extent, ∼100-150 pc, to the centimeter wave emission due to supernovae. They are therefore identified with the known starburst nuclear disks. The smaller components in both nuclei have about a few 10 pc sizes and peak brightness temperatures (Tb) more than twice higher than those in previous single-Gaussian fitting. They correspond to the dust emission that we find centrally concentrated in both nuclei by subtracting the plasma emission measured at 33 GHz. The dust emission in the western nucleus is found to have a peak Tb ≈ 530 K and an FWHM of about 20 pc. This component is estimated to have a bolometric luminosity on the order of 1012.5,Lo˙ and a 20 pc scale luminosity surface density 1015.5, Lo˙ kpc-2. A luminous active galactic nucleus is a plausible energy source for these high values while other explanations remain to be explored. Our continuum image also reveals a third structural component of the western nucleus - a pair of faint spurs perpendicular to the disk major axis. We attribute it to a bipolar outflow from the highly inclined (i ≈ 60°) western nuclear disk.
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| 6. |
- Solaki, Maria, et al.
(author)
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Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia
- 2022
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In: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 43:7, s. 832-858
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Journal article (peer-reviewed)abstract
- Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been associated with ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6), the majority of these being implicated in the cone phototransduction cascade. CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors and is one of the major disease-associated genes for ACHM. Herein, we provide a comprehensive overview of the CNGA3 variant spectrum in a cohort of 1060 genetically confirmed ACHM patients, 385 (36.3%) of these carrying “likely disease-causing” variants in CNGA3. Compiling our own genetic data with those reported in the literature and in public databases, we further extend the CNGA3 variant spectrum to a total of 316 variants, 244 of which we interpreted as “likely disease-causing” according to ACMG/AMP criteria. We report 48 novel “likely disease-causing” variants, 24 of which are missense substitutions underlining the predominant role of this mutation class in the CNGA3 variant spectrum. In addition, we provide extensive in silico analyses and summarize reported functional data of previously analyzed missense, nonsense and splicing variants to further advance the pathogenicity assessment of the identified variants.
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