Recently, we reported downregulated circulating levels of the microRNAs miR‐19b, miR‐29a, and miR‐29c in Parkinson disease. Here we investigated the expression of these microRNAs in serum samples ...from 56 patients with idiopathic rapid eye movement sleep behavior disorder, before and after their conversion into a synucleinopathy. Compared to controls, we found that the expression level of miR‐19b is downregulated in patients with idiopathic rapid eye movement sleep behavior disorder and antedates the diagnosis of Parkinson disease and dementia with Lewy bodies after 4.67 ± 2.61 years of follow‐up. Our findings indicate that dysregulation of the microRNA miR‐19b occurs in the prodromal stage of synucleinopathies. Ann Neurol 2015;77:895–901
Active and fossil subduction systems consisting of two adjacent plates with opposite retreating directions occur in several areas on Earth, as the Mediterranean or Western Pacific. The goal of this ...work is to better understand the first‐order plate dynamics of these systems using the results of experimental models. The laboratory model is composed of two separate plates made of silicon putty representing the lithosphere, on top of a tank filled with glucose syrup representing the mantle. The set of experiments is designed to test the influence of the width of plates and the initial separation between them on the resulting trench velocities, deformation of plates, and mantle flow. Results show that the mantle flow induced by both plates is asymmetric relative to the axis of each plate causing a progressive merging of the toroidal cells that prevents a steady state phase of the subduction process and generates a net outward drag perpendicular to the plates. Trench velocities increase when trenches approach each other and decrease when they separate after their intersection. The trench curvature of both plates increases linearly with time during the entire evolution of the process regardless their width and initial separation. The interaction between the return flows associated with each retreating plate, particularly in the interplate region, is stronger for near plate configurations and correlates with variations of rollback velocities. We propose that the inferred first‐order dynamics of the presented analog models can provide relevant clues to understand natural complex subduction systems.
Key Points
Mantle flow induced by opposed adjacent plates is asymmetrical showing a progressive merging of the toroidal cells when trenches approach
Trench retreat velocities are not steady and increase/decrease while trenches approach/separate
The first‐order consequences of the dynamics of double subduction systems are relevant in natural scenarios
To assess the effect of dexamethasone (DEX) 0.7 mg (Ozurdex™) on refractory and treatment-naïve diffuse diabetic macular edema.
A prospective study was conducted in 76 patients (40 refractory and 36 ...naïve) with visual acuities (VA) of 15-72 ETDRS letters, central macular thickness (CMT) >300 µm and intraocular pressure (IOP) <25 mm Hg. After the DEX implant (±photocoagulation), VA, CMT and total macular volume (TMV) were assessed monthly for 6 months.
At every visit, VA improved significantly from baseline (p < 0.001) in both groups, but values were significantly better in the naïve group, while CMT and TMV decreased significantly (p < 0.001) and similarly in both groups. The naïve group received more photocoagulations (p = 0.001). There were 7.9% transient IOP increases >10 mm Hg.
Substantial improvements in VA and CMT were achieved in both groups, and a gain of 1 ETDRS line was observed in the treatment-naïve group as compared to the refractory group, with a good safety profile in both.
In this work we study the dynamics of double subduction systems with opposite polarity in adjacent segments. A combined approach of numerical and analog experiments allows us to compare results and ...exploit the strengths of both methodologies. High‐resolution numerical experiments complement laboratory results by providing quantities difficult to measure in the laboratory such as stress state, flow patterns, and energy dissipation. Results show strong asymmetries in the mantle flow that produce in turn asymmetries in the trench and in the downgoing slab deformation. The mantle flow pattern varies with time; the toroidal cells between the plates evolve until merging into one unique cell when the trenches align. In that moment the maximum upward flow is observed close to the trenches. The interaction between the mantle flow produced by each subducting plate makes the rollback processes slower than in a single subduction case. This is consistent with the observed energy dissipation rate that is smaller in the double subduction system than in two single subductions. Moreover, we provide a detailed analysis on the setup and boundary conditions required to numerically reproduce the analog experiments. Boundary conditions at the bottom of the domain are crucial to reproduce their analog counterparts. Numerical results are compared to natural examples of multi‐slab subduction systems in terms of upper mantle seismic anisotropy, relative trench retreat velocities, and composition of subduction‐related magmatism.
Key Points
Numerical models of double subduction have been developed to reproduce laboratory experiments and to understand the dynamics of the system
The interaction between the induced mantle flows slows down the evolution of the system and generates additional deformation of plates
In the horizontal plane mantle flow forms four toroidal cells with symmetry axes that rotate during trench retreat
Most patients with idiopathic REM sleep behavior disorder (IRBD) are diagnosed with the synucleinopathies Parkinson disease (PD) and dementia with Lewy bodies. Conversion rates have been estimated to ...be 35% at 5 years, 73% at 10 years, and 92% at 14 years after IRBD diagnosis.1 Accordingly, IRBD is considered as a marker of the prodromal stage of synucleinopathies. In PD, RBD occurs in about 50% of the patients and in 18% of them, RBD symptoms precede the onset of parkinsonism.2 Most cases of PD are sporadic, but approximately 5% to 10% of cases encompass monogenic forms caused by mutations in PD-associated genes. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common genetic cause of both familial PD and sporadic PD (sPD). Indeed, the G2019S mutation has been detected in up to 6% of familial and 3% of sPD cases in Europeans.3 Moreover, the LRRK2-associated PD form (LRRK2-PD) is clinical and neuropathologically similar to sPD lacking LRRK2 mutations.3
Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar ...dysfunction (MSA-C).
To identify novel disease mechanisms we performed a blood transcriptomic study investigating differential gene expression changes and biological process alterations in MSA and its clinical subtypes.
We compared the transcriptome from rigorously gender and age-balanced groups of 10 probable MSA-P, 10 probable MSA-C cases, 10 controls from the Catalan MSA Registry (CMSAR), and 10 Parkinson Disease (PD) patients.
Gene set enrichment analyses showed prominent positive enrichment in processes related to immunity and inflammation in all groups, and a negative enrichment in cell differentiation and development of the nervous system in both MSA-P and PD, in contrast to protein translation and processing in MSA-C. Gene set enrichment analysis using expression patterns in different brain regions as a reference also showed distinct results between the different synucleinopathies.
In line with the two major phenotypes described in the clinic, our data suggest that gene expression and biological processes might be differentially affected in MSA-P and MSA-C. Future studies using larger sample sizes are warranted to confirm these results.
SUMMARY
This study presents for the first time an integrated image of the crust and lithospheric mantle of Alaska and its adjacent western shelves of the Chukchi and Bering seas based on joint ...modelling of potential field data constrained by thermal analysis and seismic data. We also perform 3-D forward modelling and inversion of Bouguer anomalies to analyse density heterogeneities at the crustal level. The obtained crustal model shows northwest-directed long wavelength thickening (32–36 km), with additional localized trends of thicker crust in the Brooks Range (40 km) and in the Alaska and St Elias ranges (50 km). Offshore, 28–30-km-thick crust is predicted near the Bearing slope break and 36–38 km in the northern Chukchi Shelf. In interior Alaska, the crustal thickness changes abruptly across the Denali fault, from 34–36 to the north to above 30 km to the south. This sharp crustal thickness gradient agrees with the presence of a crustal tectonic buttress guiding block motion west and south towards the subduction zone. The average crustal density is 2810 kg m−3. The denser crust, up to 2910 kg m−3, is found south of the Denali Fault likely related to the oceanic nature of the Wrangellia Composite Terrane rocks. Offshore, less dense crust (<2800 kg m−3) is found along the sedimentary basins of the Chukchi and Beaufort shelves. At LAB levels, there is a regional SE–NW trend that coincides with the current Pacific Plate motion, with a lithospheric root underneath the Brooks Range, Northern Slope, and Chuckchi Sea, that may correspond to a relic of the Chukotka-Artic Alaska microplate. The obtained lithospheric root (above 180 km) agrees with the presence of a boundary of cold, strong lithosphere that deflects the strain towards the South. South of the Denali Fault the LAB topography is quite complex. East of 150°W, below Wrangellia and the eastern side of Chugach terranes, the LAB is much shallower than it is west of this meridian. The NW trending limit separating thinner lithosphere in the east and thicker in the west agrees with the two-tiered slab shape of the subducting Pacific Plate.
The purpose of this study was to investigate whether differential phosphorylation states of blood markers can identify patients with LRRK2 Parkinson's disease (PD). We assessed ...phospho(P)‐Ser‐935‐LRRK2 and P‐Ser‐473‐AKT levels in peripheral blood cells from patients with G2019S LRRK2‐associated PD (L2PD, n = 31), G2019S LRRK2 non‐manifesting carriers (L2NMC, n = 26), idiopathic PD (iPD, n = 25), and controls (n = 40, total n = 122). We found no differences at P‐Ser‐935‐LRRK2 between groups but detected a specific increase of P‐Ser‐473‐AKT levels in all G2019S carriers, either L2PD or L2NMC, absent in iPD. Although insensitive to LRRK2 inhibition, our study identifies P‐Ser‐473‐AKT as an endogenous candidate biomarker for peripheral inflammation in G2019S carriers using accessible blood cells. ANN NEUROL 2022;92:888–894
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