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1.
Space Sci Rev ; 219(5): 41, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37469439

RESUMEN

The two-year prime mission of the NASA Ionospheric Connection Explorer (ICON) is complete. The baseline operational and scientific objectives have been met and exceeded, as detailed in this report. In October of 2019, ICON was launched into an orbit that provides its instruments the capability to deliver near-continuous measurements of the densest plasma in Earth's space environment. Through collection of a key set of in-situ and remote sensing measurements that are, by virtue of a detailed mission design, uniquely synergistic, ICON enables completely new investigations of the mechanisms that control the behavior of the ionosphere-thermosphere system under both geomagnetically quiet and active conditions. In a two-year period that included a deep solar minimum, ICON has elucidated a number of remarkable effects in the ionosphere attributable to energetic inputs from the lower and middle atmosphere, and shown how these are transmitted from the edge of space to the peak of plasma density above. The observatory operated in a period of low activity for 2 years and then for a year with increasing solar activity, observing the changing balance of the impacts of lower and upper atmospheric drivers on the ionosphere.

2.
Ann Neurol ; 94(4): 696-712, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37255483

RESUMEN

OBJECTIVE: Primary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for accurate diagnosis of LSS in the genomic medicine era is establishing gene-disease relationships (GDRs) for this syndrome with >100 monogenic causes across both nuclear and mitochondrial genomes. METHODS: The Clinical Genome Resource (ClinGen) Mitochondrial Disease Gene Curation Expert Panel (GCEP), comprising 40 international PMD experts, met monthly for 4 years to review GDRs for LSS. The GCEP standardized gene curation for LSS by refining the phenotypic definition, modifying the ClinGen Gene-Disease Clinical Validity Curation Framework to improve interpretation for LSS, and establishing a scoring rubric for LSS. RESULTS: The GDR with LSS across the nuclear and mitochondrial genomes was classified as definitive for 31 of 114 GDRs curated (27%), moderate for 38 (33%), limited for 43 (38%), and disputed for 2 (2%). Ninety genes were associated with autosomal recessive inheritance, 16 were maternally inherited, 5 were autosomal dominant, and 3 were X-linked. INTERPRETATION: GDRs for LSS were established for genes across both nuclear and mitochondrial genomes. Establishing these GDRs will allow accurate variant interpretation, expedite genetic diagnosis of LSS, and facilitate precision medicine, multisystem organ surveillance, recurrence risk counseling, reproductive choice, natural history studies, and determination of eligibility for interventional clinical trials. ANN NEUROL 2023;94:696-712.


Asunto(s)
Enfermedad de Leigh , Enfermedades Mitocondriales , Niño , Humanos , Enfermedad de Leigh/diagnóstico , Enfermedad de Leigh/genética , Mitocondrias
3.
Space Sci Rev ; 219(3): 27, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37038438

RESUMEN

The design, principles of operation, calibration, and data analysis approaches of the Michelson Interferometer for Global High-resolution Thermospheric Imaging (MIGHTI) on the NASA Ionospheric Connection (ICON) satellite have been documented prior to the ICON launch. Here we update and expand on the MIGHTI wind data analysis and discuss the on-orbit instrument performance. In particular, we show typical raw data and we describe key processing steps, including the correction of a "signal-intensity dependent phase shift," which is necessitated by unexpected detector behavior. We describe a new zero-wind calibration approach that is preferred over the originally planned approach due to its higher precision. Similar to the original approach, the new approach is independent of any a priori data. A detailed update on the wind uncertainties is provided and compared to the mission requirements, showing that MIGHTI has met the ICON mission requirements. While MIGHTI observations are not required to produce absolute airglow brightness profiles, we describe a relative brightness profile product, which is included in the published data. We briefly review the spatial resolution of the MIGHTI wind data in addition to the data coverage and data gaps that occurred during the nominal mission. Finally, we include comparisons of the MIGHTI wind data with ground-based Fabry-Perot interferometer observations and meteor radar observations, updating previous studies with more recent data, again showing good agreement. The data processing steps covered in this work and all the derived wind data correspond to the MIGHTI data release Version 5 (v05).

4.
J Geophys Res Space Phys ; 127(6): e2022JA030527, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35864906

RESUMEN

Following the 2022 Tonga Volcano eruption, dramatic suppression and deformation of the equatorial ionization anomaly (EIA) crests occurred in the American sector ∼14,000 km away from the epicenter. The EIA crests variations and associated ionosphere-thermosphere disturbances were investigated using Global Navigation Satellite System total electron content data, Global-scale Observations of the Limb and Disk ultraviolet images, Ionospheric Connection Explorer wind data, and ionosonde observations. The main results are as follows: (a) Following the eastward passage of expected eruption-induced atmospheric disturbances, daytime EIA crests, especially the southern one, showed severe suppression of more than 10 TEC Unit and collapsed equatorward over 10° latitudes, forming a single band of enhanced density near the geomagnetic equator around 14-17 UT, (b) Evening EIA crests experienced a drastic deformation around 22 UT, forming a unique X-pattern in a limited longitudinal area between 20 and 40°W. (c) Thermospheric horizontal winds, especially the zonal winds, showed long-lasting quasi-periodic fluctuations between ±200 m/s for 7-8 hr after the passage of volcano-induced Lamb waves. The EIA suppression and X-pattern merging was consistent with a westward equatorial zonal dynamo electric field induced by the strong zonal wind oscillation with a westward reversal.

5.
Geophys Res Lett ; 49(11): e2022GL098078, 2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-35865010

RESUMEN

We present simultaneous, independent measurements of the atmospheric semidiurnal lunar tide in neutral winds and plasma velocities from NASA's Ionospheric Connection Explorer, and in atomic oxygen 135.6 nm airglow measured by the Global-scale Observations of the Limb and Disk. Westward tidal winds near 115 km at the magnetic equator occur during part of the upward phase of the in-situ plasma drift. Vertical motions associated with the field-aligned plasma velocity occur away from the magnetic equator. The morphology of the lunar tide, and the phasing between the airglow and plasma velocities are consistent with E × B drift as a mechanism for linking neutral wind and plasma perturbations. This work provides the first observational quantification of global-scale E- and F-region coupling through E × B and field-aligned vertical drifts.

6.
Nat Commun ; 13(1): 2331, 2022 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-35484145

RESUMEN

In the developing mouse forebrain, temporally distinct waves of oligodendrocyte progenitor cells (OPCs) arise from different germinal zones and eventually populate either dorsal or ventral regions, where they present as transcriptionally and functionally equivalent cells. Despite that, developmental heterogeneity influences adult OPC responses upon demyelination. Here we show that accumulation of DNA damage due to ablation of citron-kinase or cisplatin treatment cell-autonomously disrupts OPC fate, resulting in cell death and senescence in the dorsal and ventral subsets, respectively. Such alternative fates are associated with distinct developmental origins of OPCs, and with a different activation of NRF2-mediated anti-oxidant responses. These data indicate that, upon injury, dorsal and ventral OPC subsets show functional and molecular diversity that can make them differentially vulnerable to pathological conditions associated with DNA damage.


Asunto(s)
Células Precursoras de Oligodendrocitos , Animales , Daño del ADN , Ratones , Células Precursoras de Oligodendrocitos/fisiología , Oligodendroglía/metabolismo , Prosencéfalo
7.
Geophys Res Lett ; 48(15)2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34690382

RESUMEN

We report for the first time the day-to-day variation of the longitudinal structure in height of the F2 layer (hmF2) in the equatorial ionosphere using multi-satellite observations of electron density profiles by the Constellation Observing System for Meteorology, Ionosphere and Climate-2 (COSMIC-2). These observations reveal a ~3-day modulation of the hmF2 wavenumber-4 structure viewed in a fixed local time frame during January 30-February 14, 2021. Simultaneously, ~3-day planetary wave activity is discerned from zonal wind observations at ~100 km by the Ionospheric Connection Explorer (ICON) Michelson Interferometer for Global High-Resolution Thermospheric Imaging (MIGHTI). This signature is not observed at ~180-250 km altitudes, suggesting the dissipation of this wave below the F-region. We propose that the 3-day variation identified in h mF2 is likely caused by the planetary wave-tide interaction through the E-region dynamo.

8.
J Geophys Res Space Phys ; 126(6)2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34650898

RESUMEN

Coincident Ionospheric Connections Explorer (ICON) measurements of neutral winds, plasma drifts and total ion densities (:=Ne, electron density) are analyzed during January 1-21, 2020 to reveal the relationship between neutral winds and ionospheric variability on a day-to-day basis. Atmosphere-ionosphere (A-I) connectivity inevitably involves a spectrum of planetary waves (PWs), tides and secondary waves due to wave-wave nonlinear interactions. To provide a definitive attribution of dynamical origins, the current study focuses on a time interval when the longitudinal wave-4 component of the E-region winds is dominated by the eastward-propagating diurnal tide with zonal wavenumber s = -3 (DE3). DE3 is identified in winds and ionospheric parameters through its characteristic dependence on local solar time and longitude as ICON's orbit precesses. Superimposed on this trend are large variations in low-latitude DE3 wave-4 zonal winds (±40 ms-1) and topside F-region equatorial vertical drifts at periods consistent with 2-days and 6-days PWs, and a ~3-day ultra-fast Kelvin wave (UFKW), coexisting during this time interval; the DE3 winds, dynamo electric fields, and drifts are modulated by these waves. Wave-4 variability in Ne is of order 25%-35%, but the origins are more complex, likely additionally reflecting transport by ~20-25 ms-1 wave-4 in-situ winds containing strong signatures of DE3 interactions with ambient diurnal Sun-synchronous winds and ion drag. These results are the first to show a direct link between day-to-day wave-4 variability in contemporaneously measured E-region neutral winds and F-region ionospheric drifts and electron densities.

9.
J Geophys Res Space Phys ; 126(9)2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34650899

RESUMEN

In near-Earth space, variations in thermospheric composition have important implications for thermosphere-ionosphere coupling. The ratio of O to N2 is often measured using far-UV airglow observations. Taking such airglow observations from space, looking below the Earth's limb allows for the total column of O and N2 in the ionosphere to be determined. While these observations have enabled many previous studies, determining the impact of non-migrating tides on thermospheric composition has proved difficult, owing to a small contamination of the signal by recombination of ionospheric O+. New ICON observations of far UV are presented here, and their general characteristics are shown. Using these, along with other observations and a global circulation model we show that during the morning hours and at latitudes away from the peak of the equatorial ionospheric anomaly, the impact of non-migrating tides on thermospheric composition can be observed. During March - April 2020, the column O/N2 ratio was seen to vary by 3 - 4 % of the zonal mean. By comparing the amplitude of the variation observed with that in the model, both the utility of these observations and a pathway to enable future studies is shown.

10.
Pediatr Neurol ; 121: 11-19, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34111619

RESUMEN

BACKGROUND: A recurrent homozygous missense variant, c.160G>C;p.(Val54Leu) in HIKESHI, was found to cause a hypomyelinating leukodystrophy with high frequency in the Ashkenazi Jewish population. We provide extended phenotypic classification of this disorder based on clinical history of a further seven affected individuals, assess carrier frequency in the Ashkenazi Jewish population, and provide a neuropathological study. METHODS: Clinical information, neuroimaging, and biosamples were collected. Brain autopsy was performed for one case. RESULTS: Individuals with HIKESHI-related disease share common clinical features: early axial hypotonia evolving to dystonia or with progressive spasticity, hyperreflexia and clonus, feeding difficulties with poor growth, and nystagmus. Severe morbidity or death during febrile illness occurred in five of the nine affected individuals. Magnetic resonance images of seven patients were analyzed and demonstrated diffuse hypomyelination and thin corpus callosum. Genotyping data of more than 125,000 Ashkenazi Jewish individuals revealed a carrier frequency of 1 in 216. Gross pathology examination in one case revealed abnormal white matter. Microscopically, there was a near-total absence of myelin with a relative preservation of axons. The cerebral white matter showed several reactive astrocytes and microglia. CONCLUSIONS: We provide pathologic evidence for a primary disorder of the myelin in HIKESHI-related leukodystrophy. These findings are consistent with the hypomyelination seen in brain magnetic resonance imaging and with the clinical features of early-onset spastic/dystonic quadriplegia and nystagmus. The high carrier rate of the recurrent variant seen in the Ashkenazi Jewish population requires increased attention to screening and diagnosis of this condition, particularly in this population.


Asunto(s)
Proteínas Portadoras/genética , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/patología , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/fisiopatología , Niño , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Humanos , Judíos/genética , Imagen por Resonancia Magnética , Secuenciación Completa del Genoma
11.
J Neurogenet ; 35(2): 74-83, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33970744

RESUMEN

KCTD7 is a member of the potassium channel tetramerization domain-containing protein family and has been associated with progressive myoclonic epilepsy (PME), characterized by myoclonus, epilepsy, and neurological deterioration. Here we report four affected individuals from two unrelated families in which we identified KCTD7 compound heterozygous single nucleotide variants through exome sequencing. RNAseq was used to detect a non-annotated splicing junction created by a synonymous variant in the second family. Whole-cell patch-clamp analysis of neuroblastoma cells overexpressing the patients' variant alleles demonstrated aberrant potassium regulation. While all four patients experienced many of the common clinical features of PME, they also showed variable phenotypes not previously reported, including dysautonomia, brain pathology findings including a significantly reduced thalamus, and the lack of myoclonic seizures. To gain further insight into the pathogenesis of the disorder, zinc finger nucleases were used to generate kctd7 knockout zebrafish. Kctd7 homozygous mutants showed global dysregulation of gene expression and increased transcription of c-fos, which has previously been correlated with seizure activity in animal models. Together these findings expand the known phenotypic spectrum of KCTD7-associated PME, report a new animal model for future studies, and contribute valuable insights into the disease.


Asunto(s)
Epilepsias Mioclónicas Progresivas/genética , Canales de Potasio/genética , Animales , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Mutación , Epilepsias Mioclónicas Progresivas/fisiopatología , Linaje , Fenotipo , Pez Cebra
12.
J Geophys Res Space Phys ; 126(2)2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33828935

RESUMEN

Observations of the nighttime thermospheric wind from two ground-based Fabry-Perot Interferometers are compared to the level 2.1 and 2.2 data products from the Michelson Interferometer Global High-resolution Thermospheric Imaging (MIGHTI) onboard National Aeronautics and Space Administration's Ionospheric Connection Explorer to assess and validate the methodology used to generate measurements of neutral thermospheric winds observed by MIGHTI. We find generally good agreement between observations approximately coincident in space and time with mean differences less than 11 m/s in magnitude and standard deviations of about 20-35 m/s. These results indicate that the independent calculations of the zero-wind reference used by the different instruments do not contain strong systematic or physical biases, even though the observations were acquired during solar minimum conditions when the measured airglow intensity is weak. We argue that the slight differences in the estimated wind quantities between the two instrument types can be attributed to gradients in the airglow and thermospheric wind fields and the differing viewing geometries used by the instruments.

13.
J Geophys Res Space Phys ; 126(3)2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33868889

RESUMEN

We compare coincident thermospheric neutral wind observations made by the Michelson Interferometer for Global High-Resolution Thermospheric Imaging (MIGHTI) on the Ionospheric Connection Explorer (ICON) spacecraft, and four ground-based specular meteor radars (SMRs). Using the green-line MIGHTI channel, we analyze 1158 coincidences between Dec 2019 and May 2020 in the altitude range from 94 to 104 km where the observations overlap. We find that the two datasets are strongly correlated (r = 0.82) with a small mean difference (4.5 m/s). Although this agreement is good, an analysis of known error sources (e.g., shot noise, calibration errors, and analysis assumptions) can only account for about a quarter of the disagreement variance. The unexplained variance is 27.8% of the total signal variance and could be caused by unknown errors. However, based on an analysis of the spatial and caused by temporal variability of the wind on scales ≲70 min. The observed magnitudes agree well during temporal averaging of the two measurement modalities, we suggest that some of the disagreement is likely the night, but during the day, MIGHTI observes 16%-25% faster winds than the SMRs. This remains unresolved but is similar in certain ways to previous SMR-satellite comparisons.

14.
Nat Geosci ; 14: 893-898, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35003329

RESUMEN

Earth's equatorial ionosphere exhibits substantial and unpredictable day-to-day variations in density and morphology. This presents challenges in preparing for adverse impacts on geopositioning systems and radio communications even 24 hours in advance. The variability is now theoretically understood as a manifestation of thermospheric weather, where winds in the upper atmosphere respond strongly to a spectrum of atmospheric waves that propagate into space from the lower and middle atmosphere. First-principles simulations predict related, large changes in the ionosphere, primarily through modification of wind-driven electromotive forces: the wind-driven dynamo. Here we show the first direct evidence of the action of a wind dynamo in space, using the coordinated, space-based observations of winds and plasma motion made by the National Aeronautics and Space Administration Ionospheric Connection Explorer. A clear relationship is found between vertical plasma velocities measured at the magnetic equator near 600 km and the thermospheric winds much farther below. Significant correlations are found between the plasma and wind velocities during several successive precession cycles of the Ionospheric Connection Explorer's orbit. Prediction of thermospheric winds in the 100-150 km altitude range emerges as the key to improved prediction of Earth's plasma environment.

15.
J Geophys Res Space Phys ; 126(11)2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35070616

RESUMEN

A quasi-2-day wave (Q2DW) event during January-February, 2020, is investigated in terms of its propagation from 96 to 250 km as a function of latitude (10°S to 30°N), its nonlinear interactions with migrating tides to produce 16 and 9.6-h secondary waves (SWs), and the plasma drift and density perturbations that it produces in the topside F-region (590-607 km) between magnetic latitudes 18°S and 18°N. This is accomplished through analysis of coincident Ionospheric Connections Explorer (ICON) measurements of neutral winds, plasma drifts and ion densities, and wind measurements from four low-latitude (±15°) specular meteor radars (SMRs). The Q2DW westward-propagating components that existed during this period consist of zonal wavenumbers s = 2 and s = 3, that is, Q2DW+2 and Q2DW+3 (e.g., He, Chau et al., 2021, https://doi.org/10.1029/93jd00380). SWs in the ICON measurements are inferred from Q2DW+2 and Q2DW+3 characteristics derived from traditional longitude-UT fits that potentially contain aliasing contributions from SWs ("apparent" Q2DWs), from fits to space-based zonal wavenumbers that each reflect the aggregate signature of either Q2DW+2 or Q2DW+3 and its SWs combined ("effective" Q2DWs), and based on information contained in published numerical simulations. The total Q2DW ionospheric responses consists of F-region field-aligned and meridional drifts of order ±25 ms-1 and ±5-7 ms-1, respectively, and total ion density perturbations of order (±10%-25%). It is shown that the SWs can sometimes make substantial contributions to the Q2DW winds, drifts, and plasma densities.

16.
Earth Space Sci ; 7(10): e2020EA001164, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33134433

RESUMEN

The Michelson Interferometer for Global High-resolution Thermospheric Imaging (MIGHTI) on NASA's Ionospheric Connection Explorer (ICON) mission is designed to measure the neutral wind and temperature between 90 and ∼300 km altitude. Using the Doppler Asymmetric Spatial Heterodyne (DASH) spectroscopy technique, observations from MIGHTI can be used to derive thermospheric winds by measuring Doppler shifts of the atomic oxygen red line (630.0 nm) and green line (557.7 nm). Harding et al. (2017, https://doi.org/10.1007/s11214-017-0359-3) (Harding17) describe the wind retrieval algorithm in detail and point out the large uncertainties that result near the solar terminators and equatorial arcs, regions of large spatial gradients in airglow volume emission rates (VER). The uncertainties originate from the assumption of a constant VER at every given altitude, resulting in errors where the assumption is not valid when limb sounders, such as MIGHTI, observe regions with significant VER gradients. In this work, we introduce a new wind retrieval algorithm (Wu20) with the ability to account for VER that is asymmetric along the line of sight with respect to the tangent point. Using the predicted ICON orbit and simulated global VER variation, the greatest impact of the symmetric airglow assumption to the ICON vector wind product is found within 30° from the terminator when the spacecraft is in the dayside, causing an error of at least 10 m/s. The new algorithm developed in this study reduces the error near the terminator by a factor of 10. Although Wu20 improves the accuracy of the retrievals, it loses precision by 75% compared to Harding17.

17.
J Neurosurg Pediatr ; 26(4): 431-438, 2020 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-32619987

RESUMEN

OBJECTIVE: The authors' aim was to characterize a single-center experience of brain biopsy in pediatric cryptogenic neurological disease. METHODS: The authors performed a retrospective review of consecutive brain biopsies at a tertiary pediatric neurosciences unit between 1997 and 2017. Children < 18 years undergoing biopsy for neurological pathology were included. Those with presumed neoplasms and biopsy performed in the context of epilepsy surgery were excluded. RESULTS: Forty-nine biopsies in 47 patients (25 females, mean age ± SD 9.0 ± 5.3 years) were performed during the study period. The most common presenting symptoms were focal neurological deficit (28.6%) and focal seizure (26.5%). Histopathological, microbiological, and genetic analyses of biopsy material were contributory to the diagnosis in 34 cases (69.4%). Children presenting with focal seizures or with diffuse (> 3 lesions) brain involvement on MRI were more likely to yield a diagnosis at biopsy (OR 3.07 and 2.4, respectively). Twelve patients were immunocompromised and were more likely to yield a diagnosis at biopsy (OR 6.7). Surgery was accompanied by severe complications in 1 patient. The most common final diagnoses were infective (16/49, 32.7%), followed by chronic inflammatory processes (10/49, 20.4%) and occult neoplastic disease (9/49, 18.4%). In 38 cases (77.6%), biopsy was considered to have altered clinical management. CONCLUSIONS: Brain biopsy for cryptogenic neurological disease in children was contributory to the diagnosis in 69.4% of cases and changed clinical management in 77.6%. Biopsy most commonly revealed underlying infective processes, chronic inflammatory changes, or occult neoplastic disease. Although generally safe, the risk of severe complications may be higher in immunocompromised and myelosuppressed children.

18.
J Neuropathol Exp Neurol ; 79(4): 458-462, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-32106287

RESUMEN

MIRAGE syndrome is a multisystem disorder characterized by myelodysplasia, infections, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. Mutations in the sterile alpha motif domain containing 9 (SAMD9) gene which encodes a protein involved in growth factor signal transduction are thought to cause MIRAGE syndrome. SAMD9 mutations lead to an antiproliferative effect resulting in a multisystem growth restriction disorder. Though rare, a few patients with SAMD9 mutations were reported to have hydrocephalus and/or cerebellar hypoplasia on imaging. The neuropathologic features of MIRAGE syndrome have not been previously described. Here, we describe the postmortem neuropathologic examinations of 2 patients with a clinical diagnosis of MIRAGE syndrome and confirmed SAMD9 mutations. Common features included microcephaly, hydrocephalus, white matter abnormalities, and perivascular calcifications. One of the 2 cases showed marked cerebellar hypoplasia with loss of Purkinje and granule neurons as well as multifocal polymicrogyria and severe white matter volume loss; similar findings were not observed in the second patient. These cases demonstrate the variation in neuropathologic findings in patients with MIRAGE syndrome. Interestingly, the findings are similar to those reported in ataxia-pancytopenia syndrome caused by mutations in SAMD9L, a paralogue of SAMD9.


Asunto(s)
Insuficiencia Suprarrenal/complicaciones , Encéfalo/patología , Enfermedades del Sistema Nervioso Central/complicaciones , Enfermedades del Sistema Nervioso Central/patología , Enfermedades Pulmonares/complicaciones , Síndromes Mielodisplásicos/complicaciones , Insuficiencia Suprarrenal/genética , Enfermedades del Sistema Nervioso Central/genética , Femenino , Humanos , Lactante , Péptidos y Proteínas de Señalización Intracelular/genética , Síndromes Mielodisplásicos/genética , Neuropatología , Nacimiento Prematuro
19.
J Neuropathol Exp Neurol ; 78(12): 1100-1111, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31617914

RESUMEN

Dysembryoplastic neuroepithelial tumors (DNT) lacking key diagnostic criteria are challenging to diagnose and sometimes fall into the broader category of mixed neuronal-glial tumors (MNGT) or the recently described polymorphous low-grade neuroepithelial tumor of the young (PLNTY). We examined 41 patients with DNT, MNGT, or PLNTY for histologic features, genomic findings, and progression-free survival (PFS). Genomic analysis included sequence and copy number variants and RNA-sequencing. Classic DNT (n = 26) was compared with those with diffuse growth without cortical nodules (n = 15), 6 of which exhibited impressive CD34 staining classifying them as PLNTY. Genomic analysis was complete in 33, with sequence alterations recurrently identified in BRAF, FGFR1, NF1, and PDGFRA, as well as 7 fusion genes involving FGFR2, FGFR1, NTRK2, and BRAF. Genetic alterations did not distinguish between MNGTs, DNTs, or PLNTYs; however, FGFR1 alterations were confined to DNT, and PLNTYs contained BRAF V600E or FGFR2 fusion genes. Analysis of PFS showed no significant difference by histology or genetic alteration; however, numbers were small and follow-up time short. Further molecular characterization of a PLNTY-related gene fusion, FGFR2-CTNNA3, demonstrated oncogenic potential via MAPK/PI3K/mTOR pathway activation. Overall, DNT-MNGT spectrum tumors exhibit diverse genomic alterations, with more than half (19/33) leading to MAPK/PI3K pathway alterations.


Asunto(s)
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Sistema de Señalización de MAP Quinasas , Neoplasias Neuroepiteliales/genética , Neoplasias Neuroepiteliales/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Adolescente , Adulto , Encéfalo/patología , Neoplasias Encefálicas/metabolismo , Niño , Preescolar , Femenino , Genómica , Humanos , Masculino , Neoplasias Neuroepiteliales/metabolismo , Supervivencia sin Progresión , Adulto Joven
20.
Appl Opt ; 58(13): 3613-3619, 2019 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-31044863

RESUMEN

The mean fringe phase measured by Doppler asymmetric spatial heterodyne spectroscopy is a direct measure of atmospheric wind. The uncertainty in measuring the mean phase is investigated and found to be accurately predicted by an analytic formula for moderate and high signal-to-noise ratios. At lower signal-to-noise ratios, numeric issues in the phase calculation result in non-Gaussian distributions of mean phase. Analysis techniques are described to mitigate these numeric issues to the extent possible.

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