The Aicardi-Goutières syndrome (AGS) was first described in 1984, and over the following years was defined by the clinical and radiological features of an early onset, severe, neurologic disorder ...with intracranial calcification, leukoencephalopathy, and cerebral atrophy, usually associated with a cerebrospinal fluid (CSF) pleocytosis and elevated CSF interferon α activity. It is now recognized that mutations in any of the following seven genes may result in the classical AGS phenotype:
(AGS1),
(AGS2),
(AGS3),
(AGS4),
(AGS5),
(AGS6), and
(AGS7). All of these genes encode proteins involved in nucleotide metabolism and/or sensing. Mutations in these genes result in the induction of type 1 interferon production and an upregulation of interferon stimulated genes. As more patients harboring mutations in these genes have been described, in particular facilitated by the advent of whole exome sequencing, a remarkably broad spectrum of associated neurologic phenotypes has been revealed, which we summarize here. We propose that the term AGS has continued clinical utility in the designation of a characteristic phenotype, which suggests relevant diagnostic investigations and can inform outcome predictions. However, we also suggest that the use of the term "type 1 interferonopathy" is appropriate for the wider spectrum of disease consequent upon dysfunction of these genes and proteins since it implies the possibility of a common "anti-interferon" approach to therapy as such treatments become available.
Exoplanets orbiting pre-main-sequence stars are laboratories for studying planet evolution processes, including atmospheric loss, orbital migration, and radiative cooling. V1298 Tau, a young solar ...analog with an age of 23 4 Myr, is one such laboratory. The star is already known to host a Jupiter-sized planet on a 24 day orbit. Here, we report the discovery of three additional planets-all between the sizes of Neptune and Saturn-based on our analysis of K2 Campaign 4 photometry. Planets c and d have sizes of 5.6 and 6.4 , respectively, and with orbital periods of 8.25 and 12.40 days reside 0.25% outside of the nominal 3:2 mean-motion resonance. Planet e is 8.7 in size but only transited once in the K2 time series and thus has a period longer than 36 days, but likely shorter than 223 days. The V1298 Tau system may be a precursor to the compact multiplanet systems found to be common by the Kepler mission. However, the large planet sizes stand in sharp contrast to the vast majority of Kepler multiplanet systems, which have planets smaller than 3 . Simple dynamical arguments suggest total masses of <28 and <120 for the c-d and d-b planet pairs, respectively. The implied low masses suggest that the planets may still be radiatively cooling and contracting, and perhaps losing atmosphere. The V1298 Tau system offers rich prospects for further follow-up including atmospheric characterization by transmission or eclipse spectroscopy, dynamical characterization through transit-timing variations, and measurements of planet masses and obliquities by radial velocities.
Treatments in Aicardi–Goutières syndrome Crow, Yanick J; Shetty, Jayakara; Livingston, John H
Developmental medicine and child neurology,
January 2020, Letnik:
62, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Comprehensive reviews of the clinical characteristics and pathogenesis of Aicardi–Goutières syndrome (AGS), particularly its contextualization within a putative type I interferonopathy framework, ...already exist. However, recent reports of attempts at treatment suggest that an assessment of the field from a therapeutic perspective is warranted at this time. Here, we briefly summarize the neurological phenotypes associated with mutations in the seven genes so far associated with AGS, rehearse current knowledge of the pathology as it relates to possible treatment approaches, critically appraise the potential utility of therapies, and discuss the challenges in assessing clinical efficacy.
What this paper adds
Progress in understanding AGS disease pathogenesis has led to the first attempts at targeted treatment.
Further rational therapies are expected to become available in the short‐ to medium‐term.
What this paper adds
Progress in understanding AGS disease pathogenesis has led to the first attempts at targeted treatment.
Further rational therapies are expected to become available in the short‐ to medium‐term.
The Upper Scorpius OB association is the nearest region of recent massive star formation and thus an important benchmark for investigations concerning stellar evolution and planet formation ...timescales. We present nine eclipsing binaries (EBs) in Upper Scorpius, three of which are newly reported here and all of which were discovered from K2 photometry. Joint fitting of the eclipse photometry and radial velocities from newly acquired Keck I/HIRES spectra yields precise masses and radii for those systems that are spectroscopically double-lined. The binary orbital periods in our sample range from 0.6 to 100 days, with total masses ranging from 0.2 to 8 M . At least 33% of the EBs reside in hierarchical multiples, including two triples and one quadruple. We use these EBs to develop an empirical mass-radius relation for pre-main-sequence stars and evaluate the predictions of widely used stellar evolutionary models. We report evidence for an age of 5-7 Myr, which is self-consistent in the mass range of 0.3-5 M and based on the fundamentally determined masses and radii of EBs. Evolutionary models including the effects of magnetic fields imply an age of 9-10 Myr. Our results are consistent with previous studies that indicate that many models systematically underestimate the masses of low-mass stars by 20%-60% based on Hertzsprung-Russell diagram analyses. We also consider the dynamical states of several binaries and compare with expectations from tidal dissipation theories. Finally, we identify RIK 72 b as a long-period transiting brown dwarf (M = 59.2 6.8 MJup, R = 3.10 0.31 RJup, P 97.8 days) and an ideal benchmark for brown dwarf cooling models at 5-10 Myr.
Abstract
We identify targets in the Kepler field that may be characterized by transit timing variations and are detectable by the Transiting Exoplanet Survey Satellite (TESS). Despite the reduced ...signal-to-noise ratio of TESS transits compared to Kepler, we recover 48 transits from 13 systems in Sectors 14, 15, 26, 40 and 41. We find strong evidence of a nontransiting perturber orbiting Kepler-396 (KOI-2672) and explore two possible cases of a third planet in that system that could explain the measured transit times. We update the ephemerides and mass constraints where possible at KOI-70 (Kepler-20), KOI-82 (Kepler-102), KOI-94 (Kepler-89), KOI-137 (Kepler-18), KOI-244 (Kepler-25), KOI-245 (Kepler-37), KOI-282 (Kepler-130), KOI-377 (Kepler-9), KOI-620 (Kepler-51), KOI-806 (Kepler-30), KOI-1353 (Kepler-289), and KOI-1783 (Kepler-1662).
Abstract
We present high-resolution speckle interferometric imaging observations of TESS exoplanet host stars using the NN-EXPLORE Exoplanet and Stellar Speckle Imager instrument at the 3.5 m WIYN ...telescope. Eight TESS objects of interest that were originally discovered by Kepler were previously observed using the Differential Speckle Survey Instrument. Speckle observations of 186 TESS stars were carried out, and 45 (24%) likely bound companions were detected. This is approximately the number of companions we would expect to observe given the established 46% binarity rate in exoplanet host stars. For the detected binaries, the distribution of stellar mass ratio is consistent with that of the standard Raghavan distribution and may show a decrease in high-
q
systems as the binary separation increases. The distribution of binary orbital periods, however, is not consistent with the standard Ragahavan model, and our observations support the premise that exoplanet-hosting stars with binary companions have, in general, wider orbital separations than field binaries. We find that exoplanet-hosting binary star systems show a distribution peaking near 100 au, higher than the 40–50 au peak that is observed for field binaries. This fact led to earlier suggestions that planet formation is suppressed in close binaries.
Sixty Validated Planets from K2 Campaigns 5-8 Livingston, John H.; Crossfield, Ian J. M.; Petigura, Erik A. ...
The Astronomical journal,
12/2018, Letnik:
156, Številka:
6
Journal Article
Recenzirano
Odprti dostop
We present a uniform analysis of candidates from the second year of NASA's K2 mission (Campaigns 5-8), yielding statistically validated planets spanning a range of properties with median values of Rp ...= , P = days, Teq = K, and J = mag. The sample includes planets in 11 multiplanetary systems, as well as 18 false positives and remaining planet candidates. Of particular interest are planets smaller than 2 , five orbiting stars brighter than J = 10 mag, and a system of four small planets orbiting the solar-type star EPIC 212157262. We compute planetary transit parameters and false-positive probabilities using a robust statistical framework and present a complete analysis incorporating the results of an intensive campaign of high-resolution imaging and spectroscopic observations. This work brings the K2 yield to over 360 planets, and by extrapolation, we expect that K2 will have discovered ∼600 planets before the expected depletion of its onboard fuel in late 2018.
Intracranial calcification (ICC) is a common finding on neuroimaging in paediatric neurology practice. In approximately half of all cases the calcification occurs in damaged, neoplastic, or malformed ...brain. For the large number of other disorders in which ICC occurs, no common pathogenetic mechanism can be suggested. Congenital infection, particularly with cytomegalovirus, accounts for a significant proportion of all cases. However, some genetic diseases, in particular Aicardi–Goutières syndrome, Band‐like calcification, and RNASET2‐related disease, may mimic congenital infection; therefore, a full consideration of the radiological and clinical features is necessary before concluding that congenital infection is the cause. In some disorders calcification is a universal finding, in others it is a frequent occurrence, and in some it is only an occasional finding. Characteristic patterns of calcification are seen in a number of conditions, and a systematic approach to the identification and description of radiological findings, taken together in the context of the clinical scenario, allows a diagnosis to be made in many cases. Nonetheless, there remain a number of presumed genetic disorders associated with ICC for which the underlying molecular cause has not yet been identified.
What this paper adds
This review considers the many aetiologies of ICC and describes those disorders in which characteristic neuroimaging features may indicate the diagnosis.
A diagnostic approach for the consideration of a scan with possible intracranial calcification is proposed.
We report on the discovery of three transiting planets around GJ 9827. The planets have radii of 1.75 0.18, 1.36 0.14, and R⊕, and periods of 1.20896, 3.6480, and 6.2014 days, respectively. The ...detection was made in Campaign 12 observations as part of our K2 survey of nearby stars. GJ 9827 is a V = 10.39 mag K6V star at a distance of 30.3 1.6 parsecs and the nearest star to be found hosting planets by Kepler and K2. The radial velocity follow-up, high-resolution imaging, and detection of multiple transiting objects near commensurability drastically reduce the false positive probability. The orbital periods of GJ 9827 b, c, and d planets are very close to the 1:3:5 mean motion resonance. Our preliminary analysis shows that GJ 9827 planets are excellent candidates for atmospheric observations. Besides, the planetary radii span both sides of the rocky and gaseous divide, hence the system will be an asset in expanding our understanding of the threshold.
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