Aging brains undergo cognitive decline, associated with decreased neuronal synapse number and function and altered metabolism. Astrocytes regulate neuronal synapse formation and function in ...development and adulthood, but whether these properties change during aging, contributing to neuronal dysfunction, is unknown. We addressed this by generating aged and adult astrocyte transcriptomes from multiple mouse brain regions. These data provide a comprehensive RNA-seq database of adult and aged astrocyte gene expression, available online as a resource. We identify astrocyte genes altered by aging across brain regions and regionally unique aging changes. Aging astrocytes show minimal alteration of homeostatic and neurotransmission-regulating genes. However, aging astrocytes upregulate genes that eliminate synapses and partially resemble reactive astrocytes. We further identified heterogeneous expression of synapse-regulating genes between astrocytes from different cortical regions. We find that alterations to astrocytes in aging create an environment permissive to synapse elimination and neuronal damage, potentially contributing to aging-associated cognitive decline.
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•Provide astrocyte transcriptome from multiple regions of aged and adult mouse brain•Astrocytes have a region-dependent aging response, are moderately reactive in aging•Aged astrocytes increase synapse elimination genes, decrease cholesterol synthesis•Most astrocyte-enriched genes are differentially expressed between regions
The aging brain has reduced synapse number and decreased neuronal activity, functions regulated by neighboring astrocytes. Boisvert et al. investigated if aging astrocytes are contributing to these changes and found that aged astrocytes show increased expression of genes for inflammatory and synapse elimination pathways and decreased cholesterol synthesis enzymes.
Context. The radius of an exoplanet is one of its most important parameters. Studies of planetary interiors and their evolution require 1% precision in the radius determination. Transiting exoplanets ...offer a unique oppurtunity to measure the radius of exoplanets in stellar units. These radius measurements and their precision are strongly affected by our knowledge of limb darkening. Aims. We study how the precision of the exoplanet radius determination is affected by our present knowledge of limb darkening in two cases: when we fix the limb darkening coefficients and when we adjust them. We also investigate the effects of spots in one-colour photometry. Methods. We study the effect of limb darkening on the planetary radius determination both via analytical expressions and by numerical experiments. We also compare some of the existing limb darkening tables. When stellar spots affect the fit, we replace the limb darkening coefficients, calculated for the unspotted cases, with effective limb darkening coefficients to describe the effect of the spots. Results. There are two important cases. (1) When one fixes the limb darkening values according to some theoretical predictions, the inconsistencies of the tables do not allow us to reach accuracy in the planetary radius of better than 1−10% (depending on the impact parameter) if the host star’s surface effective temperature is higher than 5000 K. Below 5000 K the radius ratio determination may contain even 20% error. (2) When one allows adjustment of the limb darkening coefficients, the a/Rs ratio, the planet-to-stellar radius ratio, and the impact parameter can be determined with sufficient accuracy (<1%), if the signal-to-noise ratio is high enough. However, the presence of stellar spots and faculae can destroy the agreement between the limb darkening tables and the fitted limb darkening coefficients, but this does not affect the precision of the planet radius determination. We also find that it is necessary to fit the contamination factor, too. Conclusions. We conclude that the present inconsistencies of theoretical stellar limb darkening tables suggests one should not fix the limb darkening coefficients. When one allows them to be adjusted, then the planet radius, impact parameter, and the a/Rs can be obtained with the required precision.
Astrocytes regulate the formation and function of neuronal synapses via multiple signals; however, what controls regional and temporal expression of these signals during development is unknown. We ...determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expression of synapse-regulating genes and synaptic development is also altered when astrocyte signaling is blunted by diminishing calcium release from astrocyte stores. Single-nucleus RNA sequencing identified groups of astrocytic genes regulated by neuronal and astrocyte activity, and a cassette of genes that show layer-specific enrichment. Thus, the development of cortical circuits requires coordinated signaling between astrocytes and neurons, highlighting astrocytes as a target to manipulate in neurodevelopmental disorders.
BART: bioinformatics array research tool Amaral, Maria Luisa; Erikson, Galina A; Shokhirev, Maxim N
BMC bioinformatics,
08/2018, Letnik:
19, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Microarray experiments comprise more than half of all series in the Gene Expression Omnibus (GEO). However, downloading and analyzing raw or semi-processed microarray data from GEO is not intuitive ...and requires manual error-prone analysis and a bioinformatics background. This is due to a lack of standardization in array platform fabrication as well as the lack of a simple interactive tool for clustering, plotting, differential expression testing, and testing for functional enrichment.
We introduce the Bioinformatics Array Research Tool (BART), an R Shiny web application that automates the microarray download and analysis process across diverse microarray platforms. It provides an intuitive interface, automatically downloads and parses data from GEO, suggests groupings of samples for differential expression testing, performs batch effect correction, outputs quality control plots, converts probe IDs, generates full lists of differentially expressed genes, and performs functional enrichment analysis. We show that BART enables a more comprehensive analysis of a wider range of microarray datasets on GEO by comparing it to four leading online microarray analysis tools.
BART allows a scientist with no bioinformatics background to extract knowledge from their own microarray data or microarray experiments available from GEO. BART is functional on more microarray experiments and provides more comprehensive analyses than extant microarray analysis tools. BART is hosted on bart.salk.edu , includes a user tutorial, and is available for download from https://bitbucket.org/Luisa_amaral/bart .
Studies of long-lived individuals have revealed few genetic mechanisms for protection against age-associated disease. Therefore, we pursued genome sequencing of a related phenotype—healthy aging—to ...understand the genetics of disease-free aging without medical intervention. In contrast with studies of exceptional longevity, usually focused on centenarians, healthy aging is not associated with known longevity variants, but is associated with reduced genetic susceptibility to Alzheimer and coronary artery disease. Additionally, healthy aging is not associated with a decreased rate of rare pathogenic variants, potentially indicating the presence of disease-resistance factors. In keeping with this possibility, we identify suggestive common and rare variant genetic associations implying that protection against cognitive decline is a genetic component of healthy aging. These findings, based on a relatively small cohort, require independent replication. Overall, our results suggest healthy aging is an overlapping but distinct phenotype from exceptional longevity that may be enriched with disease-protective genetic factors.
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•Healthy aging is a complex polygenic trait related but distinct from longevity•Healthy aging is associated with decreased genetic risk for select diseases•Healthy aging is potentially linked to protection against cognitive decline•Genome data are made available for further analysis
The genomic characterization of humans that age without developing diseases suggests that healthy aging is a distinct phenotype from exceptional longevity and that it may be enriched with disease-protective genetic factors, such as resistance against cognitive decline.
Abstract
We report the discovery in K2's Campaign 10 of a transiting terrestrial planet in an ultra-short-period orbit around an M3-dwarf. K2-137 b completes an orbit in only 4.3 h, the second ...shortest orbital period of any known planet, just 4 min longer than that of KOI 1843.03, which also orbits an M-dwarf. Using a combination of archival images, adaptive optics imaging, radial velocity measurements, and light-curve modelling, we show that no plausible eclipsing binary scenario can explain the K2 light curve, and thus confirm the planetary nature of the system. The planet, whose radius we determine to be 0.89 ± 0.09 R⊕, and which must have an iron mass fraction greater than 0.45, orbits a star of mass 0.463 ± 0.052 M⊙ and radius 0.442 ± 0.044 R⊙.
We announce the discovery of K2-139 b (EPIC 218916923 b), a transiting warm-Jupiter (Teq = 547 ± 25 K) on a 29-d orbit around an active (log R'_HK = -4.46 ± 0.06) K0V star in K2 Campaign 7. We derive ...the system's parameters by combining the K2 photometry with ground-based follow-up observations. With a mass of 0.387_-0.075^+0.083 M_J and radius of 0.808_-0.033^+0.034 R_J, K2-139 b is one of the transiting warm Jupiters with the lowest mass known to date. The planetary mean density of 0.91_-0.20^+0.24 g/cm^3 can be explained with a core of ~50 M⊕. Given the brightness of the host star (V = 11.653 mag), the relatively short transit duration (~5 h), and the expected amplitude of the Rossiter-McLaughlin effect (~25m/s), K2-139 is an ideal target to measure the spin-orbit angle of a planetary system hosting a warm Jupiter.
We announce the discovery of a planetary system with seven transiting planets around a Kepler target, a current record for transiting systems. Planets b, c, e, and f are reported for the first time ...in this work. Planets d, g, and h were previously reported in the literature, although here we revise their orbital parameters and validate their planetary nature. Planets h and g are gas giants and show strong dynamical interactions. The orbit of planet g is perturbed in such a way that its orbital period changes by 25.7 hr between two consecutive transits during the length of the observations, which is the largest such perturbation found so far. The rest of the planets also show mutual interactions: planets d, e, and f are super-Earths close to a mean motion resonance chain (2:3:4), and planets b and c, with sizes below 2 Earth radii, are within 0.5% of the 4:5 mean motion resonance. This complex system presents some similarities to our solar system, with small planets in inner orbits and gas giants in outer orbits. It is, however, more compact. The outer planet has an orbital distance around 1 AU, and the relative position of the gas giants is opposite to that of Jupiter and Saturn, which is closer to the expected result of planet formation theories. The dynamical interactions between planets are also much richer.
We report on an intensive observational campaign carried out with HARPS at the 3.6 m telescope at La Silla on the star CoRoT-7. Additional simultaneous photometric measurements carried out with the ...Euler Swiss telescope have demonstrated that the observed radial velocity variations are dominated by rotational modulation from cool spots on the stellar surface. Several approaches were used to extract the radial velocity signal of the planet(s) from the stellar activity signal. First, a simple pre-whitening procedure was employed to find and subsequently remove periodic signals from the complex frequency structure of the radial velocity data. The dominant frequency in the power spectrum was found at 23 days, which corresponds to the rotation period of CoRoT-7. The 0.8535 day period of CoRoT-7b planetary candidate was detected with an amplitude of 3.3 m s-1. Most other frequencies, some with amplitudes larger than the CoRoT-7b signal, are most likely associated with activity. A second approach used harmonic decomposition of the rotational period and up to the first three harmonics to filter out the activity signal from radial velocity variations caused by orbiting planets. After correcting the radial velocity data for activity, two periodic signals are detected: the CoRoT-7b transit period and a second one with a period of 3.69 days and an amplitude of 4 m s-1. This second signal was also found in the pre-whitening analysis. We attribute the second signal to a second, more remote planet CoRoT-7c . The orbital solution of both planets is compatible with circular orbits. The mass of CoRoT-7b is $4.8\pm0.8$ ($M_{\oplus}$) and that of CoRoT-7c is $8.4\pm 0.9$ ($M_{\oplus}$), assuming both planets are on coplanar orbits. We also investigated the false positive scenario of a blend by a faint stellar binary, and this may be rejected by the stability of the bisector on a nightly scale. According to their masses both planets belong to the super-Earth planet category. The average density of CoRoT-7b is $\rho=5.6\pm 1.3\mathrm{\,g\,cm^{-3}}$, similar to the Earth. The CoRoT-7 planetary system provides us with the first insight into the physical nature of short period super-Earth planets recently detected by radial velocity surveys. These planets may be denser than Neptune and therefore likely made of rocks like the Earth, or a mix of water ice and rocks.
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