GABAergic circuits are critical for the synchronization and higher order function of brain networks. Defects in this circuitry are linked to neuropsychiatric diseases, including bipolar disorder, ...schizophrenia, and autism. Work in cultured neurons has shown that ankyrin-G plays a key role in the regulation of GABAergic synapses on the axon initial segment and somatodendritic domain of pyramidal neurons, where it interacts directly with the GABA
receptor-associated protein (GABARAP) to stabilize cell surface GABA
receptors. Here, we generated a knock-in mouse model expressing a mutation that abolishes the ankyrin-G/GABARAP interaction (Ank3 W1989R) to understand how ankyrin-G and GABARAP regulate GABAergic circuitry in vivo. We found that Ank3 W1989R mice exhibit a striking reduction in forebrain GABAergic synapses resulting in pyramidal cell hyperexcitability and disruptions in network synchronization. In addition, we identified changes in pyramidal cell dendritic spines and axon initial segments consistent with compensation for hyperexcitability. Finally, we identified the ANK3 W1989R variant in a family with bipolar disorder, suggesting a potential role of this variant in disease. Our results highlight the importance of ankyrin-G in regulating forebrain circuitry and provide novel insights into how ANK3 loss-of-function variants may contribute to human disease.
The 2006 World Health Organization Air Quality Guidelines recommend using particulate matter having a diameter of under 2.5 micra (PM
2.5) rather than PM
10 as an indicator of air particle ...concentration, a pattern followed by new European directives. Nevertheless, few studies have analysed this new indicator's impact at a European level on daily mortality among a high-risk group, such as persons aged over 75 years.
This study sought to analyse and quantify the effect of PM
2.5 on daily cause-specific mortality among the over-75 age group in the city of Madrid.
Using Poisson regression with Generalized Additive Models (GAM), a longitudinal, ecological time-series study examined the following causes of death: all causes except accidents (International Classification of Diseases-9th revision (ICD 9): 1-799); circulatory causes (ICD 9: 390-459); and respiratory causes (ICD 9: 460-519). These were adjusted for other chemical, biotic and acoustic pollutants. Further control variables considered were: trend; seasonality; influenza epidemics; and autocorrelation between mortality series.
A significant statistical association was detected between daily mean PM
2.5 particle concentrations and all-cause mortality in the city of Madrid. This association was not in evidence for PM
10 concentrations. The Relative Risks found for an increase of 25 µg/m
3 in PM
2.5 concentrations were as follows: all-cause mortality, 1.057 (1.025–1.088); circulatory-cause mortality, 1.088 (1.041–1.135); and respiratory-cause mortality, 1.122 (1.056–1.189). The Attributable Risks were 5.41%, 8.12% and 10.90% respectively. This effect was observed in the short term (lags 1–2).
Our results indicate a strong impact of PM
2.5 concentrations on daily mortality among the over-75 age group in Madrid, and underscore the need for measures aimed at lowering the concentration levels of this primary air pollutant in large cities, particularly by reducing motor vehicle traffic, the main source of such pollutant emission in urban atmospheres.
Context
. The first stars marked the end of the cosmic dark ages, produced the first heavy elements, and set the stage for the formation of the first galaxies. Accurate chemical abundances of ultra ...metal-poor stars (Fe/H < −4) can be used to infer the properties of the first stars and thus the formation mechanism for low-mass second-generation stars in the early Universe. Spectroscopic studies have shown that most second-generation stars are carbon enhanced. A notable exception is SDSS J102915.14+172927.9, which is the most metal-poor star known to date, largely by virtue of the low upper limits of the carbon abundance reported in earlier studies.
Aims
. We re-analysed the composition of SDSS J102915.14+172927.9 with the aim of providing improved observational constraints on the lowest metallicity possible for low-mass star formation and constraining the properties of its Population III progenitor star.
Methods
. We developed a tailored three-dimensional model atmosphere for SDSS J102915.14+172927.9 with the
Stagger
code, making use of an improved surface gravity estimate based on the
Gaia
DR3 parallax. Snapshots from the model were used as input in the radiative transfer code
Balder
to compute 3D non-local thermodynamic equilibrium (non-LTE) synthetic spectra. These spectra were then used to infer abundances for Mg, Si, Ca, Fe, and Ni as well as upper limits on Li, Na, and Al. Synthetic 3D LTE spectra were computed with
Scate
to infer the abundance of Ti and upper limits on C and N.
Results
. In contrast to earlier works based on 1D non-LTE corrections applied to 3D LTE results, we are able to achieve ionisation balance for Ca
I
and Ca
II
when employing our consistent 3D non-LTE treatment. The elemental abundances are systematically higher than those found in earlier works. In particular, Fe/H is increased by 0.57 dex, and the upper limits of C and N are larger by 0.90 dex and 1.82 dex, respectively.
Conclusions
. We find that Population III progenitors with masses 10–20
M
⊙
exploding with energy
E
⪅ 3 × 10
51
erg can reproduce our 3D non-LTE abundance pattern. Our 3D non-LTE abundances are able to better constrain the progenitor mass and explosion energy as compared to our 1D LTE abundances. Contrary to previous work, we obtain higher upper limits on the carbon abundance that are ‘marginally consistent’ with star formation through atomic line cooling, and consequently, these results prevent us from drawing strong conclusions about the formation mechanism of this low-mass star.
In January 2020, the Chinese authorities identified a new virus of the Coronaviridae family as the cause of several cases of pneumonia of unknown aetiology. The outbreak was initially confined to ...Wuhan City, but then spread outside Chinese borders. On 31 January 2020, the first case was declared in Spain. On 11 March 2020, The World Health Organization (WHO) declared the coronavirus outbreak a pandemic. On 16 March 2020, there were 139 countries affected. In this situation, the Scientific Societies SEMICYUC and SEEIUC have decided to draw up this Contingency Plan to guide the response of the Intensive Care Services. The objectives of this plan are to estimate the magnitude of the problem and identify the necessary human and material resources. This is to provide the Spanish Intensive Medicine Services with a tool to programme optimal response strategies.
We report high spatial resolution i' band imaging of the multiple T Tauri system LkHα 262/LkHα 263 obtained during the first commissioning period of the Adaptive Optics Lucky Imager (AOLI) at the ...4.2-m William Herschel Telescope, using its Lucky Imaging mode. AOLI images have provided photometry for each of the two components LkHα 263 A and B (0.41 arcsec separation) and marginal evidence for an unresolved binary or a disc in LkHα 262. The AOLI data combined with previously available and newly obtained optical and infrared imaging show that the three components of LkHα 263 are comoving, that there is orbital motion in the AB pair, and, remarkably, that LkHα 262-263 is a common proper motion system with less than 1 mas yr−1 relative motion. We argue that this is a likely five-component gravitationally bounded system. According to BT-settl models the mass of each of the five components is close to 0.4 M⊙ and the age is in the range 1–2 Myr. The presence of discs in some of the components offers an interesting opportunity to investigate the formation and evolution of discs in the early stages of multiple very low mass systems. In particular, we provide tentative evidence that the disc in 263C could be coplanar with the orbit of 263AB.
In the original version of this article, affiliation 3 was given as: "Division of Life Sciences, State Key Laboratory of Molecular Neuroscience, Hong Kong, University of Science and Technology, Clear ...Water Bay, Kowloon, Hong Kong, China". This has now been corrected to: "Division of Life Sciences, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China".Additionally in the 'Data availability' section an incorrect accession code was given. The accession code has now been changed from 'PDB A9X (AnkG:GABARAPL)' to 'PDB 6A9X (AnkG:GABARAP)'.These errors have been corrected in both the PDF and HTML versions of the Article.
The impacts of the historical geologic and climatic events on the diversity and genetic structure of Neotropical taxa have recently become a subject of study. However, annual plants associated with ...tropical dry forests remain under-studied. The exploration of additional taxa in contrasting environments will improve the current understanding of responses of the Neotropical biota to these events. Here, we explore the species distribution and geographic structure of the annual herb Tithonia rotundifolia. We sampled 175 individuals from 19 populations of T. rotundifolia. Species distribution modelling and six microsatellite chloroplast loci were used to infer its population history. We identified areas of historical climate suitability and then tested if there is genetic structuring among these areas. Haplotypes showed strong phylogeographic structure. Historical climatic suitability areas were found along the Pacific coast; however, a gap was found at the Isthmus of Tehuantepec (IT). Although Bayesian analysis showed population structuring, amova revealed that the IT is not its main driver. Instead, a subdivision into a higher number of regions had higher F
values. Also, populations to the east of the IT showed evidence of recent population expansion and migration in a south-north direction. Pleistocene climate fluctuations partially explain the geographic structure of T. rotundifolia. However, life-history characteristics such as limited seed dispersal and the patchy distribution of suitable habitats explain the high haplotype diversity and population sub-structuring and diversity. Lastly, the absence of geographic structure of some haplotypes may indicate long-distance dispersal, or hybridisation with the closely related T. tubaeformis.
ABSTRACT Stellar activity may induce Doppler variability at the level of a few m s−1 which can then be confused by the Doppler signal of an exoplanet orbiting the star. To first order, linear ...correlations between radial velocity measurements and activity indices have been proposed to account for any such correlation. The likely presence of two super-Earths orbiting Kapteyn's star was reported in Anglada-Escudé et al., but this claim was recently challenged by Robertson et al., who argued for evidence of a rotation period (143 days) at three times the orbital period of one of the proposed planets (Kapteyn's b, P = 48.6 days) and the existence of strong linear correlations between its Doppler signal and activity data. By re-analyzing the data using global statistics and model comparison, we show that such a claim is incorrect given that (1) the choice of a rotation period at 143 days is unjustified, and (2) the presence of linear correlations is not supported by the data. We conclude that the radial velocity signals of Kapteyn's star remain more simply explained by the presence of two super-Earth candidates orbiting it. We note that analysis of time series of activity indices must be executed with the same care as Doppler time series. We also advocate for the use of global optimization procedures and objective arguments, instead of claims based on residual analyses which are prone to biases and incorrect interpretations.
•The secretion profile of PC3 cancer prostate cells induces a phenotypic change in macrophages from M1 to M2.•This phenomenon is related to phosphorylation of the transcription factor ...STAT3.•Macrophages treated with a STAT3 inhibitor were induced towards an M1 phenotype.
Transcription factor STAT3 has a prominent innate immunity effect on cancer progression. We determined the regulation of STAT3 in the immunophenotype modulation of macrophages from M1 into M2 induced by the cell-culture supernatant of the Prostate-Cancer line PC3.
Monocytes-macrophages from healthy donors were cultured in the supernatant of PC3 cells, membrane proteins, and intracytoplasmic and phosphorylated STAT3 were measured using flow cytometry, while cytokines and growth factors were studied using luminescence. Cytotoxicity and nitric oxide were evaluated via colorimetric assays.
The supernatant of PC3 prostate-tumor cells effectively induced macrophages toward an M2 profile, and the expression of phosphorylated STAT3 in the monocytes-macrophages notably increased, and mainly related to IL-10. In the group of monocytes-macrophages treated with a STAT3 inhibitor, the macrophages were induced toward an M1 phenotype.
In this study, we showed that the secretion profile of PC3 prostate-cancer cells induces a change in macrophage phenotype from M1 into M2, and that the phenomenon is related to phosphorylation of transcription factor STAT3 and IL-10.
Context.
Stellar granulation generates fluctuations in photometric and spectroscopic data whose properties depend on the stellar type, composition, and evolutionary state. Characterizing granulation ...is key for understanding stellar atmospheres and detecting planets.
Aims.
We aim to detect the signatures of stellar granulation, link spectroscopic and photometric signatures of convection for main-sequence stars, and test predictions from 3D hydrodynamic models.
Methods.
For the first time, we observed two bright stars (
T
eff
= 5833 and 6205 K) with high-precision observations taken simultaneously with CHEOPS and ESPRESSO. We analyzed the properties of the stellar granulation signal in each individual dataset. We compared them to
Kepler
observations and 3D hydrodynamic models. While isolating the granulation-induced changes by attenuating and filtering the
p
-mode oscillation signals, we studied the relationship between photometric and spectroscopic observables.
Results.
The signature of stellar granulation is detected and precisely characterized for the hotter F star in the CHEOPS and ESPRESSO observations. For the cooler G star, we obtain a clear detection in the CHEOPS dataset only. The TESS observations are blind to this stellar signal. Based on CHEOPS observations, we show that the inferred properties of stellar granulation are in agreement with both
Kepler
observations and hydrodynamic models. Comparing their periodograms, we observe a strong link between spectroscopic and photometric observables. Correlations of this stellar signal in the time domain (flux versus radial velocities, RV) and with specific spectroscopic observables (shape of the cross-correlation functions) are however difficult to isolate due to S/N dependent variations.
Conclusions.
In the context of the upcoming PLATO mission and the extreme precision RV surveys, a thorough understanding of the properties of the stellar granulation signal is needed. The CHEOPS and ESPRESSO observations pave the way for detailed analyses of this stellar process.
PDF
