Trop-2 is a calcium signal transducer that is associated with transformed cell growth in experimental systems. However, its role in human cancer remains essentially unknown. In this study, we ...profiled Trop-2 expression in normal human tissues at the mRNA and protein levels. We then systematically compared Trop-2 mRNA and protein levels in tumours with their tissues of origin. We find that Trop-2 expression is invariably upregulated in tumours, regardless of baseline expression in normal tissues, which suggests a corresponding selective advantage. Thus, we investigated the outcome of Trop-2 upregulation on tumour growth. Overexpression of wild-type Trop-2 was shown to be necessary and sufficient to drive cancer growth in a widely invariant manner across cell type and species. Upregulation of Trop-2 was shown to quantitatively stimulate tumour growth, as proportional to expression levels in vivo, and tumour cell growth was abrogated by somatic knockdown of Trop-2 expression. On the other hand, we found no evidence of tumour-associated TROP2 mutations, nor of TROP2 induction of oncogenic transformation per se. Our data support a model where above-baseline expression of wild-type Trop-2 is a key driver of human cancer growth.
The abundance of oxygen in galaxies is widely used in furthering our understanding of galaxy formation and evolution. Unfortunately, direct measurements of O/H in the neutral gas are extremely ...difficult to obtain, as the only O i line available within the Hubble Space Telescope (HST) UV wavelength range (1150-3200 ) is often saturated. As such, proxies for oxygen are needed to indirectly derive O/H via the assumption that solar ratios based on local Milky Way sight lines hold in different environments. In this paper we assess the validity of using two such proxies, P ii and S ii, within more typical star-forming environments. Using HST-Cosmic Origins Spectrograph (COS) far-UV (FUV) spectra of a sample of nearby star-forming galaxies (SFGs) and the oxygen abundances in their ionized gas, we demonstrate that both P and S are mildly depleted with respect to O and follow a trend, log(P ii/S ii) , in excellent agreement with the solar ratio of over the large range of metallicities (0.03-3.2 Z ) and H i column densities ( (H i)/cm−2 =18.44-21.28) spanned by the sample. From literature data we show evidence that both elements individually trace oxygen according to their respective solar ratios across a wide range of environments. Our findings demonst-rate that the solar ratios of and can both be used to derive reliable O/H abundances in the neutral gas of local and high-redshift SFGs. The difference between O/H in the ionized- and neutral gas phases is studied with respect to metallicity and H i content. The observed trends are consistent with galactic outflows and/or star formation inefficiency affecting the most metal-poor galaxies, with the possibility of primordial gas accretion at all metallicities.
ABSTRACT We obtained O iii narrow-band imaging and multi-slit MXU spectroscopy of the blue compact dwarf (BCD) galaxy NGC 1705 with FORS2@VLT to derive chemical abundances of planetary nebulae and H ...ii regions and, more in general, to characterize the properties of the ionized gas. The auroral O iii line was detected in all but 1 of the 11 analyzed regions, allowing for a direct estimate of their electron temperature. The only object for which the O iii line was not detected is a possible low-ionization PN, the only one detected in our data. For all the other regions, we derived the abundances of nitrogen, oxygen, neon, sulfur, and argon out to ∼1 kpc from the galaxy center. We detect for the first time in NGC 1705 a negative radial gradient in the oxygen metallicity of dex kpc−1. The element abundances are all consistent with values reported in the literature for other samples of dwarf irregular and BCD galaxies. However, the average (central) oxygen abundance, , is ∼0.26 dex lower than previous literature estimates for NGC 1705 based on the O iii line. From classical emission line diagnostic diagrams, we exclude a major contribution from shock excitation. On the other hand, the radial behavior of the emission line ratios is consistent with the progressive dilution of radiation with increasing distance from the center of NGC 1705. This suggests that the strongest starburst located within the central ∼150 pc is responsible for the ionization of the gas out to at least ∼1 kpc. The gradual dilution of the radiation with increasing distance from the center reflects the gradual and continuous transition from the highly ionized H ii regions in the proximity of the major starburst into the diffuse ionized gas.
We present an analysis of the positions and ages of young star clusters in eight local galaxies to investigate the connection between the age difference and separation of cluster pairs. We find that ...star clusters do not form uniformly but instead are distributed so that the age difference increases with the cluster pair separation to the 0.25-0.6 power, and that the maximum size over which star formation is physically correlated ranges from ∼200 pc to ∼1 kpc. The observed trends between age difference and separation suggest that cluster formation is hierarchical both in space and time: clusters that are close to each other are more similar in age than clusters born further apart. The temporal correlations between stellar aggregates have slopes that are consistent with predictions of turbulence acting as the primary driver of star formation. The velocity associated with the maximum size is proportional to the galaxy's shear, suggesting that the galactic environment influences the maximum size of the star-forming structures.
ABSTRACT
We present the star formation history (SFH) of the extremely metal-poor dwarf galaxy DDO 68, based on our photometry with the Advanced Camera for Surveys. With a metallicity of only
and a ...very isolated location, DDO 68 is one of the most metal-poor galaxies known. It has been argued that DDO 68 is a young system that started forming stars only ∼0.15 Gyr ago. Our data provide a deep and uncontaminated optical color–magnitude diagram (CMD) that allows us to disprove this hypothesis since we find a population of at least ∼1 Gyr old stars. The star formation activity has been fairly continuous over all the look-back time. The current rate is quite low, and the highest activity occurred between 10 and 100 Myr ago. The average star formation rate over the whole Hubble time is ≃0.01
M
⊙
yr
−1
, corresponding to a total astrated mass of ≃1.3 × 10
8
M
⊙
. Our photometry allows us to infer the distance from the tip of the red giant branch,
D
= 12.08 ± 0.67 Mpc; however, to let our synthetic CMD reproduce the observed ones, we need a slightly higher distance,
D
= 12.65 Mpc, or (
m
−
M
)
0
= 30.51, still inside the errors of the previous determination, and we adopt the latter. DDO 68 shows a very interesting and complex history, with its quite disturbed shape and a long tail, probably due to tidal interactions. The SFH of the tail differs from that of the main body mainly for enhanced activity at recent epochs likely triggered by the interaction.
This is the first in a series of three papers describing a project with the Cosmic Origins Spectrograph on the Hubble Space Telescope to measure abundances of the neutral interstellar medium (ISM) in ...a sample of nine nearby star-forming galaxies. The goal is to assess the (in)homogeneities of the multiphase ISM in galaxies where the bulk of metals can be hidden in the neutral phase, yet the metallicity is inferred from the ionized gas in the HII regions. The sample, spanning a wide range in physical properties, is to date the best suited to investigate the metallicity behavior of the neutral gas at redshift z = 0. ISM absorption lines were detected against the far-ultraviolet spectra of the brightest star-forming region(s) within each galaxy. Here we report on the observations, data reduction, and analysis of these spectra. Column densities were measured by a multicomponent line-profile fitting technique, and neutral-gas abundances were obtained for a wide range of elements. Several caveats were considered, including line saturation, ionization corrections, and dust depletion. Ionization effects were quantified with ad hoc cloudy models reproducing the complex photoionization structure of the ionized and neutral gas surrounding the UV-bright sources. An "average spectrum of a redshift z = 0 star-forming galaxy" was obtained from the average column densities of unsaturated profiles of neutral-gas species. This template can be used as a powerful tool for studies of the neutral ISM at both low and high redshift.
We present an investigation of the relationship between giant molecular cloud (GMC) properties and the associated stellar clusters in the nearby flocculent galaxy NGC 7793. We combine the star ...cluster catalogue from the HST LEGUS (Legacy ExtraGalactic UV Survey) programme with the 15 pc resolution ALMA CO(2-1) observations. We find a strong spatial correlation between young star clusters and GMCs such that all clusters still associated with a GMC are younger than 11 Myr and display a median age of 2 Myr. The age distribution increases gradually as the cluster-GMC distance increases, with star clusters that are spatially unassociated with molecular gas exhibiting a median age of 7 Myr. Thus, star clusters are able to emerge from their natal clouds long before the time-scale required for clouds to disperse. To investigate if the hierarchy observed in the stellar components is inherited from the GMCs, we quantify the amount of clustering in the spatial distributions of the components and find that the star clusters have a fractal dimension slope of -0.35 +/- 0.03, significantly more clustered than the molecular cloud hierarchy with slope of -0.18 +/- 0.04 over the range 40-800 pc. We find, however, that the spatial clustering becomes comparable in strength for GMCs and star clusters with slopes of -0.44 +/- 0.03 and -0.45 +/- 0.06, respectively, when we compare massive (> 10(5) M-circle dot) GMCs to massive and young star clusters. This shows that massive star clusters trace the same hierarchy as their parent GMCs, under the assumption that the star formation efficiency is a few per cent.
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•Frontal midline θ (Fmθ) increases when tracking error exceed a threshold in controls.•Above threshold Fmθ scales with tracking error in controls.•Fmθ failed to increase and scale ...with error following cerebellar damage.•Cerebellum generates prediction error entraining θ rhythm in frontal midline cortex.•Cerebellum activates the executive network when above-threshold errors occur.
Frontal midline θ (Fmθ) activity occurs in medial prefrontal cortices (mPFC), when expected and actual outcomes conflict. Cerebellar forward models could inform the mPFC about this mismatch.
To verify this hypothesis we correlated the mPFC activation during a visuomotor tracking task (VM) with performance accuracy, in control and cerebellum-lesioned participants. Additionally, purely visual (V), motor (M) and a motor plus visual tasks (V + M) were performed.
An Independent Component, with a mid-frontal topography scalp map and equivalent dipole location in the dorsal anterior cingulate cortex accounted for Fmθ.
In control participants Fmθ power increased during VM, when the error level crossed a threshold, but not during V + M, M and V. This increase scaled with tracking error.
Fmθ power failed to increase during VM in cerebellar participants, even at highest tracking errors.
Thus, in control participants, activation of mPFC is induced when a continuous monitoring effort for online error detection is required. The presence of a threshold error for enhancing Fmθ, suggests the switch from an automatic to an executive tracking control, which recruits the mPFC.
Given that the cerebellum stores forward models, the absence of Fmθ increases during tracking errors in cerebellar participants indicates that cerebellum is necessary for supplying the mPFC with prediction error-related information. This occurs when automatic control falters, and a deliberate correction mechanism needs to be triggered.
Further studies are needed to verify if this alerting function also occurs in the context of the other cognitive and non-cognitive functions in which the cerebellum is involved.
ABSTRACT
The morphology of H ii regions around young star clusters provides insight into the time-scales and physical processes that clear a cluster’s natal gas. We study ∼700 young clusters (≤10 ...Myr) in three nearby spiral galaxies (NGC 7793, NGC 4395, and NGC 1313) using Hubble Space Telescope (HST) imaging from LEGUS (Legacy ExtraGalactic Ultraviolet Survey). Clusters are classified by their H α morphology (concentrated, partially exposed, no-emission) and whether they have neighbouring clusters (which could affect the clearing time-scales). Through visual inspection of the HST images, and analysis of ages, reddenings, and stellar masses from spectral energy distributions fitting, together with the (U− B), (V − I) colours, we find (1) the median ages indicate a progression from concentrated (∼3 Myr), to partially exposed (∼4 Myr), to no H α emission (>5 Myr), consistent with the expected temporal evolution of H ii regions and previous results. However, (2) similarities in the age distributions for clusters with concentrated and partially exposed H α morphologies imply a short time-scale for gas clearing (≲1 Myr). Also, (3) our cluster sample’s median mass is ∼1000 M⊙, and a significant fraction ($\sim 20{{\ \rm per\ cent}}$) contain one or more bright red sources (presumably supergiants), which can mimic reddening effects. Finally, (4) the median E(B − V) values for clusters with concentrated H α and those without H α emission appear to be more similar than expected (∼0.18 versus ∼0.14, respectively), but when accounting for stochastic effects, clusters without H α emission are less reddened. To mitigate stochastic effects, we experiment with synthesizing more massive clusters by stacking fluxes of clusters within each H α morphological class. Composite isolated clusters also reveal a colour and age progression for H α morphological classes, consistent with analysis of the individual clusters.