Background & Aims: Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in ...such patients and correlated genotypes with residual protein detection and risk of malignancy. Methods: Patients with intrahepatic cholestasis suggestive of BSEP deficiency were investigated by single-strand conformation polymorphism analysis and sequencing of ABCB11 . Genotypes sorted by likely phenotypic severity were correlated with data on BSEP immunohistochemistry and clinical outcome. Results: Eighty-two different mutations (52 novel) were identified in 109 families (9 nonsense mutations, 10 small insertions and deletions, 15 splice-site changes, 3 whole-gene deletions, 45 missense changes). In 7 families, only a single heterozygous mutation was identified despite complete sequence analysis. Thirty-two percent of mutations occurred in >1 family, with E297G and/or D482G present in 58% of European families (52/89). On immunohistochemical analysis (88 patients), 93% had abnormal or absent BSEP staining. Expression varied most for E297G and D482G, with some BSEP detected in 45% of patients (19/42) with these mutations. Hepatocellular carcinoma or cholangiocarcinoma developed in 15% of patients (19/128). Two protein-truncating mutations conferred particular risk; 38% (8/21) of such patients developed malignancy versus 10% (11/107) with potentially less severe genotypes (relative risk, 3.7 confidence limits, 1.7–8.1; P = .003). Conclusions: With this study, >100 ABCB11 mutations are now identified. Immunohistochemically detectable BSEP is typically absent, or much reduced, in severe disease. BSEP deficiency confers risk of hepatobiliary malignancy. Close surveillance of BSEP-deficient patients retaining their native liver, particularly those carrying 2 null mutations, is essential.
We present measurements of the growth rate of cosmological structure from the modelling of the anisotropic galaxy clustering measured in the final data release of the VIPERS survey. The analysis is ...carried out in configuration space and based on measurements of the first two even multipole moments of the anisotropic galaxy auto-correlation function, in two redshift bins spanning the range 0.5 <z< 1.2. We provide robust and cosmology-independent corrections for the VIPERS angular selection function, allowing recovery of the underlying clustering amplitude at the percent level down to the Mpc scale. We discuss several improvements on the non-linear modelling of redshift-space distortions (RSD) and perform detailed tests of a variety of approaches against a set of realistic VIPERS-like mock realisations. This includes using novel fitting functions to describe the velocity divergence and density power spectra Pθθ and Pδθ that appear in RSD models. These tests show that we are able to measure the growth rate with negligible bias down to separations of 5 h-1 Mpc. Interestingly, the application to real data shows a weaker sensitivity to the details of non-linear RSD corrections compared to mock results. We obtain consistent values for the growth rate times the matter power spectrum normalisation parameter of fσ8 = 0.55 ± 0.12 and 0.40 ± 0.11 at effective redshifts of z = 0.6 and z = 0.86 respectively. These results are in agreement with standard cosmology predictions assuming Einstein gravity in a ΛCDM background.
The ALPINE-ALMA [CII] survey Cassata, P.; Morselli, L.; Faisst, A. ...
Astronomy and astrophysics (Berlin),
11/2020, Volume:
643
Journal Article
Peer reviewed
Open access
Context.
The Lyman-
α
line in the ultraviolet (UV) and the CII line in the far-infrared (FIR) are widely used tools to identify galaxies in the early Universe and to obtain insights into interstellar ...medium (ISM) properties in high-redshift galaxies. By combining data obtained with ALMA in band 7 at ∼320 GHz as part of the ALMA Large Program to INvestigate CII at Early Times (ALPINE) with spectroscopic data from DEIMOS at the Keck Observatory, VIMOS and FORS2 at the Very Large Telescope, we assembled a unique sample of 53 main-sequence star-forming galaxies at 4.4 <
z
< 6 in which we detect both the Lyman-
α
line in the UV and the CII line in the FIR.
Aims.
The goal of this paper is to constrain the properties of the Ly
α
emission in these galaxies in relation to other properties of the ISM.
Methods.
We used CII, observed with ALMA, as a tracer of the systemic velocity of the galaxies, and we exploited the available optical spectroscopy to obtain the Ly
α
-CII and ISM-CII velocity offsets.
Results.
We find that 90% of the selected objects have Ly
α
-CII velocity offsets in the range 0 < Δ
v
Ly
α
− CII
< 400 km s
−1
, in line with the few measurements available so far in the early Universe, and significantly smaller than those observed at lower redshifts. At the same time, we observe ISM-CII offsets in the range −500 < Δ
v
ISM−CII
< 0 km s
−1
, in line with values at all redshifts, which we interpret as evidence for outflows in these galaxies. We find significant anticorrelations between Δ
v
Ly
α
−CII
and the Ly
α
rest-frame equivalent width
EW
0
(Ly
α
) (or equivalently, the Ly
α
escape fraction
f
esc
(Ly
α
)): galaxies that show smaller Δ
v
Ly
α
−CII
have larger
EW
0
(Ly
α
) and
f
esc
(Ly
α
).
Conclusions.
We interpret these results in the framework of available models for the radiative transfer of Ly
α
photons. According to the models, the escape of Ly
α
photons would be favored in galaxies with high outflow velocities, producing large
EW
0
(Ly
α
) and small Δ
v
Ly
α
-CII
, in agreement with our observations. The uniform shell model would also predict that the Ly
α
escape in galaxies with slow outflows (0 <
v
out
< 300 km s
−1
) is mainly determined by the neutral hydrogen column density (NHI) along the line of sight, while the alternative model by Steidel et al. (2010, ApJ, 717, 289) would more highly favor a combination of NHI at the systemic velocity and covering fraction as driver of the Ly
α
escape. We suggest that the increase in Ly
α
escape that is observed in the literature between
z
∼ 2 and
z
∼ 6 is not due to a higher incidence of fast outflows at high redshift, but rather to a decrease in average NHI along the line of sight, or alternatively, a decrease in HI covering fraction.
This study evaluated the effect of 250, 333, or 400 IU of a commercial porcine stimulating-follicle hormone (pFSH) on follicular growth, superovulatory (SOV) response, and embryo yield in White ...Dorper sheep. Ewes received an induced-ovulation protocol (D0 = progesterone (P4) device insertion) and superovulation starting 60 h before P4 withdrawal (D9), which consisted of six decreasing doses of 250 IU (G250; n = 15), 333 IU (G333; n = 15), or 400 IU (G400; n = 14) of pFSH. Ewes also received 50 µg of gonadotropin-releasing hormone (GnRH) analog on D10 and 300 IU of hCG on D13. Ewes were mated and submitted to non-surgical embryo recovery (NSER). Ultrasound evaluations were performed on D6, D7, D8, D9, and D16. The overall responding donor rate (≥3 CL) was 86.4% (38/44). The mean number of large follicles was higher (P < 0.05) in all groups on D8 (6.2 ± 0.9, 7.7 ± 0.9, and 8.3 ± 1.1) and D9 (11.1 ± 0.6, 10.4 ± 1.0, and 11.5 ± 0.9). Non-surgical embryo recovery procedures were successfully performed in 60.5% (23/38) of females. The CL count in successfully flushed ewes was greater (P < 0.05) in G333 (12.7 ± 2.3) and G400 (12.0 ± 1.3) than in G250 (6.0 ± 1.1). The recovery rate (44.4%, 57.3%, and 50.0%) and numbers of transferable embryos (2.3 ± 1.1, 6.1 ± 2.6, and 4.5 ± 1.3) did not differ (P > 0.05) among groups. All protocols were efficient in promoting follicular growth and adequate superovulatory response and embryo yield.
•Treatments with 250, 333 or 400IU were efficient to promote superovulation response.•Treatment with 333 or 400IU of pFSH increased CL count in ewes successfully flushed.•Selection of donors before superovulation is necessary to avoid NSER failures.
The contribution of the merging process to the early phase of galaxy assembly at z > 1 and, in particular, to the build-up of the red sequence, still needs to be accurately assessed. We aim to ...measure the major merger rate of star-forming galaxies at 0.9 < z < 1.8, using close pairs identified from integral field spectroscopy (IFS). Merging of star-forming galaxies is frequent at around the peak in star formation activity. Our results show that gasrich mergers make an important contribution to the growth of massive galaxies since z ~1.5, particularly on the build-up of the red sequence.
Long gamma-ray bursts (LGRBs) are associated to the deaths of massive stars and could thus be used as a potentially powerful tool to trace cosmic star formation. However the conditions needed to ...produce a LGRBs may introduce a bias in the LGRB rate versus star formation rate (SFR) relation (called LGRB efficiency hereafter). We have undertaken a study of the properties of the host galaxies of the BAT6 complete sample of LGRB to improve our knowledge on the LGRB efficiency, its redshift evolution, and the factor affecting it. This is the base to properly use LGRBs as SFR tracers. We show that at z < 1 LGRBs are not direct SFR tracers because they tend to avoid high-metallicity galaxies. The use of the BAT6 complete sample keeps this result from being affected by possible biases that could have influenced past results based on incomplete samples. The preference for low (but not extremely low) metallicities can be a consequence of the particular conditions needed for the progenitor star to produce a GRB.
Context. Using Chandra observations we identified a sample of seven off-nuclear X-ray sources in the redshift range z = 0.072–0.283, located within optically bright galaxies in the COSMOS Survey. All ...of them, if associated with their closest bright galaxy, would have L0.5–7 keV > 1039 erg s-1 and therefore can be classified as ultraluminous X-ray sources (ULXs). Aims. Using the multi-wavelength coverage available in the COSMOS field, we studied the properties of the host galaxies of these ULXs. In detail, we derived their star formation rate from Hα measurements and their stellar masses using SED fitting techniques with the aim to compute the probability to have an off-nuclear source based on the host galaxy properties. We divided the host galaxies in different morphological classes with the available ACS/HST imaging. Methods. We selected off-nuclear candidates with the following criteria: 1) the distance between the X-ray and the optical centroid has to be larger than 0.9´´, larger than 1.8 times the radius of the Chandra positional error circle and smaller than the Petrosian radius of the host galaxy; 2) the optical counterpart is a bright galaxy (RAB<22); 3) the redshift of the counterpart is lower than z = 0.3; 4) the source has been observed in at least one Chandra pointing at an off-axis angle smaller than 5´; 5) the X-ray positional error is smaller than 0.8´´. We verified each candidate super-imposing the X-ray contours on the optical/IR images. We expect less than one misidentified AGN due to astrometric errors and on average 1.3 serendipitous background source matches. Results. We find that our ULXs candidates are located in regions of the SFR versus ${\rm M}_\star$ plane where one or more off-nuclear detectable sources are expected. From a morphological analysis of the ACS imaging and the use of rest-frame colours, we find that our ULXs are hosted both in late and early type galaxies. Finally, we find that the fraction of galaxies hosting a ULX ranges from ≈0.5% to ≈0.2% going from $L_{0.5{-}2~{\rm keV}}$ = 3 × 1039 erg s-1 to $L_{0.5{-}2~{\rm keV}}$ = 2 × 1040 erg s-1.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP-binding cassette (ABC) transporter superfamily. CFTR controls the flow of anions through the apical membrane of ...epithelia. Dysfunctional CFTR causes the common lethal genetic disease cystic fibrosis. Transitions between open and closed states of CFTR are regulated by ATP binding and hydrolysis on the cytosolic nucleotide binding domains, which are coupled with the transmembrane (TM) domains forming the pathway for anion permeation. Lack of structural data hampers a global understanding of CFTR and thus the development of “rational” approaches directly targeting defective CFTR. In this work, we explored possible conformational states of the CFTR gating cycle by means of homology modeling. As templates, we used structures of homologous ABC transporters, namely TM(287–288), ABC-B10, McjD, and Sav1866. In the light of published experimental results, structural analysis of the transmembrane cavity suggests that the TM(287–288)-based CFTR model could correspond to a commonly occupied closed state, whereas the McjD-based model could represent an open state. The models capture the important role played by Phe-337 as a filter/gating residue and provide structural information on the conformational transition from closed to open channel.
Background: CFTR, which controls Cl− permeation across epithelia, is an ABC transporter whose structure is not known.
Results: We modeled CFTR using the crystal structure of four homologous transporters.
Conclusion: We identified possible open and closed conformations of CFTR.
Significance: The models help the interpretation of experimental data and provide new hypotheses to test with experiments.
We study the evolution of the star formation rate (SFR) - stellar mass (M-star) relation and specific star formation rate (sSFR) of star-forming galaxies (SFGs) since a redshift z similar or equal to ...5.5 using 2435 (4531) galaxies with highly reliable spectroscopic redshifts in the VIMOS Ultra-Deep Survey (VUDS). It is the first time that these relations can be followed over such a large redshift range from a single homogeneously selected sample of galaxies with spectroscopic redshifts. The log(SFR) - log(M-star) relation for SFGs remains roughly linear all the way up to z = 5, but the SFR steadily increases at fixed mass with increasing redshift. We find that for stellar masses M-star \textgreater= 3.2 x 10(9) M-circle dot the SFR increases by a factor of similar to 13 between z = 0.4 and z = 2.3. We extend this relation up to z = 5, finding an additional increase in SFR by a factor of 1.7 from z = 2.3 to z = 4.8 for masses M-star = 1010 M-circle dot. We observe a turn-off in the SFR-M-star relation at the highest mass end up to a redshift z similar to 3.5. We interpret this turn-off as the signature of a strong on-going quenching mechanism and rapid mass growth. The sSFR increases strongly up to z similar to 2, but it grows much less rapidly in 2 \textless z \textless 5. We find that the shape of the sSFR evolution is not well reproduced by cold gas accretion-driven models or the latest hydrodynamical models. Below z similar to 2 these models have a flatter evolution (1+z)(Phi) with Phi = 2-2.25 compared to the data which evolves more rapidly with Phi = 2.8 +/- 0.2. Above z similar to 2, the reverse is happening with the data evolving more slowly with Phi = 1.2 +/- 0.1. The observed sSFR evolution over a large redshift range 0 \textless z \textless 5 and our finding of a non-linear main sequence at high mass both indicate that the evolution of SFR and M-star is not solely driven by gas accretion. The results presented in this paper emphasize the need to invoke a more complex mix of physical processes including major and minor merging to further understand the co-evolution of the SFR and stellar mass growth.
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