Further constraining galaxy evolution models through the Size Function of SDSS Early-type galaxies

We discuss how the effective radius Phi(Re) function (ERF) recently worked out by Bernardi et al. (2009) represents a new testbed to improve the current understanding of Semi-analytic Models of Galaxy formation. In particular, we here show that a detailed hierarchical model of structure formation can broadly reproduce the correct peak in the size distribution of local early-type galaxies, although it significantly overpredicts the number of very compact and very large galaxies. This in turn is reflected in the predicted size-mass relation, much flatter than the observed one, due to too large (~3 kpc) low-mass galaxies (<10^11 \msun), and to a non-negligible fraction of compact ( 10^11 \msun). We also find that the latter discrepancy is smaller than previously claimed, and limited to only ultracompact (Re < 0.5 kpc) galaxies when considering elliptical-dominated samples. We explore several causes behind these effects. We conclude that the former problem might be linked to the initial conditions, given that large and low-mass galaxies are present at all epochs in the model. The survival of compact and massive galaxies might instead be linked to their very old ages and peculiar merger histories. Overall, knowledge of the galactic stellar mass {\em and} size distributions allows a better understanding of where and how to improve models.Comment: 15 pages, 10 Figures. Accepted by MNRA

Evolution of blue E/S0 galaxies from z~1: merger remnants or disk rebuilding galaxies?

Studying outliers from the bimodal distribution of galaxies in the color-mass space, such as morphological early-type galaxies residing in the blue cloud, can help to better understand the physical mechanisms that lead galaxy migrations in this space. In this paper we study the evolution of the properties of 210 M*/Msol>10^10 blue E/S0s between z~1.4 and z~0.2 in the COSMOS field with confirmed spectroscopic redshifts from the zCOSMOS 10k release. We first observe that the threshold mass, defined at z=0 in previous studies as the mass below which the population of blue early-type galaxies starts to be abundant relative to passive E/S0s, evolves from log(M*/Msol)~10.1 at z~0.3 to log(M*/Msol)~10.9 at z~1. Second, there seems to be a turn-over mass in the nature of blue E/S0 galaxies. Above log(M*/Msol)~10.8 blue E/S0 resemble to merger remnants probably migrating to the red-sequence in a time-scale of ~3 Gyr. Below this mass, they seem to be closer to normal late-type galaxies as if they were the result of minor mergers which triggered the central star-formation and built a central bulge component or were (re)building a disk from the surrounding gas, suggesting that they are moving back or staying in the blue-cloud. This turn-over mass does not seem to evolve significantly from z~1 in contrast with the threshold mass and therefore does not seem to be linked with the relative abundance of blue E/S0s.Comment: accepted for publication in A&

Polyglutamine expansion affects huntingtin conformation in multiple Huntington's disease models

Conformational changes in disease-associated or mutant proteins represent a key pathological aspect of Huntington's disease (HD) and other protein misfolding diseases. Using immunoassays and biophysical approaches, we and others have recently reported that polyglutamine expansion in purified or recombinantly expressed huntingtin (HTT) proteins affects their conformational properties in a manner dependent on both polyglutamine repeat length and temperature but independent of HTT protein fragment length. These findings are consistent with the HD mutation affecting structural aspects of the amino-terminal region of the protein, and support the concept that modulating mutant HTT conformation might provide novel therapeutic and diagnostic opportunities. We now report that the same conformational TR-FRET based immunoassay detects polyglutamine-and temperaturedependent changes on the endogenously expressed HTT protein in peripheral tissues and post-mortem HD brain tissue, as well as in tissues from HD animal models. We also find that these temperatureand polyglutamine-dependent conformational changes are sensitive to bona-fide phosphorylation on S13 and S16 within the N17 domain of HTT. These findings provide key clinical and preclinical relevance to the conformational immunoassay, and provide supportive evidence for its application in the development of therapeutics aimed at correcting the conformation of polyglutamine-expanded proteins as well as the pharmacodynamics readouts to monitor their efficacy in preclinical models and in HD patients

Advancing drug discovery through assay development: a survey of tool compounds within the human solute carrier superfamily

With over 450 genes, solute carriers (SLCs) constitute the largest transporter superfamily responsible for the uptake and efflux of nutrients, metabolites, and xenobiotics in human cells. SLCs are associated with a wide variety of human diseases, including cancer, diabetes, and metabolic and neurological disorders. They represent an important therapeutic target class that remains only partly exploited as therapeutics that target SLCs are scarce. Additionally, many small molecules reported in the literature to target SLCs are poorly characterized. Both features may be due to the difficulty of developing SLC transport assays that fulfill the quality criteria for high-throughput screening. Here, we report one of the main limitations hampering assay development within the RESOLUTE consortium: the lack of a resource providing high-quality information on SLC tool compounds. To address this, we provide a systematic annotation of tool compounds targeting SLCs. We first provide an overview on RESOLUTE assays. Next, we present a list of SLC-targeting compounds collected from the literature and public databases; we found that most data sources lacked specificity data. Finally, we report on experimental tests of 19 selected compounds against a panel of 13 SLCs from seven different families. Except for a few inhibitors, which were active on unrelated SLCs, the tested inhibitors demonstrated high selectivity for their reported targets. To make this knowledge easily accessible to the scientific community, we created an interactive dashboard displaying the collected data in the RESOLUTE web portal (https://re-solute.eu). We anticipate that our open-access resources on assays and compounds will support the development of future drug discovery campaigns for SLCs

On the buildup of massive early-type galaxies at z<~1. I- Reconciling their hierarchical assembly with mass-downsizing

Several studies have tried to ascertain whether or not the increase in abundance of the early-type galaxies (E-S0a's) with time is mainly due to major mergers, reaching opposite conclusions. We have tested it directly through semi-analytical modelling, by studying how the massive early-type galaxies with log(M_*/Msun)>11 at z~0 (mETGs) would have evolved backwards-in-time, under the hypothesis that each major merger gives place to an early-type galaxy. The study was carried out just considering the major mergers strictly reported by observations at each redshift, and assuming that gas-rich major mergers experience transitory phases of dust-reddened, star-forming galaxies (DSFs). The model is able to reproduce the observed evolution of the galaxy LFs at z<~1, simultaneously for different rest-frame bands (B, I, and K) and for different selection criteria on color and morphology. It also provides a framework in which apparently-contradictory results on the recent evolution of the luminosity function (LF) of massive, red galaxies can be reconciled, just considering that observational samples of red galaxies can be significantly contaminated by DSFs. The model proves that it is feasible to build up ~50-60% of the present-day mETG population at z<~1 and to reproduce the observational excess by a factor of ~4-5 of late-type galaxies at 0.8<z<1 through the coordinated action of wet, mixed, and dry major mergers, fulfilling global trends that are in general agreement with mass-downsizing. The bulk of this assembly takes place during ~1 Gyr elapsed at 0.8<z<1. The model suggests that major mergers have been the main driver for the observational migration of mass from the massive-end of the blue galaxy cloud to that of the red sequence in the last ~8 Gyr.(Abridged)Comment: Accepted for publication in Astronomy & Astrophysics; 21 pages, 8 figures. Minor corrections included, shortened title. Results and conclusions unchange

Clinical efficacy of botulinum toxin type A in patients with traumatic brain injury, spinal cord injury, or multiple sclerosis: An observational longitudinal study

Botulinum toxin type A (BoNT-A) is the treatment of choice for focal spasticity, with a concomitant effect on pain reduction and improvement of quality of life (QoL). Current evidence of its efficacy is based mainly on post stroke spasticity. This study aims to clarify the role of BoNT-A in the context of non-stroke spasticity (NSS). We enrolled 86 patients affected by multiple sclerosis, spinal cord injury, and traumatic brain injury with clinical indication to perform BoNT-A treatment. Subjects were evaluated before injection and after 1, 3, and 6 months. At every visit, spasticity severity using the modified Ashworth scale, pain using the numeric rating scale, QoL using the Euro Qol Group EQ-5D-5L, and the perceived treatment effect using the Global Assessment of Efficacy scale were recorded. In our population BoNT-A demonstrated to have a significant effect in improving all the outcome variables, with different effect persistence over time in relation to the diagnosis and the number of treated sites. Our results support BoNT-A as a modifier of the disability condition and suggest its implementation in the treatment of NSS, delivering a possible starting point to generate diagnosis-specific follow-up programs.Clinical trial identifierNCT04673240

Euclid preparation: XXVI. the Euclid Morphology Challenge: Towards structural parameters for billions of galaxies

The various Euclid imaging surveys will become a reference for studies of galaxy morphology by delivering imaging over an unprecedented area of 15 000 square degrees with high spatial resolution. In order to understand the capabilities of measuring morphologies from Euclid-detected galaxies and to help implement measurements in the pipeline of the Organisational Unit MER of the Euclid Science Ground Segment, we have conducted the Euclid Morphology Challenge, which we present in two papers. While the companion paper focusses on the analysis of photometry, this paper assesses the accuracy of the parametric galaxy morphology measurements in imaging predicted from within the Euclid Wide Survey. We evaluate the performance of five state-of-the-art surface-brightness-fitting codes, DeepLeGATo, Galapagos-2, Morfometryka, ProFit and SourceXtractor++, on a sample of about 1.5 million simulated galaxies (350 000 above 5σ) resembling reduced observations with the Euclid VIS and NIR instruments. The simulations include analytic Sérsic profiles with one and two components, as well as more realistic galaxies generated with neural networks. We find that, despite some code-specific differences, all methods tend to achieve reliable structural measurements (< 10% scatter on ideal Sérsic simulations) down to an apparent magnitude of about IE = 23 in one component and IE = 21 in two components, which correspond to a signal-to-noise ratio of approximately 1 and 5, respectively. We also show that when tested on non-analytic profiles, the results are typically degraded by a factor of 3, driven by systematics. We conclude that the official Euclid Data Releases will deliver robust structural parameters for at least 400 million galaxies in the Euclid Wide Survey by the end of the mission. We find that a key factor for explaining the different behaviour of the codes at the faint end is the set of adopted priors for the various structural parameters

Euclid preparation XXVI. The Euclid Morphology Challenge. Towards structural parameters for billions of galaxies

The various Euclid imaging surveys will become a reference for studies of galaxy morphology by delivering imaging over an unprecedented area of 15 000 square degrees with high spatial resolution. In order to understand the capabilities of measuring morphologies from Euclid-detected galaxies and to help implement measurements in the pipeline, we have conducted the Euclid Morphology Challenge, which we present in two papers. While the companion paper by Merlin et al. focuses on the analysis of photometry, this paper assesses the accuracy of the parametric galaxy morphology measurements in imaging predicted from within the Euclid Wide Survey. We evaluate the performance of five state-of-the-art surface-brightness-fitting codes DeepLeGATo, Galapagos-2, Morfometryka, Profit and SourceXtractor++ on a sample of about 1.5 million simulated galaxies resembling reduced observations with the Euclid VIS and NIR instruments. The simulations include analytic S\'ersic profiles with one and two components, as well as more realistic galaxies generated with neural networks. We find that, despite some code-specific differences, all methods tend to achieve reliable structural measurements (10% scatter on ideal S\'ersic simulations) down to an apparent magnitude of about 23 in one component and 21 in two components, which correspond to a signal-to-noise ratio of approximately 1 and 5 respectively. We also show that when tested on non-analytic profiles, the results are typically degraded by a factor of 3, driven by systematics. We conclude that the Euclid official Data Releases will deliver robust structural parameters for at least 400 million galaxies in the Euclid Wide Survey by the end of the mission. We find that a key factor for explaining the different behaviour of the codes at the faint end is the set of adopted priors for the various structural parameters.Comment: Accepted by A&A. 30 pages, 23+6 figures, Euclid pre-launch key paper. Companion paper: Euclid Collaboration XXV: Merlin et al. 2022 Minor corrections after journal revie