AMICO galaxy clusters in KiDS-DR3: weak-lensing mass calibration

We present the mass calibration for galaxy clusters detected with the AMICO code in KiDS DR3 data. The cluster sample comprises $\sim$ 7000 objects and covers the redshift range 0.1 < $z$ < 0.6. We perform a weak lensing stacked analysis by binning the clusters according to redshift and two different mass proxies provided by AMICO, namely the amplitude $A$ (measure of galaxy abundance through an optimal filter) and the richness $\lambda^*$ (sum of membership probabilities in a consistent radial and magnitude range across redshift). For each bin, we model the data as a truncated NFW profile plus a 2-halo term, taking into account uncertainties related to concentration and miscentring. From the retrieved estimates of the mean halo masses, we construct the $A$-$M_{200}$ and the $\lambda^*$-$M_{200}$ relations. The relations extend over more than one order of magnitude in mass, down to $M_{200} \sim 2 (5) \times 10^{13} M_\odot/h$ at $z$ = 0.2 (0.5), with small evolution in redshift. The logarithmic slope is $\sim 2.0$ for the $A$-mass relation, and $\sim 1.7$ for the $\lambda^*$-mass relation, consistent with previous estimations on mock catalogues and coherent with the different nature of the two observables.Comment: 19 pages, 16 figures, accepted by MNRA

villas on islands cost effective energy refurbishment in mediterranean coastline houses

Abstract This paper aims to underline the variability of constructions in Mediterranean regions, where different climates, architectural techniques and kinds of building uses determine different optimal energy refurbishments of residential buildings placed on the coastline. More in detail, by considering two different construction technologies (i.e., a lightweight house in reinforced concrete and a massive tuff-made villa), two different climates (Greek coast, climate of Athens and Italian coast, climate of Naples), two cost-optimal energy retrofits are presented. The optimized energy retrofit, performed by coupling transient energy simulations and genetic algorithm for generating improved models, have taken into account all levers of energy efficiency, and thus optimization of building envelope (thermal insulation, reflectance, windows and solar screens), active energy systems (daylight control, HVAC systems for the regulation of indoor conditions) and renewable energy sources at the building scale (namely, solar photovoltaic)

Neurophysiological Measures and Alcohol Use Disorder (AUD): Hypothesizing Links between Clinical Severity Index and Molecular Neurobiological Patterns

In 1987, Cloninger proposed a clinical description and classification of different personality traits genetically defined and independent from each other. Moreover, he elaborated a specific test the TCI to investigate these traits/states. The study of craving in Alcohol Use Disorder (AUD) assumed a greater significance, since ever more data seems to suggest a direct correlation between high levels of craving and a higher risk of relapse in alcoholics. Thus, our study aim is to explore the possible correlations among TCI linked molecular neurobiological pattern (s), craving and alcohol addiction severity measures in a sample of Italian alcoholics

Combined Point of Care Tools Are Able to Improve Treatment Adherence and Health-Related Quality of Life in Patients with Severe Hemophilia: An Observational Prospective Study

Introduction: Ultrasound (US) assessment of joints is an evolving point of care tool for the detection of early joint arthropathy (Napolitano M, Kessler CM. Hemophilia A and B. Consultative Hemostasis and Thrombosis, Kitchens, 4th edition); population pharmacokinetic (pop-PK) studies are adopted as a useful instrument to set the prophylaxis regimen for patients with hemophilia, they may improve adherence (Nagao A.et al. Thromb Res. 2019 Jan; 173:79-84) and reduce the annual bleeding rate (ABR). Adherence to continuous intravenous administrations of factor VIII or Factor IX products is challenging, thus patients may experience breakthrough bleedings while on prophylaxis. Repeated US examinations of joint status have recently been advocated to attempt to remedy sub-optimal medication adherence (Di Minno A et al., Blood Rev. 2019 Jan;33:106-116). Aim of the current prospective analysis was to evaluate the impact of combined US assessment and pop-PK study on adherence to treatment and health related quality of life in patients with severe hemophilia A(HA) and B (HB) under regular prophylaxis. Material and methods: This prospective observational study was performed at a single tertiary center from January 2017 to June 2019. Research was conducted following the Helsinki Declaration. All patients included in the study provided a written informed consent for study participation. Patients with severe HA and HB routinely underwent, as part of regular 12-months follow-up visits, the following: US joints evaluation of elbows, knees and ankles using the HEAD-US protocol, treatment adherence evaluation by VERITAS-Pro questionnaire, health –related quality of life assessment by the standardized EQ-5D,EQ-VAS and pop-PK study (WAPPS-Hemo, McMaster University) as needed (i.e.in case of changes in life style, planned treatment switch); each patient visualised US and his estimated PK profile during medial encounters. Compliance to the prescribed treatment was also determined by analysis of patient diaries with infusion logs. Statistical analysis was performed using the SPSS software version 25.0 (SPSS Chicago, IL). Statistical tests were 2-sided, with a significance threshold of 0.05. Results: Twenty consecutive males with severe haemophilia were included in the current analysis, 13 with severe HA, 2 with HA with previous inhibitors and 5 HB, with a median age of 30 (range 14- 56) years and a median ABR of 5 (range:0-12). Nine patients were under primary prophylaxis, 8 under secondary prophylaxis and 3 under tertiary prophylaxis, they all self-infused at home. Four patients had one target joint and 3 patients had multiple target joints. For each enrolled subject, HEAD-US score, VERITAS-pro, EQ5D and EQ-VAS score were assessed at enrolment (T0) and at 12 (T12) and 24 (T24) months follow-up visits, respectively. Pop-PK was assessed in 11 patients: in 7 (5 HA,2 HB) it was assessed twice, before and after treatment switch to extended half-life (EHL) products, in 4 it was assessed once to modify prophylaxis treatment schedules for a more active life-style (N=2) or weight changes (N=2). Median ABR was 4 at T12 and 3.8 at T24. Reported breakthrough bleeds at T12 were 14, mainly trauma-related (N= 8) or affecting target joints (N=4), they were not reported at T24 in patients with PK-driven modified schedules (N=4) and in 4 patients under EHL treatments. Mean HEAD-US score at T0 resulted 8 (range:0-16), at T24 it was 6 (range:0-16). Mean Veritas-Pro score values were 42.7 at TO, 40.1 at T12 and 38.7 at T24. At T0, EQ-5D mean utility score was 0.82 (range: 0.68-1), at T24, the mean was 0.87 (range:0.72-1). In detail, at 24 months follow-up, there was a statistically significant (p&lt;0.05) improvement in adherence to treatment with particular reference to the dimensions of communication and skipped doses. A tendency toward improved HEAD-US score, higher adherence and better quality of life scores, was observed in particular in patients switched to EHL products at T24, at a mean of 10 months after switching (range: 6-22 months). Conclusion: Several combined measures of haemophilia treatment monitoring, allowing visual assessment of joints status and PK profile estimates by patients have here shown to improve treatment adherence and quality of life in patients with HA and HB, this may be not only related to new available treatments but also to an increased awareness and education of patients

Regulation of internal promoters in a zinc-responsive operon is influenced by transcription from upstream promoters

In the cyanobacterium Anabaena sp. strain PCC 7120 (also known as Nostoc sp. strain PCC 7120), a zinc-responsive operon (all4725-all4721) has been described, which contains 4 distinct promoters. The two most upstream ones bind Zur with high affinity, whereas the other two do not or do so with a very low affinity. In this paper, a detailed characterization of the four promoters is presented, showing that all four were induced by metal depletion, and they were constitutively derepressed in a zur mutant, despite the two downstream promoters not being direct targets for this regulator. Crucially, induction by metal depletion of the two downstream promoters was abrogated when transcription initiated at the upstream promoters was interrupted by a polar insertion midway in the operon. In contrast, insertion of a nitrogen-responsive promoter at a roughly similar position provoked the two downstream promoters to adopt a regulatory pattern mimicking that of the inserted promoter. Thus, regulation of the two downstream promoters is apparently influenced by transcription from promoters upstream. Evidence is presented indicating that the activity of the two downstream promoters is kept basal in Anabaena by repression. A regulatory model compatible with these results is proposed, where promoters controlled by repression in bacterial operons may be subjected to a hierarchical regulation depending on their position in the operon. According to this model, internal promoters may respond to stimuli governing the activity of promoters upstream by an indirect regulation and to specific stimuli by a direct regulation.Ministerio de Ciencia e Innovación y European Social Fund BFU2010-19544Junta de Andalucía y FEDER CVI2007-0316

Drug repositioning : a machine-learning approach through data integration

Existing computational methods for drug repositioning either rely only on the gene expression response of cell lines after treatment, or on drug-to-disease relationships, merging several information levels. However, the noisy nature of the gene expression and the scarcity of genomic data for many diseases are important limitations to such approaches. Here we focused on a drug-centered approach by predicting the therapeutic class of FDA-approved compounds, not considering data concerning the diseases. We propose a novel computational approach to predict drug repositioning based on state-of-the-art machine-learning algorithms. We have integrated multiple layers of information: i) on the distances of the drugs based on how similar are their chemical structures, ii) on how close are their targets within the protein-protein interaction network, and iii) on how correlated are the gene expression patterns after treatment. Our classifier reaches high accuracy levels (78%), allowing us to re-interpret the top misclassifications as re-classifications, after rigorous statistical evaluation. Efficient drug repurposing has the potential to significantly impact the whole field of drug development. The results presented here can significantly accelerate the translation into the clinics of known compounds for novel therapeutic uses

AMICO galaxy clusters in KiDS-DR3: galaxy population properties and their redshift dependence

A catalogue of galaxy clusters was obtained in an area of 414 sq deg up to a redshift $z\sim0.8$ from the Data Release 3 of the Kilo-Degree Survey (KiDS-DR3), using the Adaptive Matched Identifier of Clustered Objects (AMICO) algorithm. The catalogue and the calibration of the richness-mass relation were presented in two companion papers. Here we describe the selection of the cluster central galaxy and the classification of blue and red cluster members, and analyze the main cluster properties, such as the red/blue fraction, cluster mass, brightness and stellar mass of the central galaxy, and their dependence on redshift and cluster richness. We use the Illustris-TNG simulation, which represents the state-of-the-art cosmological simulation of galaxy formation, as a benchmark for the interpretation of the results. A good agreement with simulations is found at low redshifts ($z \le 0.4$), while at higher redshifts the simulations indicate a lower fraction of blue galaxies than what found in the KiDS-AMICO catalogue: we argue that this may be due to an underestimate of star-forming galaxies in the simulations. The selection of clusters with a larger magnitude difference between the two brightest central galaxies, which may indicate a more relaxed cluster dynamical status, improves the agreement between the observed and simulated cluster mass and stellar mass of the central galaxy. We also find that at a given cluster mass the stellar mass of blue central galaxies is lower than that of the red ones.Comment: 14 pages, 16 figures, accepted for publication on MNRA

Characterization of the response to zinc deficiency in the cyanobacterium Anabaena sp. strain PCC 7120

Zur regulators control zinc homeostasis by repressing target genes under zinc-sufficient conditions in a wide variety of bacteria. This paper describes how part of a survey of duplicated genes led to the identification of the open reading frame all2473 as the gene encoding the Zur regulator of the cyanobacterium Anabaena sp. strain PCC 7120. All2473 binds to DNA in a zinc-dependent manner, and its DNA-binding sequence was characterized, which allowed us to determine the relative contribution of particular nucleotides to Zur binding. A zur mutant was found to be impaired in the regulation of zinc homeostasis, showing sensitivity to elevated concentrations of zinc but not other metals. In an effort to characterize the Zur regulon in Anabaena, 23 genes containing upstream putative Zur-binding sequences were identified and found to be regulated by Zur. These genes are organized in six single transcriptional units and six operons, some of them containing multiple Zur-regulated promoters. The identities of genes of the Zur regulon indicate that Anabaena adapts to conditions of zinc deficiency by replacing zinc metalloproteins with paralogues that fulfill the same function but presumably with a lower zinc demand, and with inducing putative metallochaperones and membrane transport systems likely being involved in the scavenging of extracellular zinc, including plasma membrane ABC transport systems and outer membrane TonB-dependent receptors. Among the Zur-regulated genes, the ones showing the highest induction level encode proteins of the outer membrane, suggesting a primary role for components of this cell compartment in the capture of zinc cations from the extracellular medium.Ministerio de Ciencia e Innovación y Fondo Social Europeo BFU2007-66589/BMC BFU2010-19544Junta de Andalucía y FEDER P07-CVI-0316

Trans-oligomerization of duplicated aminoacyl-tRNA synthetases maintains genetic code fidelity under stress

Aminoacyl-tRNA synthetases (aaRSs) play a key role in deciphering the genetic message by producing charged tRNAs and are equipped with proofreading mechanisms to ensure correct pairing of tRNAs with their cognate amino acid. Duplicated aaRSs are very frequent in Nature, with 25,913 cases observed in 26,837 genomes. The oligomeric nature of many aaRSs raises the question of how the functioning and oligomerization of duplicated enzymes is organized. We characterized this issue in a model prokaryotic organism that expresses two different threonyl-tRNA synthetases, responsible for Thr-tRNAThr synthesis: one accurate and constitutively expressed (T1) and another (T2) with impaired proofreading activity that also generates mischarged Ser-tRNAThr. Low zinc promotes dissociation of dimeric T1 into monomers deprived of aminoacylation activity and simultaneous induction of T2, which is active for aminoacylation under low zinc. T2 either forms homodimers or heterodimerizes with T1 subunits that provide essential proofreading activity in trans. These findings evidence that in organisms with duplicated genes, cells can orchestrate the assemblage of aaRSs oligomers that meet the necessities of the cell in each situation. We propose that controlled oligomerization of duplicated aaRSs is an adaptive mechanism that can potentially be expanded to the plethora of organisms with duplicated oligomeric aaRSs.Ministerio de Economía y Competitividad BFU2010–19544, BFU2013–44686-

hedgehog pathway influence in the immune escape of tumor cells through pdl 1 modulation

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