The Mbd1-Atf7ip-Setdb1 pathway contributes to the maintenance of X chromosome inactivation.

BackgroundX chromosome inactivation (XCI) is a developmental program of heterochromatin formation that initiates during early female mammalian embryonic development and is maintained through a lifetime of cell divisions in somatic cells. Despite identification of the crucial long non-coding RNA Xist and involvement of specific chromatin modifiers in the establishment and maintenance of the heterochromatin of the inactive X chromosome (Xi), interference with known pathways only partially reactivates the Xi once silencing has been established. Here, we studied ATF7IP (MCAF1), a protein previously characterized to coordinate DNA methylation and histone H3K9 methylation through interactions with the methyl-DNA binding protein MBD1 and the histone H3K9 methyltransferase SETDB1, as a candidate maintenance factor of the Xi.ResultsWe found that siRNA-mediated knockdown of Atf7ip in mouse embryonic fibroblasts (MEFs) induces the activation of silenced reporter genes on the Xi in a low number of cells. Additional inhibition of two pathways known to contribute to Xi maintenance, DNA methylation and Xist RNA coating of the X chromosome, strongly increased the number of cells expressing Xi-linked genes upon Atf7ip knockdown. Despite its functional importance in Xi maintenance, ATF7IP does not accumulate on the Xi in MEFs or differentiating mouse embryonic stem cells. However, we found that depletion of two known repressive biochemical interactors of ATF7IP, MBD1 and SETDB1, but not of other unrelated H3K9 methyltransferases, also induces the activation of an Xi-linked reporter in MEFs.ConclusionsTogether, these data indicate that Atf7ip acts in a synergistic fashion with DNA methylation and Xist RNA to maintain the silent state of the Xi in somatic cells, and that Mbd1 and Setdb1, similar to Atf7ip, play a functional role in Xi silencing. We therefore propose that ATF7IP links DNA methylation on the Xi to SETDB1-mediated H3K9 trimethylation via its interaction with MBD1, and that this function is a crucial feature of the stable silencing of the Xi in female mammalian cells

The Study of Historical Indoor Microclimate (HIM) to Contribute towards Heritage Buildings Preservation

Knowledge of building techniques, materials and their decay is nowadays quite vast, as well as on the solutions and methodologies of a restoration project, which depends on the goal of the restoration itself. Even the choices on the new usage of historic buildings are often well considered. In the last few years, we have conducted some monitoring campaigns to obtain data related to four distinct buildings, differing in construction times, typology, location, current and historical uses. What has been discovered is that these buildings appear to be able to guarantee historical microclimates surprisingly overlapping to the parameters nowadays considered appropriate to conserve them and the historical patrimony they contain. In this article we show some explanatory results of four case studies from our research. The monitoring control, moreover, allowed us to develop the analysis further, from survey to virtual simulation. In this way it was possible to verify the effects of minimal variations in the architectural characteristics, such as opening or closing a window, covering an open yard, or else removing a cover, reducing the source of light etc. All of these managerial and architectural interventions have a significant effect on the indoor environment of buildings and can improve the conservation status of architecture, sometimes to such an extent that more costly and invasive restorations become unnecessary

Recent applications of vibrational mid-Infrared (IR) spectroscopy for studying soil components: a review

The present review highlights the recent applications of mid-infrared spectroscopy and in particular of diffuse reflectance spectroscopy (DRIFT) and attenuated total reflectance (ATR) and processing methods (e.g., deconvolution, derivative and chemometrics) to rapidly provide valuable information on soil composition and organic geochemistry. Research has demonstrated that both DRIFT and ATR techniques can be considered useful tools for the analysis of a large number of soil samples, giving not only typical spectral patterns but permitting an accurate prediction of quantitative parameters such as, e.g., total carbon, total nitrogen, C/Nratio, lignin, dissolved OC, carbonyl-C, aromatic-C, O-alkyl-C, and alkyl-C contents.Based on literature results, infrared spectroscopy can be recognized as one of the most promising analytical techniques for investigating soil science

Geomatic 3D modeling of a statue (also) for structural analysis and risk evaluation: the example of San Giovannino Martelli in Florence

This work has been developed among the researches of a PhD thesis in Civil and Environmental Engineering and Architecture of the University of Udine in cooperation with the GECO Laboratory of the University of Florence. It focuses on the interaction between Geomatics and Structural Analysis, both applied to cultural heritage, and expressly to artefacts and structures in stone materials, like the case study of this paper, the marble statue called “San Giovannino Martelli” (Saint John the Baptist) conserved in Florence. At the beginning, some interesting examples of surveying and structural analyses on statues are reported, in order to remind the complementary tasks and requirements of geomatics and structural analysis. Current laser scanning systems can accurately survey the geometry of a statue or any cultural heritage artefact, essential to understand their structural behaviour and resilience capability. Afterwards, following the few Italian regulations in this field, the possible risks of museum goods are described: topics of this part are more familiar for structural engineers as object classification, seismic reactions, damage mechanisms, possible movements (adherent, slipping and oscillation), dynamic domains, anyway necessary steps to evaluate the risk and so to define eventual interventions. The artistic description of the statue, its debated attribution to Donatello or/and to Desiderio da Settignano and its history is later recalled, remembering that the surveying has been done for the idea to 3D print a replica and to place it in the original place. Having used a close range laser scanner, the obtained 3D model has an impressive geometrical Level of Detail (LoD), whose geometric features are explained in the paper, underlying that such extremely detailed mesh is directly given as output from the laser scanner software. The model simplifications by four decimation are therefore explained and also changes to geometry, like shifts on centre of the mass or barycentre with respect to the original one, are evaluated: since these are pretty null, all the models can be used for structural analysis. Software Scan-and-Solve, a Rhinoceros plug-in, has been employed for Finite Elements Method (FEM) analysis, considering the sole weight and also a horizontal force, as a seismic event or an accidental push, that can synthesize the possible statue risks. The force intensity and geometry have been computed considering the resistance to the overturning for the adherence among statue and pedestal. The more numerically accurate results has been obtained with the more simplified model, having only 7% of initial triangles, since this situation better exploits the computational resources for solver precision and for congruent geometrical LoD and FEM resolution

Library Indoor microclimate monitoring with and without heating system. A Bologna University Library case study

This paper aims to illustrate and give an interpretation of the results emerged from a pilot activity developed within the ROCK project, by the Department of Architecture of the University of Bologna, Alma Mater Studiorum. Through this activity, we studied the indoor microclimate of the University Library of Bologna (BUB), in the Archive and in the Lecture Hall, with the aim to detect how these spaces are affected by the influence of factors such as the outdoor climate and the cooling and heating systems. Moreover, the paper presents the customisation of the probes’ alert system and of the probes itself, used for a one-year monitoring campaign started on the 20th of December 2018. In addition, we calculated the Heritage Microclimate Risk index, to verify the level of risk to which the heritage in the Library is exposed due to the indoor microclimate, and the Predicted Risk of Damage index, that evaluate the more specific risks of damage to which precise objects hosted in there are exposed. Therefore, this paper enriches the research field of Historic Indoor Microclimate, started in 2013, which concerns issues as preventive conservation and restoration in historic buildings. The new insights about the Bologna University Library facilitate the possibility to draw up a specific ‘Indoor Microclimate Management Protocol (IMMP)’ aimed at the preventive conservation of manuscripts and books in historical libraries

Ecosistemi per la ricerca Atti Convegno ACNP/NILDE. Trieste, 22-23 maggio 2014

Il secondo convegno congiunto ACNP / NILDE: ecosistemi per la ricerca è stato ospitato dal 22 al 23 maggio 2014 dall’Università di Trieste. Sono stati affrontati in un’ottica internazionale i temi del rapporto tra cataloghi collettivi e servizi interbibliotecari, e il più generale ambito dei servizi bibliografici per la ricerca scientifica. ACNP e NILDE possono essere considerati un vero e proprio ecosistema. Le biblioteche e i bibliotecari collaborano tra di loro in maniera reciproca e secondo modalità interconnesse, offrendo agli utenti servizi sempre più evoluti e dinamici. Questo ecosistema, essendo aperto, mette i propri servizi a disposizione della ricerca scientifica in senso generale. Il convegno di Trieste ha offerto l’occasione di investigare e proporre soluzioni innovative, interconnessioni e relazioni nuove e più proficue

Mutant MYO1F alters the mitochondrial network and induces tumor proliferation in thyroid cancer

Familial aggregation is a significant risk factor for the development of thyroid cancer and Familial Non-Medullary Thyroid Cancer (FNMTC) accounts for 5-7% of all NMTC. Whole Exome Sequencing analysis in the family affected by FNMTC with oncocytic features where our group previously identified a predisposing locus on chromosome 19p13.2, revealed a novel heterozygous mutation (c.400G>A, NM_012335; p.Gly134Ser) in exon 5 of MYO1F, mapping to the linkage locus. In the thyroid FRTL-5 cell model stably expressing the mutant MYO1F p.Gly134Ser protein we observed an altered mitochondrial network, with increased mitochondrial mass and a significant increase of both intracellular and extracellular Reactive Oxygen Species, compared to cells expressing the wild-type protein or carrying the empty vector. The mutation conferred a significant advantage in colony formation, invasion and anchorage independent growth. These data were corroborated by in vivo studies in zebrafish, since we demonstrated that the mutant MYO1F p.Gly134Ser, when overexpressed, can induce proliferation in whole vertebrate embryos, compared to the wild-type one. MYO1F screening in additional 192 FNMTC families identified another variant in exon 7, which leads to exon skipping, and is predicted to alter the ATP-binding domain in MYO1F. Our study identified for the first time a role for MYO1F in NMTC. This article is protected by copyright. All rights reserved

Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation

Naive human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X chromosome state has remained unresolved. Here, we show that the inactive X chromosome (Xi) of primed hESCs was reactivated in naive culture conditions. Like cells of the blastocyst, the resulting naive cells contained two active X chromosomes with XIST expression and chromosome-wide transcriptional dampening and initiated XIST-mediated X inactivation upon differentiation. Both establishment of and exit from the naive state (differentiation) happened via an XIST-negative XaXaintermediate. Together, these findings identify a cell culture system for functionally exploring the two X chromosome dosage compensation processes in early human development: X dampening and X inactivation. However, remaining differences between naive hESCs and embryonic cells related to mono-allelic XIST expression and non-random X inactivation highlight the need for further culture improvement. As the naive state resets Xiabnormalities seen in primed hESCs, it may provide cells better suited for downstream applications

Insulin resistance, diabetic kidney disease, and all-cause mortality in individuals with type 2 diabetes. a prospective cohort study

BACKGROUND: It is unclear whether insulin resistance (IR) contributes to excess mortality in patients with type 2 diabetes independent of diabetic kidney disease (DKD), which is strongly associated with IR and is a major risk factor for cardiovascular disease (CVD), the main cause of death in these individuals. We tested this hypothesis in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian Multicentre Study.METHODS: This observational, prospective, cohort study enrolled 15,773 patients with type 2 diabetes attending 19 Italian Diabetes Clinics in 2006-2008. Insulin sensitivity was assessed as estimated glucose disposal rate (eGDR), which was validated against the euglycaemic-hyperinsulinemic clamp technique. Vital status on October 31, 2015, was retrieved for 15,656 patients (99.3%). Participants were stratified by eGDR tertiles from T1 (≥ 5.35mg/kg/min) to T3 (≤ 4.14mg/kg/min, highest IR).RESULTS: CVD risk profile was worse in T2 and T3 vs T1. eGDR tertiles were independently associated with micro- and macroalbuminuria and the albuminuric DKD phenotypes (albuminuria with preserved or reduced estimated glomerular filtration rate [eGFR]) as well as with eGFR categories or the nonalbuminuric DKD phenotype. Over a 7.4-year follow-up, unadjusted death rates and mortality risks increased progressively across eGDR tertiles, but remained significantly elevated after adjustment only in T3 vs T1 (age- and gender- adjusted death rate, 22.35 vs 16.74 per 1000 person-years, p<0.0001, and hazard ratio [HR] adjusted for multiple confounders including DKD, 1.140 [95% confidence interval [CI], 1.049-1.238], p=0.002). However, eGDR was independently associated with mortality in participants with no DKD (adjusted HR, 1.214 [95% CI, 1.072-1.375], p=0.002) and in those with nonalbuminuric DKD (1.276 [1.034-1.575], p=0.023), but not in those with the albuminuric DKD phenotypes. Moreover, the association was stronger in males and in younger individuals and was observed in those without but not with prior CVD, though interaction was significant only for age.CONCLUSIONS: The proxy of insulin sensitivity eGDR predicts all-cause mortality in type 2 diabetes, independent of confounders including DKD. However, the impact of IR in individuals with albuminuric DKD may be mediated by its relationship with albuminuria.TRIAL REGISTRATION: ClinicalTrials.gov , NCT00715481, retrospectively registered 15 July 2008