122 research outputs found
DNA Methylation variability among individuals is related to CpGs cluster density and evolutionary signatures
No full textBackground: In recent years, epigenetics has gained a central role in the understanding of the process of natural selection. It is now clear how environmental impacts on the methylome could promote methylation variability with direct effects on disease etiology as well as phenotypic and genotypic variations in evolutionary processes. To identify possible factors influencing inter-individual methylation variability, we studied methylation values standard deviation of 166 healthy individuals searching for possible associations with genomic features and evolutionary signatures. Results: We analyzed methylation variability values in relation to CpG cluster density and we found a strong association between them (p-value <2.2×10-16). Furthermore, we found that genes related to CpGs with high methylation variability values were enriched for immunological pathways; instead, those associated with low ones were enriched for pathways related to basic cellular functions. Finally, we found an association between methylation variability values and signals of both ancient (p-value <2.2×10-16) and recent selective pressure (p-value <1×10-4). Conclusion: Our results indicate the presence of an intricate interplay between genetics, epigenetic code and evolutionary constraints in humans
Evidence for evolutionary and nonevolutionary forces shaping the distribution of human genetic variants near transcription start sites.
No full textThe regions surrounding transcription start sites (TSSs) of genes play a critical role in the regulation of gene expression. At the same time, current evidence indicates that these regions are particularly stressed by transcription-related mutagenic phenomena. In this work we performed a genome-wide analysis of the distribution of single nucleotide polymorphisms (SNPs) inside the 10 kb region flanking human TSSs by dividing SNPs into four classes according to their frequency (rare, two intermediate classes, and common). We found that, in this 10 kb region, the distribution of variants depends on their frequency and on their localization relative to the TSS. We found that the distribution of variants is generally different for TSSs located inside or outside of CpG islands. We found a significant relationship between the distribution of rare variants and nucleosome occupancy scores. Furthermore, our analysis suggests that evolutionary (purifying selection) and nonevolutionary (biased gene conversion) forces both play a role in determining the relative SNP frequency around TSSs. Finally, we analyzed the potential pathogenicity of each class of variant using the Combined Annotation Dependent Depletion score. In conclusion, this study provides a novel and detailed view of the distribution of genomic variants around TSSs, providing insight into the forces that instigate and maintain variability in such critical regions
Il verde nella casa dell’uomo “compendio di gioie essenziali” / Nature in Homes, a “compendium of essential joys”
No full textNel 1950 Luigi Figini pubblica L’elemento “verde” e l’abitazione: il contributo più rilevante e più appassionato sul rapporto tra costruito, natura, modi di vivere, da parte di un architetto del razionalismo italiano. Guardando alla storia e pensando al presente, egli sviluppa le riflessioni maturate nel periodo tra le due guerre e traccia un itinerario originale tra il verde e il progetto moderno; ne identifica le componenti, illustra esempi e propone soluzioni, lasciando un messaggio di grande significato e attualità per la cultura architettonica: allora come oggi.
Il libro è riproposto in edizione anastatica per rispettare non solo il testo, ma anche le scelte grafiche di Figini, ed è arricchito da un’introduzione di Ornella Selvafolta (in italiano e inglese) che ne spiega l’origine in rapporto alle esperienze architettoniche, culturali e artistiche dell’autore.
In 1950 Luigi Figini published the book L’elemento “verde” e l’abitazione (The element of ‘Nature’ and Dwellings: the most important and most fervent contribution about the relationship between architecture and nature, by an architect of the Italian Rationalism. Linking history to the present, he brings to maturity ideas and experiences of the Thirties and traces an original route between green, home, and modern architecture, showing examples and proposing solutions, thus leaving a message of great significance and relevance for architectural culture and practice: then and now.
The book is presented in a facsimile edition to meet not only the text, but also the graphical choices by Figini, and is introduced by an essay of Ornella Selvafolta that explains its origin in relation to the architectural experiences and culture of the author
M’illumino d’immenso. La scala del palazzo Cassano Ayerbo d’Aragona | M’illumino d’immenso. The staircase of the Palcae Cassano Ayerbo d’Aragona
No full textL’eccezionalità del caso vede, in questo volume, la presenza di un’autorevole firma: Alfonso Gambardella, massimo studioso internazionale dell’architetto Ferdinando Sanfelice a cui rinvia il progetto della scala del palazzo Cassano Ayerbo d’Aragona a Napoli. Incerte sono le fonti archivistiche che documentano le trasformazioni del palazzo nobiliare, attualmente Casa Morra - Archivio d’Arte Contemporanea, e il nome dell’architetto ideatore della sua imponente scala settecentesca. La grandiosità della scala di palazzo Cassano Ayerbo d’Aragona consiste nell’essere un ‘fuori scala’ sia materiale che immateriale, un evento narrativo di grande emozione nella concezione ‘immensa’ di spazio architettonico. A pianta esagonale, il disegno dell’impianto planimetrico e altimetrico nasce dalla sapiente abilità del progettista di articolare forme geometriche elementari in uno spazio plastico e dinamico, vibrante di tensioni strutturali e visioni multiple, simmetriche e asimmetriche. Elementi, questi, tutti riconducibili alla poetica progettuale di Ferdinando Sanfelice. Questo libro nasce dall’interesse nei confronti della scala del palazzo Cassano Ayerbo d’Aragona da parte della curatrice, Ornella Zerlenga, e del noto gallerista napoletano, Giuseppe Morra. La ricerca si sviluppa sulla base del protocollo d’intesa firmato fra la Fondazione Morra e il Dipartimento di Architettura e Disegno Industriale dell’Università degli Studi della Campania ‘Luigi Vanvitelli’ per avviare collaborazioni scientifiche, ma anche azioni con ricadute attive sul territorio in termini di accrescimento culturale. In tal senso, il rilievo e la rappresentazione della grandiosa scala di palazzo Cassano Ayerbo d’Aragona, nella sua unità spaziale e sistematicità metodologica di ricerca monografica, è stato qui svolto per la prima volta nel corso del 2017 da un team di studio del suddetto Dipartimento, coordinato scientificamente da Ornella Zerlenga con Vincenzo Cirillo e svolto da Gianluca Delle Rose, Brigida Di Costanzo, Gessica Friello. Introdotto dai ruoli istituzionali, Teresa Carnevale (Presidente Fondazione Morra), Giuseppe Paolisso (Rettore UniCampania), Luigi Maffei (Direttore Dipartimento), il volume raccoglie i contributi di Pasquale Persico, economista e co-ideatore del piano di riqualificazione sociale “Il Quartiere dell’Arte”; Massimo Pica Ciamarra, co-autore del progetto di riuso del palazzo aperto al quartiere; Igor Todisco, i cui ‘punti di vista’ fotografici concludono la descrizione di una scala spazialmente mutevole.The exceptionality of the case presented in this monograph includes the presence of an authoritative expert: Alfonso Gambardella, the greatest international scholar of the architect Ferdinando Sanfelice, to whom the project of the staircase in Palazzo Cassano Ayerbo d’Aragona in Naples refers. The archival sources that document the transformations of the noble palace, currently Casa Morra - Archivio d’Arte Contemporanea, and the name of the architect who conceived its impressive eighteenth-century staircase are uncertain. The grandeur of the staircase consists of being both materially and immaterially ‘out of scale’, a narrative event of boundless emotion in the ‘immense’ concept of architectural space. With a hexagonal plan, the design of the planimetric and altimetric layout is the result of the skilful ability of the designer to articulate elementary geometric forms in a plastic and dynamic space, vibrating with structural tensions as well as multiple symmetrical and asymmetrical visions. These are all elements that can be traced back to Ferdinando Sanfelice. This book originates from the interest in the staircase of Palazzo Cassano Ayerbo d’Aragona of both the editor, Ornella Zerlenga, as well as the famous Neapolitan gallerist, Giuseppe Morra. The research is developed on the basis of the memorandum of understanding signed between the Fondazione Morra and the Department of Architecture and Industrial Design of the University of Campania ‘Luigi Vanvitelli’ to not only collaborate scientifically, but also to carry out initiatives that will positively influence the cultural growth of the territory. In this sense, the surveying and representation of the grandiose staircase of Palazzo Cassano Ayerbo d’Aragona, in its spatial unity and methodological systematization of monographic research, was carried out for the first time in 2017 by a research team of the aforementioned Department, scientifically coordinated by Ornella Zerlenga with Vincenzo Cirillo and undertaken by Gianluca Delle Rose, Brigida Di Costanzo, Gessica Friello. Introduced by the institutional roles, Tersa Carnevale (President of the Fondazione Morra), Giuseppe Paolisso (Rector UniCampania), Luigi Maffei (Director of the Department), this book includes contributions by Pasquale Persico, economist and co-creator of the social redevelopment plan “Il Quartiere dell’Arte”; Massimo Pica Ciamarra, co-author of the reuse project of the building open to the neighbourhood; Igor Todisco whose ‘points of view’ conclude the description of a spatially changing staircase
Targeted genetic analysis unveils novel associations between ACE I/D and APO T158C polymorphisms with D-dimer levels in severe COVID-19 patients with pulmonary embolism
No full textOnly a percentage of COVID-19 patients develop thrombotic complications. We hypothesized that genetic profiles may explain part of the inter-individual differences. Our goal was to evaluate the genotypic distribution of targeted DNA polymorphisms in COVID-19 patients complicated (PE+) or not (PE−) by pulmonary embolism. We designed a retrospective observational study enrolling N = 94 consecutive patients suffering severe COVID-19 with pulmonary embolism (PE+, N = 47) or not (PE−, N = 47) during hospitalization. A panel of N = 13 prothrombotic DNA polymorphisms (FV R506Q and H1299R, FII G20210A, MTHFR C677T and A1298C, CBS 844ins68, PAI-1 4G/5G, GPIIIa HPA-1 a/b, ACE I/D, AGT T9543C, ATR-1 A1166C, FGB − 455G > A, FXIII103G > T) and N = 2 lipid metabolism-related DNA polymorphisms (APOE T 112C and T158C) were investigated using Reverse Dot Blot technique. Then, we investigated possible associations between genotypic subclasses and demographic, clinical, and laboratory parameters including age, obesity, smoking, pro-inflammatory cytokines, drug therapy, and biomarkers of thrombotic risk such as D-dimer (DD). We found that 58.7% of PE+ had homozygous mutant D/D genotype at ACE I/D locus vs. PE− (40.4%) and 87% of PE+ had homozygous mutant C/C genotype at APOE T158C locus vs. PE− (68.1%). In PE+ group, DD levels were significantly higher in D/D and I/D genotypes at ACE I/D locus (P = 0.00066 and P = 0.00023, respectively) and in C/C and T/C genotypes at APOE T158C locus (P = 1.6e−06 and P = 0.0012, respectively) than PE− group. For the first time, we showed significant associations between higher DD levels and ACE I/D and APOE T158C polymorphisms in PE+ vs. PE− patients suggesting potential useful biomarkers of poor clinical outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11239-022-02728-z
Evolution of intra-tumoral heterogeneity across different pathological stages in papillary thyroid carcinoma
No full textIntra-tumor heterogeneity (ITH) results from the continuous accumulation of mutations during disease progression, thus impacting patients' clinical outcome. How the ITH evolves across papillary thyroid carcinoma (PTC) different tumor stages is lacking
Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression
No full textThe identification of the molecular mechanisms controlling early cell fate decisions in mammals is of paramount importance as the ability to determine specific lineage differentiation represents a significant opportunity for new therapies. Pancreatic Progenitor Cells (PPCs) constitute a regenerative reserve essential for the maintenance and regeneration of the pancreas. Besides, PPCs represent an excellent model for understanding pathological pancreatic cellular remodeling. Given the lack of valid markers of early endoderm, the identification of new ones is of fundamental importance. Both products of the Ink4a/Arf locus, in addition to being critical cell-cycle regulators, appear to be involved in several disease pathologies. Moreover, the locus’ expression is epigenetically regulated in ES reprogramming processes, thus constituting the ideal candidates to modulate PPCs homeostasis. In this study, starting from mouse embryonic stem cells (mESCs), we analyzed the early stages of pancreatic commitment. By inducing mESCs commitment to the pancreatic lineage, we observed that both products of the Cdkn2a locus, Ink4a and Arf, mark a naïve pancreatic cellular state that resembled PPC-like specification. Treatment with epi-drugs suggests a role for chromatin remodeling in the CDKN2a (Cycline Dependent Kinase Inhibitor 2A) locus regulation in line with previous observations in other cellular systems. Our data considerably improve the comprehension of pancreatic cellular ontogeny, which could be critical for implementing pluripotent stem cells programming and reprogramming toward pancreatic lineage commitment
4D-Flow Cardiovascular Magnetic Resonance Sequence for Aortic Assessment: Multi-Vendor and Multi-Magnetic Field Reproducibility in Healthy Volunteers
No full textObjectives: Four-dimensional (4D) flow cardiac magnetic resonance (CMR) represents an emerging technique for non-invasive evaluation of the aortic flow. The aim of this study was to investigate a 4D-flow CMR sequence for the assessment of thoracic aorta comparing different vendors and different magnetic fields of MR scanner in fifteen healthy volunteers. Methods: CMR was performed on three different MRI scanners: one at 1.5 T and two at 3 T. Flow parameters and planar wall shear stress (WSS) were extracted from six transversal planes along the full thoracic aorta by three operators. Inter-vendor comparability as well as scan–rescan, intra- and interobserver reproducibility were examined. Results: A high heterogeneity was found in the comparisons for each operator and for each scanner in the six transversal planes analysis (Friedman rank-sum test; p-value ≤ 0.05). Among all, the most reproducible measures were extracted for the sinotubular junction plane and for the flow parameters. Conclusions: Our results suggest that standardized procedures have to be defined to make more comparable and reproducible 4D-flow parameters and mainly, clinical impactfulness. Further studies on sequences development are needed to validate 4D-flow MRI assessment across vendors and magnetic fields also compared to a missing gold standard
Epigenetic modifications induced by Helicobacter pylori infection through a direct microbe-gastric epithelial cells cross-talk.
No full textCandidate genes and pathways downstream of PAX8 involved in ovarian high-grade serous carcinoma
No full textUnderstanding the biology and molecular pathogenesis of ovarian epithelial cancer (EOC) is key to developing improved diagnostic and prognostic indicators and effective therapies. Although research has traditionally focused on the hypothesis that high-grade serous carcinoma (HGSC) arises from the ovarian surface epithelium (OSE), recent studies suggest that additional sites of origin exist and a substantial proportion of cases may arise from precursor lesions located in the Fallopian tubal epithelium (FTE). In FTE cells, the transcription factor PAX8 is a marker of the secretory cell lineage and its expression is retained in 96% of EOC. We have recently reported that PAX8 is involved in the tumorigenic phenotype of ovarian cancer cells. In this study, to uncover genes and pathways downstream of PAX8 involved in ovarian carcinoma we have determined the molecular profiles of ovarian cancer cells and in parallel of Fallopian tube epithelial cells by means of a silencing approach followed by an RNA-seq analysis. Interestingly, we highlighted the involvement of pathways like WNT signaling, epithelial-mesenchymal transition, p53 and apoptosis. We believe that our analysis has led to the identification of candidate genes and pathways regulated by PAX8 that could be additional targets for the therapy of ovarian carcinom
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