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NSD1, NSD2 and NSD3 proteins constitute a family of histone 3 lysine 36 (H3K36) methyltransferases with similar domain architecture, but diversified activities, in part, dependent on their non-enzymatic domains. These domains, despite their high sequence identity, recruit the hosting proteins to different chromatin regions through the recognition of diverse epigenetic marks and/or associations to distinct interactors. In this sense, the PHDvC5HCH finger tandem domain represents a paradigmatic example of functional divergence within the NSD family. In this work, we prove and give a structural rationale for the uniqueness of the PHDvC5HCH domain of NSD1 in recognizing the C2HR Zinc finger domain of Nizp1 (NSD1 interacting Zn finger protein). Importantly, we show that, in a leukaemogenic context, Nizp1 is pivotal in driving the unscheduled expression of HoxA genes and of genes involved in the type I IFN pathway, triggered by the expression of the fusion protein NUP98-NSD1. These data provide the first insight into the pathophysiological relevance of the Nizp1-NSD1 functional association. Targeting of this interaction might open new therapeutic windows to inhibit the NUP98-NSD1 oncogenic properties.

lt;bgt;lt;igt;Background:lt;/igt;lt;/bgt; The Go Wish Game (GWG) is a practical tool developed to ease advance care planning (ACP) conversations regarding end-of-life (EOL) issues. The game consists of a guide and 35 cards to help persons think about their personal values and priorities in the context of care and to discuss and share those concerns with families and health care professionals (HPs).lt;bgt;lt;igt;Objectives:lt;/igt;lt;/bgt; To promote ACP conversations in the Italian context, we developed an Italian version of the GWG by linguistic translation and cultural adaptation.lt;bgt;lt;igt;Design:lt;/igt;lt;/bgt; Cross-cultural adaptation process developed by Beaton et al.lt;bgt;lt;igt;Measurements:lt;/igt;lt;/bgt; We started with a back-and-forth translation to guarantee linguistic appropriateness. A prefinal Italian version was developed and then qualitatively evaluated by two focus groups (FGs) to assess content validity and cultural appropriateness. Participants' suggestions were discussed by the research groups and included in the final Italian version.lt;bgt;lt;igt;Data analysis:lt;/igt;lt;/bgt; The FGs' transcripts were analyzed by thematic analysis.lt;bgt;lt;igt;Sample:lt;/igt;lt;/bgt; One FG included HPs potentially involved in ACP, the second FG involved representative from local patient associations (RLPAs) with chronic, degenerative, and potentially terminal disease. Participants were purposefully selected. The two FGs involved eight HPs and five RLPAs, respectively.lt;bgt;lt;igt;Results:lt;/igt;lt;/bgt; Fewer explicit statements concerning EOL choices and a broader emphasis on the role of HPs in this discussion characterized the prefinal version. Our analysis identified three themes and five subthemes: (1)lt;igt;improving translationlt;/igt;: linguistic redefinition and practical clarification; (2)lt;igt;how to play the GWGlt;/igt;: needs and suggestions; and (3)lt;igt;more than a gamelt;/igt;.lt;bgt;lt;igt;Conclusion:lt;/igt;lt;/bgt; The Italian version developed in this study presents several cultural peculiarities. The rigorous translation and cultural adaptation process applied can enrich the existing literature by spreading a practical tool for initiating ACP in other languages and cultures. Further studies are needed to evaluate this tool's effectiveness in supporting ACP and training HPs to promote the ACP process.

📚 Cuidado, Tecnologia, Terapia / Care, Technology, Therapy 👥 Eds. Joaquim Braga e Marcela Uchôa 🖊️ Auths. António Dores, Beatriz Rayón Viña, Carlo Botrugno, Catarina Rebelo, João Emanuel Diogo, Joaquim Braga, Marcela Uchôa, Paulo Alexandre e Castro, Vasco Cordovil Cardoso 🏡 Instituto de Estudos Filosóficos 🌐 eQuodlibet: https://www.uc.pt/fluc/uidief/publica/equodlibet/ 🇵🇹 O volume "Cuidado, Tecnologia, Terapia" lança-nos no cerne do cuidado, da tecnologia e da terapia. É um convite para embarcarmos numa viagem através da ética, dos cuidados de saúde e da inovação, levando avante as fronteiras da investigação. Mediante lentes que refletem a envergadura do universo que se desdobra e a complexidade das dinâmicas interpessoais, esta obra induz-nos a repensar o significado da tecnologia na prestação de cuidados e na terapia. 🇬🇧 The volume "Care, Technology, Therapy" plunges us to the heart of care, technology, and therapy. It invites us on a journey through ethics, healthcare, and innovation, pushing forward the frontiers of inquiry. Through lenses reflecting the breadth of the unfolding universe and the intricacy of interpersonal dynamics, this book prompts us to reconsider the meaning of technology in caring and therapy. _ - Boas leituras / Enjoy reading 🧐 e... / and... Saudações Filosóficas! / Philosophical Greetings! 🦉, eQuodlibet 15

Recent efforts have succeeded in surveying open chromatin at the single-cell level, but high-throughput, single-cell assessment of heterochromatin and its underlying genomic determinants remains challenging. We engineered a hybrid transposase including the chromodomain (CD) of the heterochromatin protein-1α (HP-1α), which is involved in heterochromatin assembly and maintenance through its binding to trimethylation of the lysine 9 on histone 3 (H3K9me3), and developed a single-cell method, single-cell genome and epigenome by transposases sequencing (scGET-seq), that, unlike single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq), comprehensively probes both open and closed chromatin and concomitantly records the underlying genomic sequences. We tested scGET-seq in cancer-derived organoids and human-derived xenograft (PDX) models and identified genetic events and plasticity-driven mechanisms contributing to cancer drug resistance. Next, building upon the differential enrichment of closed and open chromatin, we devised a method, Chromatin Velocity, that identifies the trajectories of epigenetic modifications at the single-cell level. Chromatin Velocity uncovered paths of epigenetic reorganization during stem cell reprogramming and identified key transcription factors driving these developmental processes. scGET-seq reveals the dynamics of genomic and epigenetic landscapes underlying any cellular processes.

This book includes the program, the abstracts and all remaining details pertaining to the 2nd IEF International Colloquium ROADS TO CARE,held at the Faculty of Arts and Humanities of the University of Coimbra between October 19 and 21, 2022,organized by the R&D Unit IEF - Institute for Philosophical Studies, funded by the FCT -Foundation for Science and Technology, I.P., of the Ministry of Science, Technology and Higher Education of the Government of the Portuguese Republic, under the UIDB/00010/2020 project.

The construction sector is experiencing a period of renewal in recent years, encouraged by international directives and national regulations worldwide. The most evident advances are represented by the introduction of BIM-based technology. Ensuring safety and security for the built environment is a concern for policy makers, regulations bodies, building owners and managers and for professionals. Applying BIM to address such a relevant objective can bring several benefits such as a better control over the project, greater quality and an optimized planning and execution of emergency management operations. In this paper, a systematic literature review is carried out to evaluate papers dealing with safety and security threats to civil engineering works enabled by BIM and published in 2019–2020. In particular, safety and security aspects are investigated according to three types of threats: 1. structural related issues; 2. exceptional events (e.g., atmospheric phenomena or fires); 3. external attacks or human errors (e.g. acts of terrorism or mistakes in maintenance operations). Furthermore, selected papers are classified based on the involved application domain and BIM dimension. Results show that greater attention is paid to the first and second kind of threat, while a few papers focus on the management of issues potentially caused by external attacks or human errors. The majority of the papers regards the sixth BIM dimension of different kind of buildings while infrastructures and working sites are less studied. Advantages and limitations for the BIM-based safety and security are discussed and serve as a basis for the proposal of future research directions.