Epigenetic DNA Modifications Are Correlated With B Chromosomes and Sex in the Cichlid Astatotilapia latifasciata

Supernumerary B chromosomes are dispensable elements found in several groups of eukaryotes, and their impacts in host organisms are not clear. The cichlid fish Astatotilapia latifasciata presents one or two large metacentric B chromosomes. These elements affect the transcription of several classes of RNAs. Here, we evaluated the epigenetic DNA modification status of B chromosomes using immunocytogenetics and assessed the impact of B chromosome presence on the global contents of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) and the molecular mechanisms underlying these variations. We found that the B chromosome of A. latifasciata has an active pattern of DNA epimarks, and its presence promotes the loss of 5mC in gonads of females with B chromosome (FB+) and promotes the loss of 5hmC in the muscle of males with the B element (MB+). Based on the transcriptional quantification of DNA modification genes (dnmt, tet, and tdg) and their candidate regulators (idh genes, microRNAs, and long non-coding RNAs) and on RNA-protein interaction prediction, we suggest the occurrence of passive demethylation in gonads of FB+ and 5hmC loss by Tet inhibition or by 5hmC oxidation in MB+ muscle. We suggest that these results can also explain the previously reported variations in the transcription levels of several classes of RNA depending on B chromosome presence. The DNA modifications detected here are also influenced by sex. Although the correlation between B chromosomes and sex has been previously reported, it remains unexplained. The B chromosome of A. latifasciata seems to be active and impacts cell physiology in a very complex way, including at the epigenetic level

Inovações cirúrgicas na abordagem de doenças neurodegenerativas

This article is an integrative review of surgical innovations in the treatment of neurodegenerative diseases. In response to the growing interest in the intersection between surgery, neuroscience and emerging technologies, it seeks to understand current and future trends in surgical interventions for the treatment of these conditions. The methodology adopted followed strict guidelines for conducting an integrative review. A systematic search was carried out in scientific databases such as PubMed, Scopus and Scielo, using specific keywords. Inclusion and exclusion criteria were established for the selection of references, taking into account their relevance to surgical innovations in neurodegenerative diseases. Critical analysis of the selected references revealed a wide range of surgical innovations applied in the context of neurodegenerative diseases. Approaches such as neurostimulation, brain-machine interfaces, deep brain stimulation and other advanced surgical techniques stand out. Results indicate significant benefits in terms of cognitive improvement, motor control and quality of life for patients undergoing these interventions. The integrative review provided a comprehensive overview of surgical innovations in the approach to neurodegenerative diseases. Technological advances and innovative surgical approaches present promising therapeutic prospects. However, challenges such as personalization of treatments and long-term evaluation still require further investigation. The conclusion underscores the continued importance of research in this field to improve the efficacy and safety of these interventions, thus contributing to advances in the treatment of neurodegenerative diseases.O presente artigo realiza uma revisão integrativa abordando as inovações cirúrgicas na abordagem de doenças neurodegenerativas. Em resposta ao crescente interesse na interseção entre cirurgia, neurociência e tecnologias emergentes, busca-se compreender as tendências atuais e futuras nas intervenções cirúrgicas para o tratamento dessas condições. A metodologia adotada seguiu diretrizes rigorosas para a realização de uma revisão integrativa. Foi realizada uma busca sistemática em bases de dados científicas, como PubMed, Scopus e Scielo, utilizando palavras-chave específicas. Foram estabelecidos critérios de inclusão e exclusão para a seleção das referências, levando em consideração a relevância para inovações cirúrgicas em doenças neurodegenerativas. A análise crítica das referências selecionadas revelou uma ampla gama de inovações cirúrgicas aplicadas no contexto das doenças neurodegenerativas. Destacam-se abordagens como neuroestimulação, interfaces cérebro-máquina, estimulação cerebral profunda e outras técnicas cirúrgicas avançadas. Resultados indicam benefícios significativos em termos de melhoria cognitiva, controle motor e qualidade de vida para os pacientes submetidos a essas intervenções. A revisão integrativa proporcionou uma visão abrangente das inovações cirúrgicas na abordagem de doenças neurodegenerativas. Os avanços tecnológicos e as abordagens cirúrgicas inovadoras apresentam promissoras perspectivas terapêuticas. Contudo, desafios como a personalização dos tratamentos e a avaliação a longo prazo ainda requerem investigações mais aprofundadas. A conclusão ressalta a importância contínua da pesquisa nesse campo para aprimorar a eficácia e a segurança dessas intervenções, contribuindo assim para o avanço do tratamento de doenças neurodegenerativas

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

Pathogen-sugar interactions revealed by universal saturation transfer analysis

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an “end-on” manner. uSTA-guided modeling and a high-resolution cryo–electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis

Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%

NUOVA ESPERIENZA ABITATIVA NEL “VILLAGGIO BARCA”: Prospettive di rigenerazione urbana, ambientale ed energetica del Quartiere CEP-INA Casa Barca a BOLOGNA

Il progetto si occupa della rigenerazione urbana, ambientale ed energetica del “Villaggio Barca”, situato nella zona a Ovest della città di Bologna. Il quartiere fa parte del patrimonio di edilizia residenziale Ina-Casa, realizzato tra il 1957 e il ’63 da un gruppo di progettisti coordinato da Giuseppe Vaccaro. L’area è costituita da edifici bassi e poco densificati di interesse culturale-testimoniale; è ben connesso al centro e raggiungibile sia con i mezzi pubblici sia privati; è stato il primo quartiere della città a adottare un sistema di teleriscaldamento; sono presenti molte aree verdi ed è vicina al parco fluviale. La posizione periferica, negli anni, ha contribuito ad un parziale abbandono della zona. Presenta spazi all’aperto trascurati e sottoutilizzati, edifici in uno stato di degrado, con una bassa efficienza energetica e una preferenza per la mobilità pesante. In seguito a questa analisi, è stata proposta la riprogettazione dell’area con l’adozione di strategie molteplici. Gli obiettivi sono: potenziare la mobilità sostenibile e riqualificare gli edifici esistenti per ridurre l’inquinamento; ripensare gli alloggi per rispondere alla domanda abitativa; realizzare due Hub per le associazioni e il turismo; riqualificare gli spazi aperti per migliorare i rapporti di comunità; valorizzare la natura urbana e fluviale per preservare la biodiversità in un'ottica di sostenibilità ambientale; valutare l’impatto degli interventi sul benessere psicofisico dei residenti. Per attestare il miglioramento della qualità ambientale del “Villaggio”, sono state condotte delle simulazioni nelle condizioni attuali e dopo gli interventi, utilizzando due software: Envimet per valutare microclima urbano; Termolog per verificare le prestazioni dell’involucro costruttivo. Il progetto presta particolare attenzione a preservare il carattere architettonico del portico del “Treno”, riconosciuto come patrimonio UNESCO e valorizzarne il potenziale all’interno del quartiere

Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome

Background and Aims: A few case reports of autoimmune hepatitis–like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. Approach and Results: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18–79) years at presentation. Liver injury was diagnosed a median 15 (range: 3–65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3–4 liver injury than for grade 1–2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. Conclusions: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.Fil: Efe, Cumali. Harran University Hospital; TurquíaFil: Kulkarni, Anand V.. Asian Institute of Gastroenterology Hospitals; IndiaFil: Terziroli Beretta Piccoli, Benedetta. Università Della Svizzera Italiana; Suiza. Epatocentro Ticino; SuizaFil: Magro, Bianca. ASST Papa Giovanni XXIII-Bergamo; ItaliaFil: Stättermayer, Albert. Medizinische Universität Wien; AustriaFil: Cengiz, Mustafa. Gülhane Training and Research Hospital; TurquíaFil: Clayton Chubb, Daniel. Alfred Health; AustraliaFil: Lammert, Craig. University School of Medicine; Estados UnidosFil: Bernsmeier, Christine. University Centre for Gastrointestinal and Liver Diseases; Suiza. Universidad de Basilea; SuizaFil: Gül, Özlem. Kırıkkale University; TurquíaFil: de la Tijera, Fatima Higuera. Hospital General de México; MéxicoFil: Anders, Margarita. Hospital Alemán; ArgentinaFil: Lytvyak, Ellina. University of Alberta; CanadáFil: Akın, Mete. Akdeniz University Faculty of Medicine; TurquíaFil: Purnak, Tugrul. University of Texas; Estados UnidosFil: Liberal, Rodrigo. World Gastroenterology Organization; Portugal. Centro Hospitalar E Universitário de São João; PortugalFil: Peralta, Mirta. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Latin American Liver Research Educational And Awareness Network; ArgentinaFil: Ebik, Berat. Gazi Yaşargil Education and Research Hospita; TurquíaFil: Duman, Serkan. Gazi Yaşargil Education and Research Hospita; TurquíaFil: Demir, Nurhan. Haseki Training and Research Hospital; TurquíaFil: Balaban, Yasemin. Hacettepe University; TurquíaFil: Urzua, Álvaro. Universidad de Chile; ChileFil: Contreras, Fernando. Centro de Gastroenterología Avanzada; República DominicanaFil: Venturelli, Maria Grazia. Clinica Stella Maris; PerúFil: Bilgiç, Yılmaz. Inönü University School of Medicine; TurquíaFil: Medina, Adriana. Hospital de Clínicas; ParaguayFil: Girala, Marcos. Hospital de Clínicas; ParaguayFil: Günşar, Fulya. Ege University School of Medicine; TurquíaFil: Londoño, Maria Carlota. Hospital Sant Joan de Deu Barcelona; EspañaFil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentin