25 research outputs found
New Cases and Mutations in SEC23B Gene Causing Congenital Dyserythropoietic Anemia Type II
Hereditary anemias; Ineffective erythropoiesis; Rare blood diseaseAnĂšmies hereditĂ ries; Eritropoesi ineficaç; Malaltia rara de la sangAnemias hereditarias; Eritropoyesis ineficaz; Enfermedad rara de la sangreCongenital dyserythropoietic anemia type II (CDA II) is an inherited autosomal recessive blood disorder which belongs to the wide group of ineffective erythropoiesis conditions. It is characterized by mild to severe normocytic anemia, jaundice, and splenomegaly owing to the hemolytic component. This often leads to liver iron overload and gallstones. CDA II is caused by biallelic mutations in the SEC23B gene. In this study, we report 9 new CDA II cases and identify 16 pathogenic variants, 6 of which are novel. The newly reported variants in SEC23B include three missenses (p.Thr445Arg, p.Tyr579Cys, and p.Arg701His), one frameshift (p.Asp693GlyfsTer2), and two splicing variants (c.1512-2A>G, and the complex intronic variant c.1512-3delinsTT linked to c.1512-16_1512-7delACTCTGGAAT in the same allele). Computational analyses of the missense variants indicated a loss of key residue interactions within the beta sheet and the helical and gelsolin domains, respectively. Analysis of SEC23B protein levels done in patient-derived lymphoblastoid cell lines (LCLs) showed a significant decrease in SEC23B protein expression, in the absence of SEC23A compensation. Reduced SEC23B mRNA expression was only detected in two probands carrying nonsense and frameshift variants; the remaining patients showed either higher gene expression levels or no expression changes at all. The skipping of exons 13 and 14 in the newly reported complex variant c.1512-3delinsTT/c.1512-16_1512-7delACTCTGGAAT results in a shorter protein isoform, as assessed by RT-PCR followed by Sanger sequencing. In this work, we summarize a comprehensive spectrum of SEC23B variants, describe nine new CDA II cases accounting for six previously unreported variants, and discuss innovative therapeutic approaches for CDA II.This work was supported by NEOTEC grant SNEO-20191246 from Spanish CDTI to C.T., RETOS COLABORACION grant RTC2019-007074-1 from: MCIN/AEI/10.13039/501100011033 from Spanish Ministry of Science and Innovation (MICINN) to C.T. and M.S.; ARETHA grant PID2021-122436OB-I00 funded by MCIN/AEI/10.13039/501100011033 to M.S.; RTI-2018-101735-B-I100 from MCIN/AEI/10.13039/501100011033/ERDF âA way to make Europeâ from the Spanish Ministry of Science and Innovation (MICINN) to M.S. M.M.M. is supported by a Marie Curie Fellowship from the European Commission under Horizon 2020 Framework Program Project: 894737. G.H. is supported by funds provided by the APU and ADISCON patient associations. L.R.-C. holds an FI-AGAUR predoctoral fellowship (2020FI-B00038) from Generalitat de Catalunya. X.F.-C. is partially supported by funds provided by the grant RTI-2018-101735-B-I100 from MCIN/AEI/10.13039/501100011033/ERDF âA way to make Europeâ. V.V. was supported by funds provided by APU and ADISCON patient associations and UIC postdoctoral scholarship; she is currently supported by funds provided by RETOS COLABORACION grant RTC2019-007074-1 from MCIN/AEI/10.13039/501100011033 from Spanish Ministry of Science and Innovation (MICINN)
Schistosomiasis mansoni in urban Northeast Brazil: influence of rainfall regime on the population dynamics of Biomphalaria sp.
Introduction Our objective was to evaluate the influence of rainfall regime on the population dynamics of Biomphalaria in a potential urban focus of schistosomiasis in Aracaju, Brazil, during 2009-2010. Methods Snails were collected monthly and were counted, measured and identified; the level of infection and fecal contamination at the sampling sites was determined; rainfall data were obtained. Results High levels of fecal contamination were observed, and the abundance of Biomphalaria glabrata increased during the rainy and post-rainy seasons. The snails' size was variable, and infected snails were identified independently of rainfall. Conclusions These results provide evidence of anthropogenic and climate interference in an urban focus of schistosomiasis in the Aracaju metropolitan area.65465
The SARS-CoV-2 spike protein binds and modulates estrogen receptors
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 as its primary infection mechanism. Interactions between S and endogenous proteins occur after infection but are not well understood. We profiled binding of S against >9000 human proteins and found an interaction between S and human estrogen receptor alpha (ER alpha). Using bioinformatics, supercomputing, and experimental assays, we identified a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 sub-unit. In cultured cells, S DNA transfection increased ER alpha cytoplasmic accumulation, and S treatment induced ER-dependent biological effects. Non-invasive imaging in SARS-CoV-2-infected hamsters localized lung pathology with increased ER alpha lung levels. Postmortem lung experiments from infected hamsters and humans confirmed an increase in cytoplasmic ER alpha and its colocalization with S in alveolar macrophages. These findings describe the discovery of a S-ER alpha interaction, imply a role for S as an NRC, and advance knowledge of SARS-CoV-2 biology and coronavirus disease 2019 pathology
The reference site collaborative network of the european innovation partnership on active and healthy ageing
Seventy four Reference Sites of the European Innovation
Partnership on Active and Healthy Ageing (EIP on AHA)
have been recognised by the European Commission in
2016 for their commitment to excellence in investing and
scaling up innovative solutions for active and healthy
ageing. The Reference Site Collaborative Network
(RSCN) brings together the EIP on AHA Reference Sites
awarded by the European Commission, and Candidate
Reference Sites into a single forum. The overarching goals
are to promote cooperation, share and transfer good
practice and solutions in the development and scaling up
of health and care strategies, policies and service delivery
models, while at the same time supporting the action
groups in their work. The RSCN aspires to be recognized
by the EU Commission as the principal forum and
authority representing all EIP on AHA Reference Sites.
The RSCN will contribute to achieve the goals of the EIP
on AHA by improving health and care outcomes for
citizens across Europe, and the development of sustainable
economic growth and the creation of jobs
La rete Food PRIDE Italia: buone pratiche per il contrasto alla povertĂ alimentare e allo spreco.
La rete Food PRIDE Italia (Partecipazione, Recupero, Inclusione, Distribuzione, Educazione) nasce nel 2019 da unâiniziativa torinese, sostenuta dalla Compagnia di San Paolo, che unisce inizialmente nel gruppo Food Pride Torino decine di realtĂ associative della cittĂ impegnate nella lotta allo spreco alimentare e allâesclusione sociale delle persone in difficoltĂ
Families and Food in Hard Times: European comparative research
Families and Food in Hard Times: European comparative researc
Le politiche giovanili e i sistemi di welfare: un'analisi comparata (Italia, Grecia, Bulgaria, Estonia), in "Autonomie locali e servizi sociali, Quadrimestrale di studi e ricerche sul welfare
Food welfare as a new paradigm to deal with food poverty. The case study of Turin
The present research aims to highlight the political systemsâ inability to address
emergency and incidental approaches behind food aid, on one side. On the other side, we mean to debate how local political systems may develop innovative transversal approaches to deal with food security. Much effort is put into the comprehension of the
issue of âfood welfareâ, meant as a new conceptual term through which it may be possible to set up a series of structural measures regarding food accessibility. The research is carried out by addressing a theoretical level in which we analyse the literature advancements regarding the theme of âfood welfareâ; successively, we intend to carry out empirical research in the City of Turin to determine the number of food aid-related actors, their locations and their capacity of providing solutions for peopleâs needs. Hence, we intend to figure out how food aid is conceived and structured in Turin. The third and final part of the research consists in interviewing a series of policy-makers from the City of Turin meaning to comprehend their perceptions regarding the necessity of stronger and more effective food aid strategies, inserting them in a broader food welfare approach