Novel mutation in addition to functional TMPRSS6 gene polymorphisms originate an IRIDA-like phenotype in an African child

Iron-refractory iron deficiency anemia (IRIDA) is a rare autosomal recessive anemia often unresponsive to oral iron intake and partially responsive to parenteral iron treatment. The disease originates from mutations in TMPRSS6 gene, encoding Matriptase 2, a transmembrane serine protease that plays an essential role in down-regulating hepcidin. Once TMPRSS6 is mutated, the corresponding protein is absent or inactive at the hepatocyte membrane leading to uncontrolled high levels of hepcidin and impaired iron absorption. This study aimed to investigate a 4-year-old boy of sub-Saharan ancestry (Mozambique/Angola), presenting with microcytic hypochromic anemia, low transferrin saturation, normal ferritin, and having a partial response to intravenous iron treatment. He is a -α3.7-thalassemia carrier. TMPRSS6 was screened for variants by Next-Generation Sequencing using Nextera XT libraries in a MiSeq platform (Illumina). Genetic variants found were validated by Sanger sequencing. In silico analyses were performed in HSF, SIFT, Poly-Phen2 and Missense3D softwares. A novel missense mutation (c.871G>A) was found in heterozygosity, in TMPRSS6 exon 8. In silico analysis indicates the conserved amino acid change (G291S) may be damaging to the protein stability. Due to its location in the CUB1 domain, it may also affect the enzyme activation and substrate recognition. Additionally, 3 SNPs previously associated with a greater risk of developing iron deficiency anemia (K253E, V736A and Y739Y) were also identified in TMPRSS6. Although IRIDA is known as an autosomal recessive disease, we conclude that, in this case, the result of a digenic inheritance of the novel damaging mutation (c.871G>A; G291S) and the 3 common modulating SNPs in the same gene and a co-inheritance of the α-thalassemia HBA deletion may lead to an IRIDA-like phenotype. Further functional studies of the mutated protein as well as family studies should be conducted.This work was partially supported by INSA_2013DGH910 and GenomePT (POCI-01-0145-FEDER-022184).info:eu-repo/semantics/publishedVersio

ATXN1 N-terminal region explains the binding differences of wild-type and expanded forms

Background Wild-type (wt) polyglutamine (polyQ) regions are implicated in stabilization of protein-protein interactions (PPI). Pathological polyQ expansion, such as that in human Ataxin-1 (ATXN1), that causes spinocerebellar ataxia type 1 (SCA1), results in abnormal PPI. For ATXN1 a larger number of interactors has been reported for the expanded (82Q) than the wt (29Q) protein. Methods To understand how the expanded polyQ affects PPI, protein structures were predicted for wt and expanded ATXN1, as well as, for 71 ATXN1 interactors. Then, the binding surfaces of wt and expanded ATXN1 with the reported interactors were inferred. Results Our data supports that the polyQ expansion alters the ATXN1 conformation and that it enhances the strength of interaction with ATXN1 partners. For both ATXN1 variants, the number of residues at the predicted binding interface are greater after the polyQ, mainly due to the AXH domain. Moreover, the difference in the interaction strength of the ATXN1 variants was due to an increase in the number of interactions at the N-terminal region, before the polyQ, for the expanded form. Conclusions There are three regions at the AXH domain that are essential for ATXN1 PPI. The N-terminal region is responsible for the strength of the PPI with the ATXN1 variants. How the predicted motifs in this region affect PPI is discussed, in the context of ATXN1 post-transcriptional modifications.Xunta de Galicia | Ref. ED481B 2016/068–0Xunta de Galicia | Ref. ED431C2018/55-GRCFEDER | Ref. Norte-01-0145-FEDER-00000

Heritable components of the human fecal microbiome are associated with visceral fat

Background: Variation in the human fecal microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio-metabolic disease risk factor. Here, we explore links between the fecal microbiota and abdominal adiposity using body composition as measured by dual-energy X-ray absorptiometry in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures.Results: We profile six adiposity measures in 3666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android/gynoid ratio. We confirm the association of lower diversity of the fecal microbiome with obesity and adiposity measures, and then compare the association between fecal microbial composition and the adiposity phenotypes in a discovery subsample of twins. We identify associations between the relative abundances of fecal microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI as a surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project and the extended TwinsUK cohort. Meta-analyses across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity.Conclusions: Our results provide novel insights into the role of the fecal microbiota in cardio-metabolic disease with clear potential for prevention and novel therapies

The reproductive microbiome – clinical practice recommendations for fertility specialists

The interest in and understanding of the human microbiome has grown remarkably over recent years. Advances in molecular techniques have allowed researchers to identify and study the microbiota and also use this information to develop therapeutic solutions for a spectrum of conditions. Alongside the growing interest in the microbiome, societal changes have resulted in many couples looking to start families later in life, therefore increasing the demand for as

Theories of Change and Mediators of Psychotherapy Effectiveness in Adolescents With Externalising Behaviours: A Systematic Review

bstract Background Externalising behaviours are becoming a remarkably prevalent problem during adolescence, often precipitating both externalising and internalising disorders in later adulthood. Psychological treatments aim to increase the social functioning of adolescents in order for them to live a more balanced life and prevent these negative trajectories. However, little is known of the intervening variables and mediators involved in these treatments' change mechanisms. We conducted a systematic review, exploring the available evidence on mediators of psychological treatments for externalising behaviours and symptoms amongst adolescents (10 to 19 years old). Methods A systematic search was performed on Medline and PsycINFO databases, which identified studies from inception to February 23, 2020. Eligible studies included randomised controlled trials that enrolled adolescents with externalising symptoms and behaviours as, at least, one of the primary outcomes. A group of 20 reviewers from the COST-Action TREATme (CA16102) were divided into 10 pairs. Each pair independently screened studies for inclusion, extracted information from the included studies, and assessed the methodological quality of the included studies and the requirements for mediators, following Kazdin's criteria. Risk of bias of RCTs was assessed by the Mixed Methods Appraisal Tool. Extracted data from the included studies were reported using a narrative synthesis. Results Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), after removing duplicates, 3,660 articles were screened. Disagreements were resolved by consensus. In a second stage, 965 full-text articles were assessed for eligibility. A total of 14 studies fulfilled all inclusion criteria. The majority were related to systemic psychological treatment approaches. Two types of mediators were identified as potentially being involved in the mechanisms of change for better social improvements of adolescents: to increase healthier parent–adolescent relationships and parental discipline. However, there were significant and non-significant results amongst the same mediators, which led to discussing the results tentatively. Conclusions Family variables were found to be the largest group of investigated mediators, followed by relational, behavioural, and emotional variables. No cognitive or treatment-specific mediators were identified. Both adequate behavioural control of adolescents' peer behaviour and a better positive balance in their relationships with their parents seemed to buffer the effects of externalising behaviours in adolescents. Several methodological limitations concerning mediation testing design, outcome measures, and mediator selection have been identified. Ethics and Dissemination Ethical approval was not required. PROSPERO registration number: CRD42021231835

An actionable guide to creating Educational Escape Rooms: handbook

Sem resumo disponível.publishe

El álbum poético en portugués y en español: sinergia estética entre palabras e ilustraciones

Este estudo procurou problematizar a relação textual que se observa entre a palavra e a imagem em um tipo de texto especialmente concebido para crianças: o álbum poético. Para tal, utilizamos alguns exemplos textuais significativos desse subgênero literário/editorial ainda em emergência tanto em Portugal quanto na Espanha, e propusemos uma definição e uma caracterização baseadas no comentário de sequências poéticas nas quais a ilustração sustenta o conteúdo verbal. Efetivamente, centrando a atenção no álbum poético de potencial recepção infanto-juvenil, sugere-se uma análise de diversos títulos de autoria portuguesa e espanhola, assente em uma leitura dialógica do texto verbal e do visual. A sinergia que se concretiza entre as duas componentes enunciadas alicerça essa nova construção estética que tem, na verdade e na sua essência, a poesia como matriz e, em larga medida, é devedora dos efeitos expressivos da metáfora.This study aimed to discuss the relation between words and images in a type of text especially directed to children: the picture-poetry book. From significant examples of this literary subgenre still emerging in both Portugal and Spain, we propose a definition and characterization based on the review of poetic sequences in which illustrations support the verbal content. By focusing on picture-poetry books potentially aimed for adolescents and children, we present an analysis of several titles by Portuguese and Spanish authors, based on the dialogic reading between verbal and visual texts. The synergy found between these two components creates de foundantions of a new aesthetic construction which, in truth and in essence, has poetry as its matrix and owes its expressive effects to metaphors.Este estudio ha tenido como objetivo discutir la relación textual que existe entre la palabra y la imagen en un tipo texto especialmente creado para niños: el álbum poético. Para ello, utilizamos algunos ejemplos textuales significativos de un subgénero literario en emergencia tanto en Portugal cuanto en España, y hemos propuesto una definición de este subgénero y su caracterización a partir del comentario de secuencias poéticas en las cuales la imagen sustenta el contenido verbal. De hecho, centrando la atención en el álbum poético de potencial recepción infantil y juvenil, proponemos un análisis de diversos títulos de autoría portuguesa y española basado en la lectura dialógica entre el texto verbal y el texto ilustrativo. La sinergia que se establece entre estos dos componentes enunciados facilita una nueva construcción estética que da pie, en su esencia, a un tipo de poesía que, en gran medida, es deudora de los efectos expresivos de la metáfora.CIEC - Centro de Investigação em Estudos da Criança, IE, UMinho (UI 317 da FCT), Portugal. Fundos Nacionais através da FCT (Fundação para a Ciência e a Tecnologia) e cofinanciado pelo Fundo Europeu de Desenvolvimento Regional (FEDER) através do COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) no âmbito do CIEC (Centro de Investigação em Estudos da Criança, da Universidade do Minho) com a referência POCI-01-0145-FEDER-007562info:eu-repo/semantics/publishedVersio

Characterization of Contaminants from a Sanitized Milk Processing Plant

Milk processing lines offer a wide variety of microenvironments where a diversity of microorganisms can proliferate. We sampled crevices and junctions where, due to deficient reach by typical sanitizing procedures, bacteria can survive and establish biofilms. The sampling sites were the holding cell, cold storage tank, pasteurizer and storage tank - transfer pump junction. The culturable bacteria that were isolated after the sanitation procedure were predominantly Pseudomonas spp., Serratia spp, Staphylococcus sciuri and Stenotrophomonas maltophilia. We assayed several phenotypic characteristics such as the ability to secrete enzymes and siderophores, as well as the capacity of the strains to form biofilms that might contribute to their survival in a mixed species environment. The Pseudomonas spp. isolates were found to either produce proteases or lecithinases at high levels. Interestingly, protease production showed an inverse correlation with siderophore production. Furthermore, all of the Serratia spp. isolates were strong biofilm formers and spoilage enzymes producers. The organisms identified were not mere contaminants, but also producers of proteins with the potential to lower the quality and shelf-life of milk. In addition, we found that a considerable number of the Serratia and Pseudomonas spp. isolated from the pasteurizer were capable of secreting compounds with antimicrobial properties