Rare autosomal dominant hereditary hemochromatosis associated with SLC40A1 gene: ferroportin disease or type 4 hereditary hemochromatosis?

Ferroportin (FPN1), encoded by the SLC40A1 gene, is the unique cellular iron exporter identified in mammals. FPN1 transfers iron from the intestine and macrophages into the bloodstream. This function is negatively regulated by hepcidin. Mutations in SLC40A1 may affect FPN1 function, originating distinct autosomal dominant diseases: (i) the Ferroportin Disease (FD), due to loss-of-function mutations, is characterized by decreased iron export from enterocytes and severely affected iron transfer in macrophages, giving rise to a marked iron accumulation in spleen and liver; and (ii) the Type 4 Hereditary Hemochromatosis (HH), resulting from gain-of-function mutations conferring resistance to hepcidin-mediated FPN1 degradation and consequently high cellular iron export. In this study, 335 individuals suspected of having non-classic HH were enrolled. Six genes related with iron metabolism were analysed by SSCP, dHPLC or NGS. The latter used TruSeq or Nextera XT libraries and a MiSeq platform (Illumina). Genetic variants found were validated by Sanger sequencing. Predictive consequences at protein level were evaluated using Polyphen-2 and SIFT softwares. From all patients analysed, three SLC40A1 pathogenic variants were detected in heterozygosity in three women: two missense, c.238G>A, p.Gly80Ser and c.610G>A, p.Gly204Ser; and one deletion, c.485_487delTTG; p.Val162del. These variants had been reported in public databases, but they were not known to be present in the Portuguese population. The p.Gly80Ser and the p.Val162del are FPN1 loss-of-function mutations and were found associated with hyperferritinemia and low transferrin saturation (FD). In contrast, the p.Gly204Ser induced a gain of FPN1 function with a full iron export capacity giving the patient a type 4-HH phenotype, which includes iron overload, hyperferritinemia and high transferrin saturation. Detailed clinical evaluation of the suspected patients are useful to unravel the effect of different mutations in FPN1 function, expression and regulation.This work was partially supported by INSA_2013DGH910 and GenomePT (POCI-01-0145-FEDER-022184).info:eu-repo/semantics/publishedVersio

Proteoliposomes as matrix vesicles' biomimetics to study the initiation of skeletal mineralization

During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix by promoting the formation of hydroxyapatite (HA) seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Ion transporters control the availability of phosphate and calcium needed for HA deposition. The lipidic microenvironment in which MV-associated enzymes and transporters function plays a crucial physiological role and must be taken into account when attempting to elucidate their interplay during the initiation of biomineralization. In this short mini-review, we discuss the potential use of proteoliposome systems as chondrocyte- and osteoblast-derived MVs biomimetics, as a means of reconstituting a phospholipid microenvironment in a manner that recapitulates the native functional MV microenvironment. Such a system can be used to elucidate the interplay of MV enzymes during catalysis of biomineralization substrates and in modulating in vitro calcification. As such, the enzymatic defects associated with disease-causing mutations in MV enzymes could be studied in an artificial vesicular environment that better mimics their in vivo biological milieu. These artificial systems could also be used for the screening of small molecule compounds able to modulate the activity of MV enzymes for potential therapeutic uses. Such a nanovesicular system could also prove useful for the repair/treatment of craniofacial and other skeletal defects and to facilitate the mineralization of titanium-based tooth implants

Experiências de Cyberbullying relatadas por estudantes do ensino superior politécnico

As TIC trouxeram múltiplos benefícios mas acarretam também riscos, nomeadamente o cyberbullying, ou seja, a prática de atos agressivos, intencionais e repetidos com recurso a dispositivos eletrónicos para, por exemplo, enviar mensagens insultuosas ou criar websites que difamam e hostilizam os outros. Este estudo teve por objetivos conhecer a frequência e os tipos de cyberbullying praticados, sofridos e observados por estudantes do ensino superior politécnico; saber se se veriicam diferenças entre géneros e cursos; identiicar as emoções associadas aos diferentes papéis no cyberbullying; identiicar os motivos invocados pelos agressores para explicar este tipo de comportamento. Para o efeito construiu-se um questionário quantitativo que foi aplicado a 170 estudantes que frequentavam várias licenciaturas de uma instituição de ensino superior politécnico de Portugal. Os resultados revelaram que 30,6% dos estudantes já tinham sido vítimas de cyberbullying e 8,2% admitiu ter praticado cyberbullying, pelo menos algumas vezes. Um dos motivos mais evocados pelos agressores para esta prática foi a vingança relativamente a episódios ocorridos anteriormente. Não se veriicaram diferenças signiicativas entre sexos mas o fenómeno era mais frequente em cursos de engenharia comparativamente aos de educação e ciências humanas. Equaciona-se a prevenção do cyberbullying a partir da utilização dos próprios meios de comunicação social para promoção da partilha de informação sobre como utilizar as TIC de forma ética e segura, bem como através da criação de programas e plataformas envolvendo estudantes de vários níveis de ensino com vista à prevenção deste fenómeno

Responsive bystander behaviour in cyberbullying: a path through self-efficacy

Bystander behaviour and self-efficacy beliefs play an important role in cyberbullying incidence. This study tested the relationship between the Bystander Intervention Model phases and the mediating role of adolescents’ self-efficacy beliefs. Children from the fifth to twelfth grade (N = 676) participated in this study by responding to questionnaires concerning the various phases of the Bystander Intervention Model and self-efficacy beliefs to resolve cyberbullying-related problems. Through structural equation modelling, noticing an incident of cyberbullying had a direct and indirect effect on aggressive behaviour, and an indirect effect on reporting and problem-solving behaviour. The indirect effect of interpreting the event through attributing responsibility was significant for aggressive and problem-solving behaviour. The mediator role of reflective decision-making had a stronger effect on direct problem-solving. Self-efficacy beliefs significantly affected the relationship between interpreting the event and all behaviour, but stronger for direct problem-solving. These findings help explain empirically how bystanders respond to incidents of cyberbullying.info:eu-repo/semantics/acceptedVersio

OptFlux3: an improved platform for in silico design of cellular factories

The rational design of cellular factories for industrial biotechnology aims to create optimized organisms for the production of bulk chemicals, pharmaceuticals, food ingredients and enzymes, among others. Metabolic engineering (ME) plays a key role in this process, supported by the latest advances in genetic engineering in combination with computational tools to define targets for strain improvement. OptFlux is an open-source reference computational platform for the optimization of cellular factories by the application of in silico ME methods, designed for non-computational experts by providing a user-friendly interface. It allows to load genome-scale models from several sources to be used in the prediction of cellular behavior and identification of metabolic targets for genetic engineering. Its latest version, OptFlux3, allows to perform the simulation of wild type and mutant strains (allowing the simulation of gene/ reaction deletion and over/under expression). Regarding strain optimization, the new architecture opts for a multi-objective framework, allowing users to easily add different goals as optimization targets in a flexible way. Specialized multi-objective algorithms, co-exist with traditional single objectives algorithms to be applied for each case. Also, OptFlux3 includes a new visualization framework for metabolic models and phenotype simulations and a new plug-in management interface that allows to install and remove plug-ins in execution time. Currently available plug-ins include the calculation and visualization of elementary modes, topological analysis and the ability to add reactions/ pathways to existing models. OptFlux is made freely available for all major operating systems, together with suitable documentation in www.optflux.org

NGS4Cloud: Cloud-based NGS Data Processing

Motivation and challenges: Next-Generation Sequencing (NGS) technologies are greatly increasing the amount of genomic computer data, revolutionizing the biosciences field and leading to the development of more complex NGS Data Analysis techniques [2]. These techniques, known as pipelines or workflows, consist of running and refining a series of intertwined computational analysis and visualization tasks on large amounts of data. These pipelines involve the use of multiple software tools and data resources in a staged fashion, with the output of one tool being passed as input to the next one. To simplify the design and execution of biomedical workflows by end users, especially those that use multiple software tools and data resources, a number of scientific workflow systems have been developed over the past decade. Examples include Galaxy [1] and Swift [3]. However, most of these scientific workflow systems cannot be easily deployed and most of the times are only available to users with access to specialized IT support. There are two main issues to address in the design of an execution environment to these pipelines. First, due to the complexity of configuring and parametrizing pipelines, the use of NGS Data Analysis techniques is not an easy task for a user without IT knowledge. Second, knowing input data can be as much as terabytes and petabytes, pipelines execution require, in general, a great amount of computational resources.info:eu-repo/semantics/publishedVersio

MÍDIAS E TECNOLOGIAS DIGITAIS NA LICENCIATURA: NOVAS REALIDADES, NOVAS FORMAÇÕES

The article presents a reflection on challenges for a preservice teacher education in the Digital Age that can empower them to promote innovation in teaching practices in a school that shows a new cognitive ecology because of information and communication digital technologies. In the development of the article, is reported an innovative experience in Biology preservice teacher education involving new literacies, with Web 2.0 resources, and the use of new languages, in the form of infographic, with the use of mobile devices. It also presents the results of a survey taken with students at the end of the activity.El artículo presenta una reflexión sobre los retos para la formación inicial del profesorado en la Era Digital que puede darles la posibilidad de promover la innovación en las prácticas de enseñanza en una escuela que muestra una nueva ecología cognitiva debido a tecnologías digitales de información y comunicación. En el desarrollo del artículo, se relata un experimento innovador en la formación inicial de maestros de Biología que implicó en nuevas alfabetizaciones, envolviendo recursos de la Web 2.0, y el uso de nuevos lenguajes, en forma de infografía, con el uso de dispositivos móviles. También se presentan algunos resultados de una encuesta realizada entre los estudiantes al final de la actividad.O artigo traz uma reflexão sobre desafios para uma formação inicial de professores na Era Digital que possa potencializá-los a promover inovações nas práticas pedagógicas em uma escola que exibe uma nova ecologia cognitiva por conta das tecnologias digitais de informação e comunicação. No desenvolvimento do artigo, é relatada uma experiência inovadora na formação inicial de professores de Biologia que envolveu novos letramentos, envolvendo recursos da Web 2.0, e a utilização de novas linguagens, na forma de infográfico, com o uso de dispositivos móveis. Também se apresentam os resultados de uma enquete feita junto aos estudantes ao final da atividade

Mídias e Tecnologias Digitais nas licenciaturas: novas realidades, novas formações

O artigo traz uma reflexão sobre desafios para uma formação inicial de professores na Era Digital que possa potencializá-los a promover inovações nas práticas pedagógicas em uma escola que exibe uma nova ecologia cognitiva por conta das tecnologias digitais de informação e comunicação. No desenvolvimento do artigo, é relatada uma experiência inovadora na formação inicial de professores de Biologia que envolveu novos letramentos, envolvendo recursos da Web 2.0, e a utilização de novas linguagens, na forma de infográfico, com o uso de dispositivos móveis. Também se apresentam os resultados de uma enquete feita junto aos estudantes ao final da atividade