Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

A new Raman metric for the characterisation of graphene oxide and its derivatives

Raman spectroscopy is among the primary techniques for the characterisation of graphene materials, as it provides insights into the quality of measured graphenes including their structure and conductivity as well as the presence of dopants. However, our ability to draw conclusions based on such spectra is limited by a lack of understanding regarding the origins of the peaks. Consequently, traditional characterisation techniques, which estimate the quality of the graphene material using the intensity ratio between the D and the G peaks, are unreliable for both GO and rGO. Herein we reanalyse the Raman spectra of graphenes and show that traditional methods rely upon an apparent G peak which is in fact a superposition of the G and D’ peaks. We use this understanding to develop a new Raman characterisation method for graphenes that considers the D’ peak by using its overtone the 2D’. We demonstrate the superiority and consistency of this method for calculating the oxygen content of graphenes, and use the relationship between the D’ peak and graphene quality to define three regimes. This has important implications for purification techniques because, once GO is reduced beyond a critical threshold, further reduction offers limited gain in conductivity

Measurement of radon-induced backgrounds in the NEXT double beta decay experiment

The measurement of the internal $^{222}$Rn activity in the NEXT-White detector during the so-called Run-II period with $^{136}$Xe-depleted xenon is discussed in detail, together with its implications for double beta decay searches in NEXT. The activity is measured through the alpha production rate induced in the fiducial volume by $^{222}$Rn and its alpha-emitting progeny. The specific activity is measured to be $(38.1\pm 2.2~\mathrm{(stat.)}\pm 5.9~\mathrm{(syst.)})$~mBq/m$^3$. Radon-induced electrons have also been characterized from the decay of the $^{214}$Bi daughter ions plating out on the cathode of the time projection chamber. From our studies, we conclude that radon-induced backgrounds are sufficiently low to enable a successful NEXT-100 physics program, as the projected rate contribution should not exceed 0.1~counts/yr in the neutrinoless double beta decay sample.Comment: 28 pages, 10 figures, 6 tables. Version accepted for publication in JHE

Relatório de Estágio da Prática de Ensino Supervisionada

Se partirmos do princípio que a evolução da criança acontece de uma forma contínua e integrada, estimulando o seu desenvolvimento global e tendo em vista a sua plena inserção na sociedade como ser autónomo, livre e solidário (OCEPE, 2007, p. 51), então facilmente se compreende que a temática da educação para a sexualidade, é uma temática transversal ao currículo desenvolvido nas salas de pré-escolar. Nesta perspetiva pareceu-nos que a metodologia de projeto seria a mais adequada ao desenvolvimento e implementação de um projeto nesta área, permitindo às crianças envolvimento e motivação para a construção de aprendizagens significativas. O desenvolvimento deste projeto teve como principal objetivo, alargar o campo de conhecimentos das crianças, no âmbito dos saberes sociais e do conhecimento do mundo e conhecer as conceções alternativas das crianças sobre esta temática. Verificámos que as crianças são constantemente influenciadas pelas ideias que o meio social e familiar lhes transmite o que dificulta a abordagem a conteúdos relativos à educação para a sexualidade. A fase de avaliação do projeto permitiu-nos verificar que as crianças desenvolveram as suas competências de expressão oral e de conhecimento do corpo, mas não alteraram a forma de designar os órgãos sexuais do corpo, ou seja, continuaram a designá-los de acordo com o seu meio social e familiar. Este facto evidencia a importância de envolver, neste tipo de projetos, a família e a comunidade

A Bourdieusian analysis of the participation of Polish students in the ERASMUS programme:Cultural and social capital perspectives

In this paper we examine the perceptions of ERASMUS agents’ of Polish students’ participation in the EP. We provide a Bourdieusian analyse of the cultural and social capital acquisition of students based on the qualitative data, collected through semi-structured, in-depth interviews with Erasmus agents, of a European research project. We argue that: Polish students’ participation in the EP has a positive impact on their academic achievement, cultural, social and linguistic capital, but, at the same time, it has a negative impact on degree completion of students as they get highly paid jobs, which prevent them from fully developing their cultural capital; ERASMUS Tourism has its value and place in the EP, because it provides students with the opportunity to develop their cultural, social and linguistic capital; and a Bourdieusian analysis of the experiences of ERASMUS students provides a better understanding of the impact student participation in the EP on their development

High capacity silicon anodes enabled by MXene viscous aqueous ink

The ever-increasing demands for advanced lithium-ion batteries have greatly stimulated the quest for robust electrodes with a high areal capacity. Producing thick electrodes from a high-performance active material would maximize this parameter. However, above a critical thickness, solution-processed films typically encounter electrical/mechanical problems, limiting the achievable areal capacity and rate performance as a result. Herein, we show that two-dimensional titanium carbide or carbonitride nanosheets, known as MXenes, can be used as a conductive binder for silicon electrodes produced by a simple and scalable slurry-casting technique without the need of any other additives. The nanosheets form a continuous metallic network, enable fast charge transport and provide good mechanical reinforcement for the thick electrode (up to 450 µm). Consequently, very high areal capacity anodes (up to 23.3 mAh cm−2) have been demonstrated

Hemotin, a regulator of phagocytosis encoded by a small ORF and xonserved across metazoans

Translation of hundreds of small ORFs (smORFs) of less than 100 amino acids has recently been revealed in vertebrates and Drosophila. Some of these peptides have essential and conserved cellular functions. In Drosophila, we have predicted a particular smORF class encoding ~80 aa hydrophobic peptides, which may function in membranes and cell organelles. Here, we characterise hemotin, a gene encoding an 88aa transmembrane smORF peptide localised to early endosomes in Drosophila macrophages. hemotin regulates endosomal maturation during phagocytosis by repressing the cooperation of 14-3-3ζ with specific phosphatidylinositol (PI) enzymes. hemotin mutants accumulate undigested phagocytic material inside enlarged endo-lysosomes and as a result, hemotin mutants have reduced ability to fight bacteria, and hence, have severely reduced life span and resistance to infections. We identify Stannin, a peptide involved in organometallic toxicity, as the Hemotin functional homologue in vertebrates, showing that this novel regulator of phagocytic processing is widely conserved, emphasizing the significance of smORF peptides in cell biology and disease