Metallothioneins as dynamic markers for brain disease in lysosomal disorders

Objective: To facilitate development of novel disease-modifying therapies for lysosomal storage disorder (LSDs) characterized by nervous system involvement such as metachromatic leukodystrophy (MLD), molecular markers for monitoring disease progression and therapeutic response are needed. To this end, we sought to identify blood transcripts associated with the progression of MLD. Methods: Genome-wide expression analysis was performed in primary T lymphocytes of 24 patients with MLD compared to 24 age- and sex-matched healthy controls. Genes associated with MLD were identified, confirmed on a quantitative polymerase chain reaction platform, and replicated in an independent patient cohort. mRNA and protein expression of the prioritized gene family of metallothioneins was evaluated in postmortem patient brains and in mouse models representing 6 other LSDs. Metallothionein expression during disease progression and in response to specific treatment was evaluated in 1 of the tested LSD mouse models. Finally, a set of in vitro studies was planned to dissect the biological functions exerted by this class of molecules. Results: Metallothionein genes were significantly overexpressed in T lymphocytes and brain of patients with MLD and generally marked nervous tissue damage in the LSDs here evaluated. Overexpression of metallothioneins correlated with measures of disease progression in mice and patients, whereas their levels decreased in mice upon therapeutic treatment. In vitro studies indicated that metallothionein expression is regulated in response to oxidative stress and inflammation, which are biochemical hallmarks of lysosomal storage diseases. Interpretation Metallothioneins are potential markers of neurologic disease processes and treatment response in LSDs

Buddhist Manuscript Cultures in Premodern Japan

Recent discoveries and scholarship on Japanese Buddhist manuscripts have illuminated new areas of research and raised previously unexplored questions in Buddhist studies and East Asian religions. This article introduces some of the recent finds and approaches to these materials. It focuses on three sets of sources: scriptorium documents from an imperial treasure house known as the Shōsōin, canonical manuscripts (issaikyō) based on texts translated or composed in China, and sacred works (shōgyō) produced and collected by Japanese monks for use in temple life. In addition to surveying these sources and the most influential secondary literature on them, this article proposes methodological alternatives to philological studies by focusing on what I call ritual, curricular, social, and material approaches

Morphogenesis and heterogeneity in liquid-grown streptomyces cultures

The filamentous bacteria Streptomyces are widespread inhabitants of terrestrial soils. Streptomycetes are not only among the most potent producers of valuable secondary metabolites (e.g. antibiotics), but also the source of various industrially relevant hydrolytic enzymes. The mode-of-growth of streptomycetes under industrial conditions is markedly different to that observed in their natural habitat. Most species form dense particles called pellets. Pellets are heterogeneous in size; more specifically at least two populations of differently-sized pellets exist in submerged cultures. Importantly, pellet size and production have been shown to be to be tightly correlated in streptomycetes. The study and control of pellet size heterogeneity in streptomycetes is the subject of the research presented in this thesis. Here, the various phenomena occurring throughout growth are characterized with the aim of understanding the factors underlying this phenomenon. Subsequently, the obtained knowledge is applied to obtain homogeneously-sized pellets of the industrial workhorse Streptomyces lividans. The work described in this thesis also addresses the fate of pellets at late stages of growth and a growth strategy representing a valuable alternative to conventional liquid cultures.Technology Foundation STWMicrobial Biotechnolog

Digital media in primary schools: literacy or technology? Analyzing government and media discourses

This article examines the political and the media discourses concerning the Portuguese governmental program responsible for delivering a laptop named “Magalhães” to all primary school children. The analysis is based on the official documents related to the launch and development of the initiative as well as the press coverage of this topic. The main purpose is to recognize the dominant public discourses and to find out what the media select for the debate in the public sphere. This analysis was done with a particular focus on the critical media literacy framework. The results reveal that the press highlighted the negative aspects of that program and that this framing could have a strong impact on how it was accepted and understood by the public opinion. Analysis also reveals that the governmental initiative was predominantly driven by technological objectives, in particular the access to technology, rather than media literacy objectives.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This paper is part of a three years project named "Navigating with 'Magalhaes': Study on the Impact of Digital Media in Schoolchildren" funded by FCT - Fundacao para a Ciencia e a Tecnologia (Portuguese Foundation for Science and Technology) and co-funded by FEDER - Fundo Europeu de Desenvolvimento Regional (ERDF: European Regional Development Fund) through COMPETE - Programa Operacional Factores de Competitividade (Operational Competitiveness Programme)

Exploring alternative routes for oxygen administration

none5siHypoxemia may compromise cell metabolism and organ function. Supplemental oxygen (O2) at high concentrations may prove ineffective, and issues relating to hyperoxia, barotrauma, mechanical ventilation, and extracorporeal oxygenation are well documented. Old reports suggest the potential safety and efficacy of alternative routes for O2 administration, such as intravenous or intestinal. We re-explored these routes in rat models of hypoxemia.Damiani, Elisa; Dyson, Alex; Zacchetti, Lucia; Donati, Abele; Singer, MervynDamiani, Elisa; Dyson, Alex; Zacchetti, Lucia; Donati, Abele; Singer, Mervy