The 5'-3' exoribonuclease Pacman (Xrn1) regulates expression of the heat shock protein Hsp67Bc and the microRNA miR-277-3p in Drosophila wing imaginal discs

Pacman/Xrn1 is a highly conserved exoribonuclease known to play a critical role in gene regulatory events such as control of mRNA stability, RNA interference and regulation via miRNAs. Although Pacman has been well studied in Drosophila tissue culture cells, the biologically relevant cellular pathways controlled by Pacman in natural tissues are unknown. This study shows that a hypomorphic mutation in pacman (pcm5) results in smaller wing imaginal discs. These tissues, found in the larva, are known to grow and differentiate to form wing and thorax structures in the adult fly. Using microarray analysis, followed by quantitative RT-PCR, we show that eight mRNAs were increased in level by >2 fold in the pcm5 mutant wing discs compared to the control. The levels of pre mRNAs were tested for five of these mRNAs; four did not increase in the pcm5 mutant, showing that they are regulated at the post-transcriptional level and therefore could be directly affected by Pacman. These transcripts include one that encodes the heat-shock protein Hsp67Bc, which is upregulated 11.9-fold at the post-transcriptional level and 2.3-fold at the protein level. One miRNA, miR-277-3p, is 5.6-fold downregulated at the post-transcriptional level in mutant discs, suggesting that Pacman affects its processing in this tissue. Together, these data show that a relatively small number of mRNAs and miRNAs substantially change in abundance in pacman mutant wing imaginal discs. Since Hsp67Bc is known to regulate autophagy and protein synthesis, it is possible that Pacman may control the growth of wing imaginal discs by regulating these processes

Serious Game Evaluation as a Meta-game

Purpose – This paper aims to briefly outline the seamless evaluation approach and its application during an evaluation of ORIENT, a serious game aimed at young adults. Design/methodology/approach – In this paper, the authors detail a unobtrusive, embedded evaluation approach that occurs within the game context, adding value and entertainment to the player experience whilst accumulating useful data for the development team. Findings – The key result from this study was that during the “seamless evaluation” approach, users were unaware that they had been participating in an evaluation, with instruments enhancing rather than detracting from the in-role game experience. Practical implications – This approach, seamless evaluation, was devised in response to player expectations, perspectives and requirements, recognising that in the evaluation of games the whole process of interaction including its evaluation must be enjoyable and fun for the user. Originality/value – Through using seamless evaluation, the authors created an evaluation completely embedded within the “magic circle” of an in-game experience that added value to the user experience whilst also yielding relevant results for the development team

Medición de las condiciones habitacionales: una propuesta metodológica para analizar desigualdades inter e intraterritorios urbanos

La medición de las condiciones habitacionales de un territorio resulta de especial interés para la implementación de políticas públicas. Los métodos tradicionales se concentran en la medición de los déficits y dejan de lado aquella parte de la población que se encuentra cerca del umbral. Con base en propuestas específicas, estándares de organismos internacionales, legislación nacional y la importante participación de especialistas, en este estudio se genera una metodología cuantitativa, que evita esa pérdida de información al incluir a toda la población de un territorio, asignándole un puntaje a cada persona de acuerdo a las características del hogar que habita. Para validar la propuesta, se presenta una aplicación con datos de Argentina, donde se constata su versatilidad, dado que permite detectar problemáticas particulares en cada dimensión, y también consigue analizar el nivel promedio, la distribución intra e interterritorios y la pérdida de bienestar por desigualdad.The measurement of the housing conditions of a territory is particularly important for the implementation of public policies. Traditional methods focus on the measurement of deficits and leave aside that part of the population which is closer to the threshold. Based on specific proposals, the standards of international organizations, national legislation, and a significant participation of specialists, this study proposes a quantitative methodology, which avoids said loss of information by including the entire population of a territory, assigning a score to each person according to the characteristics of the household they live in. To validate this proposal, we present an application with data from Argentina, where its versatility is verified given that it allows for the detection of issues in each dimension while also getting to analyze the average level, the intra and interterritorial distribution, and the welfare loss due to inequality.Fil: Actis Di Pasquale, Eugenio. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina

Identifying the Coping Strategies of Nonoffending Pedophilic and Hebephilic Individuals From Their Online Forum Posts

Individuals who identify as pedophilic or hebephilic, and who do not offend, are increasingly visible in online discourse and as a focus of research. Developing knowledge about this population will offer insights into their psychological needs and, potentially, into the mechanisms and strategies individuals use to live offense-free lives. This study examined coping strategies among members of an online forum supporting pedohebephilic individuals who do not wish to offend. Forum users’ posts were analyzed using thematic analysis. Eleven themes emerged which were classifiable into three superordinate themes around (1) the acceptance of pedophilia, (2) strategies to stay safe, and (3) dealing with sexual arousal. These themes offer insight into the varying strategies used by these individuals to cope with stress and/or to remain offense free. Understanding whether these strategies are adaptive or maladaptive may help develop better support services for those who have not offended and may inform prevention efforts

How Virtual Powers Plants Can Advance Electrification and Mitigate Infrastructure Needs As We Race to Meet Our Climate Challenges

This paper explores three contemporary case studies of how distributed energy resources have been aggregated into Virtual Power Plants (VPPs) to provide resilient, low carbon solutions for our climate challenge in a manner that can mitigate demands on our energy infrastructure. These recent case studies will analyze distributed energy resources and how they can be aggregated to participate in wholesale electric markets to reduce the demand for larger utility scale resources while also providing grid services locally. These case studies build on previous research on distributed energy resources we have performed at our Institute for Energy and the Environment. The cases will consider how Federal Energy Regulatory Commission (“FERC” or “Commission”) Orders 841 and 2222 will help remove the barriers to effective participation in regional markets and explore the remaining conflicts with overlapping state and federal jurisdiction. We will conclude with lessons learned to promote the growth of VPPs in a manner that enhances electrification and promotes resilience as we transition to a low carbon future

The immunogenicity of midbrain dopaminergic neurons and the implications for neural grafting trials in Parkinson's disease.

Dopaminergic (DA) cell replacement therapies are a promising experimental treatment for Parkinson's disease (PD) and a number of different types of DA cell-based therapies have already been trialled in patients. To date, the most successful have been allotransplants of foetal ventral midbrain but even then, the results have been inconsistent. This coupled to the ethical and logistical problems with using this tissue has meant that an alternative cell source has been sought of which human pluripotent stem cells (hPSCs) sources have proven very attractive. Robust protocols for making mesencephalic DA (mesDA) progenitor cells from hPSCs now exist and the first in-human clinical trials have or are about to start. However, while their safety and efficacy are well understood, relatively little is known about their immunogenicity and in this review, we briefly summarise this with reference mainly to the limited literature on human foetal DA cells