Several features of the yeast mitochondrial genome, including high mutation rate, dynamic genomic structure, small effective population size, and dispensability for cellular viability, make it a promising candidate for generating hybrid incompatibility and driving speciation. Cytonuclear incompatibility, a specific type of Dobzhansky‐Muller genetic incompatibility caused by improper interactions between mitochondrial and nuclear genomes, has previously been observed in a variety of organisms, yet its role in speciation remains obscure. Recent studies in Saccharomyces yeast species provide a new insight, with experimental (...) evidence that cytonuclear incompatibility and DNA sequence divergence are both causes of the reproductive isolation of different yeast species. Interestingly, these two mechanisms seem to be perfectly complementary to each other in terms of their effects and evolutionary trajectories. Direct molecular analyses of the incompatible genes in yeasts have started to shed light on the evolutionary forces driving speciation. Editor's suggested further reading in BioEssaysThe cytoplasmic structure hypothesis for ribosome assembly, vertical inheritance, and phylogeny AbstractMitochondrial bioenergetics as a major motive force of speciation Abstract. (shrink)

Objectives Disclosures of funding sources and conflicts of interests (COI) in published peer-reviewed journal articles have recently begun to receive some attention, but many critical questions remain, for example, how often such reporting occurs concerning research conducted in the developing world and what factors may be involved. Design Of all articles indexed in Medline reporting on human subject HIV research in 2007 conducted in four countries (India, Thailand, Nigeria and Uganda), this study explored how many disclosed a funding source and (...) COI, and what factors are involved. Results Of 221 articles that met the criteria, 67.9% (150) disclosed the presence or absence of a funding source, but only 20% (44) disclosed COI. Studies from Uganda were more likely, and those from Nigeria were less likely to mention a funding source (p<0.001). Of articles in journals that had adopted International Committee of Medical Journal Editors (ICMJE) guidelines, 56% did not disclose COI. Disclosure of funding was more likely when: ≥50% of the authors and the corresponding author were from the sponsoring country, the sponsor country was the USA, and the articles were published in journals in which more of the editors were from the sponsoring countries. Conclusions Of the published studies examined, over a third did not disclose funding source (ie, whether or not there was a funding source) and 80% did not disclose whether COI existed. Most articles in ICMJE-affiliated journals did not disclose COI. These data suggest the need to consider alteration of policies to require that published articles include funding and COI information, to allow readers to assess articles as fully as possible. (shrink)

Adolescent young carers (AYCs) are a sub-group of young carers who carry out significant or substantial caring tasks and assume a level of responsibility which would usually be associated with an adult. They are a potentially vulnerable group of minors because of the risk factors associated with their caring role. AYCs face a critical transition phase from adolescence to adulthood often with a lack of tailored support from service providers. The recently completed European funded ‘ME-WE’ project, which forms the focus (...) of this paper, aimed to change the ‘status quo’ by advancing the situation of AYCs in Europe, via responsive research and knowledge translation actions. This paper outlines the participatory, co-creation approach employed in the project to optimise AYC’s involvement. It describes the ethical framework adopted by the project consortium to ensure the wellbeing of AYCs within all project activities. Ethical issues that arose in the field study work in all six countries are presented, followed by a discussion of the level of success or otherwise of the consortium to address these issues. The paper concludes with lessons learned regarding ethically responsible research with and for AYCs that are likely transferable to other vulnerable research groups and pan-European projects. (shrink)

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

Many recent events have contributed to the resurgence of the historically cyclical debate over euthanasia. Now, the focus rests on physician-assisted suicide. Many landmark events regarding physician-assisted suicide have occurred within the last year alone. For example, Derek Humphry's Final Exit recently became a best seller, giving people the detailed knowledge of how to “self-deliver” In The New England Journalbf Medicine, Dr. Timothy Quill shared his touching experience of assisting his patient “Diane” after she chose to decline treatment options for (...) leu- kemia. Dr. Jack Kevorkian made use of his highly publicized “death machine” to help Janet Adkins and subsequently, several other women, end their lives. (shrink)

Ponto de partida do artigo é a consideração de que o problema da relação entre Filosofia e Espiritualidade, ainda que problemático, é filosoficamente pensável e pode ser historicamente reconstruído. Com efeito, o artigo mostra de que modo o problema foi objecto de uma sistematização paradoxal, ainda que coerente e exemplar, por parte de S. Boaventura, cuja reflexão, tematizando a espiritualidade minorítica, radica em S. Francisco de Assis, ainda que também através da mediação de Santo António de Lisboa. Segundo S. Boaventura, (...) Deus manifesta-se de forma natural no livro da natureza mediante o Verbo incriado, cognoscível mediante a razão natural na ciência natural, que é a Filosofia; e revela-se sobrenaturalmente no livro da Escritura mediante o Verbo incarnado, cognoscível mediante a razão iluminada pela fé na ciência sobrenatural, que é a Teologia; mas também se comunica pessoalmente e concretamente no coração dos crentes mediante o Verbo inspirado, ou seja, o Cristo feito presente pelo Espírito Santo na "vida espiritual", num processo ascético-místico, cujo primeiro estádio é, paradoxalmente, a própria Filosofia, aqui entendida como a busca da sabedoria através das virtudes cardeais. Por outro lado, o artigo mostra também como o próprio paradigma da reedificação interior através das virtudes parece estabelecer um vínculo entre S. Francisco de Assis e Santo António de Lisboa, bem como entre os dois e S. Boaventura, o qual, hipotiza o autor do artigo, não só leu alguma coisa dos Sermões de Santo António, como deles retirou elementos para as suas reflexões mais maduras. /// The starting point of this article is the consideration that the problem of the relation between Philosophy and Spirituality, even if problematic, can be philosophically thought and historically reconstructed. In effect, the article shows how this problem was object of a paradoxical systematization, coherent and exemplar, on the part of Saint Bonaventure, whose reflection, typical of the Franciscan spirituality, is rooted in Saint Francis of Assisi, even if also through the mediation of Saint Anthony of Lisbon. According to Saint Bonaventure, God reveals Godself naturally in the Book of nature by means of the uncreated Logos, knowable through natural reason in the natural science, which is Philosophy; and God reveals Godself supernaturally in the Book of Scripture by means of the incarnated Logos knowable by means of reason illuminated by faith in the supernatural science, which is Theology; but God also communicates Godself personally and concretely in the hearts of the believers by means of the inspired Logos, i.e., the Christ made present through the Holy Spirit in the "spiritual life", in an ascetic-mystical process, whose first stage is, paradoxically, Philosophy itself, here understood as the search for Wisdom through the cardinal virtues. On the other hand, the article also shows how the paradigm of the interior edification through the virtues seems to establish a link between Saint Francis of Assisi and Saint Anthony of Lisbon, as well as between the two and Saint Bonaventure, who, according to the article, not only has read something of Saint Anthony's Sermons, but also has taken something from them for his mature reflexions. (shrink)