Septins restrict inflammation and protect zebrafish larvae from Shigella infection

Shigella flexneri, a Gram-negative enteroinvasive pathogen, causes inflammatory destruction of the human intestinal epithelium. Infection by S. flexneri has been well-studied in vitro and is a paradigm for bacterial interactions with the host immune system. Recent work has revealed that components of the cytoskeleton have important functions in innate immunity and inflammation control. Septins, highly conserved cytoskeletal proteins, have emerged as key players in innate immunity to bacterial infection, yet septin function in vivo is poorly understood. Here, we use S. flexneri infection of zebrafish (Danio rerio) larvae to study in vivo the role of septins in inflammation and infection control. We found that depletion of Sept15 or Sept7b, zebrafish orthologs of human SEPT7, significantly increased host susceptibility to bacterial infection. Live-cell imaging of Sept15-depleted larvae revealed increasing bacterial burdens and a failure of neutrophils to control infection. Strikingly, Sept15-depleted larvae present significantly increased activity of Caspase-1 and more cell death upon S. flexneri infection. Dampening of the inflammatory response with anakinra, an antagonist of interleukin-1 receptor (IL-1R), counteracts Sept15 deficiency in vivo by protecting zebrafish from hyper-inflammation and S. flexneri infection. These findings highlight a new role for septins in host defence against bacterial infection, and suggest that septin dysfunction may be an underlying factor in cases of hyper-inflammation

Activation of p38MAPK Contributes to Expanded Polyglutamine-Induced Cytotoxicity

The signaling pathways that may modulate the pathogenesis of diseases induced by expanded polyglutamine proteins are not well understood.Herein we demonstrate that expanded polyglutamine protein cytotoxicity is mediated primarily through activation of p38MAPK and that the atypical PKC iota (PKCiota) enzyme antagonizes polyglutamine-induced cell death through induction of the ERK signaling pathway. We show that pharmacological blockade of p38MAPK rescues cells from polyglutamine-induced cell death whereas inhibition of ERK recapitulates the sensitivity observed in cells depleted of PKCiota by RNA interference. We provide evidence that two unrelated proteins with expanded polyglutamine repeats induce p38MAPK in cultured cells, and demonstrate induction of p38MAPK in an in vivo model of neurodegeneration (spinocerebellar ataxia 1, or SCA-1).Taken together, our data implicate activated p38MAPK in disease progression and suggest that its inhibition may represent a rational strategy for therapeutic intervention in the polyglutamine disorders

Earth at rest. Aesthetic experience and students' grounding in science education

publishedVersio

Science Education for a Better World? Reflections on Embodiment, Language and Sensitive Action

Postprin

Promoting Students’ Collective Socio-scientific Activism: Teachers’ Perspectives

This chapter describes analyses for the ‘We Act’ project, which is intended to foster development, implementation and study of materials and meth- odologies aimed at supporting teachers and students in taking informed and nego- tiated actions to address social and environmental issues associated with the fields of science and technology. This project combines development, action and research components and crosses three different areas: (1) the promotion of an active inquiry-based learning regarding real-life controversies associated with science and technology; (2) the stimulation of students’ participation in collective demo- cratic problem-solving action; and (3) the support of the first two areas with art initiatives and uses of Web 2.0 tools. Through a qualitative approach, this chapter discusses teachers’ motivations for participating in such a project and also difficul- ties they identify in their students’ enrolment in activism on social and environ- mental issues associated with science and technology. The data obtained through an online questionnaire and semi-structured interviews involving all the teachers in the project were submitted to content analysis. Teachers’ participation in the project is mainly motivated by a strong willingness to find ways to: (a) change what they consider to be students’ apathy concerning school science activities; and (b) empower them for democratic problem-solving action regarding social and environmental problems affecting society. Through the involvement in the project and actions implemented by their students, they began: (a) considering research- informed action as a major aspect of scientific literacy; and (b) recognizing students as important agents of change (capable of implementing, with success, impacting actions on their families and groups of friends) and, consequently, as ‘citizens’ (as opposed to ‘future citizens’). However, they face important obstacles in the implementation of these collective actions; namely, time restrictions imposed by overcrowded curricula and difficulties in finding the ‘proper’ controversial topics capable of overcoming student apathy