Constitutive MAP-kinase Activation Suppresses Germline Apoptosis in NTH-1 DNA Glycosylase Deficient \u3ci\u3eC. elegans\u3c/i\u3e

Oxidation of DNA bases, an inevitable consequence of oxidative stress, requires the base excision repair (BER) pathway for repair. Caenorhabditis elegans is a well-established model to study phenotypic consequences and cellular responses to oxidative stress. To better understand how BER affects phenotypes associated with oxidative stress, we characterised the C. elegans nth-1 mutant, which lack the only DNA glycosylase dedicated to repair of oxidative DNA base damage, the NTH-1 DNA glycosylase. We show that nth-1 mutants have mitochondrial dysfunction characterised by lower mitochondrial DNA copy number, reduced mitochondrial membrane potential, and increased steady-state levels of reactive oxygen species. Consistently, nth-1 mutants express markers of chronic oxidative stress with high basal phosphorylation of MAP-kinases (MAPK) but further activation of MAPK in response to the superoxide generator paraquat is attenuated. Surprisingly, nth-1 mutants also failed to induce apoptosis in response to paraquat. The ability to induce apoptosis in response to paraquat was regained when basal MAPK activation was restored to wild type levels. In conclusion, the failure of nth-1 mutants to induce apoptosis in response to paraquat is not a direct effect of the DNA repair deficiency but an indirect consequence of the compensatory cellular stress response that includes MAPK activation

Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species

Alzheimer's disease is the most common age-associated neurodegenerative disorder and the most frequent form of dementia in our society. Aging is a complex biological process concurrently shaped by genetic, dietary and environmental factors and natural compounds are emerging for their beneficial effects against age-related disorders. Besides their antioxidant activity often described in simple model organisms, the molecular mechanisms underlying the beneficial effects of different dietary compounds remain however largely unknown. In the present study, we exploit the nematode Caenorhabditis elegans as a widely established model for aging studies, to test the effects of different natural compounds in vivo and focused on mechanistic aspects of one of them, quercetin, using complementary systems and assays. We show that quercetin has evolutionarily conserved beneficial effects against Alzheimer's disease (AD) pathology: it prevents Amyloid beta (A beta)-induced detrimental effects in different C. elegans AD models and it reduces A beta-secretion in mammalian cells. Mechanistically, we found that the beneficial effects of quercetin are mediated by autophagy-dependent reduced expression of Abl tyrosine kinase. In turn, autophagy is required upon Abl suppression to mediate quercetin's protective effects against A beta toxicity. Our data support the power of C. elegans as an in vivo model to investigate therapeutic options for AD

Active transcriptomic and proteomic reprogramming in the C-elegans nucleotide excision repair mutant xpa-1

Peer reviewe

The flavonoid 4,4′-dimethoxychalcone promotes autophagy-dependent longevity across species

Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4′- dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischaemia. Concomitantly, DMC induces autophagy, which is essential for its cytoprotective effects from yeast to mice. This pro-autophagic response induces a conserved systemic change in metabolism, operates independently of TORC1 signalling and depends on specific GATA transcription factors. Notably, we identify DMC in the plant Angelica keiskei koidzumi, to which longevity- and health-promoting effects are ascribed in Asian traditional medicine. In summary, we have identified and mechanistically characterised the conserved longevity-promoting effects of a natural anti-ageing drug

Dark Matter Cinema Tarot - Out of a State of Emergency

The Dark Matter Cinema Tarot was developed by Silvia Maglioni & Graeme Thomson during their residency common infra/ctions at Les Laboratoires d’Aubervilliers and constitutes what the artists refer to as a “vernacular technology”. After being invited to CA2M, Madrid, where several readings were made as part of JORNADAS DE ESTUDIO DE LA IMAGEN 2016, it has now become a fully nomadic practice, assuming a different form each time a Nocturnal Committee takes place. Whenever a Nocturnal Committee is called, members of the assembled group may pose questions to the cards, and through the collective reading that ensues, explore ways in which the images can open up new channels of inter- and infra-subjective perception, connecting different realms of personal, aesthetic and political experience and enquiry by reaching towards the dark matter that haunts the cinematographic image. At the same time, they can tease out alternative narratives and divinatory or therapeutic possibilities that may lie in the constellation of figures and forms resulting from each fall of the cards. In conceiving the DMC Tarot, the artists have replaced the Major and Minor Arcana with a selection of still images drawn from the history of cinema. No longer tied to the symbolism of the classical tarot, suspended between contingency and fatality, the DMC cards refract the questions posed to them through a process of speculative description and collective fabulation and story-telling, with each reading forming a singular montage of gestures, situations and relations. Readings are frequently interwoven with screenings of film sequences and the playing or performance of durational sound pieces that expand upon territories of infra-perception unveiled by the cards

Dark Matter Cinema Tarot - Desde un estado de emergencia

Dark Matter Cinema Tarot fue desarrollado por Silvia Maglioni y Graeme Thomson durante su residencia common infra/ctions en Los laboratorios de Aubervilliers y constituye lo que los artistas denominan “una tecnología vernácula”. Tras ser invitados al CA2M de Madrid, donde se llevaron a cabo una serie de lecturas dentro de las Jornadas de Estudio de la Imagen 2016, esta obra es ahora una práctica nómada que adopta formas diversas cada vez que el Comité Nocturno se reúne. Cuando se convoca un Comité nocturno, los integrantes del grupo pueden hacer preguntas a las cartas y, a través de su lectura colectiva, explorar maneras en las que las imágenes pueden abrir nuevos canales para la percepción inter e infra subjetiva, conectando la pesquisa con espacios diversos de experiencia personal, estética y política, acercándose a la materia oscura que acecha la imagen cinematográfica. Al mismo tiempo, los miembros del grupo pueden tantear las narrativas alternativas y posibilidades adivinatorias o terapéuticas contenidas en la constelación de formas y figuras resultantes de cada tirada de cartas. Al concebir el Cine tarot de la materia oscura los artistas sustituyeron los Arcanos Mayor y Menor con una selección de imágenes de la historia del cine. Desprendidas del simbolismo del tarot clásico, suspendidas entre la contingencia y la fatalidad, las cartas del Cine tarot de la materia oscura rebotan las preguntas que reciben a través de un proceso de descripción especulativa, fabulación colectiva y narración de historias, en el que cada lectura forma un singular montaje de gestos, situaciones y relaciones. Las lecturas suelen estar entretejidas con proyecciones de secuencias de cine, además de la reproducción o actuación de piezas de sonido duracionales que se expanden hacia los territorios de infrapercepción descubiertos por las cartas

Lo que hay en el “entre”

El presente texto constituye una narrativa sobre la película de los autores, Facts of life, que partió de 18 horas de vídeo de los cursos de Gilles Deleuze en la universidad de Vincennes, en 1975-76, un material en bruto grabado por Marielle Burkhalter como parte de su proyecto de Máster de “filmar el pensamiento en su devenir”

Lo que hay en el “entre”

The present text establishes a narrative of the filmmaking process by the authors ofFacts of life. A film developed with 18 hours of video from Gilles Deleuze´s courses at the university of Vincennes (1975-76). A working material taped by Marielle Burkhalter as part of her Master Project ‘film thought in its becoming’.El presente texto constituye una narrativa sobre la película de los autores, Facts of life, que partió de 18 horas de vídeo de los cursos de Gilles Deleuze en la universidad de Vincennes, en 1975-76, un material en bruto grabado por Marielle Burkhalter como parte de su proyecto de Máster de “filmar el pensamiento en su devenir”

What lies between

The present text establishes a narrative of the filmmaking process by the authors ofFacts of life. A film developed with 18 hours of video from Gilles Deleuze´s courses at the university of Vincennes (1975-76). A working material taped by Marielle Burkhalter as part of her Master Project ‘film thought in its becoming’