Ministerio de Economía y Competitividad

Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids

Carmen Menacho, Satoshi Okawa, Iris Álvarez‐Merz, Annika Wittich et autres

Leigh syndrome (Leigh) is an untreatable mitochondrial disorder characterized by lactic acidosis and basal ganglia and midbrain pathology, leading to psychomotor regression and early death. We previously uncovered impaired neuronal morphogenesis in Leigh cerebral organoids carrying SURF1 gene variants. Leveraging this phenotype, …

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Mitochondrial DNA replication is regulated by endoplasmic reticulum-mitochondrial contact sites, the mitochondrial calcium uniporter, and manganese

Amaia López de Arbina, Angelica Zamudio‐Ochoa, Mikel Muñoz‐Oreja, Diego Pérez‐Rodríguez et autres

Mitochondrial DNA replication occurs at contact sites between the endoplasmic reticulum (ER) and mitochondria (ERMCS). Beyond the known role of the tubular ER protein RTN4, the factors regulating this process are poorly defined. Here, we show that repressing the ER protein ERLIN2 …

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Aspartame decreases fat deposits in mice at a cost of mild cardiac hypertrophy and reduced cognitive performance

Irati Aiestaran-Zelaia, María Jesús Sánchez-Guisado, Marta Beraza, Libe López-Arandia et autres

Artificial sweeteners, such as aspartame, are widely used to reduce sugar intake to control body weight; however, their long-term metabolic and behavioral effects are unknown. To assess the long-term consequences, we evaluated the systemic effects of aspartame administration in male C57BL/6 mice …

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Evaluation of the effectiveness of cognitive–behavioural therapy for insomnia delivered by nurses and physicians for patients in primary care (the NPD study): protocol for a cluster randomised controlled trial

Maria del Mar Torrens-Darder, Isabel Torrens, Susana González Torrente, Caterina Vicens et autres

INTRODUCTION: Insomnia is the most common sleep disorder, and it adversely impacts daily living and increases the risk of chronic and acute health problems. Of the few individuals who seek treatment for insomnia, most pursue help in primary care settings. The management …

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Deep learning-driven neuromorphogenesis screenings identify repurposable drugs for mitochondrial disease

Carmen Menacho, Satoshi Okawa, Iris Álvarez‐Merz, Annika Wittich et autres

Summary Mitochondrial disease encompasses untreatable conditions affecting tissues with high energy demands. A severe manifestation of mitochondrial disease is Leigh syndrome (Leigh), which causes defects in basal ganglia and midbrain regions, psychomotor regression, lactic acidosis, and early death. We previously generated isogenic …

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Impaired astrocytic synaptic function by peripheral cholesterol metabolite 27-hydroxycholesterol

Fokion Spanos, Gorka Gereñu, Julen Goikolea, María Latorre‐Leal et autres

Astrocytes represent the most abundant cell type in the brain, where they play critical roles in synaptic transmission, cognition, and behavior. Recent discoveries show astrocytes are involved in synaptic dysfunction during Alzheimer’s disease (AD). AD patients have imbalanced cholesterol metabolism, demonstrated by …

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Mitochondrial DNA competition: starving out the mutant genome

Antonella Spinazzola, Diego Pérez‐Rodríguez, Jan Ježek, Ian Holt

High levels of pathogenic mitochondrial DNA (mtDNA) variants lead to severe genetic diseases, and the accumulation of such mutants may also contribute to common disorders. Thus, selecting against these mutants is a major goal in mitochondrial medicine. Although mutant mtDNA can drift …

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Energy scarcity and impaired mitochondrial translation induce perinuclear stress granule clustering

Uxoa Fernández‐Pelayo, Mikel Muñoz‐Oreja, Marina Villar-Fernandez, Amaia López de Arbina et autres

ABSTRACT Many proteins linked to amyotrophic lateral sclerosis and fronto-temporal dementia (ALS-FTD) change their cellular location and coalesce in cytoplasmic inclusion bodies in the disease state; yet the factors that govern protein relocation and organization remain unclear. Here, we show that inhibition …

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Metabolic Malfunction Mars Muscle Mitochondria

Guido Primiano, Ian Holt

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Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation

Mikel Muñoz‐Oreja, Abigail Sandoval, Ove Bruland, Diego Pérez‐Rodríguez et autres

Aberrant cholesterol metabolism causes neurological disease and neurodegeneration, and mitochondria have been linked to perturbed cholesterol homeostasis via the study of pathological mutations in the ATAD3 gene cluster. However, whether the cholesterol changes were compensatory or contributory to the disorder was unclear, …

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Las producciones de tradición Cogotas I en el territorio argárico: El caso de Peñalosa (Baños de la Encina, Jaén).

Laura Vico Triguero, Francisco Contreras Cortés, Francisco José Martín‐Peinado

Se presentan los resultados obtenidos del estudio arqueométrico de las cerámicas con decoración de tradición Cogotas I del poblado argárico de Peñalosa (Baños de la Encina, Jaén). El empleo de técnicas procedentes de las Ciencias de la Tierra (petrografía mediante lámina delgada, …

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Actitudes y comportamientos de Justicia social del profesorado en contextos desafiantes: un estudio de caso

Irene Moreno-Medina

Esta investigación busca conocer cuáles son las actitudes y comportamientos del profesorado de escuelas situadas contextos desafiantes y comprender cómo muchos de ellos se convierten en docentes socialmente justos. Para alcanzar este objetivo se utiliza el enfoque metodológico de estudios de casos …

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