Papers by Fabiola Pérez Rojas
TesisLa cocina peruana está en su mejor momento, reconocida a nivel nacional como patrimonio cult... more TesisLa cocina peruana está en su mejor momento, reconocida a nivel nacional como patrimonio cultural que contribuye a la consolidación de nuestra identidad nacional1 y galardonada internacionalmente como mejor destino culinario del mundo2, creando empleos y excelentes oportunidades de apostar la enseñanza de la gastronomía peruana como carrera profesional. Sin embargo, la formación culinaria y gastronómica es inminentemente privada, no contamos con una infraestructura de formación – investigación nacional de la gastronomía peruana. Actualmente, las entidades privadas brindan enseñanza técnica segmentada y muy comercial, ofreciendo salones atestados de alumnos y /o espacios que no están aptos para el desempeño y desenvolvimiento culinario. Por esta razón, la presente tesis propone desarrollar un proyecto arquitectónico para la formación, difusión e investigación de la gastronomía peruana; planteando una infraestructura pública educativa basada en un estudio de los actuales modelos formativos y sistemas de investigación de la gastronomía, con criterios óptimos espaciales para las experiencias y actividades gastronómicas, con el fin de reforzar la calidad arquitectónica-funcional y profesional, de tal manera que se encuentre al nivel de cualquier gran institución culinaria del mundo. Asimismo, una de las ideas planteadas, como infraestructura pública, es consolidar el proyecto a nivel urbano; potenciándolo, integrándolo y relacionándolo con el lugar en donde se va a desenvolver, generando la interrelación de la sociedad mediante los espacios públicos para el desarrollo y difusión recreativo-cultural de la gastronomía. Es válido acotar, que siendo una institución del estado va a estar al servicio de la sociedad para fomentar la educación, la investigación y el conocimiento; así como promover más el turismo en el país
Clinical Epigenetics, 2020
Background Hexanucleotide repeat expansions of the G4C2 motif in a non-coding region of the C9ORF... more Background Hexanucleotide repeat expansions of the G4C2 motif in a non-coding region of the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Tissues from C9ALS/FTD patients and from mouse models of ALS show RNA foci, dipeptide-repeat proteins, and notably, widespread alterations in the transcriptome. Epigenetic processes regulate gene expression without changing DNA sequences and therefore could account for the altered transcriptome profiles in C9ALS/FTD; here, we explore whether the critical repressive marks H3K9me2 and H3K9me3 are altered in a recently developed C9ALS/FTD BAC mouse model (C9BAC). Results Chromocenters that constitute pericentric constitutive heterochromatin were visualized as DAPI- or Nucblue-dense foci in nuclei. Cultured C9BAC astrocytes exhibited a reduced staining signal for H3K9me3 (but not for H3K9me2) at chromocenters that was accompanied by a marked decline in the global nuclear level ...
Journal of neuroinflammation, Jan 29, 2017
Neuroinflammation involves cytokine release, astrocyte reactivity and migration. Neuronal Thy-1 p... more Neuroinflammation involves cytokine release, astrocyte reactivity and migration. Neuronal Thy-1 promotes DITNC1 astrocyte migration by engaging αVβ3 Integrin and Syndecan-4. Primary astrocytes express low levels of these receptors and are unresponsive to Thy-1; thus, inflammation and astrocyte reactivity might be necessary for Thy-1-induced responses. Wild-type rat astrocytes (TNF-activated) or from human SOD1(G93A) transgenic mice (a neurodegenerative disease model) were used to evaluate cell migration, Thy-1 receptor levels, signaling molecules, and reactivity markers. Thy-1 induced astrocyte migration only after TNF priming. Increased expression of αVβ3 Integrin, Syndecan-4, P2X7R, Pannexin-1, Connexin-43, GFAP, and iNOS were observed in TNF-treated astrocytes. Silencing of β3 Integrin prior to TNF treatment prevented Thy-1-induced migration, while β3 Integrin over-expression was sufficient to induce astrocyte reactivity and allow Thy-1-induced migration. Finally, hSOD1(G93A) ast...
Revista Chilena de Fonoaudiología, 2016
Through school years, the main linguistic changes are in semantic, syntactic and pragmatic areas.... more Through school years, the main linguistic changes are in semantic, syntactic and pragmatic areas. Many foreign studies propose that older child have a higher semantic development, specifically in word definition skills, lexical comprehension and understanding of figurative language. However, in national context, there is a little information about this topic. The objective was to determine performance in semantic skills in students of 2 nd and 4 th grade and their association with academic performance. Method non experimental, analytic, comparative and transversal study which considers 58 children of a school in Santiago. The semantic skills were measured with the "Test de Vocabulario en Imágenes" (TEVI-R) and a test of semantic abilities created in this study. The academic performance considered the mean of qualifications during 2 nd trimester in subjects of Language, Math, Natural and Social Science. The created test showed validity and reliability to assess semantic abilities relevant with word definition skills and understanding of figurative language. Statistically significant difference was found between both groups performance in semantic skills studies, with a higher performance in 4 th grade students. No statistically significant difference was found between academic performance and semantic abilities mentioned. As school grade increases, children improve their performance in semantic skills of word definition, lexical comprehension and understanding of figurative language. However, there is no relation between academic performance and semantic abilities studied.
Journal of Cellular Physiology, 2017
This article has been accepted for publication and undergone full peer review but has not been th... more This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Frontiers in Cellular Neuroscience, 2015
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which pathogenesis an... more Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which pathogenesis and death of motor neurons are triggered by non-cell-autonomous mechanisms. We showed earlier that exposing primary rat spinal cord cultures to conditioned media derived from primary mouse astrocyte conditioned media (ACM) that express human SOD1 G93A (ACM-hSOD1 G93A) quickly enhances Na v channelmediated excitability and calcium influx, generates intracellular reactive oxygen species (ROS), and leads to death of motoneurons within days. Here we examined the role of mitochondrial structure and physiology and of the activation of c-Abl, a tyrosine kinase that induces apoptosis. We show that ACM-hSOD1 G93A , but not ACM-hSOD1 WT , increases c-Abl activity in motoneurons, interneurons and glial cells, starting at 60 min; the c-Abl inhibitor STI571 (imatinib) prevents this ACM-hSOD1 G93A-mediated motoneuron death. Interestingly, similar results were obtained with ACM derived from astrocytes expressing SOD1 G86R or TDP43 A315T. We further find that co-application of ACM-SOD1 G93A with blockers of Na v channels (spermidine, mexiletine, or riluzole) or anti-oxidants (Trolox, esculetin, or tiron) effectively prevent c-Abl activation and motoneuron death. In addition, ACM-SOD1 G93A induces alterations in the morphology of neuronal mitochondria that are related with their membrane depolarization. Finally, we find that blocking the opening of the mitochondrial permeability transition pore with cyclosporine A, or inhibiting mitochondrial calcium uptake with Ru360, reduces ROS production and c-Abl activation. Together, our data point to a sequence of events in which a toxic factor(s) released by ALS-expressing astrocytes rapidly induces hyperexcitability, which in turn increases calcium influx and affects mitochondrial structure and physiology. ROS production, mediated at least in part through mitochondrial alterations, trigger c-Abl signaling and lead to motoneuron death.
Frontiers in Cellular Neuroscience, 2014
Amyotrophic lateral sclerosis (ALS) is a fatal paralytic disorder caused by dysfunction and degen... more Amyotrophic lateral sclerosis (ALS) is a fatal paralytic disorder caused by dysfunction and degeneration of motor neurons. Multiple disease-causing mutations, including in the genes for SOD1 and TDP-43, have been identified in ALS. Astrocytes expressing mutant SOD1 are strongly implicated in the pathogenesis of ALS: we have shown that media conditioned by astrocytes carrying mutant SOD1 G93A contains toxic factor(s) that kill motoneurons by activating voltage-sensitive sodium (Na v) channels. In contrast, a recent study suggests that astrocytes expressing mutated TDP43 contribute to ALS pathology, but do so via cell-autonomous processes and lack non-cell-autonomous toxicity. Here we investigate whether astrocytes that express diverse ALS-causing mutations release toxic factor(s) that induce motoneuron death, and if so, whether they do so via a common pathogenic pathway. We exposed primary cultures of wild-type spinal cord cells to conditioned medium derived from astrocytes (ACM) that express SOD1 (ACM-SOD1 G93A and ACM-SOD1 G86R) or TDP43 (ACM-TDP43 A315T) mutants; we show that such exposure rapidly (within 30-60 min) increases dichlorofluorescein (DCF) fluorescence (indicative of nitroxidative stress) and leads to extensive motoneuron-specific death within a few days. Co-application of the diverse ACMs with anti-oxidants Trolox or esculetin (but not with resveratrol) strongly improves motoneuron survival. We also find that co-incubation of the cultures in the ACMs with Na v channel blockers (including mexiletine, spermidine, or riluzole) prevents both intracellular nitroxidative stress and motoneuron death. Together, our data document that two completely unrelated ALS models lead to the death of motoneuron via non-cell-autonomous processes, and show that astrocytes expressing mutations in SOD1 and TDP43 trigger such cell death through a common pathogenic pathway that involves nitroxidative stress, induced at least in part by Na v channel activity.
Journal of Neurophysiology, 2013
Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and... more Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motoneurons starting in adulthood. Recent studies using cell or animal models document that astrocytes expressing disease-causing mutations of human superoxide dismutase 1 (hSOD1) contribute to the pathogenesis of ALS by releasing a neurotoxic factor(s). Neither the mechanism by which this neurotoxic factor induces motoneuron death nor its cellular site of action has been elucidated. Here we show that acute exposure of primary wild-type spinal cord cultures to conditioned medium derived from astrocytes expressing mutant SOD1 (ACM-hSOD1G93A) increases persistent sodium inward currents (PCNa), repetitive firing, and intracellular calcium transients, leading to specific motoneuron death days later. In contrast to TTX, which paradoxically increased twofold the amplitude of calcium transients and killed motoneurons, reduction of hyperexcitability by other specific (mexiletine...
Autophagy, 2013
Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron disease with no current effective treat... more Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron disease with no current effective treatment. Accumulation of abnormal protein inclusions containing SOD1, TARDBP, FUS, among other proteins, is a pathological hallmark of ALS. Autophagy is the major degradation pathway involved in the clearance of damaged organelles and protein aggregates. Although autophagy has been shown to efficiently degrade ALS-linked mutant protein in cell culture models, several studies suggest that autophagy impairment may also contribute to disease pathogenesis. In this report, we tested the potential use of trehalose, a disaccharide that induces MTOR-independent autophagy, in the development of experimental ALS. Administration of trehalose to mutant SOD1 transgenic mice significantly prolonged life span and attenuated the progression of disease signs. These effects were associated with decreased accumulation of SOD1 aggregates and enhanced motoneuron survival. The protective effects of trehalose were associated with increased autophagy levels in motoneurons. cell culture experiments demonstrated that trehalose led to mutant SOD1 degradation by autophagy in NSc34 motoneuron cells and also protected primary motoneurons against the toxicity of conditioned media from mutant SOD1 transgenic astrocytes. At the mechanistic level, trehalose treatment led to a significant upregulation in the expression of key autophagy-related genes at the mRNA level including Lc3, Becn1, Sqstm1 and Atg5. consistent with these changes, trehalose administration enhanced the nuclear translocation of FOXO1, an important transcription factor involved in the activation of autophagy in neurons. This study suggests a potential use of trehalose and enhancers of MTOR-independent autophagy for the treatment of ALS.
Uploads
Papers by Fabiola Pérez Rojas