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During ripening, 'Hass' avocado skin changes from green to purple/black. Low-temperature storage with a controlled atmosphere (CA) is the most widely used method for avocado storage; however, few studies have simulated this technology and considered the days of regular air (RA) storage prior to CA storage. Herein, the effect of delaying the storage of 'Hass' avocado (>30% dry matter) in a CA was examined. Long-term storage conditions (5 °C for 50 days) corresponded to (i) regular air storage (RA), (ii) CA (4 kPa O2 and 6 kPa CO2) and (iii) 10 days in RA + 40 days in a CA and (iv) 20 days in RA + 30 days in a CA. Evaluations were performed during storage and at the ready-to-eat (RTE) stage. Skin color remained unchanged during storage, but at the RTE stage, more color development was observed for fruits stored under CA conditions, as these fruits were purple/black (>50%). At the RTE stage, the anthocyanin content increased, and compared to fruit under RA, fruit under a CA contained a five-fold greater content. A 20-day delay between harvest and CA storage increased the fruit softening rate and skin color development after cold storage, reducing the effectiveness of CA as a postharvest technology for extending storage life.
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BACKGROUND: Rett syndrome is a neuropediatric disease occurring due to mutations in MECP2 and characterized by a regression in the neuronal development following a normal postnatal growth, which results in the loss of acquired capabilities such as speech or purposeful usage of hands. While altered neurotransmission and brain development are the center of its pathophysiology, alterations in mitochondrial performance have been previously outlined, shaping it as an attractive target for the disease treatment. METHODS: We have thoroughly described mitochondrial performance in two Rett models, patients' primary fibroblasts and female Mecp2tm1.1Bird-/+ mice brain, discriminating between different brain areas. The characterization was made according to their bioenergetics function, oxidative stress, network dynamics or ultrastructure. Building on that, we have studied the effect of leriglitazone, a PPARγ agonist, in the modulation of mitochondrial performance. For that, we treated Rett female mice with 75 mg/kg/day leriglitazone from weaning until sacrifice at 7 months, studying both the mitochondrial performance changes and their consequences on the mice phenotype. Finally, we studied its effect on neuroinflammation based on the presence of reactive glia by immunohistochemistry and through a cytokine panel. RESULTS: We have described mitochondrial alterations in Rett fibroblasts regarding both shape and bioenergetic functions, as they displayed less interconnected and shorter mitochondria and reduced ATP production along with increased oxidative stress. The bioenergetic alterations were recalled in Rett mice models, being especially significant in cerebellum, already detectable in pre-symptomatic stages. Treatment with leriglitazone recovered the bioenergetic alterations both in Rett fibroblasts and female mice and exerted an anti-inflammatory effect in the latest, resulting in the amelioration of the mice phenotype both in general condition and exploratory activity. CONCLUSIONS: Our studies confirm the mitochondrial dysfunction in Rett syndrome, setting the differences through brain areas and disease stages. Its modulation through leriglitazone is a potential treatment for this disorder, along with other diseases with mitochondrial involvement. This work constitutes the preclinical necessary evidence to lead to a clinical trial.
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Síndrome de Rett , Humanos , Femenino , Ratones , Animales , Síndrome de Rett/tratamiento farmacológico , Síndrome de Rett/genética , Síndrome de Rett/metabolismo , Mitocondrias/metabolismo , Encéfalo , Estrés Oxidativo , Modelos Animales de EnfermedadRESUMEN
Increasing evidence suggests that the peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, plays an important role in physiological processes in the central nervous system (CNS) and is involved in cellular metabolism and repair. Cellular damage caused by acute brain injury and long-term neurodegenerative disorders is associated with alterations of these metabolic processes leading to mitochondrial dysfunction, oxidative stress, and neuroinflammation. PPARγ agonists have demonstrated the potential to be effective treatments for CNS diseases in preclinical models, but to date, most drugs have failed to show efficacy in clinical trials of neurodegenerative diseases including amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. The most likely explanation for this lack of efficacy is the insufficient brain exposure of these PPARγ agonists. Leriglitazone is a novel, blood-brain barrier (BBB)-penetrant PPARγ agonist that is being developed to treat CNS diseases. Here, we review the main roles of PPARγ in physiology and pathophysiology in the CNS, describe the mechanism of action of PPARγ agonists, and discuss the evidence supporting the use of leriglitazone to treat CNS diseases.
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Enfermedades del Sistema Nervioso Central , Enfermedades Neurodegenerativas , Humanos , Enfermedades del Sistema Nervioso Central/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neuroinflamatorias , PPAR gamma/metabolismoRESUMEN
The novel brain-penetrant peroxisome proliferator-activated receptor gamma agonist leriglitazone, previously validated for other rare neurodegenerative diseases, is a small molecule that acts as a regulator of mitochondrial function and exerts neuroprotective, anti-oxidative and anti-inflammatory effects. Herein, we tested whether leriglitazone can be effective in ameliorating the mitochondrial defects that characterize an hiPS-derived model of Pantothenate kinase-2 associated Neurodegeneration (PKAN). PKAN is caused by a genetic alteration in the mitochondrial enzyme pantothenate kinase-2, whose function is to catalyze the first reaction of the CoA biosynthetic pathway, and for which no effective cure is available. The PKAN hiPS-derived astrocytes are characterized by mitochondrial dysfunction, cytosolic iron deposition, oxidative stress and neurotoxicity. We monitored the effect of leriglitazone in comparison with CoA on hiPS-derived astrocytes from three healthy subjects and three PKAN patients. The treatment with leriglitazone did not affect the differentiation of the neuronal precursor cells into astrocytes, and it improved the viability of PKAN cells and their respiratory activity, while diminishing the iron accumulation similarly or even better than CoA. The data suggest that leriglitazone is well tolerated in this cellular model and could be considered a beneficial therapeutic approach in the treatment of PKAN.
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Omega-3 rich vegetable oils, such as walnut oil, are gaining interest because of their health benefits. Synthetized homologous series of hydroxytyrosol alkyl esters (HTEs) with different alkyl chain lengths (C4-C18) were incorporated in purified walnut oil (PWO) spray-dried microparticles, designed with Capsul® (C) as encapsulating agent and sodium alginate (SA) as outer layer (PWO-C/SA). The encapsulation efficiency (>87%) and Tg of PWO-C/SA microparticles were not affected by the HTEs. The incorporation of HTE-C10 increased the melting point (185.0 ± 1.3 °C), decreasing the formation of Dimers + Polymers (1.12 ± 0.05% at day 35 of storage) and the crystallinity of the microparticles (>170 °C). The highest stability of PWO-C(HTE-C10)/SA suggests a specific location of HTE-C10 at the oil:water interface. The SA layer delayed the release of fatty acids during in vitro digestion. The incorporation of HTEs of medium chain length can be a suitable strategy to protect unsaturated oils encapsulated by spray-drying.
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Antioxidantes , Juglans , Alginatos , Ésteres , Alcohol Feniletílico/análogos & derivadosRESUMEN
The entomopathogenic fungus Beauveria pseudobassiana strain RGM 2184 can reach a maximum efficacy of 80% against the quarantine pest Lobesia botrana in field assays. In this study, the RGM 2184 genome was sequenced, and genome mining analyses were performed to predict the factors involved in its insecticidal activity. Additionally, the metabolic profiling of the RMG 2184 culture's supernatants was analyzed by mass spectrometry, and the insecticidal activity from one of these extracts was evaluated in Galleria mellonella larvae. The genome analysis resulted in 114 genes encoding for extracellular enzymes, four biosynthetic gene clusters reported as producers of insecticidal and bactericidal factors (oosporein, beauvericin, desmethylbassianin, and beauveriolide), 20 toxins, and at least 40 undescribed potential biocontrol factors (polyketides and nonribosomal peptides). Comparative genomic analysis revealed that 65-95% of these genes are Beauveria genus-specific. Metabolic profiling of supernatant extracts from RGM 2184 cultures exhibited secondary metabolites such as beauveriolide, oosporein, inflatin C, and bassiatin. However, a number of detected metabolites still remain undescribed. The metabolite extract caused 79% mortality of Galleria mellonella larvae at 28 days. The results of this research lay the groundwork for the study of new insecticidal molecules.
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Pressurized liquid extraction (PLE) is a clean and environmentally friendly alternative for the recovery of bioactive compounds from fruit by-products. Herein we focused on PLE for the extraction of bioactive compounds from pomegranate peel using a combination of pressurized water and ethanol. The main aim was to determine the optimal PLE conditions, i.e., ethanol percentage and process temperature, to obtain a pomegranate peel extract (PPE) with maximum total phenolic content (TPC), punicalagin content, and antimicrobial activity (AMA). The experimental design was conducted using a central composite design with axial points. Response surface methodology was applied to optimize the response variables using the desirability function. Multiple response optimization indicated a process temperature of 200 °C and ethanol of 77% as optimal conditions. The TPC and the punicalagin content of PPE-PLE obtained under optimal conditions were 164.3 ± 10.7 mg GAE/g DW and 17 ± 3.6 mg/g DW, respectively. Our findings support the efficacy of PLE on TPC recovery but not in punicalagin recovery. The AMA against S. aureus was 14 mm. The efficacy of PPE-PLE in food applications must continue to be studied in order to achieve adequate information on its potential for developing new food additives.
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Friedreich ataxia (FRDA), the most common autosomal recessive ataxia, is characterized by degeneration of the large sensory neurons and spinocerebellar tracts, cardiomyopathy, and increased incidence in diabetes. The underlying pathophysiological mechanism of FRDA, driven by a significantly decreased expression of frataxin (FXN), involves increased oxidative stress, reduced activity of enzymes containing ironsulfur clusters (ISC), defective energy production, calcium dyshomeostasis, and impaired mitochondrial biogenesis, leading to mitochondrial dysfunction. The peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcriptional factor playing a key role in mitochondrial function and biogenesis, fatty acid storage, energy metabolism, and antioxidant defence. It has been previously shown that the PPARγ/PPARγ coactivator 1 alpha (PGC-1α) pathway is dysregulated when there is frataxin deficiency, thus contributing to FRDA pathogenesis and supporting the PPARγ pathway as a potential therapeutic target. Here we assess whether MIN-102 (INN: leriglitazone), a novel brain penetrant and orally bioavailable PPARγ agonist with an improved profile for central nervous system (CNS) diseases, rescues phenotypic features in cellular and animal models of FRDA. In frataxin-deficient dorsal root ganglia (DRG) neurons, leriglitazone increased frataxin protein levels, reduced neurite degeneration and α-fodrin cleavage mediated by calpain and caspase 3, and increased survival. Leriglitazone also restored mitochondrial membrane potential and partially reversed decreased levels of mitochondrial Na+/Ca2+ exchanger (NCLX), resulting in an improvement of mitochondrial functions and calcium homeostasis. In frataxin-deficient primary neonatal cardiomyocytes, leriglitazone prevented lipid droplet accumulation without increases in frataxin levels. Furthermore, leriglitazone improved motor function deficit in YG8sR mice, a FRDA mouse model. In agreement with the role of PPARγ in mitochondrial biogenesis, leriglitazone significantly increased markers of mitochondrial biogenesis in FRDA patient cells. Overall, these results suggest that targeting the PPARγ pathway by leriglitazone may provide an efficacious therapy for FRDA increasing the mitochondrial function and biogenesis that could increase frataxin levels in compromised frataxin-deficient DRG neurons. Alternately, leriglitazone improved the energy metabolism by increasing the fatty acid ß-oxidation in frataxin-deficient cardiomyocytes without elevation of frataxin levels. This could be linked to a lack of significant mitochondrial biogenesis and cardiac hypertrophy. The results reinforced the different tissue requirement in FRDA and the pleiotropic effects of leriglitazone that could be a promising therapy for FRDA.
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Ataxia de Friedreich/metabolismo , Proteínas de Unión a Hierro/efectos de los fármacos , Gotas Lipídicas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Neuronas/efectos de los fármacos , PPAR gamma/agonistas , Tiazolidinedionas/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Ataxia de Friedreich/patología , Ataxia de Friedreich/fisiopatología , Humanos , Proteínas de Unión a Hierro/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Mitocondrias/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Neuritas/efectos de los fármacos , Neuritas/patología , Neuronas/metabolismo , Neuronas/patología , Ratas , FrataxinaRESUMEN
Purified walnut oil (PWO) microparticles with Capsul® (C, encapsulating agent), sodium alginate (SA) as outer layer and ascorbic acid (AA) as oxygen scavenger were obtained by spray drying using a three-fluid nozzle. AA was incorporated in the inner infeed (PWO-C(AA)/SA), in the outer infeed (PWO-C/SA(AA)) and in both infeed (PWO-C(AA)/SA(AA)). PWO-C(AA)/SA (4.56 h) and POW-C(AA)/SA(AA) (2.60 h) microparticles showed higher induction period than POW-C/SA(AA) (1.17 h), and lower formation of triacylglycerol dimers and polymers during storage (40 °C). Therefore, AA located in the inner infeed improved the oxidative stability of encapsulated PWO by removing the residual oxygen. AA in the SA outer layer did not improve the oxidative stability of encapsulated PWO since oxygen diffusion through the microparticles was limited and/or AA weakened the SA layer structure. The specific-location of AA (inner infeed) is a strategy to obtain stable spray-dried polyunsaturated oil-based microparticles for the design of foods enriched with omega-3 fatty acids.
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Cellular prion protein (PrPC) is largely responsible for transmissible spongiform encephalopathies (TSEs) when it becomes the abnormally processed and protease resistant form PrPSC. Physiological functions of PrPC include protective roles against oxidative stress and excitotoxicity. Relevantly, PrPC downregulates tau levels, whose accumulation and modification are a hallmark in the advance of Alzheimer's disease (AD). In addition to the accumulation of misfolded proteins, in the initial stages of AD-affected brains display both increased reactive oxygen species (ROS) markers and levels of PrPC. However, the factors responsible for the upregulation of PrPC are unknown. Thus, the aim of this study was to uncover the different molecular actors promoting PrPC overexpression. In order to mimic early stages of AD, we used ß-amyloid-derived diffusible ligands (ADDLs) and tau cellular treatments, as well as ROS generation, to elucidate their particular roles in human PRNP promoter activity. In addition, we used specific chemical inhibitors and site-specific mutations of the PRNP promoter sequence to analyze the contribution of the main transcription factors involved in PRNP transcription under the analyzed conditions. Our results revealed that tau is a new modulator of PrPC expression independently of ADDL treatment and ROS levels. Lastly, we discovered that the JNK/c-jun-AP-1 pathway is involved in increased PRNP transcription activity by tau but not in the promoter response to ROS.
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Proteínas Priónicas/metabolismo , Transcripción Genética , Proteínas tau/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Sitios de Unión , Células HEK293 , Humanos , Ligandos , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Priónicas/genética , Proteínas Priónicas/ultraestructura , Regiones Promotoras Genéticas/genética , Inhibidores de Proteínas Quinasas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Solubilidad , Proteínas tau/ultraestructuraRESUMEN
Purple flesh cultivated potato (PP) is a foodstuff scarcely cultivated in the world but with high potential because of its anthocyanin content. Moreover, it has been little explored as a source of anthocyanins (AT) for further applications in formulated food products. The main goal of this research was to study the effect of maltodextrin (MD) and spray drying conditions on the encapsulation efficiency (EE) and bioaccesibility of AT from purple flesh cultivated potato extract (PPE). The anthocyanin-rich extract was obtained from PP and microencapsulated by spray-drying, using MD as the encapsulating agent. A statistical optimization approach was used to obtain optimal microencapsulation conditions. The PPE microparticles obtained under optimal conditions showed 86% of EE. The protector effect of microencapsulation on AT was observed to be stable during storage and in vitro digestion. The AT degradation rate constant was significantly lower for the PPE-MD than for the PPE. The assessed bioaccesibility of AT from the PPE-MD was 20% higher than that of the PPE, which could be explained by the protective effect of encapsulation against environmental conditions. In conclusion, microencapsulation is an effective strategy to protect AT from PP, suggesting that AT may be an alternative as a stable colorant for use in the food industry.
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Antocianinas/química , Extractos Vegetales/química , Solanum tuberosum/química , Color , Composición de Medicamentos/métodos , Industria de Alimentos/métodos , Modelos Biológicos , Polisacáridos/químicaRESUMEN
Genome-wide association studies (GWAS) have identified PICALM as one of the most significant susceptibility loci for late-onset Alzheimer's disease (AD) after APOE and BIN1. PICALM is a clathrin-adaptor protein and plays critical roles in clathrin-mediated endocytosis and in autophagy. PICALM modulates brain amyloid ß (Aß) pathology and tau accumulation. We have previously reported that soluble PICALM protein level is reduced in correlation with abnormalities of autophagy markers in the affected brain areas of neurodegenerative diseases including AD, sporadic tauopathies and familial cases of frontotemporal lobar degeneration with tau-immunoreactive inclusions (FTLD-tau) with mutations in the microtubule-associated protein tau (MAPT) gene. It remains unclarified whether in vivo PICALM reduction could either trigger or influence tau pathology progression in the brain. In this study, we confirmed a significant reduction of soluble PICALM protein and autophagy deficits in the post-mortem human brains of FTLD-tau-MAPT (P301L, S364S and L266V). We generated a novel transgenic mouse line named Tg30xPicalm+/- by crossing Tg30 tau transgenic mice with Picalm-haploinsufficient mice to test whether Picalm reduction may modulate tau pathology. While Picalm haploinsufficiency did not lead to any motor phenotype or detectable tau pathology in mouse brains, Tg30xPicalm+/- mice developed markedly more severe motor deficits than Tg30 by the age of 9 months. Tg30xPicalm+/- had significantly higher pathological tau levels in the brain, an increased density of neurofibrillary tangles compared to Tg30 mice and increased abnormalities of autophagy markers. Our results demonstrate that Picalm haploinsufficiency in transgenic Tg30 mice significantly aggravated tau pathologies and tau-mediated neurodegeneration, supporting a role for changes in Picalm expression as a risk/sensitizing factor for development of tau pathology and as a mechanism underlying the AD risk associated to PICALM.
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Proteínas de Ensamble de Clatrina Monoméricas/genética , Tauopatías/genética , Tauopatías/patología , Animales , Encéfalo/patología , Modelos Animales de Enfermedad , Femenino , Demencia Frontotemporal/metabolismo , Haploinsuficiencia , Humanos , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Proteínas de Ensamble de Clatrina Monoméricas/metabolismo , Tauopatías/metabolismo , Proteínas tau/genéticaRESUMEN
A purple cactus pear (Opuntia ficus-indica) extract (CP) was encapsulated in double emulsions (DE) gelled with gelatin (DE-CP-G) and with gelatin and transglutaminase (DE-CP-GT), as well as in a DE with a liquid external aqueous phase (DE-CP), in order to study the retention of betanin as colorant agent. Both gelled DEs showed a predominantly elastic behavior, in contrast with DE-CP. The degradation rate constant of betanin was significantly higher in DE-CP-GT (90.2 x 10-3 days-1) than in DE-CP-G (11.0 x 10-3 days-1) and DE-CP (14.6 x 10-3 days-1) during cold-storage (4 °C). A shift towards yellow color was found in all the systems during cold-storage (4 °C) and after thermal treatment (70°C/30 min), especially in DE-CP-GT, denoting a higher degradation of betanin. Betalamic acid, cyclo-Dopa 5-O-ß-glucoside, 17-decarboxy-betanin and neobetanin were identified by UHPLC-MS/MS as degradation products of betanin.
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Betacianinas/química , Geles/química , Opuntia/química , Extractos Vegetales/química , Betalaínas/química , Betalaínas/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Emulsiones/química , Frutas/química , Pigmentos Biológicos/química , Piridinas/química , Piridinas/aislamiento & purificación , Espectrometría de Masas en Tándem , Transglutaminasas/químicaRESUMEN
Human tauopathies are neurodegenerative diseases with accumulation of abnormally phosphorylated and aggregated tau proteins forming neurofibrillary tangles. We investigated the development of tau pathology in aged cat brains as a model of neurofibrillary tangle formation occurring spontaneously during aging. In 4 of 6 cats aged between 18 and 21 years, we found a somatodendritic accumulation of phosphorylated and aggregated tau in neurons and oligodendrocytes. Two of these 4 cats had no amyloid immunoreactivity. These tau inclusions were mainly composed of 4R tau isoforms and straight filaments and colocalized with the active form of the glycogen synthase kinase-3 (GSK3). Cat brains with a tau pathology showed a significant cortical atrophy and neuronal loss. We demonstrate in this study the presence of a tau pathology in aged cat brains that develop independently of amyloid deposits. The colocalization of the active form of the GSK3 with tau inclusions as observed in human tauopathies suggests that this kinase could be responsible for the abnormal tau phosphorylation observed in aged cat brains, representing a mechanism of tau pathology development shared between a naturally occurring tauopathy in aged cats and human tauopathies.
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Envejecimiento/metabolismo , Encéfalo/metabolismo , Tauopatías/etiología , Proteínas tau/metabolismo , Animales , Encéfalo/patología , Gatos , Glucógeno Sintasa Quinasa 3 , Humanos , Ovillos Neurofibrilares , Neuronas/metabolismo , Fosforilación , Placa Amiloide , Tauopatías/metabolismo , Tauopatías/patologíaRESUMEN
Neuropathological analysis in Alzheimer's disease (AD) and experimental evidence in transgenic models overexpressing frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) mutant tau suggest that amyloid-ß pathology enhances the development of tau pathology. In this work, we analyzed this interaction independently of the overexpression of an FTDP-17 mutant tau, by analyzing tau pathology in wild-type (WT), 5xFAD, APP-/- and tau-/- mice after stereotaxic injection in the somatosensory cortex of short-length native human AD-PHF. Gallyas and phosphotau-positive tau inclusions developed in WT, 5xFAD, and APP-/- but not in tau-/- mice. Ultrastructural analysis demonstrated their intracellular localization and that they were composed of straight filaments. These seeded tau inclusions were composed only of endogenous murine tau exhibiting a tau antigenic profile similar to tau aggregates in AD. Insoluble tau level was higher and ipsilateral anteroposterior and contralateral cortical spreading of tau inclusions was more important in AD-PHF-injected 5xFAD mice than in WT mice. The formation of large plaque-associated dystrophic neurites positive for oligomeric and phosphotau was observed in 5xFAD mice injected with AD-PHF but never in control-injected or in non-injected 5xFAD mice. An increased level of the p25 activator of CDK5 kinase was found in AD-PHF-injected 5xFAD mice. These data demonstrate in vivo that the presence of Aß pathology enhances experimentally induced tau seeding of endogenous, wild-type tau expressed at physiological level, and demonstrate the fibrillar nature of heterotopically seeded endogenous tau. These observations further support the hypothesis that Aß enhances tau pathology development in AD through increased pathological tau spreading.
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Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Ovillos Neurofibrilares/patología , Proteínas tau/metabolismo , Animales , Humanos , Ratones , Ratones NoqueadosRESUMEN
Rhinella spinulosa is distributed from Peru to Argentina (from 1200 to 5000â¯m elevation), inhabiting arid mountain valleys of the Andes, characterized by salty soils. The variations in soil salinity, caused by high evapotranspiration of water, can create an osmotic constraint and high thermal oscillations for metamorphsed Andean toad (R. spinulosa), affecting their thermoregulation and extreme thermal tolerances. We investigated the changes in thermal tolerance parameters (critical thermal maximum and crystallization temperature) of a population of metamorphosed R. spinulosa from the Monte Desert of San Juan, Argentina, under different substrate salinity conditions. Our results suggest that the locomotor performance of metamorphs of R. spinulosa is affected by increasing salinity concentrations in the environment where they develop. On the other hand, the thermal extremes of metamorphs of R. spinulosa also showed changes associated with different salinity conditions. According to other studies on different organisms, the increase of the osmolarity of the internal medium may increase the thermal tolerance of this species. More studies are needed to understand the thermo-osmolar adjustments of the metamorphs of toads to environmental variability.
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Bufonidae/fisiología , Locomoción , Salinidad , Tolerancia a la Sal , Termotolerancia , Animales , Argentina , Conducta Animal , TemperaturaRESUMEN
Fish-oil (FO) was encapsulated with hydroxypropylcelullose (HPC) by conventional spray-drying with water (FO-water) and solvent spray-drying with ethanol (FO-EtOH), methanol (FO-MeOH) and acetone (FO-Acet) in order to study the effect of the solvent on the encapsulation efficiency (EE), microparticle properties and stability of FO during storage at 40⯰C. Results showed that FO-Acet presented the highest EE of FO (92.0%), followed by FO-EtOH (80.4%), FO-MeOH (75.0%) and FO-water (71.1%). A decrease of the dielectric constant increased the EE of FO, promoting triglyceride-polymer interactions instead of oil-in-water emulsion retention. FO release profile in aqueous model was similar for all FO-microparticles, releasing only the surface FO, according to Higuchi model. Oxidative stability of FO significantly improved by spray-drying with MeOH, both in surface and encapsulated oil fractions. In conclusion, encapsulation of FO by solvent spray-drying can be proposed as an alternative technology for encapsulation of hydrophobic molecules.
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Aceites de Pescado/química , Solventes/química , Celulosa/análogos & derivados , Celulosa/química , Cromatografía Líquida de Alta Presión , Ácidos Docosahexaenoicos/análisis , Ácidos Docosahexaenoicos/aislamiento & purificación , Ácido Eicosapentaenoico/análisis , Ácido Eicosapentaenoico/aislamiento & purificación , Higroscópicos/química , Extracción en Fase Sólida , Agua/químicaRESUMEN
Gerstmann-Sträussler-Scheinker (GSS) syndrome is a fatal autosomal dominant neurodegenerative prionopathy clinically characterized by ataxia, spastic paraparesis, extrapyramidal signs and dementia. In some GSS familiar cases carrying point mutations in the PRNP gene, patients also showed comorbid tauopathy leading to mixed pathologies. In this study we developed an induced pluripotent stem (iPS) cell model derived from fibroblasts of a GSS patient harboring the Y218N PRNP mutation, as well as an age-matched healthy control. This particular PRNP mutation is unique with very few described cases. One of the cases presented neurofibrillary degeneration with relevant Tau hyperphosphorylation. Y218N iPS-derived cultures showed relevant astrogliosis, increased phospho-Tau, altered microtubule-associated transport and cell death. However, they failed to generate proteinase K-resistant prion. In this study we set out to test, for the first time, whether iPS cell-derived neurons could be used to investigate the appearance of disease-related phenotypes (i.e, tauopathy) identified in the GSS patient.
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Enfermedad de Gerstmann-Straussler-Scheinker/genética , Enfermedad de Gerstmann-Straussler-Scheinker/patología , Células Madre Pluripotentes Inducidas/patología , Mutación/genética , Proteínas Priónicas/genética , Proteínas tau/metabolismo , Astrocitos/metabolismo , Astrocitos/patología , Secuencia de Bases , Encéfalo/patología , Diferenciación Celular , Células Cultivadas , Femenino , Gliosis/patología , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Persona de Mediana Edad , Mitocondrias/metabolismo , Neuronas/metabolismo , Neuronas/patología , FosforilaciónRESUMEN
Single nucleotide polymorphisms in PICALM, a key component of clathrin-mediated endocytosis machinery, have been identified as genetic susceptibility loci for late onset Alzheimer's disease (LOAD). We previously reported that PICALM protein levels were decreased in AD brains and that PICALM was co-localised with neurofibrillary tangles in LOAD, familial AD with PSEN1 mutations and Down syndrome. In the present study, we analysed PICALM expression, cell localisation and association with pathological cellular inclusions in other tauopathies and in non-tau related neurodegenerative diseases. We observed that PICALM was associated with neuronal tau pathology in Pick disease and in progressive supranuclear palsy (PSP) and co-localised with both 3R and 4R tau positive inclusions unlike in corticobasal degeneration (CBD) or in frontotemporal lobar degeneration (FTLD)-MAPT P301L. PICALM immunoreactivities were not detected in tau-positive tufted astrocytes in PSP, astrocytic plaques in CBD, Lewy bodies in Lewy body disease, diffuse type (LBD) and in TDP-43-positive inclusions in FTLD. In the frontal cortex in tauopathies, the ratio of insoluble to soluble PICALM was increased while the level of soluble PICALM was decreased and was inversely correlated with the level of phosphotau. PICALM decrease was also significantly correlated with increased LC3-II and decreased Beclin-1 levels in tauopathies and in non-tau related neurodegenerative diseases. These results suggest that there is a close relationship between abnormal PICALM processing, tau pathology and impairment of autophagy in human neurodegenerative diseases.