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deciphering the role of PGC-1α in neurological disorders: from mitochondrial dysfunction to synaptic failure

Neural Regeneration Research 2022年第2期17卷 237-245页

作者： Jessica D.Panes Aline Wendt Oscar Ramirez-Molina Patricio A.Castro Jorge Fuentealba Laboratorio de Screening de Compuestos Neuroactivos(LSCN) Departamento de FisiologiaFacultad de Ciencias BiologicasUniversidad de ConcepcionConcepcionChile Centro de Investigaciones Avanzadas en Biomedicina(CIAB-UdeC) Facultad de Ciencias BiologicasUniversidad de ConcepcionConcepcionChile departamento de Fisiologia Facultad de Ciencias BiologicasUniversidad de ConcepcionConcepcionChile

The onset and mechanisms underlying neurodegenerative diseases remain uncertain. The main features of neurodegenerative diseases have been related with cellular and molecular events like neuronal loss, mitochondrial dysfunction and aberrant accumulation of misfolded proteins or peptides in specific areas of the brain. The most prevalent neurodegenerative diseases belonging to age-related pathologies are Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Interestingly, mitochondrial dysfunction has been observed to occur during the early onset of several neuropathological events associated to neurodegenerative diseases. The master regulator of mitochondrial quality control and energetic metabolism is the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α). Additionally, it has been observed that PGC-1α appears to be a key factor in maintaining neuronal survival and synaptic transmission. In fact, PGC-1α downregulation in different brain areas(hippocampus, substantia nigra, cortex, striatum and spinal cord) that occurs in function of neurological damage including oxidative stress, neuronal loss, and motor disorders has been seen in several animal and cellular models of neurodegenerative diseases. Current evidence indicates that PGC-1α upregulation may serve as a potent therapeutic approach against development and progression of neuronal damage. Remarkably, increasing evidence shows that PGC-1α deficient mice have neurodegenerative diseases-like features, as well as neurological abnormalities. Finally, we discuss recent studies showing novel specific PGC-1α isoforms in the central nervous system that appear to exert a key role in the age of onset of neurodegenerative diseases and have a neuroprotective function in the central nervous system, thus opening a new molecular strategy for treatment of neurodegenerative diseases. The purpose of this review is to provide an up-to-date overview of the PGC-1α role in the physio

关键词： Alzheimer's disease amyotrophic lateral sclerosis Huntington's disease mitochondrial dysfunction Parkinson's disease PGC-1α synaptic function vascular dementia

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Multiple responses optimization in the development of a headspace gas chromatography method for the determination of residual solvents in pharmaceuticals

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Journal of Pharmaceutical Analysis 2015年第5期5卷 296-306页

作者： Carla M.Teglia Milagros Montemurro María M.de Zan María S.Cmara Laboratorio de Control de Calidad de Medicamentos Facultad de Bioquimica y Ciencias BiologicasUniversidad Nacional del Litoral

An efficient generic static headspace gas chromatography （HSGC） method was developed, optimized and validated for the routine determination of several residual solvents （RS） in drug substance, using a strategy with two sets of calibration. Dimethylsulfoxide （DMSO） was selected as the sample diluent and internal standards were used to minimize signal variations due to the preparative step. A gas chroma- tograph from Agilent Model 6890 equipped with flame ionization detector （FID） and a DB-624 （30 m × 0.53 mm i.d., 3.00 μm film thickness） column was used. The inlet split ratio was 5：1. The influ- encing factors in the chromatographic separation of the analytes were determined through a fractional factorial experimental design. Significant variables： the initial temperature （IT）, the final temperature （FT） of the oven and the carrier gas flow rate （F） were optimized using a central composite design. Response transformation and desirability function were applied to find out the optimal combination of the chromatographic variables to achieve an adequate resolution of the analytes and short analysis time. These conditions were 30 ℃ for IT, 158 ℃ for FT and 1.90 mL/min for F. The method was proven to be accurate, linear in a wide range and very sensitive for the analyzed solvents through a comprehensive validation according to the ICH guidelines.

关键词： Headspace gas chromatographyResidual solventsPharmaceuticalsSurface response methodologydesirabiliW function

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Novel Kdr mutations (K964R and A943V) in pyrethroid-resistant populations of Triatoma mazzottii and Triatoma longipennisUoro Mexico and detoxifying enzymes

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Insect Science 2019年第5期26卷 809-820页

作者： Jesus Davila-Barboza O.Karina Villanueva-Segura Beatriz Lopez-Monroy Gustavo Ponce-Garcia Cristina Bobadilla-Utrera Mayela Montes-Rincon Zinnia J.Molina-Garza Juan I.Arredondo-Jimenez Iram P.Rodriguez-Sanchez Pablo C.Manrique-Saide Adriana E.Flores Universidad Autonoma de Nuevo Leon (UANL) Facultad de Ciencias BiologicasSan Nicolas de los GarzaNLMexico Laboratorio Estatal de Salud Publica de los Servicios de Salud de Veracruz VeracruzMexico Campus de ciencias biologicas y Agropecuarias Unidad Colaborativa para Bioensayos EntomologicosUniversidad Autonoma de YucatanMeridaYucatanMexico

Although having five different ways of transmission the vector-borne is the principal way of transmission of Chagas disease, which involves insects of the subfamily Triatominae (Hemiptera: Reduviidae). Nineteen of the 31 species that occur in Mexico are associated with humans, and all are capable of transmitting the disease. Pyrethroids are the insecticides recommended for the control of these vectors in Mexico. We determined the susceptibility to the pyrethroids dcltamethrin and permethrin of peridomestic populations of Triatoma mazzottii Usinger and two populations of Triatoma longipetmis Usinger in comparison with a reference strain for each species. Bioassays were performed for the determination of the LD50 for both field populations and reference strains. A maximum of 27 fold resistance to deltamethrin was observed in T. mazzottii, meanwhile, for permethrin, T. longipennis from Jalisco show the highest value of 3.19 fold. There was significantly increased activity of esterases in field populations in comparison with their corresponding reference strain. The results of the search of kdr mutations related to the resistance to deltamethrin and permethrin in the evaluated species show the presence of mutations in the field populations, as is the case with individuals of T. mazzottii, for which the mutation was found A943V, and for the two populations of T. longipennis included in this study, we report the presence of the kdr mutation K964R. Evaluation of the various mechanisms involved in resistance to pyrethroids in triatomines from Mexico could guide us to the real justification for insecticide resistance monitoring.

关键词： detoxifying enzymes kdr pyrethroids Triatoma longipennis Triatoma mazzottii

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Lower marine productivity increases agonistic interactions between sea lions and fur seals in Northern Pacific Patagonia

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Current Zoology 2022年第6期68卷 657-666页

作者： Felipe MONTALVA Hector PAVES Diego PEREZ-VENEGAS Karin G BARRIENTOS E Carola VALENCIA Diego MIRANDA-URBINA Mauricio SEGUEL Facultad de Ciencias Biologicas Pontificia Universidad Catolica de ChileSantiagoChile departamento de ciencias Basicas Facultad de CienciasUniversidad Santo TomasOsornoChile Centro de Investigacion y Gestion de Recursos Naturales(CIGREN) Instituto de BiologıaFacultad de CienciasUniversidad de ValparaısoValparaısoChile Programa de Doctorado en ciencias Agrarias Escuela de Graduados de laFacultad de Ciencias Agrarias y AlimentariasUniversidad Austral de ChileValdiviaChile facultad de Medicina Veterinaria Sede PatagoniaUniversidad San SebastianPuerto MonttChile Instituto de ciencias biologicas Universidad de TalcaTalcaChile department of Pathobiology Ontario Veterinary CollegeUniversity of GuelphGuelphCanada

Interspecific interactions are key drivers of individual and population-level fitness in a wide range of animals.However,in marine ecosystems,it is relatively unknown which biotic and abiotic factors impact behavioral interactions between competing species.We assessed the impact of weather,marine productivity,and population structure on the behavioral agonistic interactions between South American fur seals(SAFSs),Arctocephalus australis,and South American sea lions(SASLs),Otaria byronia,in a breeding colony of SAFS.We hypothesized that agonistic interactions between SAFSs and SASLs respond to biotic and abiotic factors such as SAFS population structure,marine productivity,and weather.We found that SASL and SAFS interactions almost always resulted in negative impacts on the social structure or reproductive success of the SAFS colony.SASL adult males initiated stampedes of SAFS and/or abducted and predated SAFS pups.Adult SAFS males abundance and severe weather events were negatively correlated with agonistic interactions between species.However,proxies for lower marine productivity such as higher sea surface temperature and lower catches of demerso-pelagic fish were the most important predictors of more frequent agonistic interactions between SAFS and SASL.Under the current scenario of decline in marine biomass due to global climate change and overfishing,agonistic interactions between competing marine predators could increase and exacerbate the negative impacts of environmental change in these species.

关键词： interspecific interactions climate change Guafo Island sea surface temperature South American fur seal South American sea lion

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Emerging Players in the Nitrate Signaling Pathway

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Molecular Plant 2017年第8期10卷 1019-1022页

作者： Grace Armijo Rodrigo A. Gutierrez departamento de Genetica Molecular y Microbiologia Facultad de Ciencias Biologicas FONDAP Center for Genome Regulation Pontificia Universidad Cat61ica de Chile Santiago 8331150 Chile departamento de Genetica Molecular y Microbiologia Facultad de Ciencias Biologicas Millennium Nucleus Center for Plant Functional Genomics Pontificia Universidad Catolica de Chile Santiago 8331150 Chile

Nitrogen （N）-based fertilizers are routinely used to increase agricultural productivity for both food and non-food uses of crops. Unfortunately, excess N fertilizers escape to the environment, leading to detrimental effects on the ecosystem and human health. Understanding how plants sense and respond to different N nutrients or metabolites to regulate metabolism, physiology, growth, and development is essential for sustained yields while reducing agriculture＇s environmental and economic costs.

关键词： ARABIDOPSIS NETWORKS RESPONSES PLANTS CHL1

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Clinicopathological alterations in wild mammals from the reservoir system of Trypanosoma cruzi:a scoping review

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Animal Diseases 2024年第1期4卷 48-58页

作者： Ricardo Sanchez Pérez JoséManuel Aranda-Coello JoséAntonio de Fuentes Vicente Oscar Rico Chavez facultad de Estudios Superiores Cuautitlan Universidad Nacional Autonoma deMexicoCuautitlan lzcalliEstadodeMexicoMexico El Colegio de la Frontera Sur-Unidad Campeche CampecheCampecheMexico Instituto de ciencias biologicas-Universidad de ciencias y Artes de Chiapas Tuxtla GutierrezChiapasMexico facultad de Medicina Veterinaria y Zootecnia-Universidad Nacional Autonoma deMexico Ciudad deMexicoMexico

Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as"kissing bugs").despite the fact that hundreds of species of wild mammals are part of the reservoir system,the morphologi-cal changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected.The aim of this review is to systematically compile the available information regarding clinicopathological altera-tions in wild mammals due to natural infection by T.cruzi.Information was obtained from six online bibliographic data search platforms,resulting in the identification of 29 publications that met the inclusion criteria.Mortality was the most common clinical manifestation,cardiac damage was the main finding at necropsy,and lymphoplas-macytic inflammation was the most frequent microscopic injury.Thus,regardless of its role as a reservoir,T.cruzi has the potential to affect the health status of wild mammals,a situation that highlights the need for further research to analyze,measure,and compare its effects at both the individual and population levels.

关键词： Trypanosoma cruzi Chagas disease American trypanosomiasis Clinicopathological alterations Natural infection Wild mammals

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Photooxidative stress activates a complex multigenic response integrating the phenylpropanoid pathway and ethylene,leading to lignin accumulation in apple(Malus domestica Borkh.)fruit

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Horticulture Research 2020年第1期7卷 2501-2513页

作者： Carolina A.Torres Constanza Azocar Patricio Ramos Ricardo Pérez-Díaz Gloria Sepulveda María A.Moya-León facultad de ciencias Agrarias Universidad de TalcaTalcaChile department of Horticulture Tree Fruit Research&Extension CenterWashington State UniversityWenatcheeWAUSA Universidad Andres Bello Facultad Ciencias BiologicasSantiagoChile Instituto de ciencias Biológicas Universidad de TalcaTalcaChile Núcleo Cientifíco Multidisciplinario-DI Universidad de TalcaTalcaChile

Photooxidative stress,when combined with elevated temperatures,triggers various defense mechanisms leading to physiological,biochemical,and morphological changes in fruit tissue.Furthermore,during sun damage,apple fruit undergo textural changes characterized by high flesh firmness compared to unexposed fruit.Fuji and Royal Gala apples were suddenly exposed to sunlight on the tree and then sampled for up to 29 days.Cell wall components and lignin biosynthetic pathway analyses were carried out on the fruit tissue.At harvest,Fuji apples with different sun exposure levels,such as exposed to direct sunlight(Exp),shaded(Non-Exp),and with severe sun damage(Sev),were also characterized.In fruit suddenly exposed to sunlight,the expression levels of phenylpropanoid-related genes,phenylalanine ammonia lyase(MdPAL),chalcone synthase(MdCHS),and flavanone-3-hydroxylase(MdF3H),were upregulated in the skin and flesh of Exp and Sev.Exposure had little effect on the lignin-related genes caffeic acid Omethyltransferase 1(MdCOMT1)and cinnamyl alcohol dehydrogenase(MdCAD)in the skin;however,the expression of these genes was highly induced in the flesh of Exp and Sev in both cultivars.Lignin deposition increased significantly in skin with sun injury(Sev);in flesh,this increase occurred late during the stress treatment.Additionally,the ethylene biosynthesis genes 1-aminocyclopropane-1-carboxylate synthase(MdACS)and 1-aminocyclopropane-1-carboxylate oxidase(MdACO)were highly expressed in the skin and flesh tissues but were more upregulated in Sev than in Exp during the time-course experiment,which paralleled the induction of the phenylpropanoid pathway and lignin accumulation.At harvest,flesh from Sev fruit exhibited higher firmness than that from Non-Exp and Exp fruit,although no differences were observed in the alcohol-insoluble residues(AIR)among groups.The fractionation of cell wall polymers revealed an increase in the uronic acid contents of the water-soluble pectin fraction(WSF)in Exp and Sev tissues compared to Non-Exp tissues,wh

关键词： stress involvement suddenly

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THEMIS,the new kid on the block for T-cell development

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Cellular & Molecular Immunology 2017年第9期14卷 721-723页

作者： Janyra A Espinoza Evelyn L Jara Alexis M Kalergis Facultad de Ciencias Biologicas Departamento de Genética Molecular y MicrobiologíaMillennium Institute on Immunology and ImmunotherapyPontificia Universidad Catolica de ChileSantiagoChile facultad de Medicina Escuela de MedicinaDepartamento de EndocrinologíaPontificia Universidad Catolica de ChileSantiagoChile

Understanding T-cell development is a major goal of the immunology field and is crucial for the elucidation of the mechanisms behind self-tolerance and the occurrence of autoimmune disorders.T-cell development is a co... 详细信息

关键词： MIS arise development

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Reliability of enzyme assays in dried blood spots for diagnosis of 4 lysosomal storage disorders

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Advances in Biological Chemistry 2011年第3期1卷 58-64页

作者： Romina Ceci Pablo N. de Francesco Juan M. Mucci Lorena N. Cancelarich Carlos A. Fossati Paula A. Rozenfeld LISIN Departamento de Ciencias Biologicas Facultad de Ciencias Exactas Universidad Nacional de La Plata

Introduction: Lysosomal storage disorders (LSD) are inherited diseases caused, in the majority of them, by the deficiency of lysosomal enzymatic activities. Ob-jectives: We aimed to analyze the usefulness of DBS samples for diagnosis of 4 LSDs, with the availability of a large quantity of patient samples. design and methods: Blood samples from previously diagnosed patients with Fabry, Gaucher, Hunter, and Maro-teaux-Lamy syndromes and normal control individ-uals, were collected and dispen-sed in filter paper, and used for enzymatic activity determination. Results: Diagnosis of hemi/homo-zygous patients with Fabry, Hunter and Maroteaux-Lamy diseases using DBS samples showed ideal parameters of 100% sensitivity and specificity. DBS assay for Gaucher disease would need a posterior confirmatory step. Conclusions: Leukocyte measu-rement is the only reliable way to diagnose Gaucher disease. For Hunter, Fabry and Maroteaux-Lamy disorders discrimination between patients and controls seems adequate by DBS.

关键词： Lysosomal Storage Disorders Diagnosis Dried Blood Spots Sensitivity Enzymatic Activity Reliability

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CURLY LEAF Regulates MicroRNA Activity by Controlling ARGONAUTE 1 degradation in Plants

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Molecular Plant 2020年第1期13卷 72-87页

作者： delfina A.Re Damian A.Cambiagno Agustin LArce Ariel HTomassi Marisol Giustozzi Paula Casati Federico DAriel Pablo A.Manavella lnstituto de Agrobiotecnologia del Litoral(CONICET-UNL) Catedra de Biologia Celulary MolecularFacultad de Bioquimica y Ciencias BiologicasUniversidad Nacional del Litoral3000 Santa FeArgentina Centro de Estudios Fotosinteticos y Bioquimicos(CEFOBI) Universidad Nacional de RosarioRosarioArgentina

CURLY LEAF ( CLF) encodes the methyltransferase subunit of the Polycomb Repressor Complex 2 (PRC2), which regulates the expression of target genes through H3K27 trimethylation. We isolated a new CLF mutant allele ( clf-78) using a genetic screen designed to identify microRNA (miRNA) deficient mutants. CLF mutant plants showed impaired miRNA activity caused by increased ubiquitination and enhanced degradation of ARGONAUTE 1 (AGO1) in specific tissues. Such CLF-mediated AGO1 regulation was evident when plants were exposed to UV radiation, which caused increased susceptibility of clf mutants to some UV-induced responses. Furthermore, we showed that CLF directly regulates FBW2, which in turn triggers AGO1 degradation in the clf mutants. Interestingly, AGO1 bound to a target appeared particularly prone to degradation in the mutant plants, a process that was exacerbated when the complex bound a non-cleavable target. Thus, prolonged AGO1–target interaction seems to favor AGO1 degradation, suggesting that non-cleavable miRNA targets may overcome translation inhibition by modulating AGO1 stability in plants.

关键词： CURLY LEAF ARGONAUTE Arabidopsis UV FBW2

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