62 research outputs found
Visualizing climate change impact with ubiquitous spatial technologies
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Trabajo de investigación y desarrollo del pensamiento y contextualización de la creatividad
1. LA ACTITUD CREATIVA
2. INSUMO CREATIVO
2.1 Vanguardia fotográfica
2.2. P.O.P. Visual merchandising.
2.3. AudiovisualesPregradoTecnólogo en Mercadeo y Diseño PublicitarioTecnología en Mercadeo y Diseño Publicitari
Calcineurin determines toxic versus beneficial responses to α-synuclein
Calcineurin (CN) is a highly conserved Ca[superscript 2+]–calmodulin (CaM)-dependent phosphatase that senses Ca[superscript 2+] concentrations and transduces that information into cellular responses. Ca[superscript 2+] homeostasis is disrupted by α-synuclein (α-syn), a small lipid binding protein whose misfolding and accumulation is a pathological hallmark of several neurodegenerative diseases. We report that α-syn, from yeast to neurons, leads to sustained highly elevated levels of cytoplasmic Ca[superscript 2+], thereby activating a CaM-CN cascade that engages substrates that result in toxicity. Surprisingly, complete inhibition of CN also results in toxicity. Limiting the availability of CaM shifts CN's spectrum of substrates toward protective pathways. Modulating CN or CN's substrates with highly selective genetic and pharmacological tools (FK506) does the same. FK506 crosses the blood brain barrier, is well tolerated in humans, and is active in neurons and glia. Thus, a tunable response to CN, which has been conserved for a billion years, can be targeted to rebalance the phosphatase’s activities from toxic toward beneficial substrates. These findings have immediate therapeutic implications for synucleinopathies.Jeffry M. and Barbara Picower FoundationJPB FoundationHoward Hughes Medical Institute (Collaborative Innovation Award)Eleanor Schwartz Charitable Foundatio
Proteomics-based monitoring of pathway activity reveals that blocking diacylglycerol biosynthesis rescues from alpha-synuclein toxicity
Proteinaceous inclusions containing alpha-synuclein (α-Syn) have been implicated in neuronal toxicity in Parkinson’s disease, but the pathways that modulate toxicity remain enigmatic. Here, we used a targeted proteomic assay to simultaneously measure 269 pathway activation markers and proteins deregulated by α-Syn expression across a panel of 33 Saccharomyces cerevisiae strains that genetically modulate α-Syn toxicity. Applying multidimensional linear regression analysis to these data predicted Pah1, a phosphatase that catalyzes conversion of phosphatidic acid to diacylglycerol at the endoplasmic reticulum membrane, as an effector of rescue. Follow-up studies demonstrated that inhibition of Pah1 activity ameliorates the toxic effects of α-Syn, indicate that the diacylglycerol branch of lipid metabolism could enhance α-Syn neuronal cytotoxicity, and suggest a link between α-Syn toxicity and the biology of lipid droplets
Comparative analysis of the intracellular responses to disease-related aggregation-prone proteins
Aggregation-prone proteins (APPs) have been implicated in numerous human diseases but the underlying mechanisms are incompletely understood. Here we comparatively analysed cellular responses to different APPs. Our study is based on a systematic proteomic and phosphoproteomic analysis of a set of yeast proteotoxicity models expressing different human disease-related APPs, which accumulate intracellular APP inclusions and exhibit impaired growth. Clustering and functional enrichment analyses of quantitative proteome-level data reveal that the cellular response to APP expression, including the chaperone response, is specific to the APP, and largely differs from the response to a more generalized proteotoxic insult such as heat shock. We further observe an intriguing association between the subcellular location of inclusions and the location of the cellular response, and provide a rich dataset for future mechanistic studies. Our data suggest that care should be taken when designing research models to study intracellular aggregation, since the cellular response depends markedly on the specific APP and the location of inclusions. Further, therapeutic approaches aimed at boosting protein quality control in protein aggregation diseases should be tailored to the subcellular location affected by inclusion formation. SIGNIFICANCE: We have examined the global cellular response, in terms of protein abundance and phosphorylation changes, to the expression of five human neurodegeneration-associated, aggregation-prone proteins (APPs) in a set of isogenic yeast models. Our results show that the cellular response to each APP is unique to that protein, is different from the response to thermal stress, and is associated with processes at the subcellular location of APP inclusion formation. These results further our understanding of how cells, in a model organism, respond to expression of APPs implicated in neurodegenerative diseases like Parkinson's, Alzheimer's, and ALS. They have implications for mechanisms of toxicity as well as of protective responses in the cell. The specificity of the response to each APP means that research models of these diseases should be tailored to the APP in question. The subcellular localization of the response suggest that therapeutic interventions should also be targeted within the cell
Chemical element changes after afforestation of former agricultural lands with spruce (PICEA ABIES(L.) KARST)
Pamestas un aizaugošas lauksaimniecības zemes ir mūsdienu Latvijas ainavas būtiska sastāvdaļa. Latvijā šī tendence parādījās pēc 1989.gada, kad notika pāreja no centralizētas jeb plānveida ekonomikas uz tirgus. Sociālekonomiskās un politiskās pārmaiņas negatīvi ietekmēja lauksaimniecību, padarot to par ekonomiski neizdevīgu nozari, tāpēc cilvēki pameta lauku teritorijas, lai pārceltos uz dzīvi pilsētās. Bakalaura darba ietvaros ir veikts pētījums par augsnes ķīmisko īpašību izmaiņām, kuras notikušas saistībā ar lauksaimniecībā izmantojamo zemju apmežošanos teritorijās, kur augsnes cilmiezi veido glacigēnie morēnas nogulumi. Apmežošanās procesa ietekme uz augsnes īpašībām ir aktuāla tēma Latvijā un Eiropā saistībā ar ilgtspējīgu augsnes apsaimniekošanu. Bakalaura darbā izvirzītais mērķis ir noskaidrot parastās egles (Picea abies (L.) Karst.) ietekmi uz augsnes fizikālo un ķīmisko īpašību izmaiņām smilts un mālsmilts augsnēs pēc apmežošanās uz glacigēnajiem morēnas nogulumiem. Pētījuma rezultāti parāda, ka 14 -15 gadu laikā pēc apmežošanās ar parasto egli, mālsmilts un smilts augsnēs apmaiņas bāzu katjoni (Ca2+, Mg2+, K+), kā arī kopējais ogleklis un kopējais slāpeklis samazinās dziļākajā augsnes slānī (11 – 20 cm), bet virsējā augsnes slānī (0-10 cm) to koncentrācija ir augstāka. Pretēja sakarība pētījumā konstatēta apmaiņas metāliem (Fe2+ un Al3+), kuru koncentrācija dziļākajā minerālajā augsnes slānī ir lielāka, nekā virsējā. Konstatēta, pozitīva sakarība starp augsnes pH vērtību un apmaiņas bāzu katjoniem, bet negatīva sakarība ar Fe2+ un Al3+ koncentrāciju, kas liecina par podzolēšanās procesa norisi. Zem egļu zonām konstatēts, ka palielinās kopējā oglekļa (%) un kopējā slāpekļa (%) saturs augsnē. Analizējot iegūtos rezultātus atbilstoši debespusēm var secināt, ka viennozīmīgas sakarības netika konstatētas. Atslēgas vārdi: egles zonas, debespuses, izskalošanās, organisko vielu akumulācija, paskābināšanās, galveno komponentu analīze.Abandoned and overgrown farmlands are an intrinsic part of modern day Latvia's scenery. This trend appeared in Latvia after 1989, when the centralized or planned economy transitioned into the market economy. Socio-economic and political changes negatively affected agriculture, making it not economically viable, therefore people left the fields to go live in the cities. A study was conducted within the scope of this Bachelor paper about the chemical characteristic changes in the soil, which occurred in relation to agricultural land afforesting in territories where the soil substrata is formed from glaciogenic moraine sediments. The effects of afforestation on soil characteristics are relevant in Latvia and Europe in regards to long-term soil maintenance. The goal set forth by this Bachelor paper is to determine the effects of the Norway spruce (Picea abies (L.) Karst.) on the changes of the physical and chemical characteristics in sand and sandy loam soils after afforestation on glaciogenic moraine sediments. The results of the study show that within a period of 14 – 15 years after afforestation with the Norway spruce, sandy loam and sand soil exchange base cations (Ca2+, Mg2+, K+), as well as the total carbon and total nitrogen decreases in the deeper soil layer (11 – 20 cm), however, its concentration in the upper soil layer (0 – 10 cm) is relatively higher. The study determined an opposite correlation between exchange metals (Fe2+ and Al3+) - their concentration in the deeper soil layer is higher than in the upper layer. A positive correlation was found between the pH value and exchange base cations, and a negative correlation with the concentration of Fe2+ and Al3+, which indicates the process of podzolization. It was found that under the spruce areas the total carbon (%) and total nitrogen (%) content increases. A conclusive correlation was not found in the analysis of the obtained results according to cardinal directions of compass. Keywords: spruce areas, cardinal directions of compass, erosion, organic material accumulation, acidification, principal component analysi
The relative delay times of catchment model storages
The original aim of this research was to determine the best means of calculating the relative delay time parameter of the Laurenson runoff routing method of flood estimation. Early testing conducted as a part of achieving this end showed that the model could be quite insensitive to the means used to calculate relative delay. Model sensitivity to the means of calculating this parameter had apparently not yet been verified, and if it was insensitive, the best means of calculating the parameter was not required. Hence it was decided to test the thesis that the model was insensitive to the means of calculating the relative delay time parameter. The thesis was tested by applying the model to a range of flood sizes on two catchments using five different means of calculating relative delay time. The differences in model output produced by these delay hypotheses were examined in relation to the average model error. In a number of cases the effects on model performance of these different delay hypotheses were quite small, but in other cases they were quite large. Hence the conclusion had to be drawn that the model is sensitive to the means of calculating relative delay time. The fact that the means of calculating relative delay. time Has unimportant in a conditional sense left the possibility that the model could be used under these conditions, if they could be defined. However, in the long term it meant that the best means of calculating relative delay time was required. During the course of the investigation a number of problems in relation to model use were encountered. The attempts made to solve these problems should provide useful information on model application in the future
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