191 research outputs found

    Preparation of OC14S, O18CS, OCS33, and CH3Cl36

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    In connection with a microwave absorption study of the nuclear spins of isotopes by Professor A. Roberts, formerly of the Physics Department of this University, we were asked to prepare samples of OC14S, O18CS, OCS33, and of CH3Cl36, starting with small quantities of the materials containing the desired isotopes. We believe that the methods employed in the synthesis of these compounds may be of use to other investigators

    Comparative analysis of the intracellular responses to disease-related aggregation-prone proteins

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    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

    Soil seed bank of the invasive Robinia pseudoacacia in planted Pinus nigra stands

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    Pinus nigra and Robinia pseudoacacia are exotic trees used for afforestation in Hungary. Pinus nigra was non-invasive, however R. pseudoacacia escaped from cultivation and invaded several vegetation types including pine plantations. It has recently been planned to cut P. nigra plantations and replace them by native tree stands, especially in nature reserves. The scattered presence of R. pseudoacacia specimens in pine stands might place constraints on planned tree replacement because of their vegetative resprouting and recolonization from an established seed bank. The aim of this study was to investigate the soil seed bank under the canopy of solitary R. pseudoacacia specimens found in P. nigra plantations. Altogether 250 soil samples were collected from the 0–6 and 6–12 cm soil layers under solitary Robinia trees of varying ages (with basal areas between 62.4 and 1089.3 cm2). Seeds were separated by sieving then scarified and germinated. Seed bank density ranged between 640 and 2285 seedsm–2 with an average distribution of 82.7% and 17.3% in the upper and lower soil layer, respectively. Total density of the seed bank and also the seed bank ratio of the lower soil layer increased with tree age. The accumulated seed bank of R. pseudoacacia should be considered in the careful planning of tree replacement operations in Pinus nigra stands

    Genome-scale modeling of the protein secretory machinery in yeast

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    The protein secretory machinery in Eukarya is involved in post-translational modification (PTMs) and sorting of the secretory and many transmembrane proteins. While the secretory machinery has been well-studied using classic reductionist approaches, a holistic view of its complex nature is lacking. Here, we present the first genome-scale model for the yeast secretory machinery which captures the knowledge generated through more than 50 years of research. The model is based on the concept of a Protein Specific Information Matrix (PSIM: characterized by seven PTMs features). An algorithm was developed which mimics secretory machinery and assigns each secretory protein to a particular secretory class that determines the set of PTMs and transport steps specific to each protein. Protein abundances were integrated with the model in order to gain system level estimation of the metabolic demands associated with the processing of each specific protein as well as a quantitative estimation of the activity of each component of the secretory machinery

    Tools and techniques for solvent selection: green solvent selection guides

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    Driven by legislation and evolving attitudes towards environmental issues, establishing green solvents for extractions, separations, formulations and reaction chemistry has become an increasingly important area of research. Several general purpose solvent selection guides have now been published with the aim to reduce use of the most hazardous solvents. This review serves the purpose of explaining the role of these guides, highlighting their similarities and differences. How they can be used most effectively to enhance the greenness of chemical processes, particularly in laboratory organic synthesis and the pharmaceutical industry, is addressed in detail

    Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases

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    Age-associated neurodegenerative disorders such as Alzheimer’s disease are a major public health challenge, due to the demographic increase in the proportion of older individuals in society. However, the relatively few currently approved drugs for these conditions provide only symptomatic relief. A major goal of neurodegeneration research is therefore to identify potential new therapeutic compounds that can slow or even reverse disease progression, either by impacting directly on the neurodegenerative process or by activating endogenous physiological neuroprotective mechanisms that decline with ageing. This requires model systems that can recapitulate key features of human neurodegenerative diseases that are also amenable to compound screening approaches. Mammalian models are very powerful, but are prohibitively expensive for high-throughput drug screens. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for neuroprotective compound screening. Here we describe how C. elegans has been used to model various human ageing-associated neurodegenerative diseases and provide an extensive list of compounds that have therapeutic activity in these worm models and so may have translational potential

    Habitat Fragmentation, Variable Edge Effects, and the Landscape-Divergence Hypothesis

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    Edge effects are major drivers of change in many fragmented landscapes, but are often highly variable in space and time. Here we assess variability in edge effects altering Amazon forest dynamics, plant community composition, invading species, and carbon storage, in the world's largest and longest-running experimental study of habitat fragmentation. Despite detailed knowledge of local landscape conditions, spatial variability in edge effects was only partially foreseeable: relatively predictable effects were caused by the differing proximity of plots to forest edge and varying matrix vegetation, but windstorms generated much random variability. Temporal variability in edge phenomena was also only partially predictable: forest dynamics varied somewhat with fragment age, but also fluctuated markedly over time, evidently because of sporadic droughts and windstorms. Given the acute sensitivity of habitat fragments to local landscape and weather dynamics, we predict that fragments within the same landscape will tend to converge in species composition, whereas those in different landscapes will diverge in composition. This ‘landscape-divergence hypothesis’, if generally valid, will have key implications for biodiversity-conservation strategies and for understanding the dynamics of fragmented ecosystems
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