| 1. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Thiele, I., et al.
(author)
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A community-driven global reconstruction of human metabolism
- 2013
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In: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 31:5, s. 419-
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Journal article (peer-reviewed)abstract
- Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including similar to 2x more reactions and similar to 1.7x more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
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| 3. |
- Warren, Wesley C, et al.
(author)
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The genome of a songbird
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 757-762
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Journal article (peer-reviewed)abstract
- The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken-the only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour.
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| 4. |
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| 5. |
- Ruiz-Velasco, A. E., et al.
(author)
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Circumstellar Envelopes of OH/IR Stars
- 2011
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In: Why Galaxies Care about AGB Stars II.
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Conference paper (peer-reviewed)abstract
- We present VLTI observations of the tip-AGB star IRAS 17020-5254 carried out with the AMBER and MIDI instruments using the 1.8-m Auxiliary Telescopes (ATs) with three different baselines. This star is an evolved oxygen-rich single star of the OH/IR type. We fit the resulting near-infrared visibilities with a model consisting of a Gaussian component plus a central uniform disk, obtaining apparent diameters of the dust shell, the central star, and their flux ratios. We also show the uniform disk diameter as a function of wavelength from both the AMBER and MIDI observations. The mid-infrared diameter is about two to three times larger than the near-infrared one. We plan to compare these data to hydrodynamic atmosphere and wind models.
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| 6. |
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| 7. |
- Magnusson, Jesper, 1984-, et al.
(author)
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Optimal design of a medium voltage hybrid fault current limiter
- 2014
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In: 2014 IEEE International Energy Conference, ENERGYCON. - : IEEE Computer Society. - 9781479924493 ; , s. 431-438
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Conference paper (peer-reviewed)abstract
- The connection of distributed generation increases the short circuit power which in turn might exceed the ratings of the installed circuit breakers. A solution is to limit the available short circuit power by increasing the grid impedance, but since there is a constant strive for lower losses and higher power transfer capabilities, this is not desired. The application of a fault current limiter (FCL) that can limit the current before the first peak enables a power system with high short circuit power and low short circuit current. This can increase the stability of the grid and reduce the requirements of other equipment. This work presents a simulation model to be used as an aid in the design of a hybrid FCL for a 12 kV AC system. The proposed model combines a transient analysis circuit model with an optimization module to obtain multiple sets of possible design parameters. The design is not straight forward since there is a trade-off between several of the design parameters.
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| 8. |
- Mariscal-Arcas, M., et al.
(author)
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Comparison of methods to evaluate the quality of the Mediterranean diet in a large representative sample of young people in Southern Spain
- 2010
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In: Nutrición Hospitalaria. - : Aula Médica Ediciones. - 0212-1611 .- 1699-5198. ; 25:6, s. 1006-1013
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Journal article (peer-reviewed)abstract
- The objective of this study was to compare the usefulness of two methods to evaluate diet quality in young people in Southern Spain: a new Mediterranean Diet Pattern (MDP) and a modification of the Diet Quality Index-International (DQI-I) for the Mediterranean area. The study population was 3190 schoolchildren aged 8-15 yrs. The questionnaires used were first validated (Bland-Altman plot and Wilcoxon tests) in a randomized sample. The DQI gives a more detailed evaluation of food components, whereas the MDS gives global information on food groups but includes foods characteristically consumed in the Mediterranean region. Highly similar results were obtained using the MDP and the adapted DQI-I, which appear to be equally useful to evaluate diet quality in a Mediterranean population. The fact that we selected the same types of food for both indices may explain the similar overall evaluations. According to these results, both methods appear to be equally appropriate for evaluating diet quality in a Mediterranean population.
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| 9. |
- Ramchandani, V A, et al.
(author)
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A genetic determinant of the striatal dopamine response to alcohol in men
- 2011
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In: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 16:8, s. 809-817
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Journal article (peer-reviewed)abstract
- Excessive alcohol use, a major cause of morbidity and mortality, is less well understood than other addictive disorders. Dopamine release in ventral striatum is a common element of drug reward, but alcohol has an unusually complex pharmacology, and humans vary greatly in their alcohol responses. This variation is related to genetic susceptibility for alcoholism, which contributes more than half of alcoholism risk. Here, we report that a functional OPRM1 A118G polymorphism is a major determinant of striatal dopamine responses to alcohol. Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions, and examined for striatal dopamine release using positron emission tomography and [(11)C]-raclopride displacement. A striatal dopamine response to alcohol was restricted to carriers of the minor 118G allele. To directly establish the causal role of OPRM1 A118G variation, we generated two humanized mouse lines, carrying the respective human sequence variant. Brain microdialysis showed a fourfold greater peak dopamine response to an alcohol challenge in h/mOPRM1-118GG than in h/mOPRM1-118AA mice. OPRM1 A118G variation is a genetic determinant of dopamine responses to alcohol, a mechanism by which it likely modulates alcohol reward.
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| 10. |
- Ruiz, M., et al.
(author)
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After failure repair optimization in dynamic flexgrid optical networks
- 2014
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In: [Host publication title missing]. - 9781557529947
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Conference paper (peer-reviewed)abstract
- We introduce the problem of reoptimizing the network after a link failure has been repaired as an effective way for reducing capacity usage and improving network performance. Numerical results show gains higher than 42%.
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