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- 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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- An, Junghwa, et al.
(author)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Journal article (peer-reviewed)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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- Berggren, Karolina, et al.
(author)
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Hydraulic impacts on urban drainage systems due to changes in rainfall, caused by climatic change
- 2012
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In: Journal of hydrologic engineering. - 1084-0699 .- 1943-5584. ; 17:1, s. 92-98
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Journal article (peer-reviewed)abstract
- The changes in climate were of a growing concern in the last decade, and will be even more so in the coming years. When investigating impacts on urban drainage systems due to changes in the climate, two challenges are (1) what type of input rainfall data to use, and (2) what parameters to measure the impacts. The overall objective of this study is to investigate the hydraulic performances ofurban drainage systems related to changes in rainfall, and through these hydraulic parameters describe impacts of climate change. Input rainfall data represents today's climate, as well as three future time periods (2011-2040, 2041-2070, and 2071-2100). The hydraulic parameters used were water levels in nodes (e.g. as the number of floods, frequency and duration of floods), and pipe flow ratio. For the study area, the number of flooded nodes and the geographical distribution of floods will increase in the future, as will both the flooding frequency and the duration of floods.
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- Berndt, Sonja I., et al.
(author)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Journal article (peer-reviewed)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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- Bjursell, Magnus K., et al.
(author)
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Adenosine Kinase Deficiency Disrupts the Methionine Cycle and Causes Hypermethioninemia, Encephalopathy, and Abnormal Liver Function
- 2011
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 89:4, s. 507-515
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Journal article (peer-reviewed)abstract
- Four inborn errors of metabolism (IEMs) are known to cause hypermethioninemia by directly interfering with the methionine cycle. Hypermethioninemia is occasionally discovered incidentally, but it is often disregarded as an unspecific finding, particularly if liver disease is involved. In many individuals the hypermethioninemia resolves without further deterioration, but it can also represent an early sign of a severe, progressive neurodevelopmental disorder. Further investigation of unclear hypermethioninemia is therefore important. We studied two siblings affected by severe developmental delay and liver dysfunction. Biochemical analysis revealed increased plasma levels of methionine, S-adenosylmethionine (Ado Met), and S-adenosylhomocysteine (AdoHcy) but normal or mildly elevated homocysteine (Hcy) levels, indicating a block in the methionine cycle. We excluded S-adenosylhomocysteine hydrolase (SAHH) deficiency, which causes a similar biochemical phenotype, by using genetic and biochemical techniques and hypothesized that there was a functional block in the SAHH enzyme as a result of a recessive mutation in a different gene. Using exome sequencing, we identified a homozygous c.902C>A (p.Ala301Glu) missense mutation in the adenosine kinase gene (ADK), the function of which fits perfectly with this hypothesis. Increased urinary adenosine excretion confirmed ADK deficiency in the siblings. Four additional individuals from two unrelated families with a similar presentation were identified and shown to have a homozygous c.653A>C (p.Asp218Ala) and c.38G>A (p.Gly13Glu) mutation, respectively, in the same gene. All three missense mutations were deleterious, as shown by activity measurements on recombinant enzymes. ADK deficiency is a previously undescribed, severe IEM shedding light on a functional link between the methionine cycle and adenosine metabolism.
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- Borris, Matthias, et al.
(author)
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Continuous simulations of urban stormwater runoff and total suspended solids loads: influence of varying climatic inputs and catchment imperviousness
- 2014
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In: Journal of Water and Climate. - : IWA Publishing. - 2040-2244 .- 2408-9354. ; 5:4, s. 593-609
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Journal article (peer-reviewed)abstract
- Potential implications of climate change for future stormwater management were addressed by undertaking continuous simulations of runoff and total suspended solids (TSS) loads for three urban catchments, with imperviousness varying from 23 to 63%, which were exposed to five rainfall regimes during the snow-free part of the year: the current climate and four climate change scenarios projecting higher rainfalls. Simulated runoff volumes increased in all the future scenarios, particularly in the sub-arctic climate and the fixed uplift scenario (plus20) indicating appreciable rainfall increases. Simulated runoff volumes increased depending on the projected increases in rainfall and increasing runoff contributions from pervious areas when more intense future rainfalls exceeded hydrologic abstractions. The increased runoff volumes then contributed higher TSS loads, which were highly variable for the rainfall regimes tested. In cold climate regions, residues of solids from winter road maintenance may contribute to high initial accumulations of TSS on the catchment surface and high washed off loads. In general, the study suggests that intermediate design-life stormwater management facilities require flexible design allowing for future step-wise adaptation by gradually increasing design capacities and modifying treatment trains.
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- Borris, Matthias, et al.
(author)
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Modelling the effects of changes in rainfall event characteristics on TSS loads in urban runoff
- 2014
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In: Hydrological Processes. - : Wiley. - 0885-6087 .- 1099-1085. ; 28:4, s. 1787-1796
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Journal article (peer-reviewed)abstract
- The effect of changes in rainfall event characteristics on urban stormwater quality, which was described by total suspended solids (TSS), was studied by means of computer simulations conducted with the Storm Water Management Model for a climate change scenario for northern Sweden. The simulation results showed that TSS event loads depended mainly on rainfall depth and intensity, but not on antecedent conditions. Storms with low-to-intermediate depths and intensities showed the highest sensitivity to changes in rainfall input, both for percentage and absolute changes in TSS wash-off loads, which was explained by the contribution of pervious areas and supply limitations. This has significant implications for stormwater management, because those relatively frequent events generally carry a high percentage of the annual pollutant load
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10. |
- Borris, Matthias, et al.
(author)
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Simulating future trends in urban stormwater quality for changing climate, urban land use and environmental controls
- 2013
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In: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 68:9, s. 2082-2089
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Journal article (peer-reviewed)abstract
- The effects of climatic changes, progressing urbanization and improved environmental controls on the simulated urban stormwater quality in a northern Sweden community were studied. Future scenarios accounting for those changes were developed and their effects simulated with the Storm Water Management Model (SWMM). It was observed that the simulated stormwater quality was highly sensitive to the scenarios, mimicking progressing urbanization with varying catchment imperviousness and area. Thus, land use change was identified as one of the most influential factors and in some scenarios, urban growth caused changes in runoff quantity and quality exceeding those caused by a changing climate. Adaptation measures, including the reduction of directly connected impervious surfaces (DCIS) through the integration of more green spaces into the urban landscape, or disconnection of DCIS were effective in reducing runoff volume and pollutant loads. Furthermore, pollutant source control measures, including material substitution, were effective in reducing pollutant loads and significantly improving stormwater quality
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