| 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. |
- Ackermann, M., et al.
(author)
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Fermi LAT observations of cosmic-ray electrons from 7 GeV to 1 TeV
- 2010
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In: PHYSICAL REVIEW D. - 1550-7998. ; 82:9, s. 092004-
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Journal article (peer-reviewed)abstract
- We present the results of our analysis of cosmic-ray electrons using about 8 x 10(6) electron candidates detected in the first 12 months on-orbit by the Fermi Large Area Telescope. This work extends our previously published cosmic-ray electron spectrum down to 7 GeV, giving a spectral range of approximately 2.5 decades up to 1 TeV. We describe in detail the analysis and its validation using beam-test and on-orbit data. In addition, we describe the spectrum measured via a subset of events selected for the best energy resolution as a cross-check on the measurement using the full event sample. Our electron spectrum can be described with a power law proportional to E-3.08+/-0.05 with no prominent spectral features within systematic uncertainties. Within the limits of our uncertainties, we can accommodate a slight spectral hardening at around 100 GeV and a slight softening above 500 GeV.
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| 3. |
- Erni, W., et al.
(author)
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Technical design report for the PANDA (AntiProton Annihilations at Darmstadt) Straw Tube Tracker
- 2013
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In: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 49:2
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Journal article (peer-reviewed)abstract
- This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole PANDA scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described.
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| 4. |
- 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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| 5. |
- Abbasi, R., et al.
(author)
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Measurement of acoustic attenuation in South Pole ice
- 2011
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In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:6, s. 382-393
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Journal article (peer-reviewed)abstract
- Using the South Pole Acoustic Test Setup (SPATS) and a retrievable transmitter deployed in holes drilled for the IceCube experiment, we have measured the attenuation of acoustic signals by South Pole ice at depths between 190 m and 500 m. Three data sets, using different acoustic sources, have been analyzed and give consistent results. The method with the smallest systematic uncertainties yields an amplitude attenuation coefficient alpha = 3.20 +/- 0.57 km(-1) between 10 and 30 kHz, considerably larger than previous theoretical estimates. Expressed as an attenuation length, the analyses give a consistent result for lambda equivalent to 1/alpha of similar to 300 m with 20% uncertainty. No significant depth or frequency dependence has been found.
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| 6. |
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| 7. |
- Speliotes, Elizabeth K., et al.
(author)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Journal article (peer-reviewed)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 8. |
- Gustafsson, Per E, et al.
(author)
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Diurnal cortisol levels, psychiatric symptoms and sense of coherence in abused adolescents.
- 2010
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In: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 64:1, s. 27-31
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Journal article (peer-reviewed)abstract
- Background. The role of the hypothalamic-pituitary-adrenal (HPA) axis in psychiatric disorders following trauma is poorly studied and most studies have been done on adults. Aims. To investigate the association of mental well-being and diurnal cortisol in abused adolescents. Methods. The present cross-sectional study examined diurnal salivary cortisol (measured three times a day during three days) in relation to psychiatric symptoms (Trauma Symptoms Checklist for Children) and the salutogenic construct “sense of coherence”, in 15 adolescents exposed to childhood abuse. Results. Significant correlations were found between symptoms and sense of coherence versus early and late morning cortisol concentrations. The correlations were most consistent for internalizing and externalizing symptoms, and somewhat less for post-traumatic symptoms and sense of coherence. In contrast, evening cortisol did not correlate with any of the psychological measures. Conclusion. These results extend previous research findings by pointing towards a relation between symptoms and higher morning cortisol and accentuated diurnal cortisol variation in abused adolescent as opposed to lower basal cortisol and a flattening of the cortisol rhythm repeatedly observed in traumatized adults. Clinical implications. The pathophysiology of the impact of trauma on youth, including the impact on biological stress systems, are important for an understanding of the consequences of trauma and may serve as a basis for the development of new treatment options.
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| 9. |
- Gustafsson, Per E, et al.
(author)
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Does quantity have a quality all its own? Cumulative adversity and up- and down-regulation of circadian salivary cortisol levels in healthy children.
- 2010
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In: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 35:9, s. 1410-1415
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Journal article (peer-reviewed)abstract
- Findings have been divergent regarding the direction of basal cortisol dysregulations resulting from stressor exposure, and seem to differ between young people and adults. Accumulated stress exposure has been suggested to be a risk factor for the development of hypocortisolism. This cross-sectional study aims to examine the impact of cumulative adversity, i.e., the number of adversities, on diurnal salivary cortisol levels, including the cortisol awakening response (CAR), in children without psychiatric disorder. The sample consisted of 130 children (mean age 12.8 years), representing one in each twin pair included in the population-based Child and Adolescent Twin Study in Sweden (CATSS). Information about socioeconomic disadvantage, negative life events and potentially traumatic life events were collected by telephone interview and questionnaires, with parents as informants. Salivary cortisol sampling was performed in the home during two school days: at awakening, +30 min post-awakening, and at bedtime. Results showed that the number of adversities was related to the CAR, diurnal decline and +30 min post-awakening cortisol levels. Children with a moderate amount of cumulative adversity displayed high cortisol measures, while those with a high amount (3 or more) of adversities instead showed levels similar to the non-exposed group, yielding an inverse U-pattern of the association between cortisol and adversity. These results indicate that the accumulation of adversity might be an explanation of patterns of basal cortisol up-regulation in children and that those most severely exposed can exhibit an early stage of down-regulation, an issue which should be further examined in longitudinal studies.
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| 10. |
- Gustafsson, Per E, et al.
(author)
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Effects of an outdoor education intervention on the mental health of schoolchildren
- 2012
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In: Journal of Adventure Education and Outdoor Learning. - : Routledge. - 1472-9679 .- 1754-0402. ; 12:1, s. 63-79
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Journal article (peer-reviewed)abstract
- This study aimed at examining the effects of an outdoor educational intervention on the mental health of schoolchildren. Two elementary schools participated (N = 230); one experimental school where the intervention was implemented, and the other a reference school. Demographic questions and the Strengths and Difficulties Questionnaire were completed by the parents. An outdoor educational intervention was implemented at the experimental school, and the data collection was repeated after one year. The results point towards a small but non-significant improvement in mental health at the experimental school while adjusting for demographics. However, this effect was significantly moderated by gender: boys generally fared better than girls at the intervention school, relative to the reference school. The results indicate that it may be important to address gender issues when educational programmes are implemented in schools.
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