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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)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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| 3. |
- ODonnell, Michael, et al.
(författare)
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Registered Replication Report: Dijksterhuis and van Knippenberg (1998)
- 2018
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Ingår i: Perspectives on Psychological Science. - : SAGE PUBLICATIONS LTD. - 1745-6916 .- 1745-6924. ; 13:2, s. 268-294
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Tidskriftsartikel (refereegranskat)abstract
- Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence (professor) subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence (soccer hooligans). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the professor category and those primed with the hooligan category (0.14%) and no moderation by gender.
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| 4. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 5. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Andersson, Anders, et al.
(författare)
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IL-36 Cytokines Promote Inflammation in the Lungs of Long-term Smokers
- 2021
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Ingår i: American journal of respiratory cell and molecular biology. - 1535-4989. ; 64:2, s. 173-182
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease with high morbidity and mortality. The IL-36 family are proinflammatory cytokines that are known to shape innate immune responses, including those critical to bacterial pneumonia. To determine whether IL-36 cytokines promote a proinflammatory milieu in the lungs of long-term smokers with and without COPD. Levels of IL-36 cytokines were measured in plasma and bronchoalveolar lavage fluid from subjects in a pilot study (n=23) of long-term smokers with and without COPD in vivo, and from a variety of lung cells (from 3-5 donors) stimulated with bacteria or cigarette smoke components in vitro. Pulmonary macrophages were stimulated with IL-36 cytokines in vitro, and chemokine and cytokine production was assessed. IL-36α and -γ are produced to varying degrees in murine and human lung cells in response to bacterial stimuli and cigarette smoke components in vitro. Moreover, while IL-36γ production is upregulated early after cigarette smoke stimulation and wanes over time, IL-36α production requires a longer duration of exposure. IL-36α and -γ are enhanced systemically and locally in long-term smokers with and without COPD, and local IL-36α levels display a positive correlation with declining ventilatory lung function and increasing proinflammatory cytokine levels. In vitro, IL-36α and -γ induce proinflammatory chemokines and cytokines in a concentration-dependent fashion that requires IL-36R and MyD88. IL-36 cytokine production is altered in long-term smokers with and without COPD and contributes to shaping a proinflammatory milieu in the lungs.
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| 7. |
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| 8. |
- Lindén, Ola, et al.
(författare)
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Radioimmunotherapy using 131I-labeled anti-CD22 monoclonal antibody (LL2) in patients with previously treated B-cell lymphomas
- 1999
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 5:10 Suppl, s. 3287-3291
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Tidskriftsartikel (refereegranskat)abstract
- Experience in using rapidly internalizing antibodies, such as the anti-CD22 antibody, for radioimmunotherapy of B-cell lymphomas is still limited. The present study was conducted to assess the efficacy and toxicity of a 131I-labeled anti-CD22 monoclonal antibody (mAb), LL2, in patients with B-cell lymphomas failing first- or second-line chemotherapy. Eligible patients were required to have measurable disease, less than 25% B cells in unseparated bone marrow, and an uptake of 99mTc-labeled LL2Fab' in at least one lymphoma lesion on immunoscintigram. Eight of nine patients examined with immunoscintigraphy were unequivocally found to have an uptake, and therapy with 131I-labeled anti-CD22 [1330 MBq/m2 (36 mCi/m2)] preceded by 20 mg of naked anti-CD22 mAb was administered. Three patients achieved partial remission (duration, 12, 3, and 2 months), and one patient with progressive lymphoma showed stable disease for 17 months. Four patients exhibited progressive disease. The toxicity was hematological. Patients with subnormal counts of neutrophils or platelets before therapy seemed to be more at risk for hematological side effects. Radioimmunotherapy in patients with B-cell lymphomas using 131I-labeled mouse anti-CD22 can induce objective remission in patients with aggressive as well as indolent lymphomas who have failed prior chemotherapy.
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| 9. |
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| 10. |
- Siebzehnrübl, Florian A., et al.
(författare)
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Early postnatal behavioral, cellular, and molecular changes in models of Huntington disease are reversible by HDAC inhibition
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:37, s. 8765-8774
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene (HTT). Although mutant HTT is expressed during embryonic development and throughout life, clinical HD usually manifests later in adulthood. A number of studies document neurodevelopmental changes associated with mutant HTT, but whether these are reversible under therapy remains unclear. Here, we identify very early behavioral, molecular, and cellular changes in preweaning transgenic HD rats and mice. Reduced ultrasonic vocalization, loss of prepulse inhibition, and increased risk taking are accompanied by disturbances of dopaminergic regulation in vivo, reduced neuronal differentiation capacity in subventricular zone stem/progenitor cells, and impaired neuronal and oligodendrocyte differentiation of mouse embryo-derived neural stem cells in vitro. Interventional treatment of this early phenotype with the histone deacetylase inhibitor (HDACi) LBH589 led to significant improvement in behavioral changes and markers of dopaminergic neurotransmission and complete reversal of aberrant neuronal differentiation in vitro and in vivo. Our data support the notion that neurodevelopmental changes contribute to the prodromal phase of HD and that early, presymptomatic intervention using HDACi may represent a promising novel treatment approach for HD.
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