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- Chu, SH, et al.
(författare)
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Integration of Metabolomic and Other Omics Data in Population-Based Study Designs: An Epidemiological Perspective
- 2019
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- It is not controversial that study design considerations and challenges must be addressed when investigating the linkage between single omic measurements and human phenotypes. It follows that such considerations are just as critical, if not more so, in the context of multi-omic studies. In this review, we discuss (1) epidemiologic principles of study design, including selection of biospecimen source(s) and the implications of the timing of sample collection, in the context of a multi-omic investigation, and (2) the strengths and limitations of various techniques of data integration across multi-omic data types that may arise in population-based studies utilizing metabolomic data.
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- Cohen, S, et al.
(författare)
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The wake-promoting drug modafinil stimulates specific hypothalamic circuits to promote adaptive stress responses in an animal model of PTSD
- 2016
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6:10, s. e917-
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacotherapeutic intervention during traumatic memory consolidation has been suggested to alleviate or even prevent the development of posttraumatic stress disorder (PTSD). We recently reported that, in a controlled, prospective animal model, depriving rats of sleep following stress exposure prevents the development of a PTSD-like phenotype. Here, we report that administering the wake-promoting drug modafinil to rats in the aftermath of a stressogenic experience has a similar prophylactic effect, as it significantly reduces the prevalence of PTSD-like phenotype. Moreover, we show that the therapeutic value of modafinil appears to stem from its ability to stimulate a specific circuit within the hypothalamus, which ties together the neuropeptide Y, the orexin system and the HPA axis, to promote adaptive stress responses. The study not only confirms the value of sleep prevention and identifies the mechanism of action of a potential prophylactic treatment after traumatic exposure, but also contributes to understanding mechanisms underlying the shift towards adaptive behavioral response.
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- Cooper, Chris E., et al.
(författare)
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Engineering tyrosine residues into hemoglobin enhances heme reduction, decreases oxidative stress and increases vascular retention of a hemoglobin based blood substitute
- 2019
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Ingår i: Free Radical Biology and Medicine. - : Elsevier BV. - 0891-5849. ; 134, s. 106-118
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Tidskriftsartikel (refereegranskat)abstract
- Hemoglobin (Hb)-based oxygen carriers (HBOC) are modified extracellular proteins, designed to replace or augment the oxygen-carrying capacity of erythrocytes. However, clinical results have generally been disappointing due to adverse side effects, in part linked to the intrinsic oxidative toxicity of Hb. Previously a redox-active tyrosine residue was engineered into the Hb β subunit (βF41Y) to facilitate electron transfer between endogenous antioxidants such as ascorbate and the oxidative ferryl heme species, converting the highly oxidizing ferryl species into the less reactive ferric (met) form. We inserted different single tyrosine mutations into the α and β subunits of Hb to determine if this effect of βF41Y was unique. Every mutation that was inserted within electron transfer range of the protein surface and the heme increased the rate of ferryl reduction. However, surprisingly, three of the mutations (βT84Y, αL91Y and βF85Y) also increased the rate of ascorbate reduction of ferric(met) Hb to ferrous(oxy) Hb. The rate enhancement was most evident at ascorbate concentrations equivalent to that found in plasma (< 100 μM), suggesting that it might be of benefit in decreasing oxidative stress in vivo. The most promising mutant (βT84Y) was stable with no increase in autoxidation or heme loss. A decrease in membrane damage following Hb addition to HEK cells correlated with the ability of βT84Y to maintain the protein in its oxygenated form. When PEGylated and injected into mice, βT84Y was shown to have an increased vascular half time compared to wild type PEGylated Hb. βT84Y represents a new class of mutations with the ability to enhance reduction of both ferryl and ferric Hb, and thus has potential to decrease adverse side effects as one component of a final HBOC product.
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- Mathé, Nora E.H., et al.
(författare)
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Between the Lifeworld and Academia : Defining Political Issues in Social Science Education
- 2019
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Ingår i: NOFA7 Abstracts. - Stockholm : Stockholm University. ; , s. 146-147
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Konferensbidrag (refereegranskat)abstract
- Objectives: While some studies have indicated that young people’s perceptions of politics focus on top- down ideas, studies have also found that young people perceive politics as being about change and shaping society. Further, researchers have argued that traditional civics instruction focuses on complex democratic processes, without enabling students to apply it to political issues. This strengthens the need to consider how to make social science education more relevant for students. The purpose of this paper is to present mutual understandings of political issues from students and academics in social science and discuss some guiding principles for defining such issues in social science education.Theoretical framework: To analyse the data, we build on Christensen’s (2015) model of knowledge domains in social studies (topical issues, structures, and processes; social scientific disciplines; students’ life- world; democratic values). We supplement this with conceptualisations of the political from political theory. Methods: This paper is based on data from interviews with six 16- year-old students and five social science academics in Norway about how they understand and define political issues. The students This paper focuses on participants’ responses to the question ‘Is it possible to talk about issues as being more or less political?’ Results:Collective: Primarily, political issues that affect society, national political issues, or beyond, were seen as more political than issues affecting smaller groups of people.Contemporary: The contemporary nature of political issues is most clearly represented in the students’ responses. All the examples of political issues mentioned by the students were contemporary issues in that they were currently ongoing. Conflictual: The conflictual nature of political issues is a theme in both students’ and academics’ responses. Such conflicts are characterized by disagreements relating to values and priorities in terms of resource use.Contextual: Context was described as an important criterion both by students and academics, cutting across the principles of collective, contemporary, and conflictual. The students frequently mentioned that “big” and “important” issues are the most political, while the social and political context was highlighted by several academics. The combination of disciplinary and student perspectives in the guiding principles enables educators to discuss issues and problems with their students and work towards in-depth understanding sensitive to students’ life-worlds. Consequently, this study contributes to social science education by suggesting an empirically founded framework to use when teaching about political issues
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- Sutcliffe, Laura M. E., et al.
(författare)
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Harnessing the biodiversity value of Central and Eastern European farmland
- 2015
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Ingår i: Diversity & distributions. - : Wiley. - 1366-9516 .- 1472-4642. ; 21:6, s. 722-730
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Tidskriftsartikel (refereegranskat)abstract
- A large proportion of European biodiversity today depends on habitat provided by low-intensity farming practices, yet this resource is declining as European agriculture intensifies. Within the European Union, particularly the central and eastern new member states have retained relatively large areas of species-rich farmland, but despite increased investment in nature conservation here in recent years, farmland biodiversity trends appear to be worsening. Although the high biodiversity value of Central and Eastern European farmland has long been reported, the amount of research in the international literature focused on farmland biodiversity in this region remains comparatively tiny, and measures within the EU Common Agricultural Policy are relatively poorly adapted to support it. In this opinion study, we argue that, 10years after the accession of the first eastern EU new member states, the continued under-representation of the low-intensity farmland in Central and Eastern Europe in the international literature and EU policy is impeding the development of sound, evidence-based conservation interventions. The biodiversity benefits for Europe of existing low-intensity farmland, particularly in the central and eastern states, should be harnessed before they are lost. Instead of waiting for species-rich farmland to further decline, targeted research and monitoring to create locally appropriate conservation strategies for these habitats is needed now.
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| 12. |
- Wei, YB, et al.
(författare)
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Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression
- 2016
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6, s. e869-
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Tidskriftsartikel (refereegranskat)abstract
- Elevation of the proinflammatory cytokine IL-6 has been implicated in depression; however, the mechanisms remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression post-transcriptionally. The lethal-7 (let-7) miRNA family was suggested to be involved in the inflammation process and IL-6 was shown to be one of its targets. In the present study, we report elevation of Il6 in the prefrontal cortex (PFC) of a genetic rat model of depression, the Flinders Sensitive Line (FSL) compared to the control Flinders Resistant Line. This elevation was associated with an overexpression of LIN28B and downregulation of let-7 miRNAs, the former an RNA-binding protein that selectively represses let-7 synthesis. Also DROSHA, a key enzyme in miRNA biogenesis was downregulated in FSL. Running was previously shown to have an antidepressant-like effect in the FSL rat. We found that running reduced Il6 levels and selectively increased let-7i and miR-98 expression in the PFC of FSL, although there were no differences in LIN28B and DROSHA expression. Pri-let-7i was upregulated in the running FSL group, which associated with increased histone H4 acetylation. In conclusion, the disturbance of let-7 family biogenesis may underlie increased proinflammatory markers in the depressed FSL rats while physical activity could reduce their expression, possibly through regulating primary miRNA expression via epigenetic mechanisms.
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