| 1. |
- Cardell, Susanna, 1959, et al.
(författare)
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Tolerization of diabetogenic CD4+T cells by intranasal treatment with CTA1R7K-DD containing specific peptide through the induction of FoxP3+Treg cells
- 2012
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Ingår i: Journal of Immunology. - 0022-1767. ; 188
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Type I diabetes (T1D) results from immune destruction of insulin producing β-cells in the pancreas islets. Diabetogenic CD4+ T cells are key cells in the autoimmune process. To achieve tolerization of diabetogenic CD4+ T cells would therefore be an important advancement in the development of treatments of T1D. We previously described that a mutated (R7K), enzyme killed, form of the cholera toxin A1 subunit based adjuvant CTA1-DD induces specific tolerance rather than enhancement of immunity. Intranasal (i n) treatment with CTA1R7K-DD containing a type II collagen peptide reduced in vitro recall responses to the peptide, and moreover, ameliorated collagen induced arthritis in mice. Here, we use CTA1R7K-DD to investigate tolerization of diabetogenic CD4+ T cells of the non-obese diabetic (NOD) mouse, exploring diabetogenic TCR transgenic BDC2.5 CD4+ T cells. I n treatment of BDC2.5 NOD mice with CTA1R7K-DD containing a peptide specific for the BDC2.5 TCR reduced proliferation and IFN-{gamma} production to in vitro peptide stimulation. Transfer of CD4+ BDC2.5 T cells to NOD.scid mice results in T1D development in 80-100% of recipient mice. In contrast, recipients of cells from BDC2.5 NOD mice treated with the CTA1R7K-DD peptide construct remained healthy. The i n treatment resulted in systemic increase in the frequency of CD4+ BDC2.5 transgenic T cells expressing FoxP3, suggesting that CTA1R7K-peptide-DD induces specific CD4+ Treg cells preventing T1D development.
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| 2. |
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| 3. |
- 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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| 5. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 6. |
- Adlerz, Linda, et al.
(författare)
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Down-regulation of amyloid precursor protein by peptide nucleic acid oligomer in cultured rat primary neurons and astrocytes
- 2003
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Ingår i: Neuroscience Letters. - 0304-3940 .- 1872-7972. ; 336:1, s. 55-59
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Tidskriftsartikel (refereegranskat)abstract
- The amyloid precursor protein (APP) and its proteolytic cleavage products, the amyloid P peptides, have been implicated as a cause of Alzheimer's disease. Peptide nucleic acids (PNA), the DNA mimics, have been shown to block the expression of specific proteins at both transcriptional and translational levels. Generally, the cellular uptake of PNA is low. However, recent studies have indicated that the effect of unmodified antisense PNA uptake is more pronounced in nervous tissue. In this study we have shown that biotinylated PNA directed to the initiator codon region of the APP mRNA (-4 - +11) was taken up into the cytoplasm of primary rat cerebellar granule cells and cortical astrocytes, using fluorescence and confocal microscopy studies. Uptake of PNA was faster in neurons than in astrocytes. Western blotting analysis showed that APP was strongly down-regulated in both neurons and astrocytes. Thus, unmodified PNA can be used for studies on the function of APP in neurons and astrocytes.
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| 7. |
- Agerström, Jens, et al.
(författare)
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Descriptive social norms and charitable giving : the power of local norms
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- By conducting a field experiment, we examined whether conveying descriptive social norms (e.g., “this is what most people do”) leads to more charitable giving compared to industry standard appeals. Moreover, we examined whether people are more likely to conform to the local norms of one’s immediate environment than to more global norms extending beyond one’s local environment. University students received a charity organization’s information brochure and were asked for a monetary contribution. An experimental descriptive norm manipulation was embedded in the brochure. We found that providing people with descriptive norms increased charitable giving substantially compared with industry standard altruistic appeals (control condition). Moreover, conveying local norms were more effective in increasing charitable giving than conveying global norms. Practical implications for charity organizations and marketing are proposed.
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| 8. |
- Agerström, Jens, 1976-, et al.
(författare)
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Using descriptive social norms to increase charitable giving : The power of local norms
- 2016
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Ingår i: Journal of Economic Psychology. - : Elsevier BV. - 0167-4870 .- 1872-7719. ; 52, s. 147-153
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Tidskriftsartikel (refereegranskat)abstract
- In a field experiment, we examined whether conveying descriptive social norms (e.g., "this is what most people do") increases charitable giving. Additionally, we examined whether people are more likely to conform to the local norms of one's immediate environment than to more global norms extending beyond one's local environment. University students received a charity organization's information brochure and were asked for a monetary contribution. An experimentaldescriptive norm manipulation was embedded in the brochure. We found that providing people with descriptive norms increased charitable giving substantially compared with industry standard altruistic appeals (control condition). Moreover, conveying local norms were more effective in increasing charitable givingthan conveying global norms. Practical implications for charity organizations and marketing are proposed.
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| 9. |
- Alamaa, Linda, et al.
(författare)
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Governmentality
- 2022
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Ingår i: Perspektiv på offentlig förvaltning : Teori i praktiken - Teori i praktiken. - 9789144153247 ; , s. 169-188
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Introducerar governmentality som ett teoretiskt perspektiv på offentlig förvaltning.
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