| 1. |
- Ainsbury, Elizabeth, et al.
(författare)
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Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans - joint RENEB and EURADOS inter-laboratory comparisons
- 2017
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 93:1, s. 99-109
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios.
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| 2. |
- Coulon, Severine, et al.
(författare)
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Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia
- 2011
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 17:11, s. 163-1456
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Tidskriftsartikel (refereegranskat)abstract
- Anemia because of insufficient production of and/or response to erythropoietin (Epo) is a major complication of chronic kidney disease and cancer. The mechanisms modulating the sensitivity of erythroblasts to Epo remain poorly understood. We show that, when cultured with Epo at suboptimal concentrations, the growth and clonogenic potential of erythroblasts was rescued by transferrin receptor 1 (TfR1)-bound polymeric IgA1 (pIgA1). Under homeostatic conditions, erythroblast numbers were increased in mice expressing human IgA1 compared to control mice. Hypoxic stress of these mice led to increased amounts of pIgA1 and erythroblast expansion. Expression of human IgA1 or treatment of wild-type mice with the TfR1 ligands pIgA1 or iron-loaded transferrin (Fe-Tf) accelerated recovery from acute anemia. TfR1 engagement by either pIgA1 or Fe-Tf increased cell sensitivity to Epo by inducing activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. These cellular responses were mediated through the TfR1-internalization motif, YXX Phi. Our results show that pIgA1 and TfR1 are positive regulators of erythropoiesis in both physiological and pathological situations. Targeting this pathway may provide alternate approaches to the treatment of ineffective erythropoiesis and anemia.
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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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| 4. |
- Schaltz-Buchholzer, Frederik, et al.
(författare)
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BCG skin reactions by 2 months of age are associated with better survival in infancy : A prospective observational study from Guinea-Bissau
- 2020
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Ingår i: BMJ Global Health. - : BMJ. - 2059-7908. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Receiving Bacille Calmette-Guérin (BCG)-Denmark vaccine at birth has been associated with ∼40% reductions in all-cause neonatal mortality. We evaluated determinants of BCG skin reaction characteristics by age 2 months and tested the association with subsequent mortality. Methods Prospective observational study amalgamating five trials providing BCG-at-birth that were conducted between 2002 and 2018 in Guinea-Bissau. The reaction status and size were evaluated at home-visits by 2 months of age among 6012 neonates; mortality from 2 to 12 months was assessed at subsequent visits. Reaction determinants were evaluated by binomial regression providing risk ratios (RRs). In Cox-models providing adjusted mortality rate ratios (aMRRs), we assessed the association between (1) having a 2-month reaction (yes/no) and (2) reaction size tertiles and subsequent all-cause mortality risk. A subgroup had their BCG reaction evaluated and were bled at age 4 weeks; their samples underwent in vitro analysis for specific and non-specific cytokine responses. Results The BCG strain was the main determinant for developing a 2-month reaction and the reaction size: the BCG-Russia/BCG-Denmark RR for large-reaction was 0.38 (0.30-0.47) and the BCG-Russia/BCG-Japan RR was 0.61 (0.51-0.72). 5804 infants (96.5%) were reactors by age 2 months; 208 (3.5%) were non-reactors. The 2-12 months mortality risk was 4.8% (10/208) for non-reactors, 2.9% (64/2213) for small reactors, 1.8% (30/1710) for medium reactors and 0.8% (15/1881) for large reactors. The reactor/non-reactor aMRR was 0.49 (0.26-0.95) and there was a linear trend of decreasing mortality with increasing reaction size (p for trend <0.001). BCG reactors had higher 4-week specific and non-specific cytokine responses, responses that were highest among those with large reactions. Conclusion Among BCG-vaccinated infants, having a BCG skin reaction by age 2 months was associated with markedly better survival, as was the reaction size. Our findings thus support that BCG has substantial effects on all-cause mortality. Emphasising at-birth vaccination with immunogenic BCG strains and revaccinating non-reactors and small reactors could have major public health benefits.
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| 5. |
- Schaltz-Buchholzer, Frederik, et al.
(författare)
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Neonatal Bacille Calmette-Guérin vaccination and tuberculin skin test reactions at 2- and 6-months : Effects on mortality up to 1 year of age
- 2021
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 39:50, s. 7286-7294
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Tidskriftsartikel (refereegranskat)abstract
- Background: In randomized trials, Bacille Calmette-Guérin (BCG) vaccine has been associated with reduced all-cause mortality. BCG-induced Tuberculin Skin Test (TST) reactions have also been associated with reduced all-cause mortality. We aimed to assess the association between TST responses and subsequent mortality in three birth cohorts and conducted a meta-analysis of existing studies. Methods: Observational study within three Guinea-Bissau BCG trial birth cohorts (conducted 2002–04, 2009–2013 and 2014–18) that encompassed children who were BCG-vaccinated within 28 days with TSTs performed at 2- (n = 1389) and 6-months (n = 2635) of age. We evaluated TST reaction determinants by binomial regression and assessed the association between TSTs > 1 mm (reactors) vs. ≤ 1 mm (non-reactors) and subsequent mortality risk up to age 12 months in Cox-models providing Mortality Rate Ratios (MRRs). We searched PubMed for studies to calculate meta-estimates of the association between TST reactivity by age 2- and 6-months and all-cause mortality. Results: Large post-vaccination wheal size was associated with 6-month TST positivity and so was receiving BCG-Denmark or BCG-Japan, compared with BCG-Russia. By age 2 months, 22% (302/1389) of infants were TST reactors with a 2–12-month mortality risk of 1.7% (5/302) vs. 3.3% (36/1087) for non-reactors, the corresponding reactor/non-reactor MRR = 0.49 (0.19–1.26). By age 6 months, 44% (1149/2635) of infants were reactors and the 6–12-month mortality risk was 0.4% (4/1149) vs. 0.6% (9/1486) for non-reactors, the MRR = 0.87 (0.27–2.86). The literature search provided 3 studies. The meta-analysis revealed a uniform pattern of reduced mortality associated with TST reactivity, a TST response by 2 months being associated with an MRR of 0.59 (0.39–0.90); for 6-month TST responses the MRR was 0.65 (0.43–1.00). Conclusion: Among BCG-vaccinated infants, TST reactions were associated with markedly reduced mortality. Improved vaccination technique and using certain BCG strains could lead to a higher TST reaction prevalence, which would enhance BCG's beneficial non-specific effects.
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