| 1. |
- Klingström, Tomas, et al.
(författare)
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Legal & ethical compliance when sharing biospecimen
- 2018
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Ingår i: Briefings in Functional Genomics & Proteomics. - Oxford : Oxford University Press. - 2041-2649 .- 2041-2657. ; 17:1, s. 1-7
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Forskningsöversikt (refereegranskat)abstract
- When obtaining samples from biobanks, resolving ethical and legal concerns is a time-consuming task where researchers need to balance the needs of privacy, trust and scientific progress. The Biobanking and Biomolecular Resources Research Infrastructure-large Prospective Cohorts project has resolved numerous such issues through intense ommunication between involved researchers and experts in its mission to unite large rospective study sets in Europe. To facilitate efficient communication, it is useful for onexperts to have an at least basic understanding of the regulatory systemformanaging biological samples. Laws regulating research oversight are based on national law and normally share core principles founded on international charters. In interview studies among donors, chief concerns are privacy, efficient sample utilization and access to information generated fromtheir samples. Despite a lack of clear evidence regarding which concern takes precedence, scientific as well as public discourse has largely focused on privacy concerns and the right of donors to control the usage of their samples. It is therefore important to roactively deal with ethical and legal issues to avoid complications that delay or prevent samples from being accessed. To help biobank professionals avoid making unnecessary mistakes, we have developed this basic primer covering the relationship between ethics and law, the concept of informed consent and considerations for returning findings to donors.
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| 2. |
- Gillman, Anna, et al.
(författare)
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Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
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Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.
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| 3. |
- Lundqvist, Johan, et al.
(författare)
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Innovative drinking water treatment techniques reduce the disinfection-induced oxidative stress and genotoxic activity
- 2019
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Ingår i: Water Research. - : Elsevier. - 0043-1354 .- 1879-2448. ; 5, s. 182-192
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Tidskriftsartikel (refereegranskat)abstract
- Disinfection of drinking water using chlorine can lead to the formation of genotoxic by-products whenchlorine reacts with natural organic matter (NOM). A vast number of such disinfection by-products(DBPs) have been identified, making it almost impossible to routinely monitor all DBPs with chemicalanalysis. In this study, a bioanalytical approach was used, measuring oxidative stress (Nrf2 activity),genotoxicity (micronucleus test), and aryl hydrocarbon receptor (AhR) activation to evaluate an innovativewater treatment process, including suspended ion exchange, ozonation, in-line coagulation,ceramic microfiltration, and granular activated carbon. Chlorination was performed in laboratory scaleafter each step in the treatment process in order to investigate the effect of each treatment process to theformation of DBPs. Suspended ion exchange had a high capacity to remove dissolved organic carbon(DOC) and to decrease UV absorbance and Nrf2 activity in non-chlorinated water. High-dose chlorination(10 mg Cl2 L-1) of raw water caused a drastic induction of Nrf2 activity, which was decreased by 70% inwater chlorinated after suspended ion exchange. Further reduction of Nrf2 activity following chlorinationwas achieved by ozonation and the concomitant treatment steps. The ozonation treatment resulted indecreased Nrf2 activity in spite of unchanged DOC levels. However, a strong correlation was found betweenUV absorbing compounds and Nrf2 activity, demonstrating that Nrf2 inducing DBPs were formedfrom pre-cursors of a specific NOM fraction, constituted of mainly aromatic compounds. Moreover, highdosechlorination of raw water induced genotoxicity. In similarity to the DOC levels, UV absorbance andNrf2 activity, the disinfection-induced genotoxicity was also reduced by each treatment step of theinnovative water treatment technique. AhR activity was observed in the water produced by the conventionalprocess and in the raw water, but the activity was clearly decreased by the ozonation step inthe innovative water treatment process.
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| 4. |
- Brunius, Carl, 1974, et al.
(författare)
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Prediction and modeling of pre-analytical sampling errors as a strategy to improve plasma NMR metabolomics data
- 2017
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1460-2059 .- 1367-4811. ; 33:22, s. 3567-3574
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks are important infrastructures for life science research. Optimal sample handling regarding e.g. collection and processing of biological samples is highly complex, with many variables that could alter sample integrity and even more complex when considering multiple study centers or using legacy samples with limited documentation on sample management. Novel means to understand and take into account such variability would enable high-quality research on archived samples. This study investigated whether pre-analytical sample variability could be predicted and reduced by modeling alterations in the plasma metabolome, measured by NMR, as a function of pre-centrifugation conditions (1-36 h pre-centrifugation delay time at 4 A degrees C and 22 A degrees C) in 16 individuals. Pre-centrifugation temperature and delay times were predicted using random forest modeling and performance was validated on independent samples. Alterations in the metabolome were modeled at each temperature using a cluster-based approach, revealing reproducible effects of delay time on energy metabolism intermediates at both temperatures, but more pronounced at 22 A degrees C. Moreover, pre-centrifugation delay at 4 A degrees C resulted in large, specific variability at 3 h, predominantly of lipids. Pre-analytical sample handling error correction resulted in significant improvement of data quality, particularly at 22 A degrees C. This approach offers the possibility to predict pre-centrifugation delay temperature and time in biobanked samples before use in costly downstream applications. Moreover, the results suggest potential to decrease the impact of undesired, delay-induced variability. However, these findings need to be validated in multiple, large sample sets and with analytical techniques covering a wider range of the metabolome, such as LC-MS.
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| 5. |
- Klingström, Tomas, et al.
(författare)
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Supporting the Development of Biobanks in Low and Medium Income Countries
- 2016
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Ingår i: 2016 IST-AFRICA WEEK CONFERENCE. - 9781905824557
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Konferensbidrag (refereegranskat)abstract
- Biobanks are an organized collection of biological material and associated data. They are a fundamental resource for life science research and contribute to the development of pharmaceutical drugs, diagnostic markers and to a deeper understanding of the genetics that regulate the development of all life on earth. Biobanks are well established in High Income Countries (HIC) and are rapidly emerging in Low and Middle Income Countries (LMIC). Surveys among biobanks operating in a LMIC setting indicate that limited resources and short term funding tied to specific projects threaten the sustainability of the biobanks. Fit-for-purpose biobanks targeting major societal challenges such as HIV and Malaria provide an excellent basis for integrating biobanks with the available research communities in LMIC regions. But to become sustainable for the future it is important that biobanks become an integrated part of local research communities. To achieve this, the cost of operating biobanks must be lowered, templates must be developed to support local ethics committees and researchers must be given the opportunity to build experience in successfully operating biobank based research projects. The B3Africa consortium is based on these conclusions and set up to support biobank based research by creating a cost efficient Laboratory Information Management System (LIMS) for developing biobanks and also contribute to the training and capacity building in the local research community. The technical platform called the eB3Kit is open source and consists of a LIMS and a bioinformatics module based on the eBiokit that allow researchers to take control over the analysis of their own data. Along with the technical platform the consortium will also contribute training and support for the associated infrastructures necessary to regulate the ethical and legal implications of biobank based research.
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| 6. |
- Gustafsson, Kerstin, et al.
(författare)
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Direct and indirect effects of the fungicide azoxystrobin in outdoor brackish water microcosms
- 2010
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Ingår i: Ecotoxicology. - : Springer Science and Business Media LLC. - 0963-9292 .- 1573-3017. ; 19:2, s. 431-444
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Tidskriftsartikel (refereegranskat)abstract
- The effects of the strobilurin fungicide azoxystrobin were studied in brackish water microcosms, with natural plankton communities and sediment. Two experiments were conducted: Experiment 1 (nominal conc. 0, 15 and 60 mu g/L, 24-L outdoor microcosms for 21 days) and a second, follow-up, Experiment 2 (nominal conc. 0, 3, 7.5, 15 mu g/L, 4-L indoor microcosms for 12 days). The microcosms represent a simplified brackish water community found in shallow semi-enclosed coastal areas in agricultural districts in the Baltic Sea region. Measured water concentrations of the fungicide (Experiment 1) were, on average, 83 and 62% of nominal concentrations directly after application, and 25 and 30% after 21 days, for the low and high dose treatments, respectively, corresponding to mean DT50-values of 15.1 and 25.8 days, for low and high dose treatments, respectively. In Experiment 1, direct toxic effects on calanoid copepods at both test concentrations were observed. Similarly, in Experiment 2, the copepod abundance was significantly reduced at all tested concentrations. There were also significant secondary effects on zooplankton and phytoplankton community structure, standing stocks and primary production. Very few ecotoxicological studies have investigated effects of plant protection products on Baltic organisms in general and effects on community structure and function specifically. Our results show that azoxystrobin is toxic to brackish water copepods at considerably lower concentrations than previously reported from single species tests on freshwater crustaceans, and that direct toxic effects on this ecologically important group may lead to cascade effects altering lower food webs and ecosystem functioning.
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| 7. |
- Landegren, Nils, et al.
(författare)
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Transglutaminase 4 as a prostate autoantigen in male subfertility
- 2015
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 7:292
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pubertal age and subsequent to prostate maturation. We assessed the animal model for APS1, the Aire-deficient mouse, and found spontaneous development of TGM4 autoantibodies specifically in males. Aire-deficient mice failed to present TGM4 in the thymus, consistent with a defect in central tolerance for TGM4. In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility.
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| 8. |
- Teixeira, Cristina, 1986, et al.
(författare)
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Application of a dynamic gastrointestinal in vitro model combined with a rat model to predict the digestive fate of barley dietary fibre and evaluate potential impact on hindgut fermentation
- 2017
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Ingår i: Bioactive Carbohydrates and Dietary Fibre. - : Elsevier BV. - 2212-6198. ; 9, s. 7-13
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Tidskriftsartikel (refereegranskat)abstract
- Processing affects the composition, structure and physico-chemical characteristics of dietary fibres, and further changes can occur along the gastro-intestinal tract before entering the colon where undigested carbohydrates may serve as a substrate for the microbiota. To elucidate the effects of dietary fibre characteristic and the impact of processing on the digestive fate of dietary fibre components, in the stomach and the small intestine, a dynamic gastrointestinal in vitro model (TIM-1) was used. Three barley malt and one brewers’ spent grain, with different contents of soluble fibre, arabinoxylan (total and soluble), and β-glucan with varying Calcofluor average molecular weight (Mcf) and molecular weight distribution were evaluated in the in vitro model. Additionally, a rat model was used to study the colonic fermentation of the dietary fibre components in the barley products. The transit time through the stomach and small intestine of the in vitro model was slowest for barley malts with the highest content of soluble fibre and β-glucan. The β-glucan Mcf decreased with digestion time for all test meals, and the molecular weight distributions in the various barley products differed markedly. The highest β-glucan Mcf was found for Cinnamon malt, which also contained the highest proportion of soluble fibre. The hindgut fermentation of fibre and the proportions of caecal propionic acid were highest in rats fed barley products high in soluble fibre, β-glucan (content and Mcf), soluble arabinoxylan, and with slowest transit during digestion in the in vitro model.
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| 9. |
- Schneider, Kara, et al.
(författare)
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Using reporters of different misfolded proteins reveals differential strategies in processing protein aggregates
- 2022
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 298:11
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Tidskriftsartikel (refereegranskat)abstract
- The accumulation of misfolded proteins is a hallmark of aging and many neurodegenerative diseases, making it important to understand how the cellular machinery recognizes and processes such proteins. A key question in this respect is whether misfolded proteins are handled in a similar way regardless of their genetic origin. To approach this question, we compared how three different misfolded proteins, guk1-7, gus1-3, and pro3-1, are handled by the cell. We show that all three are nontoxic, even though highly overexpressed, highlighting their usefulness in analyzing the cellular response to misfolding in the absence of severe stress. We found significant differences between the aggregation and disaggregation behavior of the misfolded proteins. Specifically, gus1-3 formed some aggregates that did not efficiently recruit the protein disaggregase Hsp104 and did not colocalize with the other misfolded reporter proteins. Strikingly, while all three misfolded proteins generally coaggregated and colocalized to specific sites in the cell, disaggregation was notably different; the rate of aggregate clearance of pro3-1 was faster than that of the other misfolded proteins, and its clearance rate was not hindered when pro3-1 colocalized with a slowly resolved misfolded protein. Finally, we observed using super-resolution light microscopy as well as immunogold labeling EM in which both showed an even distribution of the different misfolded proteins within an inclusion, suggesting that misfolding characteristics and remodeling, rather than spatial compartmentalization, allows for differential clearance of these misfolding reporters residing in the same inclusion. Taken together, our results highlight how properties of misfolded proteins can significantly affect processing.
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| 10. |
- Tiukova, Ievgeniia, 1987, et al.
(författare)
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Identification and characterisation of two high-affinity glucose transporters from the spoilage yeast Brettanomyces bruxellensis
- 2019
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Ingår i: FEMS microbiology letters. - : Oxford University Press (OUP). - 0378-1097 .- 1574-6968. ; 366:17
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Tidskriftsartikel (refereegranskat)abstract
- The yeast Brettanomyces bruxellensis (syn. Dekkera bruxellensis) is an emerging and undesirable contaminant in industrial low-sugar ethanol fermentations that employ the yeast Saccharomyces cerevisiae. High-affinity glucose import in B. bruxellensis has been proposed to be the mechanism by which this yeast can outcompete S. cerevisiae. The present study describes the characterization of two B. bruxellensis genes (BHT1 and BHT3) believed to encode putative high-affinity glucose transporters. In vitro-generated transcripts of both genes as well as the S. cerevisiae HXT7 high-affinity glucose transporter were injected into Xenopus laevis oocytes and subsequent glucose uptake rates were assayed using 14C-labelled glucose. At 0.1 mM glucose, Bht1p was shown to transport glucose five times faster than Hxt7p. pH affected the rate of glucose transport by Bht1p and Bht3p, indicating an active glucose transport mechanism that involves proton symport. These results suggest a possible role for BHT1 and BHT3 in the competitive ability of B. bruxellensis.
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