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- 2019
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Tidskriftsartikel (refereegranskat)
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2. |
- Hung, Craig L. H., et al.
(författare)
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An assessment of the risks associated with polychlorinated biphenyls found in the stomach contents of stranded Indo-Pacific Humpback Dolphins (Sousa chinensis) and Finless Porpoises (Neophocaena phocaenoides) from Hong Kong waters
- 2006
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 63:5, s. 845-852
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Tidskriftsartikel (refereegranskat)abstract
- The risks to Indo-Pacific Humpback Dolphins and Finless Porpoises associated with polychlorinated biphenyls (PCBs) were assessed. Stomach contents from twelve stranded Humpback Dolphins and sixteen stranded Finless Porpoises were collected. Concentrations of total and isomer-specific PCBs in the stomach contents were determined using dual-column gas chromatography equipped with electron capture detectors (GC-ECD). Risks due to the PCBs were assessed in three scenarios, based on total PCBs (summation of 41 PCB congeners), total toxicity equivalency (TEQs) and PCB 118, using the toxicity reference values (TRVs) as the threshold effects benchmarks. The calculated risk quotients (RQs) showed that risks due to PCBs were generally low or negligible. Specifically, RQs from total TEQs and total PCBs for Finless Porpoises are below one, suggesting that PCBs should be a low risk for the Finless Porpoise in Hong Kong waters. However, the Humpback Dolphin has RQs larger than 1 for total TEQs and total PCBs when the 95th percentile data were used in the evaluation. This indicates that further investigation may be needed to examine more closely the potential impact of toxic contaminants in the habitat of the Humpback Dolphin.
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- Murphy, Eileen F., et al.
(författare)
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Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity
- 2013
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 62:2, s. 220-226
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The gut microbiota is an environmental regulator of fat storage and adiposity. Whether the microbiota represents a realistic therapeutic target for improving metabolic health is unclear. This study explored two antimicrobial strategies for their impact on metabolic abnormalities in murine diet-induced obesity: oral vancomycin and a bacteriocin-producing probiotic (Lactobacillus salivarius UCC118 Bac(+)).DESIGN: Male (7-week-old) C57BL/J6 mice (9-10/group) were fed a low-fat (lean) or a high-fat diet for 20 weeks with/without vancomycin by gavage at 2 mg/day, or with L. salivarius UCC118Bac(+) or the bacteriocin-negative derivative L. salivarius UCC118Bac(-) (each at a dose of 1×10(9) cfu/day by gavage). Compositional analysis of the microbiota was by 16S rDNA amplicon pyrosequencing.RESULTS: Analysis of the gut microbiota showed that vancomycin treatment led to significant reductions in the proportions of Firmicutes and Bacteroidetes and a dramatic increase in Proteobacteria, with no change in Actinobacteria. Vancomycin-treated high-fat-fed mice gained less weight over the intervention period despite similar caloric intake, and had lower fasting blood glucose, plasma TNFα and triglyceride levels compared with diet-induced obese controls. The bacteriocin-producing probiotic had no significant impact on the proportions of Firmicutes but resulted in a relative increase in Bacteroidetes and Proteobacteria and a decrease in Actinobacteria compared with the non-bacteriocin-producing control. No improvement in metabolic profiles was observed in probiotic-fed diet-induced obese mice.CONCLUSION: Both vancomycin and the bacteriocin-producing probiotic altered the gut microbiota in diet-induced obese mice, but in distinct ways. Only vancomycin treatment resulted in an improvement in the metabolic abnormalities associated with obesity thereby establishing that while the gut microbiota is a realistic therapeutic target, the specificity of the antimicrobial agent employed is critical.
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- Collins, James, et al.
(författare)
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Fibrinogen-binding and platelet-aggregation activities of a Lactobacillus salivarius septicaemia isolate are mediated by a novel fibrinogen-binding protein.
- 2012
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Ingår i: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 85:5, s. 862-877
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Tidskriftsartikel (refereegranskat)abstract
- The marketplace for probiotic foods is burgeoning, measured in billions of euro per annum. It is imperative, however, that all bacterial strains are fully assessed for human safety. The ability to bind fibrinogen is considered a potential pathogenicity trait that can lead to platelet aggregation, serious medical complications, and in some instances, death. Here we examined strains from species frequently used as probiotics for their ability to bind human fibrinogen. Only one strain (CCUG 47825), a Lactobacillus salivarius isolate from a case of septicaemia, was found to strongly adhere to fibrinogen. Furthermore, this strain was found to aggregate human platelets at a level comparable to the human pathogen Staphylococcus aureus. By sequencing the genome of CCUG 47825, we were able to identify candidate genes responsible for fibrinogen binding. Complementing the genetic analysis with traditional molecular microbiological techniques enabled the identification of the novel fibrinogen receptor, CCUG_2371. Although only strain CCUG 47825 bound fibrinogen under laboratory conditions, homologues of the novel fibrinogen binding gene CCUG_2371 are widespread among L. salivarius strains, maintaining their potential to bind fibrinogen if expressed. We highlight the fact that without a full genetic analysis of strains for human consumption, potential pathogenicity traits may go undetected. © 2012 Blackwell Publishing Ltd.
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- Watson, Hunna J., et al.
(författare)
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Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
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Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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- Dulio, Valeria, et al.
(författare)
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The NORMAN Association and the European Partnership for Chemicals Risk Assessment (PARC) : let’s cooperate!
- 2020
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Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 32:1
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Tidskriftsartikel (refereegranskat)abstract
- The Partnership for Chemicals Risk Assessment (PARC) is currently under development as a joint research and innovation programme to strengthen the scientific basis for chemical risk assessment in the EU. The plan is to bring chemical risk assessors and managers together with scientists to accelerate method development and the production of necessary data and knowledge, and to facilitate the transition to next-generation evidence-based risk assessment, a non-toxic environment and the European Green Deal. The NORMAN Network is an independent, well-established and competent network of more than 80 organisations in the field of emerging substances and has enormous potential to contribute to the implementation of the PARC partnership. NORMAN stands ready to provide expert advice to PARC, drawing on its long experience in the development, harmonisation and testing of advanced tools in relation to chemicals of emerging concern and in support of a European Early Warning System to unravel the risks of contaminants of emerging concern (CECs) and close the gap between research and innovation and regulatory processes. In this commentary we highlight the tools developed by NORMAN that we consider most relevant to supporting the PARC initiative: (i) joint data space and cutting-edge research tools for risk assessment of contaminants of emerging concern; (ii) collaborative European framework to improve data quality and comparability; (iii) advanced data analysis tools for a European early warning system and (iv) support to national and European chemical risk assessment thanks to harnessing, combining and sharing evidence and expertise on CECs. By combining the extensive knowledge and experience of the NORMAN network with the financial and policy-related strengths of the PARC initiative, a large step towards the goal of a non-toxic environment can be taken.
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- Jeffery, Ian B, et al.
(författare)
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An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota
- 2012
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 61:7, s. 997-1006
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Tidskriftsartikel (refereegranskat)abstract
- Background and aimsIrritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that may be triggered by enteric pathogens and has also been linked to alterations in the microbiota and the host immune response. The authors performed a detailed analysis of the faecal microbiota in IBS and control subjects and correlated the findings with key clinical and physiological parameters.DesignThe authors used pyrosequencing to determine faecal microbiota composition in 37 IBS patients (mean age 37 years; 26 female subjects; 15 diarrhoea-predominant IBS, 10 constipation-predominant IBS and 12 alternating-type IBS) and 20 age- and gender-matched controls. Gastrointestinal and psychological symptom severity and quality of life were evaluated with validated questionnaires and colonic transit time and rectal sensitivity were measured.ResultsAssociations detected between microbiota composition and clinical or physiological phenotypes included microbial signatures associated with colonic transit and levels of clinically significant depression in the disease. Clustering by microbiota composition revealed subgroups of IBS patients, one of which (n=15) showed normal-like microbiota composition compared with healthy controls. The other IBS samples (n=22) were defined by large microbiota-wide changes characterised by an increase of Firmicutes-associated taxa and a depletion of Bacteroidetes-related taxa.ConclusionsDetailed microbiota analysis of a well-characterised cohort of IBS patients identified several clear associations with clinical data and a distinct subset of IBS patients with alterations in their microbiota that did not correspond to IBS subtypes, as defined by the Rome II criteria.
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- Jeffery, Ian B, et al.
(författare)
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The microbiota link to irritable bowel syndrome: An emerging story.
- 2012
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Ingår i: Gut microbes. - : Informa UK Limited. - 1949-0984 .- 1949-0976. ; 3:6, s. 572-6
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Forskningsöversikt (refereegranskat)abstract
- Irritable Bowel Syndrome (IBS) is a clinically heterogeneous disorder which is likely to involve a number of causative factors. The contribution of altered intestinal microbiota composition or function to this disorder is controversial, and is the subject of much current research. Until recently, the technical limitations of the methodologies available have not permitted an adequate survey of low-abundance microbial species. Recent technological developments have enabled the analysis of the global population of the microbiome using high through-put, culture independent, 16S rRNA amplicon pyrosequencing. Using these new methodologies, we are able to gain important biological insights into the link between functional bowel disorders and the microbiome. This addendum contextualizes and summarizes the results of these studies, and defines the future challenges and opportunities in the field.
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- O'Toole, Paul W., et al.
(författare)
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Two major classes in the M protein family in group A streptococci
- 1992
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Ingår i: Proceedings of the National Academy of Sciences. - 1091-6490. ; 89:18, s. 8661-8665
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Tidskriftsartikel (refereegranskat)abstract
- The M protein family of molecules in the group A streptococcus comprises a number of cell surface proteins that interact with the immune system of the host. One of the proteins in this family is the IgA receptor Arp4, which has C repeats similar to those that characterize the known M proteins. The streptococcal strain expressing Arp4 also expresses a second immunoglobulin-binding protein, Mrp4, which is shown here to be encoded by a gene located immediately upstream of the gene for Arp4. In addition to binding IgG, Mrp4 also binds fibrinogen, a property ascribed to M proteins. DNA sequence analysis demonstrated that the Mrp4 protein indeed is a member of the M protein family, but it was unexpectedly found to have a type of repeat that is identical to the A repeat described for FcRA76, a partially sequenced streptococcal Fc receptor. Purified FcRA76 was shown to bind fibrinogen and IgG, like Mrp4. These data show that the known molecules in the M protein family can be divided into two classes, A and C, according to the type of repeat region found. Hybridization studies with a panel of clinical isolates indicate that many streptococcal strains express class A and class C proteins, whereas some strains express only class C proteins. Class A molecules show amino-terminal sequence variation, like class C molecules, which suggests that proteins of both classes are targets for the immune response.
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