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- Nagy, E, et al.
(författare)
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Disorders of vision in neonatal hypoxic-ischaemic encephalopathy: a systematic review
- 2021
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Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 106:4, s. 357-362
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Tidskriftsartikel (refereegranskat)abstract
- Neonatal hypoxic-ischaemic encephalopathy (HIE) following perinatal asphyxia in term infants is associated with neonatal mortality and a high risk of neurodevelopmental impairment later in life. Visual disorders are an accepted complication of HIE and the association has been cited in the literature many times. This review aims to study the evidence for this association and assess the quality of the data on which this is based.DesignA systematic literature review was conducted and 922 citations were assessed using standard methods outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol.ResultsThe results demonstrate that the majority of studies have reported on various neurodevelopmental outcomes but rarely specifically vision. Based on limited currently available data, extracted from a number of small studies, an association of neonatal HIE with visual impairments seems to exist but detail is lacking. Notably, in the existing studies, there is a striking lack of consistency in the methods used to diagnose HIE and, similarly, a wide variation in the methods employed to measure visual function.ConclusionsTo explore the observed association further in terms of prognosis and the effects of HIE treatments on visual outcomes, future studies will need to address the issues of standardised diagnostic criteria, severity grading and robust, age-appropriate visual assessment.
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- Khairalla, Ahmed S., et al.
(författare)
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Nuclear trafficking, histone cleavage and induction of apoptosis by the meningococcal App and MspA autotransporters
- 2015
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 17:7, s. 1008-1020
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Tidskriftsartikel (refereegranskat)abstract
- Neisseria meningitidis, a major cause of bacterial meningitis and septicaemia, secretes multiple virulence factors, including the adhesion and penetration protein (App) and meningococcal serine protease A (MspA). Both are conserved, immunogenic, type Va autotransporters harbouring S6-family serine endopeptidase domains. Previous work suggested that both could mediate adherence to human cells, but their precise contribution to meningococcal pathogenesis was unclear. Here, we confirm that App and MspA are in vivo virulence factors since human CD46-expressing transgenic mice infected with meningococcal mutants lacking App, MspA or both had improved survival rates compared with mice infected with wild type. Confocal imaging showed that App and MspA were internalized by human cells and trafficked to the nucleus. Cross-linking and enzyme-linked immuno assay (ELISA) confirmed that mannose receptor (MR), transferrin receptor 1 (TfR1) and histones interact with MspA and App. Dendritic cell (DC) uptake could be blocked using mannan and transferrin, the specific physiological ligands for MR and TfR1, whereas in vitro clipping assays confirmed the ability of both proteins to proteolytically cleave the core histone H3. Finally, we show that App and MspA induce a dose-dependent increase in DC death via caspase-dependent apoptosis. Our data provide novel insights into the roles of App and MspA in meningococcal infection.
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- Engels, Stefan, et al.
(författare)
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A comparison of three Eurasian chironomid-climate calibration datasets on a W-E continentality gradient and the implications for quantitative temperature reconstructions
- 2014
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Ingår i: Journal of Paleolimnology. - : Springer Science and Business Media LLC. - 0921-2728 .- 1573-0417. ; 51:4, s. 529-547
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Tidskriftsartikel (refereegranskat)abstract
- Multiple regional chironomid-climate calibration datasets are available to reconstruct quantitatively July air temperatures from fossil chironomid assemblages. We examined the relationship between July air temperature and the 40 most common chironomid taxa in three independent Eurasian calibration (training) sets. The estimated temperature optimum of each chironomid taxon is systematically lower (by similar to 1-2 A degrees C) in a Norwegian calibration set compared to Finnish and Russian calibration sets. This result might partly be explained by the fact that the Norwegian calibration set extends further at the cold end of the temperature gradient. A difference in continentality between the Russian sites and the European sites might also contribute to this pattern. The number of taxa that show a statistically significant unimodal response to temperature is higher in the Norwegian calibration set (34 out of 40 taxa) compared to the modern Finnish (11 of 37 taxa; 3 common taxa absent) and the Russian calibration set (20 of 40 taxa), probably due to the longer temperature gradient incorporated in the Norwegian calibration set. We applied all three calibration sets to fossil chironomid assemblages from the high-latitude study site of Sokli (northeast Finland), a site with a unique series of lacustrine deposits covering (amongst others) the Holocene, part of early MIS 3 (at similar to 53 ka) and MIS 5d-c (at similar to 110-95 ka) and with independent proxy-records for comparison. In the early Holocene and during MIS 5c, the chironomid-based temperature inferences from all three inference models had similar values. Temperature reconstructions based on the Norwegian calibration set are 2-4 A degrees C lower for the late Holocene, early MIS 3 and MIS 5d than the inferred temperatures based on the other calibration sets. Although the lakes included in the Finnish calibration set are located closest to the site of Sokli, evaluation tests and a comparison with independent proxy data suggests that the Norwegian calibration set provides the most suitable analogues for reconstruction purposes for most of the fossil assemblages. Our results imply that when choosing a calibration set for quantitative climate reconstructions on glacial timescales, regional proximity of the fossil site may not be a sufficient basis, and the length of the temperature gradient of the calibration dataset and factors such as the continentality gradient covered by the calibration set must also be considered.
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| 8. |
- Mahdavi, J., et al.
(författare)
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A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization
- 2014
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Ingår i: Open Biology. - : The Royal Society. - 2046-2441. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Campylobacter jejuni is an important cause of human foodborne gastroenteritis; strategies to prevent infection are hampered by a poor understanding of the complex interactions between host and pathogen. Previous work showed that C. jejuni could bind human histo-blood group antigens (BgAgs) in vitro and that BgAgs could inhibit the binding of C. jejuni to human intestinal mucosa ex vivo. Here, the major flagella subunit protein (FlaA) and the major outer membrane protein (MOMP) were identified as BgAg-binding adhesins in C. jejuni NCTC11168. Significantly, the MOMP was shown to be O-glycosylated at Thr(268); previously only flagellin proteins were known to be O-glycosylated in C. jejuni. Substitution of MOMP Thr(268) led to significantly reduced binding to BgAgs. The O-glycan moiety was characterized as Gal(beta 1-3)-GalNAc(beta 1-4)-GalNAc(beta 1-4)-GalNAca1-Thr(268); modelling suggested that O-glycosylation has a notable effect on the conformation of MOMP and this modulates BgAg-binding capacity. Glycosylation of MOMP at Thr(268) promoted cell-to-cell binding, biofilm formation and adhesion to Caco-2 cells, and was required for the optimal colonization of chickens by C. jejuni, confirming the significance of this O-glycosylation in pathogenesis.
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- Appeltans, W., et al.
(författare)
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The Magnitude of Global Marine Species Diversity
- 2012
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 22:23, s. 2189-2202
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Tidskriftsartikel (refereegranskat)abstract
- Background: The question of how many marine species exist is important because it provides a metric for how much we do and do not know about life in the oceans. We have compiled the first register of the marine species of the world and used this baseline to estimate how many more species, partitioned among all major eukaryotic groups, may be discovered. Results: There are similar to 226,000 eukaryotic marine species described. More species were described in the past decade (similar to 20,000) than in any previous one. The number of authors describing new species has been increasing at a faster rate than the number of new species described in the past six decades. We report that there are similar to 170,000 synonyms, that 58,000-72,000 species are collected but not yet described, and that 482,000-741,000 more species have yet to be sampled. Molecular methods may add tens of thousands of cryptic species. Thus, there may be 0.7-1.0 million marine species. Past rates of description of new species indicate there may be 0.5 +/- 0.2 million marine species. On average 37% (median 31%) of species in over 100 recent field studies around the world might be new to science. Conclusions: Currently, between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely. More species than ever before are being described annually by an increasing number of authors. If the current trend continues, most species will be discovered this century.
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- Wray, Selina, et al.
(författare)
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Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community.
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