| 1. |
- Caraballo, Rémi, et al.
(författare)
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Triazole linker-based trivalent sialic acid inhibitors of adenovirus type 37 infection of human corneal epithelial cells
- 2015
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Ingår i: Organic and biomolecular chemistry. - 1477-0520 .- 1477-0539. ; 13:35, s. 9194-9205
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Tidskriftsartikel (refereegranskat)abstract
- Adenovirus type 37 (Ad37) is one of the principal agents responsible for epidemic keratoconjunctivitis (EKC), a severe ocular infection that remains without any available treatment. Recently, a trivalent sialic acid derivative (ME0322, Angew. Chem. Int. Ed., 2011, 50, 6519) was shown to function as a highly potent inhibitor of Ad37, efficiently preventing the attachment of the virion to the host cells and subsequent infection. Here, new trivalent sialic acid derivatives were designed, synthesized and their inhibitory properties against Ad37 infection of the human corneal epithelial cells were investigated. In comparison to ME0322, the best compound (17a) was found to be over three orders of magnitude more potent in a cell-attachment assay (IC50 = 1.4 nM) and about 140 times more potent in a cell-infection assay (IC50 = 2.9nM). X-ray crystallographic analysis demonstrated a trivalent binding mode of all compounds to the Ad37 fiber knob. For the most potent compound ophthalmic toxicity in rabbits was investigated and it was concluded that repeated eye administration did not cause any adverse effects.
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| 2. |
- Chandra, Naresh, 1987-, et al.
(författare)
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Sialic Acid-Containing Glycans as Cellular Receptors for Ocular Human Adenoviruses : Implications for Tropism and Treatment
- 2019
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Human adenoviruses (HAdV) are the most common cause of ocular infections. Species B human adenovirus type 3 (HAdV-B3) causes pharyngoconjunctival fever (PCF), whereas HAdV-D8, -D37, and -D64 cause epidemic keratoconjunctivitis (EKC). Recently, HAdV-D53, -D54, and -D56 emerged as new EKC-causing agents. HAdV-E4 is associated with both PCF and EKC. We have previously demonstrated that HAdV-D37 uses sialic acid (SA)-containing glycans as cellular receptors on human corneal epithelial (HCE) cells, and the virus interaction with SA is mediated by the knob domain of the viral fiber protein. Here, by means of cell-based assays and using neuraminidase (a SA-cleaving enzyme), we investigated whether ocular HAdVs other than HAdV-D37 also use SA-containing glycans as receptors on HCE cells. We found that HAdV-E4 and -D56 infect HCE cells independent of SAs, whereas HAdV-D53 and -D64 use SAs as cellular receptors. HAdV-D8 and -D54 fiber knobs also bound to cell-surface SAs. Surprisingly, HCE cells were found resistant to HAdV-B3 infection. We also demonstrated that the SA-based molecule i.e., ME0462, designed to bind to SA-binding sites on the HAdV-D37 fiber knob, efficiently prevents binding and infection of several EKC-causing HAdVs. Surface plasmon resonance analysis confirmed a direct interaction between ME0462 and fiber knobs. Altogether, we demonstrate that SA-containing glycans serve as receptors for multiple EKC-causing HAdVs, and, that SA-based compound function as a broad-spectrum antiviral against known and emerging EKC-causing HAdVs.
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| 3. |
- Elofsson, Katarina, et al.
(författare)
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The impact of climate information on milk demand : Evidence from a field experiment
- 2016
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Ingår i: Food Policy. - : Elsevier BV. - 0306-9192 .- 1873-5657. ; 58, s. 14-23
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that carbon labelling of food, on voluntary or non-voluntary basis, could reduce emissions of greenhouse gases. However, there is limited empirical evidence on the influence of such labels on consumer purchases. The purpose of this study was to investigate whether voluntary carbon labelling affects the demand for milk. A randomized field experiment was conducted in 17 retail stores in Sweden, where a sign provided consumers with qualitative information about the carbon impact of climate-certified milk. The results suggest that the sign increased the demand for the climate-certified milk by approximately 6-8%, and the result is robust to alternative model specifications. The effect is entirely driven by large stores, such as supermarkets. We find no statistically significant impact on total milk sales, and the dataset is too small to verify the consequences for other milk brands. The effect on the demand for the labelled milk is short-lived.
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| 4. |
- Journath, Gunilla, et al.
(författare)
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Time Trends in Incidence and Mortality of Acute Myocardial Infarction, and All-Cause Mortality following a Cardiovascular Prevention Program in Sweden
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- Background In 1988, a cardiovascular prevention program which combined an individual and a population-based strategy was launched within primary health-care in Sollentuna, a municipality in Stockholm County. The aim of this study was to investigate time trends in the incidence of and mortality from acute myocardial infarction and all-cause mortality in Sollentuna compared with the rest of Stockholm County during a period of two decades following the implementation of a cardiovascular prevention program. Materials and Methods The average population in Sollentuna was 56,589 (49% men) and in Stockholm County (Sollentuna included) 1,795,504 (49% men) during the study period of 1987-2010. Cases of hospitalized acute myocardial infarction and death were obtained for the population of Sollentuna and the rest of Stockholm County using national registries of hospital discharges and deaths. Acute myocardial infarction incidence and mortality were estimated using the average population of Sollentuna and Stockholm in 1987-2010. Results During the observation period, the incidence of acute myocardial infarction decreased more in Sollentuna compared with the rest of Stockholm County in women (-22% vs. -7%; for difference in slope <0.05). There was a trend towards a greater decline in Sollentuna compared to the rest of Stockholm County in the incidence of acute myocardial infarction (in men), acute myocardial mortality, and all-cause mortality but the differences were not significant. Conclusion During a period of steep decline in acute myocardial infarction incidence and mortality in Stockholm County the municipality of Sollentuna showed a stronger trend in women possibly compatible with favorable influence of a cardiovascular prevention program.
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