| 1. |
- van de Vegte, Yordi, et al.
(author)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 2. |
- Jiang, Rays H. Y., et al.
(author)
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Distinctive Expansion of Potential Virulence Genes in the Genome of the Oomycete Fish Pathogen Saprolegnia parasitica
- 2013
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:6, s. e1003272-
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Journal article (peer-reviewed)abstract
- Oomycetes in the class Saprolegniomycetidae of the Eukaryotic kingdom Stramenopila have evolved as severe pathogens of amphibians, crustaceans, fish and insects, resulting in major losses in aquaculture and damage to aquatic ecosystems. We have sequenced the 63 Mb genome of the fresh water fish pathogen, Saprolegnia parasitica. Approximately 1/3 of the assembled genome exhibits loss of heterozygosity, indicating an efficient mechanism for revealing new variation. Comparison of S. parasitica with plant pathogenic oomycetes suggests that during evolution the host cellular environment has driven distinct patterns of gene expansion and loss in the genomes of plant and animal pathogens. S. parasitica possesses one of the largest repertoires of proteases (270) among eukaryotes that are deployed in waves at different points during infection as determined from RNA-Seq data. In contrast, despite being capable of living saprotrophically, parasitism has led to loss of inorganic nitrogen and sulfur assimilation pathways, strikingly similar to losses in obligate plant pathogenic oomycetes and fungi. The large gene families that are hallmarks of plant pathogenic oomycetes such as Phytophthora appear to be lacking in S. parasitica, including those encoding RXLR effectors, Crinkler's, and Necrosis Inducing-Like Proteins (NLP). S. parasitica also has a very large kinome of 543 kinases, 10% of which is induced upon infection. Moreover, S. parasitica encodes several genes typical of animals or animal-pathogens and lacking from other oomycetes, including disintegrins and galactose-binding lectins, whose expression and evolutionary origins implicate horizontal gene transfer in the evolution of animal pathogenesis in S. parasitica.
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| 3. |
- Hannus, Aave, et al.
(author)
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Visual search near threshold : Some features are more equal than others.
- 2006
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In: Journal of Vision. - : Association for Research in Vision and Ophthalmology (ARVO). - 1534-7362. ; 6:4
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Journal article (peer-reviewed)abstract
- While searching for objects, we combine information from multiple visual modalities. Classical theories of visual search assume that features are processed independently prior to an integration stage. Based on this, one would predict that features that are equally discriminable in single feature search should remain so in conjunction search. We test this hypothesis by examining whether search accuracy in feature search predicts accuracy in conjunction search. Subjects searched for objects combining color and orientation or size; eye movements were recorded. Prior to the main experiment, we matched feature discriminability, making sure that in feature search, 70% of saccades were likely to go to the correct target stimulus. In contrast to this symmetric single feature discrimination performance, the conjunction search task showed an asymmetry in feature discrimination performance: In conjunction search, a similar percentage of saccades went to the correct color as in feature search but much less often to correct orientation or size. Therefore, accuracy in feature search is a good predictor of accuracy in conjunction search for color but not for size and orientation. We propose two explanations for the presence of such asymmetries in conjunction search: the use of conjunctively tuned channels and differential crowding effects for different features.
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| 4. |
- Vossen, Jack, H., et al.
(author)
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Identification of tomato phosphatidylinositol-specific phospholipase-C (PI-PLC) family members and the role of PLC4 and PLC6 in HR and disease resistance
- 2010
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In: The Plant Journal. - 0960-7412 .- 1365-313X. ; 62:2, s. 224-239
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Journal article (peer-reviewed)abstract
- The perception of pathogen-derived elicitors by plants has been suggested to involve phosphatidylinositol-specific phospholipase-C (PI-PLC) signalling. Here we show that PLC isoforms are required for the hypersensitive response (HR) and disease resistance. We characterised the tomato [Solanum lycopersicum (Sl)] PLC gene family. Six Sl PLC-encoding cDNAs were isolated and their expression in response to infection with the pathogenic fungus Cladosporium fulvum was studied. We found significant regulation at the transcriptional level of the various SlPLCs, and SlPLC4 and SlPLC6 showed distinct expression patterns in C. fulvum-resistant Cf-4 tomato. We produced the encoded proteins in Escherichia coli and found that both genes encode catalytically active PI-PLCs. To test the requirement of these Sl PLCs for full Cf-4-mediated recognition of the effector Avr4, we knocked down the expression of the encoding genes by virus-induced gene silencing. Silencing of SlPLC4 impaired the Avr4/Cf-4-induced HR and resulted in increased colonisation of Cf-4 plants by C. fulvum expressing Avr4. Furthermore, expression of the gene in Nicotiana benthamiana enhanced the Avr4/Cf-4-induced HR. Silencing of SlPLC6 did not affect HR, whereas it caused increased colonisation of Cf-4 plants by the fungus. Interestingly, Sl PLC6, but not Sl PLC4, was also required for resistance to Verticillium dahliae, mediated by the transmembrane Ve1 resistance protein, and to Pseudomonas syringae, mediated by the intracellular Pto/Prf resistance protein couple. We conclude that there is a differential requirement of PLC isoforms for the plant immune response and that Sl PLC4 is specifically required for Cf-4 function, while Sl PLC6 may be a more general component of resistance protein signalling.
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| 5. |
- Westrell, Therese, et al.
(author)
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Short- and long-term variations of norovirus concentrations in the Meuse river during a 2-year study period
- 2006
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In: Water Research. - : Elsevier BV. - 0043-1354. ; 40:14, s. 2613-2620
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Journal article (peer-reviewed)abstract
- Faecally impacted surface waters used for drinking water production may encompass risk for norovirus infections. To be able to assess a possible health risk, noroviruses should be quantified and fluctuations identified. In 2001, norovirus concentrations in the river Meuse displayed a seasonal distribution with high peaks during wintertime as determined by RT-PCR on serially diluted RNA. An intensified day-by-day sampling scheme in the winter of 2002/2003 revealed that the winter peak consisted of several peaks of varying duration and magnitude, possibly due to contamination events in the catchment. The highest estimated concentration was 1700 PCR-detectable units per litre (95% CI 250–8000), which if coinciding with failing treatment could lead to significant numbers in drinking water. Adaptive dynamic filtering was shown to adequately predict subsequent sample concentrations. If valid, such analyses could prove to be useful as early warning systems in risk management of water sources.
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