Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children from Wild-type to Population Immunity: A Prospective Multicenter Cohort Study with Real-time Reporting

Background: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data. Methods: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity. Results: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies. Conclusions: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Wood modification developments

The last decades developments in the arena of wood modification have accelerated considerably. This acceleration is due to a number of circumstances of which the environmental awareness, the increasing demand for high and constant quality and the increasing prices and availability of tropical hardwood species. This has led to the up-scaling and the market introduction of a number of wood modification techniques. Modification can be done without added chemicals by heat treatment only, or with the aid of added chemicals. Examples of both principles are given. Several products of thermally modified wood are already available on the market. More recently the first chemical modification processes have reached (or are about to reach) market introduction. Chemical modification makes wood with superior qualities of tailor-made products possible. The variability in degree of modification within wood is discussed with acetylated wood as an example. Different treatabilities in different wood species also reflect in acetic anhydride impregnation. However, in contrast to waterborne systems this does not result in sharp fronts but in more gradual profiles. The gas diffusion of the chemical into the wood plays an important role in this phenomenon. In the further process developments these effects need to be taken into account

Spring distribution of ring-necked pheasants (\u3ci\u3ePhasianus colchicus\u3c/i\u3e) following cattail reduction with glyphosate herbicide

To reduce blackbird (Icteridae) damage to field crops in the north-central United States. dense stands of cattail (Typha spp. ) are thinned with glyphosate herbicide. The stands become unusable as roosting and loafing sites, which helps to protect susceptible crops nearby, particularly sunflower (Helianthus annus). Landscape-level impacts of cattail management on non-target avian species have not been studied. We measured use of upland breeding territories by male ring-necked pheasants (Phasianus colchieus) following cattail reduction in wetlands used by pheasants for overwintering. In August 1992, glyphosate was applied to all wetlands with ≥70% cattail coverage in four 23-km2 study blocks in south-eastern North Dakota. Four other blocks were used for controls. Habitat use was inferred from territorial growing counts. No treatment effect or treatment*year interaction (all P≥ 0.05) was evident during 2 years of post-treatment observations. Although the herbicide eradicated large contiguous stands of cattail that pheasants had used for winter cover, surface water levels rose in 1993, which created additional cattail growth in untreated wetlands within the blocks. The additional cattail may have lessened the effect of the herbicide treatments. During drier periods, when cattail growth slows, cattail reduction could affect use of upland breeding sites. We recommend more research to assess the effects of glyphosate during drier periods

Baiting blackbirds (Icteridae) in stubble grain fields during spring migration in South Dakota

Blackbirds (Icteridae) annually damage US$5–8 million of ripening sunflower in the northern Great Plains. Baiting blackbirds with avicide-treated rice during spring migration might reduce the regional breeding population. In March and April 1996–1997, we simulated a baiting program in eastern South Dakota to compare attractiveness of rice-baited plots placed in fields of corn and soybean stubble. Blackbirds used plots in corn stubble more often than plots in soybean stubble and chose rice-baited plots over unbaited reference plots. We conclude that blackbirds can be successfully baited with avicide-treated rice placed in corn stubble. Copyright 2002 Elsevier Science Ltd. All rights reserved