X-Chromosomal Maternal and Fetal SNPs and the Risk of Spontaneous Preterm Delivery in a Danish/Norwegian Genome-Wide Association Study

Background

Recent epidemiological studies suggest that the maternal genome is an important contributor to spontaneous preterm delivery (PTD). There is also a significant excess of males among preterm born infants, which may imply an X-linked mode of inheritance for a subset of cases. To explore this, we examined the effect of maternal and fetal X-chromosomal single nucleotide polymorphisms (SNPs) on the risk of PTD in two independent genome-wide association studies and one replication study.

Methods

Participants were recruited from the Danish National Birth Cohort and the Norwegian Mother and Child cohort studies. Data from these two populations were first analyzed independently, and then combined in a meta-analysis. Overall, we evaluated 12,211 SNPs in 1,535 case-mother dyads and 1,487 control-mother dyads. Analyses were done using a hybrid design that combines case-mother dyads and control-mother dyads, as implemented in the Haplin statistical software package. A sex-stratified analysis was performed for the fetal SNPs. In the replication study, 10 maternal and 16 fetal SNPs were analyzed using case-parent triads from independent studies of PTD in the United States, Argentina and Denmark.

Results

In the meta-analysis, the G allele at the maternal SNP rs2747022 in the FERM domain containing 7 gene (FRMD7) increased the risk of spontaneous PTD by 1.2 (95% confidence interval (CI): 1.1, 1.4). Although an association with this SNP was confirmed in the replication study, it was no longer statistically significant after a Bonferroni correction for multiple testing.

Conclusion

We did not find strong evidence in our data to implicate X-chromosomal SNPs in the etiology of spontaneous PTD. Although non-significant after correction for multiple testing, the mother’s G allele at rs2747022 in FRMD7 increased the risk of spontaneous PTD across all populations in this study, thus warranting further investigation in other populations.     

Soluble CD36- a marker of the (pathophysiological) role of CD36 in the metabolic syndrome?

CD36 is a class B scavenger receptor observed in many cell types and tissues throughout the body. Recent literature has implicated CD36 in the pathogenesis of metabolic dysregulation such as found in obesity, insulin resistance, and atherosclerosis. Genetic variation at the CD36 loci have been associated with obesity and lipid components of the metabolic syndrome, with risk of heart disease and type 2 diabetes. Recently, non-cell bound CD36 was identified in human plasma and was termed soluble CD36 (sCD36). In this review we will describe the functions of CD36 in tissues and address the role of sCD36 in the context of the metabolic syndrome. We will also highlight recent findings from human genetic studies looking at the CD36 locus in relation to metabolic profile in the general population. Finally, we present a model in which insulin resistance, oxLDL, low-grade inflammation and liver steatosis may contribute to elevated levels of sCD36.     

Modification of nanocellulose with a xyloglucan-RGD conjugate enhances adhesion and proliferation of endothelial cells: implications for tissue engineering

This paper describes a novel method for introducing the RGD cell adhesion peptide to enhance cell adhesion onto bacterial cellulose (BC). BC and cotton linters as reference were modified with xyloglucan (XG) and xyloglugan bearing a GRGDS pentapeptide. The adsorptions followed Langmuir adsorption behavior, where both XGs probably decorate the cellulose surfaces as a monolayer. The adsorption maximum of the XGs reached around 180 mg/g on BC and only about three times as much on cotton linters. The adsorption was verified with colorimetric methods. The specific surface area of BC measured with XG and XG-GRGDS was about 200 m (2)/g and was almost three times less for cotton linters, 60 m (2)/g. The difference in the amounts of XGs adsorbed might be explained by the swollen network of bacterial cellulose and a more exposed and accessible bulk as compared to cotton linters. The nanocellulose material was modified homogeneously throughout the material, as seen by the z-scan in confocal microscopy. Moreover, the modification in the water phase, in comparison with organic solvents, was clearly advantageous for preserving the morphology, as observed with SEM. The modification slightly increased the wettability, which might explain the decrease in or undetectable adsorption of adhesive protein shown by QCM-D. Initial cell studies showed that adhesion of human endothelial cells is enhanced when the BC hydrogel is modified with XG-GRGDS. QCM-D studies further revealed that the cell enhancement is due to the presence of the RGD epitope on XG and not to a nonspecific adsorption of fibronectin from cell culture medium. Optimization and proliferation studies of human endothelial cells onto bacterial cellulose modified with XG-GRGDS are currently being carried out at the Vascular Engineering Center, Sahlgrenska University Hospital, Gothenburg.     

Activity pattern of arctic reindeer in a predator-free environment: no need to keep a daily rhythm

Arctic Cervids face considerable challenges in sustaining life in a harsh and highly seasonal environment, and when to forage is a key component of the survival strategy. We predict that a cervid maximizes net intake of energy to change the duration of feeding-ruminating cycles depending on season, and pays no attention to light or other activity-entraining cues. Still, in periods of bad weather it may pay energetically to reduce exposure and heat loss. We investigated environmental impact on the seasonal and daily activity pattern of a food-limited, predator-free arctic deer, the Svalbard reindeer. We found that the reindeer indeed had season-dependent feeding-rumination intervals, with no distinct peaks in activity at sunrise and sunset, as would be expected if animals maximize energy intake rates in predator-free environments. However, they temporarily reduced activity when exposed to low temperature and increased precipitation during winter, possibly to conserve energy. We provide insight into the behavioural strategy of Svalbard reindeer which enables them to cope with such an extreme environment.     

Elevated Atherosclerosis-Related Gene Expression,Monocyte Activation and Microparticle-Release Are Related to Increased Lipoprotein-Associated Oxidative Stress in Familial Hypercholesterolemia

Objective

Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate the hypothesis that elevated oxLDL-C induce proinflammatory monocytes and increased release of monocyte-derived microparticles (MMPs), as well as up-regulation of CD36, chemokine receptors and proinflammatory factors through CD36-dependent pathways and that this is associated with accelerated atherosclerosis in subjects with heterozygous familial hypercholesterolemia (FH), in particular in the presence of Achilles tendon xanthomas (ATX).

Approach and Results

We studied thirty FH subjects with and without ATX and twenty-three healthy control subjects. Intima-media thickness (IMT) and Achilles tendon (AT) thickness were measured by ultrasonography. Monocyte classification and MMP analysis were performed by flow cytometry. Monocyte expression of genes involved in atherosclerosis was determined by quantitative PCR. IMT and oxLDL-C were increased in FH subjects, especially in the presence of ATX. In addition, FH subjects had elevated proportions of intermediate CD14++CD16+ monocytes and higher circulating MMP levels. Stepwise linear regression identified oxLDL-C, gender and intermediate monocytes as predictors of MMPs. Monocyte expression of pro-atherogenic and pro-inflammatory genes regulated by oxLDL-C-CD36 interaction was increased in FH, especially in ATX+ subjects. Monocyte chemokine receptor CX₃CR1 was identified as an independent contributor to IMT.

Conclusions

Our data support that lipoprotein-associated oxidative stress is involved in accelerated atherosclerosis in FH, particularly in the presence of ATX, by inducing pro-inflammatory monocytes and increased release of MMPs along with elevated monocyte expression of oxLDL-C-induced atherosclerosis-related genes.     

Genome-Wide Analysis of Attention Deficit Hyperactivity Disorder in Norway

Background

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric condition, but it has been difficult to identify genes underlying this disorder. This study aimed to explore genetics of ADHD in an ethnically homogeneous Norwegian population by means of a genome-wide association (GWA) analysis followed by examination of candidate loci.

Materials and Methods

Participants were recruited through Norwegian medical and birth registries as well as the general population. Presence of ADHD was defined according to DSM-IV criteria. Genotyping was performed using Illumina Human OmniExpress-12v1 microarrays. Statistical analyses were divided into several steps: (1) genome-wide association in the form of logistic regression in PLINK and follow-up pathway analyses performed in DAPPLE and INRICH softwares, (2) SNP-heritability calculated using genome-wide complex trait analysis (GCTA) tool, (3) gene-based association tests carried out in JAG software, and (4) evaluation of previously reported genome-wide signals and candidate genes of ADHD.

Results

In total, 1.358 individuals (478 cases and 880 controls) and 598.384 autosomal SNPs were subjected to GWA analysis. No single polymorphism reached genome-wide significance. The strongest signal was observed at rs9949006 in the ENSG00000263745 gene (OR=1.51, 95% CI 1.28–1.79, p=1.38E-06). Pathway analyses of the top SNPs implicated genes involved in the regulation of gene expression, cell adhesion and inflammation. Among previously identified ADHD candidate genes, prominent association signals were observed for SLC9A9 (rs1393072, OR=1.46, 95% CI = 1.21–1.77, p=9.95E-05) and TPH2 (rs17110690, OR = 1.38, 95% CI = 1.14–1.66, p=8.31E-04).

Conclusion

This study confirms the complexity and heterogeneity of ADHD etiology. Taken together with previous findings, our results point to a spectrum of biological mechanisms underlying the symptoms of ADHD, providing targets for further genetic exploration of this complex disorder.     

Fine structure of Pyramimonas octopus sp. nov., an octoflagellated benthic species of Pyramimonas (Prasinophyceae), with some observations on its ecology

A new octoflagellated species of Pyramimonas is described from three localities in Denmark. It is characterized by its ecology, being a marine psammophilic species associated with sand grains, and by details of the scaly covering on the cell surface. In the scale cover there are similarities to P. amylifera and to P. tetrarhynchus. P. octopus is distinguished by the possession of circular body scales of a type not previously found in the genus.
The general fine structure of the new species is described with emphasis on scale structure, the internal structure of the cell body and the flagella.     

Dantrolene Prevents Glutamate Cytotoxicity and Ca2+ Release from Intracellular Stores in Cultured Cerebral Cortical Neurons

Using primary cultures of cerebral cortical neurons, it has been demonstrated that the antihyperthermia drug dantrolene completely protects against glutamate-induced neurotoxicity. Furthermore, in the presence of extracellular calcium, dantrolene reduced the glutamate-induced increase in the intracellular calcium concentration by 70%. In the absence of extracellular calcium, this glutamate response was completely blocked by dantrolene. Dantrolene did not affect the kinetics of [3H]glutamate binding to membranes prepared from similar cultures. These results indicate that release of calcium from intracellular stores is essential for the propagation of glutamate-induced neuronal damage. Because it is likely that glutamate is involved in neuronal degeneration associated with ischemia and hypoxia, the present findings might suggest that dantrolene and possibly other drugs affecting intracellular calcium pools might be of therapeutic interest.     

Exploiting volatile organic compounds in crop protection: A systematic review of 1-octen-3-ol and 3-octanone

The 21st century has brought new challenges to the agri-food industry due to population growth, global warming, and greater public awareness of environmental issues. Ensuring global food security for future generations is crucial. However, pests, weeds, and diseases still significantly contribute to crop losses, and the availability of effective conventional synthetic pesticides is decreasing. To address this, new and diverse pest management tools are needed. One pest management tool showing potential for invertebrate pest management is the exploitation of volatile organic compounds (VOCs)—in particular, the compounds 1-octen-3-ol and 3-octanone. This review aims to explore the extent to which 1-octen-3-ol and 3-octanone show potential in the future management of invertebrate crop and animal pests. A significant increase in the rate of publication of literature on the use of 1-octen-3-ol and 3-octanone in crop protection since 2018 is identified by this review, therefore, showing the potential importance of these compounds for use in future pest management. This review also identifies key interactions between naturally occurring biosynthesised 1-octen-3-ol and 3-octanone, and a range of invertebrate targets. Many of these interactions with key crop pests are sourced from the taxonomic families Lamiaceae, Fabaceae, and Trichomaceae. However, analysis of the practical application of these sources in an integrated pest management programme identifies clear limitations with the use of naturally occurring biosynthesised 1-octen-3-ol and 3-octanone. Rather, future focus should be placed on the development and exploitation of synthesised nature identical 1-octen-3-ol and 3-octanone for use as a biopesticide product. Overall, 1-octen-3-ol and 3-octanone show potential for exploitation in future crop protection, being abundant in source and diversity of invertebrate interactions. However, their use as a naturally occurring biosynthesised chemical is likely not practical for direct implementation in crop protection. Rather, focus should be placed on the development and exploitation of synthesised nature identical variants of these compounds for use as a biopesticide.