The Voltammetric Detection of Cadaverine Using a Diamine Oxidase and Multi-Walled Carbon Nanotube Functionalised Electrochemical Biosensor

Cadaverine is a biomolecule of major healthcare importance in periodontal disease; however, current detection methods remain inefficient. The development of an enzyme biosensor for the detection of cadaverine may provide a cheap, rapid, point-of-care alternative to traditional measurement techniques. This work developed a screen-printed biosensor (SPE) with a diamine oxidase (DAO) and multi-walled carbon nanotube (MWCNT) functionalised electrode which enabled the detection of cadaverine via cyclic voltammetry and differential pulse voltammetry. The MWCNTs were functionalised with DAO using carbodiimide crosslinking with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-Hydroxysuccinimide (NHS), followed by direct covalent conjugation of the enzyme to amide bonds. Cyclic voltammetry results demonstrated a pair of distinct redox peaks for cadaverine with the C-MWCNT/DAO/EDC-NHS/GA SPE and no redox peaks using unmodified SPEs. Differential pulse voltammetry (DPV) was used to isolate the cadaverine oxidation peak and a linear concentration dependence was identified in the range of 3–150 µg/mL. The limit of detection of cadaverine using the C-MWCNT/DAO/EDC-NHS/GA SPE was 0.8 μg/mL, and the biosensor was also found to be effective when tested in artificial saliva which was used as a proof-of-concept model to increase the Technology Readiness Level (TRL) of this device. Thus, the development of a MWCNT based enzymatic biosensor for the voltammetric detection of cadaverine which was also active in the presence of artificial saliva was presented in this study

Diamine Oxidase-Conjugated Multiwalled Carbon Nanotubes to Facilitate Electrode Surface Homogeneity

Carbon nanomaterials have gained significant interest over recent years in the field of electrochemistry, and they may be limited in their use due to issues with their difficulty in dispersion. Enzymes are prime components for detecting biological molecules and enabling electrochemical interactions, but they may also enhance multiwalled carbon nanotube (MWCNT) dispersion. This study evaluated a MWCNT and diamine oxidase enzyme (DAO)-functionalised screen-printed electrode (SPE) to demonstrate improved methods of MWCNT functionalisation and dispersion. MWCNT morphology and dispersion was determined using UV-Vis spectroscopy (UV-Vis) and scanning electron microscopy (SEM). Carboxyl groups were introduced onto the MWCNT surfaces using acid etching. MWCNT functionalisation was carried out using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-Hydroxysuccinimide (NHS), followed by DAO conjugation and glutaraldehyde (GA) crosslinking. Modified C-MWNCT/EDC-NHS/DAO/GA was drop cast onto SPEs. Modified and unmodified electrodes after MWCNT functionalisation were characterised using optical profilometry (roughness), water contact angle measurements (wettability), Raman spectroscopy and energy dispersive X-ray spectroscopy (EDX) (vibrational modes and elemental composition, respectively). The results demonstrated that the addition of the DAO improved MWCNT homogenous dispersion and the solution demonstrated enhanced stability which remained over two days. Drop casting of C-MWCNT/EDC-NHS/DAO/GA onto carbon screen-printed electrodes increased the surface roughness and wettability. UV-Vis, SEM, Raman and EDX analysis determined the presence of carboxylated MWCNT variants from their non-carboxylated counterparts. Electrochemical analysis demonstrated an efficient electron transfer rate process and a diffusion-controlled redox process. The modification of such electrodes may be utilised for the development of biosensors which could be utilised to support a range of healthcare related fields

A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies

peer reviewe

Runs of homozygosity implicate autozygosity as a schizophrenia risk factor

Autozygosity occurs when two chromosomal segments that are identical from a common ancestor are inherited from each parent. This occurs at high rates in the offspring of mates who are closely related (inbreeding), but also occurs at lower levels among the offspring of distantly related mates. Here, we use runs of homozygosity in genome-wide SNP data to estimate the proportion of the autosome that exists in autozygous tracts in 9,388 cases with schizophrenia and 12,456 controls. We estimate that the odds of schizophrenia increase by ~17% for every 1% increase in genome-wide autozygosity. This association is not due to one or a few regions, but results from many autozygous segments spread throughout the genome, and is consistent with a role for multiple recessive or partially recessive alleles in the etiology of schizophrenia. Such a bias towards recessivity suggests that alleles that increase the risk of schizophrenia have been selected against over evolutionary time

The Voltammetric Detection of Cadaverine Using a Diamine Oxidase and Multi-Walled Carbon Nanotube Functionalised Electrochemical Biosensor

Cadaverine is a biomolecule of major healthcare importance in periodontal disease; however, current detection methods remain inefficient. The development of an enzyme biosensor for the detection of cadaverine may provide a cheap, rapid, point-of-care alternative to traditional measurement techniques. This work developed a screen-printed biosensor (SPE) with a diamine oxidase (DAO) and multi-walled carbon nanotube (MWCNT) functionalised electrode which enabled the detection of cadaverine via cyclic voltammetry and differential pulse voltammetry. The MWCNTs were functionalised with DAO using carbodiimide crosslinking with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-Hydroxysuccinimide (NHS), followed by direct covalent conjugation of the enzyme to amide bonds. Cyclic voltammetry results demonstrated a pair of distinct redox peaks for cadaverine with the C-MWCNT/DAO/EDC-NHS/GA SPE and no redox peaks using unmodified SPEs. Differential pulse voltammetry (DPV) was used to isolate the cadaverine oxidation peak and a linear concentration dependence was identified in the range of 3–150 µg/mL. The limit of detection of cadaverine using the C-MWCNT/DAO/EDC-NHS/GA SPE was 0.8 μg/mL, and the biosensor was also found to be effective when tested in artificial saliva which was used as a proof-of-concept model to increase the Technology Readiness Level (TRL) of this device. Thus, the development of a MWCNT based enzymatic biosensor for the voltammetric detection of cadaverine which was also active in the presence of artificial saliva was presented in this study

High loading of polygenic risk for ADHD in children with comorbid aggression

Objective: Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. Method: Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. Results: Polygenic risk for ADD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by,the aggression items. Conclusions: Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity

Gene set of nuclear-encoded mitochondrial regulators is enriched for common inherited variation in obesity

There are hints of an altered mitochondrial function in obesity. Nuclear-encoded genes are relevant for mitochondrial function (3 gene sets of known relevant pathways: (1) 16 nuclear regulators of mitochondrial genes, (2) 91 genes for oxidative phosphorylation and (3) 966 nuclear-encoded mitochondrial genes). Gene set enrichment analysis (GSEA) showed no association with type 2 diabetes mellitus in these gene sets. Here we performed a GSEA for the same gene sets for obesity. Genome wide association study (GWAS) data from a case-control approach on 453 extremely obese children and adolescents and 435 lean adult controls were used for GSEA. For independent confirmation, we analyzed 705 obesity GWAS trios (extremely obese child and both biological parents) and a population-based GWAS sample (KORA F4, n = 1,743). A meta-analysis was performed on all three samples. In each sample, the distribution of significance levels between the respective gene set and those of all genes was compared using the leading-edge-fraction-comparison test (cut-offs between the 50(th) and 95(th) percentile of the set of all gene-wise corrected p-values) as implemented in the MAGENTA software. In the case-control sample, significant enrichment of associations with obesity was observed above the 50(th) percentile for the set of the 16 nuclear regulators of mitochondrial genes (p(GSEA,50) = 0.0103). This finding was not confirmed in the trios (p(GSEA,50) = 0.5991), but in KORA (p(GSEA,50) = 0.0398). The meta-analysis again indicated a trend for enrichment (p(MAGENTA,50) = 0.1052, p(MAGENTA,75) = 0.0251). The GSEA revealed that weak association signals for obesity might be enriched in the gene set of 16 nuclear regulators of mitochondrial genes

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies

A Note on False Positives and Power in G × E Modelling of Twin Data

The variance components models for gene–environment interaction proposed by Purcell in 2002 are widely used. In both the bivariate and the univariate parameterization of these models, the variance decomposition of trait T is a function of moderator M. We show that if M and T are correlated, and moderator M is correlated between twins as well, the univariate parameterization produces a considerable increase in false positive moderation effects. A simple extension of this univariate moderation model prevents this elevation of the false positive rate provided the covariance between M and T is itself not also subject to moderation. If the covariance between M and T varies as a function of M, then moderation effects observed in the univariate setting should be interpreted with care as these can have their origin in either moderation of the covariance between M and T or in moderation of the unique paths of T. We conclude that researchers should use the full bivariate moderation model to study the presence of moderation on the covariance between M and T. If such moderation can be ruled out, subsequent use of the extended univariate moderation model, as proposed in this paper, is recommended as this model is more powerful than the full bivariate moderation model