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OBJECTIVE To identify maternal second and third trimester urine metabolomic biomarkers for the detection of fetal congenital heart defects (CHDs). STUDY DESIGN This was a prospective study. Metabolomic analysis of randomly collected... more
OBJECTIVE To identify maternal second and third trimester urine metabolomic biomarkers for the detection of fetal congenital heart defects (CHDs). STUDY DESIGN This was a prospective study. Metabolomic analysis of randomly collected maternal urine was performed, comparing pregnancies with isolated, non-syndromic CHDs versus unaffected controls. Mass spectrometry (liquid chromatography and direct injection and tandem mass spectrometry, LC-MS-MS) as well as nuclear magnetic resonance spectrometry, 1H NMR, were used to perform the analyses between 14 0/7 and 37 0/7 weeks gestation. A total of 36 CHD cases and 41 controls were compared. Predictive algorithms using urine markers alone or combined with, clinical and ultrasound (US) (four-chamber view) predictors were developed and compared. RESULTS A total of 222 metabolites were identified, of which 16 were overlapping between the two platforms. Twenty-three metabolite concentrations were found in significantly altered in CHD gestations on univariate analysis. The concentration of methionine was most significantly altered. A predictive algorithm combining metabolites (histamine, choline, glucose, formate, methionine, and carnitine) plus US four-chamber view achieved an AUC = 0.894; 95% CI, 0814-0.973 with a sensitivity of 83.8% and specificity of 87.8%. Enrichment pathway analysis identified several lipid related pathways that are dysregulated in CHD, including phospholipid biosynthesis, phosphatidylcholine biosynthesis, phosphatidylethanolamine biosynthesis, and fatty acid metabolism. This could be consistent with the increased risk of CHD in diabetic pregnancies. CONCLUSIONS We report a novel, noninvasive approach, based on the analysis of maternal urine for isolated CHD detection. Further, the dysregulation of lipid- and folate metabolism appears to support prior data on the mechanism of CHD.
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<p>Groups were compared in pairs with Controls (red circles), MCI (black squares) and MCI_AD (blue triangles) indicated on OPLS-DA scores plots (<a... more
<p>Groups were compared in pairs with Controls (red circles), MCI (black squares) and MCI_AD (blue triangles) indicated on OPLS-DA scores plots (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119452#pone.0119452.g002" target="_blank">Fig. 2A, 2C and 2E</a>). (a) Ctrl vs. MCI; R2 = 97.6%; Q2 = 95.3%; (c) Ctrl vs. MCI_AD; R2 = 98.4%; Q2 = 95.7%. (f) MCI vs. MCI_AD; R2 = 98.7%; Q2 = 95.8%. Corresponding s-plots (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119452#pone.0119452.g002" target="_blank">Fig. 2B, 2D and F</a>) highlight which ions are up or down regulated in their respective group as represented by the colour and shape of the variables.</p
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Research Interests:
MotivationIdentifying pathological metabolic changes in complex disease such as Dementia with Lewy Bodies (DLB) requires a deep understanding of functional modifications in the context of metabolic networks. Network determination and... more
MotivationIdentifying pathological metabolic changes in complex disease such as Dementia with Lewy Bodies (DLB) requires a deep understanding of functional modifications in the context of metabolic networks. Network determination and analysis from metabolomics and lipidomics data remains a major challenge due to sparse experimental coverage, a variety of different functional relationships between metabolites and lipids, and only sporadically described reaction networks.ResultsDistance correlation, measuring linear and non-linear dependences between variables as well as correlation between vectors of different lengths, e.g. different sample sizes, is presented as an approach for data-driven metabolic network development. Additionally, novel approaches for the analysis of changes in pair-wise correlation as well as overall correlations for metabolites in different conditions are introduced and demonstrated on DLB data. Distance correlation and signed distance correlation was utilized ...
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Cerebral palsy (CP) is one of the most common causes of motor disability in childhood, with complex and heterogeneous etiopathophysiology and clinical presentation. Understanding the metabolic processes associated with the disease may aid... more
Cerebral palsy (CP) is one of the most common causes of motor disability in childhood, with complex and heterogeneous etiopathophysiology and clinical presentation. Understanding the metabolic processes associated with the disease may aid in the discovery of preventive measures and therapy. Tissue samples (caudate nucleus) were obtained from post-mortem CP cases (n = 9) and age- and gender-matched control subjects (n = 11). We employed a targeted metabolomics approach using both 1H NMR and direct injection liquid chromatography-tandem mass spectrometry (DI/LC-MS/MS). We accurately identified and quantified 55 metabolites using 1H NMR and 186 using DI/LC-MS/MS. Among the 222 detected metabolites, 27 showed significant concentration changes between CP cases and controls. Glycerophospholipids and urea were the most commonly selected metabolites used to develop predictive models capable of discriminating between CP and controls. Metabolomics enrichment analysis identified folate, propan...
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Epilepsy not-otherwise-specified (ENOS) is one of the most common causes of chronic disorders impacting human health, with complex multifactorial etiology and clinical presentation. Understanding the metabolic processes associated with... more
Epilepsy not-otherwise-specified (ENOS) is one of the most common causes of chronic disorders impacting human health, with complex multifactorial etiology and clinical presentation. Understanding the metabolic processes associated with the disorder may aid in the discovery of preventive and therapeutic measures. Post-mortem brain samples were harvested from the frontal cortex (BA8/46) of people diagnosed with ENOS cases (n = 15) and age- and sex-matched control subjects (n = 15). We employed a targeted metabolomics approach using a combination of proton nuclear magnetic resonance (1H-NMR) and direct injection/liquid chromatography tandem mass spectrometry (DI/LC-MS/MS). We accurately identified and quantified 72 metabolites using 1H-NMR and 159 using DI/LC-MS/MS. Among the 212 detected metabolites, 14 showed significant concentration changes between ENOS cases and controls (p < 0.05; q < 0.05). Of these, adenosine monophosphate and O-acetylcholine were the most commonly select...
Research Interests: Medicine and metabolites
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The Mediterranean diet (MD) is a dietary pattern well-known for its benefits in disease prevention. Monitoring adherence to the MD could be improved by discovery of novel dietary biomarkers. The MEDiterranean Diet in Northern Ireland... more
The Mediterranean diet (MD) is a dietary pattern well-known for its benefits in disease prevention. Monitoring adherence to the MD could be improved by discovery of novel dietary biomarkers. The MEDiterranean Diet in Northern Ireland (MEDDINI) intervention study monitored the adherence of participants to the MD for up to 12 months. This investigation aimed to profile plasma metabolites, correlating each against the MD score of participants (n = 58). Based on an established 14-point scale MD score, subjects were classified into two groups (“low” and “high”). 1H-Nuclear Magnetic Resonance (1H-NMR) metabolomic analysis found that citric acid was the most significant metabolite (p = 5.99 × 10−4*; q = 0.03), differing between ‘low’ and ‘high’. Furthermore, five additional metabolites significantly differed (p < 0.05; q < 0.35) between the two groups. Discriminatory metabolites included: citric acid, pyruvic acid, betaine, mannose, acetic acid and myo-inositol. Additionally, the top...
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Brain is a lipid-rich tissue, and fatty acids (FAs) play a crucial role in brain function, including neuronal cell growth and development. This study used GC-MS to survey all detectable FAs in the human parietal cortex (Brodmann area 7).... more
Brain is a lipid-rich tissue, and fatty acids (FAs) play a crucial role in brain function, including neuronal cell growth and development. This study used GC-MS to survey all detectable FAs in the human parietal cortex (Brodmann area 7). These FAs were accurately quantified in 27 cognitively normal age-matched controls, 16 cases of moderate Alzheimer’s disease (AD), 30 severe AD, and 14 dementia with Lewy bodies (DLB). A total of 24 FA species were identified. Multiple comparison procedures, using stepdown permutation tests, noted higher levels of 13 FAs but the majority of changes were in moderate AD and DLB, rather than severe AD. Subjects with moderate AD and DLB pathology exhibited significantly higher levels of a number of FAs (13 FAs and 12 FAs, respectively). These included nervonic, lignoceric, cis-13,16-docosadienoic, arachidonic, cis-11,14,17-eicosatrienoic, erucic, behenic, α-linolenic, stearic, oleic, cis-10-heptanoic, and palmitic acids. The similarities between moderat...
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Research Interests:
ACL rupture is a major risk factor for post-traumatic osteoarthritis (PTOA) development. Little information exists on acute systemic metabolic indicators of disease development. 36 female Lewis rats were randomized to Control or... more
ACL rupture is a major risk factor for post-traumatic osteoarthritis (PTOA) development. Little information exists on acute systemic metabolic indicators of disease development. 36 female Lewis rats were randomized to Control or noninvasive anterior cruciate ligament rupture (ACLR) and to three post-injury time points: 72 hours, 4 weeks, 10 weeks (n = 6). Serum was collected and analyzed by 1 H nuclear magnetic resonance (NMR) spectroscopy and combined direct injection and liquid chromatography (LC)-mass spectrometry (MS)/MS (DI-MS). Univariate and multivariate statistics were used to analyze metabolomic data, and predictive biomarker models were analyzed by receiver operating characteristic (ROC) analysis. Topological pathway analysis was used to identify perturbed pathways. 222 metabolites were identified by 1 H NMR and DI-MS. Differences in the serum metabolome between ACLR and Control were dominated by medium- and long-chain acylcarnitine species. Further, decreases in several t...
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Certain endogenous bile acids have been proposed as potential therapies for ameliorating Alzheimer's disease (AD) but their role, if any, in the pathophysiology of this disease is not currently known. Given recent evidence of bile... more
Certain endogenous bile acids have been proposed as potential therapies for ameliorating Alzheimer's disease (AD) but their role, if any, in the pathophysiology of this disease is not currently known. Given recent evidence of bile acids having protective and anti-inflammatory effects on the brain, it is important to establish how AD affects levels of endogenous bile acids. Using LC-MS/MS, this study profiled 22 bile acids in brain extracts and blood plasma from AD patients (n = 10) and age-matched control subjects (n = 10). In addition, we also profiled brain/plasma samples from APP/PS1 and WT mice (aged 6 and 12 months). In human plasma, we detected significantly lower cholic acid (CA, p = 0.03) in AD patients than age-matched control subjects. In APP/PS1 mouse plasma we detected higher CA (p = 0.05, 6 months) and lower hyodeoxycholic acid (p = 0.04, 12 months) than WT. In human brain with AD pathology (Braak stages V-VI) taurocholic acid (TCA) were significantly lower (p = 0.0...
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Currently little is known about the underlying pathophysiology associated with SIDS and no objective biomarkers exist for the accurate identification of those at greatest risk of dying from SIDS. Using targeted metabolomics, we aim to... more
Currently little is known about the underlying pathophysiology associated with SIDS and no objective biomarkers exist for the accurate identification of those at greatest risk of dying from SIDS. Using targeted metabolomics, we aim to profile the medulla oblongata of infants who have died from SIDS (n=16) and directly compare their biochemical profile with age matched controls. Combining data acquired using 1H NMR and targeted DI-LC-MS/MS we have identified fatty acid oxidation as a pivotal biochemical pathway perturbed in the brains of those infants who have from SIDS (p = 0.0016). Further we have identified a potential central biomarker with an AUC (95% CI) = 0.933 (0.845-1.000) having high sensitivity (0.933) and specificity (0.875) values for discriminating between control and SIDS brains. This is the first reported study to use targeted metabolomics for the study of PM brain from infants who have died from SIDS. We have identified pathways associated with the disease and centra...
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Sudden Infant Death Syndrome (SIDS) is defined as the sudden death of an infant <1 year of age that cannot be explained following a thorough investigation. Currently, no reliable clinical biomarkers are available for the prediction of... more
Sudden Infant Death Syndrome (SIDS) is defined as the sudden death of an infant <1 year of age that cannot be explained following a thorough investigation. Currently, no reliable clinical biomarkers are available for the prediction of infants who will die of SIDS. This study aimed to profile the medulla oblongata from postmortem human brain from SIDS victims (n=16) and compare their profiles with that of age-matched controls (n=7). Using LC-Orbitrap-MS, we detected 12 710 features in electrospray ionization positive (ESI+) mode and 8243 in ESI- mode from polar extracts of brain. Five features acquired in ESI+ mode produced a predictive model for SIDS with an area under the receiver operating characteristic curve (AUC) of 1 (confidence interval (CI): 0.995-1) and a predictive power of 97.4%. Three biomarkers acquired in ESI- mode produced a predictive model with an AUC of 0.866 (CI: 0.767-0.942) and a predictive power of 77.6%. We confidently identified 5 of these features (l-(+)-...
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Controversy surrounds the proposed hypothesis that exposure to β-methylamino-L-alanine (BMAA) could play a role in various neurodegenerative conditions including Alzheimer's disease (AD). Here we present the results of the most... more
Controversy surrounds the proposed hypothesis that exposure to β-methylamino-L-alanine (BMAA) could play a role in various neurodegenerative conditions including Alzheimer's disease (AD). Here we present the results of the most comprehensive scientific study on BMAA detection ever undertaken on brain samples from patients pathologically confirmed to have suffered from AD, and those from healthy volunteers. Following the full validation of a highly accurate and sensitive mass spectrometric method, no trace of BMAA was detected in the diseased brain or in the control specimens. This contradicts the findings of other reports and calls into question the significance of this compound in neurodegenerative disease. We have attempted to explain the potential causes of misidentification of BMAA in these studies.
Research Interests: Mass Spectrometry, Medicine, Brain, Humans, Female, and 4 moreDisease, Male, Aged, and Alzheimer Disease
Our primary objective was to apply metabolomic pathway analysis of first trimester maternal serum to provide an insight into the pathogenesis of late-onset preeclampsia (late-PE) and thereby identify plausible therapeutic targets for PE.... more
Our primary objective was to apply metabolomic pathway analysis of first trimester maternal serum to provide an insight into the pathogenesis of late-onset preeclampsia (late-PE) and thereby identify plausible therapeutic targets for PE. NMR-based metabolomics analysis was performed on 29 cases of late-PE and 55 unaffected controls. In order to achieve sufficient statistical power to perform the pathway analysis, these cases were combined with a group of previously analyzed specimens, 30 late-PE cases and 60 unaffected controls. Specimens from both groups of cases and controls were collected in the same clinical centers during the same time period. In addition, NMR analyses were performed in the same lab and using the same techniques. We identified abnormalities in branch chain amino acids (valine, leucine and isoleucine) and propanoate, glycolysis, gluconeogenesis and ketone body metabolic pathways. The results suggest insulin resistance and metabolic syndrome, mitochondrial dysfun...
Research Interests: Algorithms, Pathogenesis, Biomarkers, Metabolomics, Medicine, and 15 moreProspective studies, Pregnancy, Humans, Preeclampsia, Female, Adult, Gluconeogenesis, Reproducibility of Results, Metabolic pathway, Ketone Bodies, Case Control Studies, Pre Eclampsia, Leucine, Isoleucine, and Paediatrics and reproductive medicine
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Research Interests:
Huntington's disease (HD) is an autosomal neurodegenerative disorder affecting approximately 5-10 persons per 100,000 worldwide. The pathophysiology of HD is not fully understood but the age of onset is known to be highly dependent on... more
Huntington's disease (HD) is an autosomal neurodegenerative disorder affecting approximately 5-10 persons per 100,000 worldwide. The pathophysiology of HD is not fully understood but the age of onset is known to be highly dependent on the number of CAG triplet repeats in the huntingtin gene. Using (1)H NMR spectroscopy this study biochemically profiled 39 brain metabolites in post-mortem striatum (n=14) and frontal lobe (n=14) from HD sufferers and controls (n=28). Striatum metabolites were more perturbed with 15 significantly affected in HD cases, compared with only 4 in frontal lobe (p<0.05;…
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IntroductionTraumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function.ObjectivesEvaluate the use of metabolomics for the development of biomarkers of TBI for the diagnosis and... more
IntroductionTraumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function.ObjectivesEvaluate the use of metabolomics for the development of biomarkers of TBI for the diagnosis and timing of injury onset.MethodsA validated model of closed injury TBI was employed using 10 TBI mice and 8 sham operated controls. Quantitative LC–MS/MS metabolomic analysis was performed on the serum.ResultsThirty-six (24.0 %) of 150 metabolites were altered with TBI. Principal component analysis (PCA) and Partial least squares discriminant analysis (PLS-DA) analyses revealed clear segregation between TBI versus control sera. The combination of methionine sulfoxide and the lipid PC aa C34:4 accurately diagnosed TBI, AUC (95 % CI) 0.85 (0.644–1.0). A combination of metabolite markers were highly accurate in distinguishing early (4 h post TBI) from late (24 h) TBI: AUC (95 % CI) 1.0 (1.0–1.0). Spermidine, which is known to have an antioxidant effect and which is known to be metabolically disrupted in TBI, was the most discriminating biomarker based on the variable importance ranking in projection (VIP) plot. Several important metabolic pathways were found to be disrupted including: pathways for arginine, proline, glutathione, cysteine, and sphingolipid metabolism.ConclusionUsing serum metabolomic analysis we were able to identify novel putative serum biomarkers of TBI. They were accurate for detecting and determining the timing of TBI. In addition, pathway analysis provided important insights into the biochemical mechanisms of brain injury. Potential clinical implications for diagnosis, timing, and monitoring brain injury are discussed.
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IntroductionAutism spectrum disorders (ASD) is a group of neurodevelopmental disorders believed to have a multifactorial basis. Presently, diagnosis is based on behavioral and developmental signs in children before the age of 3 and no... more
IntroductionAutism spectrum disorders (ASD) is a group of neurodevelopmental disorders believed to have a multifactorial basis. Presently, diagnosis is based on behavioral and developmental signs in children before the age of 3 and no reliable clinical biomarkers are available for early detection.ObjectivesThis study aimed to biochemically profile the cerebellum from post-mortem human brain from ASD sufferers (n = 11) and compare their profiles to that of age-matched controls (n = 11) with no known brain disorder.MethodsUsing liquid chromatography combined with LTQ-Orbitrap mass spectrometry we detected 14,328 features in ESI+ mode in polar extracts of post-mortem brain.ResultsOf these only 37 were found to be statistically significantly different between ASD and controls (p < 0.05; fdr < 0.05). A panel of four features had a predictive power of 96.64 %, following statistical cross validation, for ASD detection. This model produced an AUC = 0.874 (CI 0.768–0.944) and a Fisher’s exact score of p = 4.50E−29.ConclusionWhilst at this time we were unable to chemically identify the four features of interest we believe that this study underscores the potential value of high resolution metabolomics for the study of ASD. Further characterization of the polar metabolome of post mortem ASD brains could lead to the identification of potential biomarkers and novel therapeutics for the disease. The development of accurate biomarkers could assist in the early detection of ASD and promote early intervention strategies to improve outcome.
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Research Interests:
Azaspiracid (AZA) poisoning was unknown until 1995 when shellfish harvested in Ireland caused illness manifesting by vomiting and diarrhoea. Further in vivo/vitro studies showed neurotoxicity linked with AZA exposure. However, the... more
Azaspiracid (AZA) poisoning was unknown until 1995 when shellfish harvested in Ireland caused illness manifesting by vomiting and diarrhoea. Further in vivo/vitro studies showed neurotoxicity linked with AZA exposure. However, the biological target of the toxin which will help explain such potent neurological activity is still unknown. A region of Irish coastline was selected and shellfish were sampled and tested for AZA using mass spectrometry. An outbreak was identified in 2010 and samples collected before and after the contamination episode were compared for their metabolite profile using high resolution mass spectrometry. Twenty eight ions were identified at higher concentration in the contaminated samples. Stringent bioinformatic analysis revealed putative identifications for seven compounds including, glutarylcarnitine, a glutaric acid metabolite. Glutaric acid, the parent compound linked with human neurological manifestations was subjected to toxicological investigations but ...
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Brown planthopper (BPH; Nilaparvata lugens) is a phloem feeding insect which is one of the most serious threats to rice crops in many countries throughout Asia. 1H NMR spectroscopy, combined with chemometrics, was used to analyze the... more
Brown planthopper (BPH; Nilaparvata lugens) is a phloem feeding insect which is one of the most serious threats to rice crops in many countries throughout Asia. 1H NMR spectroscopy, combined with chemometrics, was used to analyze the polar metabolome from leaf extracts of Thai Jasmine rice (brown planthopper (BPH)-susceptible KD) and its BPH resistant isogenic lines (BPH-resistant IL7 and BPH-resistant+ IL308 varieties) with and without BPH infestation at various time points (days 1, 2, 3, 4 and 8). Physiological changes of the rice isogenic lines were different based on the quantitative trait loci of BPH resistance. Multivariate models were capable of distinguishing between the susceptible and the resistant rice varieties throughout the infestation. The concentration of 10 metabolites were significantly altered (p < 0.05) between the infested and the control groups of each examined rice variety. Metabolic pathway analysis suggested that BPH infestation could perturb transamination during the early stages of infestation (days 1–3) for all rice varieties. In addition, the IL7 and IL308 varieties responded earlier (day 3) than the KD variety (day 8) by perturbing amino acid metabolism, shikimate and gluconeogenesis pathways. By day 8 of the infestation, the KD cultivar responded by activating the amino acid-mediated-de novo pathway whereas the IL308 variety activated the purine and pyrimidine compound-mediated-salvage pathway for nucleotide biosynthesis. This study has identified, for the first time, several potential metabolic pathways for acclimatization and defense mechanisms against BPH infestation. These findings provide a valuable, first insight into BPH resistance mechanisms in Thai Jasmine rice.
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To perform validation studies of previously published and newly derived first-trimester metabolomic algorithms for prediction of early preeclampsia (early-PE). Nuclear Magnetic Resonance (NMR)-based metabolomic analysis was performed on... more
To perform validation studies of previously published and newly derived first-trimester metabolomic algorithms for prediction of early preeclampsia (early-PE). Nuclear Magnetic Resonance (NMR)-based metabolomic analysis was performed on the first trimester serum in 50 women who subsequently developed early-PE and 108 first trimester controls. Random stratification and allocation was used to divide cases into a discovery group (30 early-PE and 65 controls) for generation of the biomarker model(s) and a validation group (20 early-PE and 43 controls) to ensure an unbiased assessment of the predictive algorithms. Cross Validation testing on the different algorithms was performed to confirm their robustness before use. Metabolites, demographic features, clinical characteristics and uterine Doppler pulsatility index (UtPI) data were evaluated. Area under the receiver operator characteristic curve (AUC), 95% CI, sensitivity and specificity of the biomarker models were derived. Validation t...
Research Interests: Algorithms, Biomarkers, Metabolomics, Magnetic Resonance Spectroscopy, Medicine, and 13 morePregnancy, Humans, Preeclampsia, Female, Young Adult, Adult, Internal medicine Doppler ultrasonography, Area Under Curve, Pulsatile Flow, Case Control Studies, Pre Eclampsia, Paediatrics and reproductive medicine, and Uterine Artery
Research Interests: Metabolomics and Medicine
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Alzheimer’s disease (AD) is reported to be closely linked with abnormal lipid metabolism. To gain a more comprehensive understanding of what causes AD and its subsequent development, we profiled the lipidome of postmortem (PM) human... more
Alzheimer’s disease (AD) is reported to be closely linked with abnormal lipid metabolism. To gain a more comprehensive understanding of what causes AD and its subsequent development, we profiled the lipidome of postmortem (PM) human brains (neocortex) of people with a range of AD pathology (Braak 0–6). Using high-resolution mass spectrometry, we employed a semi-targeted, fully quantitative lipidomics profiling method (Lipidyzer) to compare the biochemical profiles of brain tissues from persons with mild AD (n = 15) and severe AD (AD; n = 16), and compared them with age-matched, cognitively normal controls (n = 16). Univariate analysis revealed that the concentrations of 420 lipid metabolites significantly (p < 0.05; q < 0.05) differed between AD and controls. A total of 49 lipid metabolites differed between mild AD and controls, and 439 differed between severe AD and mild AD. Interestingly, 13 different subclasses of lipids were significantly perturbed, including neutral lipid...
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Research Interests:
This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of mild cognitive impairment (MCI; n = 16),... more
This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of mild cognitive impairment (MCI; n = 16), cases of MCI who upon subsequent follow-up developed Alzheimer's disease (MCI_AD; n = 19), and healthy age-matched controls (Ctrl; n = 37). Plasma was extracted in acetonitrile and applied to an Acquity UPLC HILIC (1.7μm x 2.1 x 100 mm) column coupled to a Xevo G2 QTof mass spectrometer using a previously optimised method. Data comprising 6751 spectral features were used to build an OPLS-DA statistical model capable of accurately distinguishing Ctrl, MCI and MCI_AD. The model accurately distinguished (R2 = 99.1%; Q2 = 97%) those MCI patients who later went on to develop AD. S-plots were used to shortlist ions of interest which were responsible for explaining the maximum amount of variation between patient groups. Metabolite database searching a...
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Disease-, age-, and gender-associated changes in brain copper, iron, and zinc were assessed in postmortem neocortical tissue (Brodmann area 7) from patients with moderate Alzheimer's disease (AD) (n = 14), severe AD (n = 28), dementia... more
Disease-, age-, and gender-associated changes in brain copper, iron, and zinc were assessed in postmortem neocortical tissue (Brodmann area 7) from patients with moderate Alzheimer's disease (AD) (n = 14), severe AD (n = 28), dementia with Lewy bodies (n = 15), and normal age-matched control subjects (n = 26). Copper was lower (20%; p < 0.001) and iron higher (10-16%; p < 0.001) in severe AD compared with controls. Intriguingly significant Group*Age interactions were observed for both copper and iron, suggesting gradual age-associated decline of these metals in healthy non-cognitively impaired individuals. Zinc was unaffected in any disease pathologies and no age-associated changes were apparent. Age-associated changes in brain elements warrant further investigation.
Research Interests: Cognitive Science, Aging, Brain, Humans, Copper, and 8 moreFemale, Male, Zinc, Iron, Clinical Sciences, Aged, Alzheimer Disease, and Neurosciences
Alzheimer's disease (AD) is associated with significant disturbances in the homeostasis of Na+ and K+ ions as well as reduced levels of Na+/K+ ATPase in the brain. This study used ICP-MS to accurately quantify Na+ and K+... more
Alzheimer's disease (AD) is associated with significant disturbances in the homeostasis of Na+ and K+ ions as well as reduced levels of Na+/K+ ATPase in the brain. This study used ICP-MS to accurately quantify Na+ and K+ concentrations in human postmortem brain tissue. We analyzed parietal cortex (Brodmann area 7) from 28 cognitively normal age-matched controls, 15 cases of moderate AD, 30 severe AD, and 15 dementia with Lewy bodies (DLB). Associations were investigated between [Na+] and [K+] and a number of variables including diagnosis, age, gender, Braak tangle stage, amyloid-β (Aβ) plaque load, tau load, frontal tissue pH, and APOE genotype. Brains from patients with severe AD had significantly higher (26%; p < 0.001) [Na+] (mean 65.43 ± standard error 2.91 mmol/kg) than controls, but the concentration was not significantly altered in moderate AD or DLB. [Na+] correlated positively with Braak stage (r = 0.45; p < 0.0001), indicating association with disease severity. [...
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In this study data generated by 1H NMR spectroscopy were combined with chemometrics to analyse beef samples aged over a 21 day period. In particular, the amino acids, of which 12 were identified were found to increase over the ageing... more
In this study data generated by 1H NMR spectroscopy were combined with chemometrics to analyse beef samples aged over a 21 day period. In particular, the amino acids, of which 12 were identified were found to increase over the ageing period with samples matured for 3 days having notably lower concentrations than carcasses aged for 21 days. This is believed to be a
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Research Interests:
Beef longissimus dorsi muscle samples matured over a 21 day period were analysed using three different analytical techniques; (1)H NMR, GC-MS and HPLC. The data from the three experimental techniques were correlated with each other to... more
Beef longissimus dorsi muscle samples matured over a 21 day period were analysed using three different analytical techniques; (1)H NMR, GC-MS and HPLC. The data from the three experimental techniques were correlated with each other to determine if the results were statistically similar to each other. From our analysis we determined that the metabolites measured using (1)H NMR were statistically similar to the compounds quantified using the chromatography techniques (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). In addition, using PCA, we were able to show that different metabolites, measured using the various analytical techniques produced very similar scores and loadings plots for all the analysis and extraction techniques undertaken across the 21 day time domain. Using a combination of these three different techniques provides a unique and holistic insight into the biochemistry behind the conversion of muscle to meat which would not be possible using any single technique alone.
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Basic vegetable blends (BVB&amp;amp;#x27;s) and soya oils, used in the animal feed industry, are sometimes adulterated with transformer and mineral oil as a means of illegally increasing profit. A set of BVB&amp;amp;#x27;s and... more
Basic vegetable blends (BVB&amp;amp;#x27;s) and soya oils, used in the animal feed industry, are sometimes adulterated with transformer and mineral oil as a means of illegally increasing profit. A set of BVB&amp;amp;#x27;s and soya oil samples adulterated with transformer oil and mineral oil ...
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Brown planthopper (BPH; Nilaparvata lugens) is a phloem feeding insect which is one of the most serious threats to rice crops in many countries throughout Asia. 1H NMR spectroscopy, combined with chemometrics, was used to analyze the... more
Brown planthopper (BPH; Nilaparvata lugens)
is a phloem feeding insect which is one of the most serious
threats to rice crops in many countries throughout Asia. 1H
NMR spectroscopy, combined with chemometrics, was
used to analyze the polar metabolome from leaf extracts of
Thai Jasmine rice (brown planthopper (BPH)-susceptible
KD) and its BPH resistant isogenic lines (BPH-resistant
IL7 and BPH-resistant? IL308 varieties) with and without
BPH infestation at various time points (days 1, 2, 3, 4 and
8). Physiological changes of the rice isogenic lines were
different based on the quantitative trait loci of BPH resistance.
Multivariate models were capable of distinguishing
between the susceptible and the resistant rice varieties
throughout the infestation. The concentration of 10
metabolites were significantly altered (p\0.05) between
the infested and the control groups of each examined rice variety. Metabolic pathway analysis suggested that BPH
infestation could perturb transamination during the early
stages of infestation (days 1–3) for all rice varieties. In
addition, the IL7 and IL308 varieties responded earlier (day
3) than the KD variety (day 8) by perturbing amino acid
metabolism, shikimate and gluconeogenesis pathways. By
day 8 of the infestation, the KD cultivar responded by
activating the amino acid-mediated-de novo pathway
whereas the IL308 variety activated the purine and
pyrimidine compound-mediated-salvage pathway for nucleotide
biosynthesis. This study has identified, for the first
time, several potential metabolic pathways for acclimatization
and defense mechanisms against BPH infestation.
These findings provide a valuable, first insight into BPH
resistance mechanisms in Thai Jasmine rice.
is a phloem feeding insect which is one of the most serious
threats to rice crops in many countries throughout Asia. 1H
NMR spectroscopy, combined with chemometrics, was
used to analyze the polar metabolome from leaf extracts of
Thai Jasmine rice (brown planthopper (BPH)-susceptible
KD) and its BPH resistant isogenic lines (BPH-resistant
IL7 and BPH-resistant? IL308 varieties) with and without
BPH infestation at various time points (days 1, 2, 3, 4 and
8). Physiological changes of the rice isogenic lines were
different based on the quantitative trait loci of BPH resistance.
Multivariate models were capable of distinguishing
between the susceptible and the resistant rice varieties
throughout the infestation. The concentration of 10
metabolites were significantly altered (p\0.05) between
the infested and the control groups of each examined rice variety. Metabolic pathway analysis suggested that BPH
infestation could perturb transamination during the early
stages of infestation (days 1–3) for all rice varieties. In
addition, the IL7 and IL308 varieties responded earlier (day
3) than the KD variety (day 8) by perturbing amino acid
metabolism, shikimate and gluconeogenesis pathways. By
day 8 of the infestation, the KD cultivar responded by
activating the amino acid-mediated-de novo pathway
whereas the IL308 variety activated the purine and
pyrimidine compound-mediated-salvage pathway for nucleotide
biosynthesis. This study has identified, for the first
time, several potential metabolic pathways for acclimatization
and defense mechanisms against BPH infestation.
These findings provide a valuable, first insight into BPH
resistance mechanisms in Thai Jasmine rice.