Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine

Trichomonas vaginalis and Tritrichomonas foetus are pathogens that parasitise, respectively, human and bovine urogenital tracts causing disease. Using LC-MS, reference metabolomic profiles were obtained for both species and stable isotope labelling with D-[U-13C6] glucose was used to analyse central carbon metabolism. This facilitated a comparison of the metabolic pathways of T. vaginalis and T. foetus, extending earlier targeted biochemical studies. 43 metabolites, whose identities were confirmed by comparison of their retention times with authentic standards, occurred at more than 3-fold difference in peak intensity between T. vaginalis and T. foetus. 18 metabolites that were removed from or released into the medium during growth also showed more than 3-fold difference between the species. Major differences were observed in cysteine and methionine metabolism in which homocysteine, produced as a bi-product of trans-methylation, is catabolised by methionine γ-lyase in T. vaginalis but converted to cystathionine in T. foetus. Both species synthesise methylthioadenosine by an unusual mechanism, but it is not used as a substrate for methionine recycling. T. vaginalis also produces and exports high levels of S-methylcysteine, whereas only negligible levels were found in T. foetus which maintains significantly higher intracellular levels of cysteine. 13C-labeling confirmed that both cysteine and S-methylcysteine are synthesised by T. vaginalis; S-methylcysteine can be generated by recombinant T. vaginalis cysteine synthase using phosphoserine and methanethiol. T. foetus contained higher levels of ornithine and citrulline than T. vaginalis and exported increased levels of putrescine, suggesting greater flux through the arginine dihydrolase pathway. T. vaginalis produced and exported hydroxy acid derivatives of certain amino acids, particularly 2-hydroxyisocaproic acid derived from leucine, whereas negligible levels of these metabolites occurred in T. foetus

Five-year outcome after laparoscopic anterior partial versus Nissen fundoplication: four randomized trials

Author version made available in accordance with the publisher's policy.Objective: To compare longer term (5-year) outcomes for reflux control and post-surgery side effects following laparoscopic anterior (90˚ and 180˚) partial vs. Nissen fundoplication for gastroesophageal reflux. Summary Background Data: Laparoscopic Nissen fundoplication is the most frequently performed surgical procedure for gastroesophageal reflux. It achieves excellent control of reflux, but in some patients is followed by troublesome side effects. To reduce the risk of side effects laparoscopic anterior partial fundoplication variants have been advocated, although some studies suggest poorer reflux control. Methods: From 1995 to 2003, 461 patients with gastroesophageal reflux were enrolled in 4 randomized controlled trials comparing anterior partial vs. Nissen fundoplication. Two trials evaluated anterior 180˚, and 2 anterior 90˚ partial fundoplication. The original trial data were combined and a re-analysis from original data was undertaken to determine outcomes at 5-years follow-up. Reflux symptom control and side effects were evaluated in a blinded fashion using standardized questionnaires, including 0-10 analog scores (0=no symptoms, 10=severe symptoms). Results: At 5 years, patients who underwent an anterior 90˚ or 180˚ partial fundoplication had less side effects compared with Nissen fundoplication and were equally satisfied with the overall outcome. Reflux control, measured by heartburn scores and antisecretory medication use, was similar for anterior 180˚ partial vs. Nissen fundoplication, but inferior after anterior 90˚ partial vs. Nissen fundoplication. Conclusions: Anterior 180˚ partial fundoplication achieves durable control of reflux symptoms and less side effects compared with Nissen fundoplication. Although reflux control following anterior 90˚ partial fundoplication appears less effective than after Nissen fundoplication. This data supports the use of anterior 180˚ partial fundoplication for the surgical treatment of gastroesophageal reflux

Acculturation is associated with left ventricular mass in a multiethnic sample: the Multi-Ethnic Study of Atherosclerosis.

BackgroundAcculturation involves stress-related processes and health behavioral changes, which may have an effect on left ventricular (LV) mass, a risk factor for cardiovascular disease (CVD). We examined the relationship between acculturation and LV mass in a multiethnic cohort of White, African-American, Hispanic and Chinese subjects.MethodsCardiac magnetic resonance assessment was available for 5004 men and women, free of clinical CVD at baseline. Left ventricular mass index was evaluated as LV mass indexed by body surface area. Acculturation was characterized based on language spoken at home, place of birth and length of stay in the United States (U.S.), and a summary acculturation score ranging from 0 = least acculturated to 5 = most acculturated. Mean LV mass index adjusted for traditional CVD risk factors was compared across acculturation levels.ResultsUnadjusted mean LV mass index was 78.0 ± 16.3 g/m(2). In adjusted analyses, speaking exclusively English at home compared to non-English language was associated with higher LV mass index (81.3 ± 0.4 g/m(2) vs 79.9 ± 0.5 g/m(2), p = 0.02). Among foreign-born participants, having lived in the U.S. for ≥ 20 years compared to < 10 years was associated with greater LV mass index (81.6 ± 0.7 g/m(2) vs 79.5 ± 1.1 g/m(2), p = 0.02). Compared to those with the lowest acculturation score, those with the highest score had greater LV mass index (78.9 ± 1.1 g/m(2) vs 81.1 ± 0.4 g/m(2), p = 0.002). There was heterogeneity in which measure of acculturation was associated with LV mass index across ethnic groups.ConclusionsGreater acculturation is associated with increased LV mass index in this multiethnic cohort. Acculturation may involve stress-related processes as well as behavioral changes with a negative effect on cardiovascular health

Prolonged transition time between colostrum and mature milk in a bear, the giant panda, Ailuropoda melanoleuca

Bears produce the most altricial neonates of any placental mammal. We hypothesized that the transition from colostrum to mature milk in bears reflects a temporal and biochemical adaptation for altricial development and immune protection. Comparison of bear milks with milks of other eutherians yielded distinctive protein profiles. Proteomic and metabolomic analysis of serial milk samples collected from six giant pandas showed a prolonged transition from colostrum to main-phase lactation over approximately 30 days. Particularly striking are the persistence or sequential appearance of adaptive and innate immune factors. The endurance of immunoglobulin G suggests an unusual duration of trans-intestinal absorption of maternal antibodies, and is potentially relevant to the underdeveloped lymphoid system of giant panda neonates. Levels of certain milk oligosaccharides known to exert anti-microbial activities and/or that are conducive to the development of neonatal gut microbiomes underwent an almost complete changeover around days 20–30 postpartum, coincident with the maturation of the protein profile. A potential metabolic marker of starvation was detected, the prominence of which may reflect the natural postpartum period of anorexia in giant panda mothers. Early lactation in giant pandas, and possibly in other ursids, appears to be adapted for the unique requirements of unusually altricial eutherian neonates

Detecting morphed passport photos : a training and individual differences approach

Our reliance on face photos for identity verification is at odds with extensive research which shows that matching pairs of unfamiliar faces is highly prone to error. This process can therefore be exploited by identity fraudsters seeking to deceive ID checkers (e.g. using a stolen passport which contains an image of similar looking individual to deceive border control officials). In this study we build on previous work which sought to quantify the threat posed by a relatively new type of fraud - morphed passport photos. Participants were initially unaware of the presence of morphs in a series of face photo arrays, and were simply asked to detect which images they thought had been digitally manipulated (i.e. “images that didn’t look quite right”). All participants then received basic information on morph fraud and rudimentary guidance on how to detect such images, followed by a morph detection training task (Training Group, N = 40), or a non-face control task (Guidance Group, N = 40). Participants also completed a post-guidance/training morph detection task, and the Models Face Matching Test (MFMT). Our findings show that baseline morph detection rates were poor, that morph detection training significantly improved the identification of these images over and above basic guidance, and accuracy on the mismatch condition of the MFMT correlated with morph detection ability. The results are discussed in relation to potential counter-measures for morph-based identity fraud

Time-Dependent Density Functional Theory of Open Quantum Systems in the Linear-Response Regime

Time-Dependent Density Functional Theory (TDDFT) has recently been extended to describe many-body open quantum systems (OQS) evolving under non-unitary dynamics according to a quantum master equation. In the master equation approach, electronic excitation spectra are broadened and shifted due to relaxation and dephasing of the electronic degrees of freedom by the surrounding environment. In this paper, we develop a formulation of TDDFT linear-response theory (LR-TDDFT) for many-body electronic systems evolving under a master equation, yielding broadened excitation spectra. This is done by mapping an interacting open quantum system onto a non-interacting open Kohn-Sham system yielding the correct non-equilibrium density evolution. A pseudo-eigenvalue equation analogous to the Casida equations of usual LR-TDDFT is derived for the Redfield master equation, yielding complex energies and Lamb shifts. As a simple demonstration, we calculate the spectrum of a C$^{2+}$ atom in an optical resonator interacting with a bath of photons. The performance of an adiabatic exchange-correlation kernel is analyzed and a first-order frequency-dependent correction to the bare Kohn-Sham linewidth based on Gorling-Levy perturbation theory is calculated.Comment: 18 pages, 4 figure

Exploring metabolic pathway disruption in the subchronic phencyclidine model of schizophrenia with the generalized singular value decomposition

The quantification of experimentally-induced alterations in biological pathways remains a major challenge in systems biology. One example of this is the quantitative characterization of alterations in defined, established metabolic pathways from complex metabolomic data. At present, the disruption of a given metabolic pathway is inferred from metabolomic data by observing an alteration in the level of one or more individual metabolites present within that pathway. Not only is this approach open to subjectivity, as metabolites participate in multiple pathways, but it also ignores useful information available through the pairwise correlations between metabolites. This extra information may be incorporated using a higher-level approach that looks for alterations between a pair of correlation networks. In this way experimentally-induced alterations in metabolic pathways can be quantitatively defined by characterizing group differences in metabolite clustering. Taking this approach increases the objectivity of interpreting alterations in metabolic pathways from metabolomic data. We present and justify a new technique for comparing pairs of networks - in our case these networks are based on the same set of nodes and there are two distinct types of weighted edges. The algorithm is based on the Generalized Singular Value Decomposition (GSVD), which may be regarded as an extension of Principle Components Analysis to the case of two data sets. We show how the GSVD can be interpreted as a technique for reordering the two networks in order to reveal clusters that are exclusive to only one. Here we apply this algorithm to a new set of metabolomic data from the prefrontal cortex (PFC) of a translational model relevant to schizophrenia, rats treated subchronically with the N-methyl-D-Aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). This provides us with a means to quantify which predefined metabolic pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolite pathway database) were altered in the PFC of PCP-treated rats. Several significant changes were discovered, notably: 1) neuroactive ligands active at glutamate and GABA receptors are disrupted in the PFC of PCP-treated animals, 2) glutamate dysfunction in these animals was not limited to compromised glutamatergic neurotransmission but also involves the disruption of metabolic pathways linked to glutamate; and 3) a specific series of purine reactions Xanthine Inosine adenylosuccinate is also disrupted in the PFC of PCP-treated animals. Network reordering via the GSVD provides a means to discover statistically validated differences in clustering between a pair of networks. In practice this analytical approach, when applied to metabolomic data, allows us to quantify the alterations in metabolic pathways between two experimental groups. With this new computational technique we identified metabolic pathway alterations that are consistent with known results. Furthermore, we discovered disruption in a novel series of purine reactions that may contribute to the PFC dysfunction and cognitive deficits seen in schizophrenia

Randomized controlled trial of laparoscopic anterior 180° partial versus posterior 270° partial fundoplication.

Article first published online: 28 NOV 2013. This item is under embargo for a period of 12 months from the date of publication, in accordance with the publisher's policy.BACKGROUND: Previous trials show good outcomes following anterior and posterior partial versus Nissen fundoplication for gastro-oesophageal reflux. However, it is unclear which partial fundoplication performs best. This study compared anterior 180° versus posterior 270° fundoplication. METHODS: At three hospitals, patients were randomized to anterior 180° versus posterior 270° partial fundoplication, and clinical outcomes were determined using a structured questionnaire at 3, 6 and 12 months. Heartburn, dysphagia and satisfaction were assessed using 0-10 analoue scales, and adverse outcomes and side effects were determined. Endoscopy, manometry and pH monitoring were performed 6 months after surgery. RESULTS: Forty-seven patients were randomized to anterior (n = 23) versus posterior (n = 24) fundoplication. Clinical outcomes for 93-98% of patients were available at each follow-up point. At 12 months, the mean heartburn score was higher following anterior fundoplication (2.7 versus 0.8, P = 0.045), although differences were not significant at earlier follow-up. Conversely, following posterior fundoplication, patients were less able to belch at 3 (56% versus 16%, P = 0.013) and 6 months (43% versus 9%, P = 0.017). No significant differences were demonstrated for dysphagia. Both groups had high rates of satisfaction with the outcome - 85% versus 86% satisfied at 12 months follow-up. CONCLUSION: Both partial fundoplications are effective treatments for gastro-oesophageal reflux. Posterior partial fundoplication is associated with less reflux symptoms offset by more side effects.Australian National Health & Medical Research Council

Temperate Grassland Yields and Nitrogen Uptake Are Influenced by Fertilizer Nitrogen Source

This research was supported under the National Development Plan through the Research Stimulus Fund administered by the Department of Agriculture, Food and the Marine (Grants RSF10-/RD/SC/716 and RSF11S138) and from the Department of Agriculture and Rural Development for Northern Ireland and by the Teagasc Walsh Fellowship Scheme.peer reviewedIn temperate grasslands, N source influences greenhouse gas emissions. Nitrification and urea hydrolysis inhibitors can reduce these losses. The objective of this study was to evaluate the impact of N source, urease inhibitors, and nitrification inhibitors on temperate grassland yields and N uptake. Experiments were conducted at three locations over 2 years (6 site-years) on the island of Ireland, covering a range of soils and climatic conditions. Results showed that calcium ammonium nitrate (CAN), urea+N-(n-butyl) thiophosphoric triamide (NBPT), urea+NBPT+dicyandiamide (DCD), and urea had equal annual dry matter yield. Urea+DCD had lower dry matter yield than CAN for 3 site-years. Calcium ammonium nitrate and urea+NBPT consistently had the same N uptake, urea+DCD had lower N uptake than CAN in 4 of 6 site-years, urea had lower N uptake than CAN in 2 site-years, and urea+NBPT+DCD had lower N uptake than CAN in 1 site-year. Urea+NBPT is a cost-effective alternative to CAN, which is consistently equal in terms of yield and N uptake in temperate grassland.Teagasc Walsh Fellowship ProgrammeDepartment of Agriculture and Rural Development for Northern IrelandDepartment of Agriculture, Food and the Marin

LC-MS metabolomics of psoriasis patients reveals disease severity-dependent increases in circulating amino acids that are ameliorated by anti-TNFα treatment

Psoriasis is an immune-mediated highly heterogeneous skin disease in which genetic as well as environmental factors play important roles. In spite of the local manifestations of the disease, psoriasis may progress to affect organs deeper than the skin. These effects are documented by epidemiological studies, but they are not yet mechanistically understood. In order to provide insight into the systemic effects of psoriasis, we performed a nontargeted high-resolution LC-MS metabolomics analysis to measure plasma metabolites from individuals with mild or severe psoriasis as well as healthy controls. Additionally, the effects of the anti-TNFα drug Etanercept on metabolic profiles were investigated in patients with severe psoriasis. Our analyses identified significant psoriasis-associated perturbations in three metabolic pathways: (1) arginine and proline, (2) glycine, serine and threonine, and (3) alanine, aspartate, and glutamate. Etanercept treatment reversed the majority of psoriasis-associated trends in circulating metabolites, shifting the metabolic phenotypes of severe psoriasis toward that of healthy controls. Circulating metabolite levels pre- and post-Etanercept treatment correlated with psoriasis area and severity index (PASI) clinical scoring (R(2) = 0.80; p < 0.0001). Although the responsible mechanism(s) are unclear, these results suggest that psoriasis severity-associated metabolic perturbations may stem from increased demand for collagen synthesis and keratinocyte hyperproliferation or potentially the incidence of cachexia. Data suggest that levels of circulating amino acids are useful for monitoring both the severity of disease as well as therapeutic response to anti-TNFα treatment