Metabolomics dataset of PPAR-pan treated rat liver

This article contains mass spectrometry (MS) data investigating small molecule changes as an effect of a triple peroxisome proliferator-activated receptor (PPAR-pan) agonist GW625019 in the liver as described in the manuscript (Ament et al., 2016) [1]. Samples were measured using gas chromatography-mass spectrometry (GC–MS) for total fatty acid content, and liquid chromatography-mass spectrometry (LC–MS) to measure intact lipids, carnitines and selected aqueous metabolites and eicosanoids. Data files comprise of Excel (Microsoft, WA, USA) spreadsheets of identified metabolites and their area ratio values for total fatty acids, carnitines, aqueous metabolites, and eicosanoids where the intensity of the analytes were normalised to the intensity of the internal standard. In the case of open profiling intact lipid data, the Excel file contains area ratio values of retention time and mass to charge ratio pairs; again, the area ratio values were calculated by normalising to the intensity of the internal standard. It should be noted that several metabolic changes are potentially indirect (secondary, tertiary and ensuing changes)

Alterations in endo-lysosomal function induce similar hepatic lipid profiles in rodent models of drug-induced phospholipidosis and Sandhoff disease

Drug-induced phospholipidosis (DIPL) is characterized by an increase in the phospholipid content of the cell and the accumulation of drugs and lipids inside the lysosomes of affected tissues, including in the liver. Although of uncertain pathological significance for patients, the condition remains a major impediment for the clinical development of new drugs. Human Sandhoff disease (SD) is caused by inherited defects of the β subunit of lysosomal β-hexosaminidases (Hex) A and B, leading to a large array of symptoms, including neurodegeneration and ultimately death by the age of 4 in its most common form. The substrates of Hex A and B, gangliosides GM2 and GA2, accumulate inside the lysosomes of the CNS and in peripheral organs. Given that both DIPL and SD are associated with lysosomes and lipid metabolism in general, we measured the hepatic lipid profiles in rodent models of these two conditions using untargeted LC/MS to examine potential commonalities. Both model systems shared a number of perturbed lipid pathways, notably those involving metabolism of cholesteryl esters, lysophosphatidylcholines, bis(monoacylglycero)phosphates, and ceramides. We report here profound alterations in lipid metabolism in the SD liver. In addition, DIPL induced a wide range of lipid changes not previously observed in the liver, highlighting similarities with those detected in the model of SD and raising concerns that these lipid changes may be associated with underlying pathology associated with lysosomal storage disorders.This work was funded by a Medical Research Council Integrative Toxicology Training Partnership grant with financial support from GlaxoSmithKline. The work on Sandhoff mice was supported by SPARKS, The Children’s Medical Research Charity. JLG’s laboratory is supported by the Wellcome Trust (Equipment grant 093,148/Z/10/Z)) and the Medical Research Council (G0801841 & UD99999906)

Erosion consequences on beach functions along the Maresme coast (NW Mediterranean, Spain)

A methodology to analyse the influence of erosion on beach functions at a regional scale is presented. The method considers erosion hazards at different timescales and assesses consequences by evaluating impacts on recreation and protection functions. To provide useful information to decision makers for managing these functions, hazard and consequences are integrated at the municipal level within a risk matrix. This methodology is applied at the Maresme, a 45-km sandy coast situated northward of Barcelona, which supports a strong urban and infrastructure development as well as an intensive beach recreational use. Obtained results indicate differentiated erosion implications along the region, depending on the management target considered. Thus, southern municipalities are more prone to erosion affecting the protection function of the beach and leisure use by the local population, whereas erosion will have a greater effect on foreign tourism in the northern municipalities. These results highlight the necessity to employ an articulated erosion risk assessment focusing on specific targets depending on the site in question. This methodology can help coastal managers to adopt tailored measures to manage erosion impacts towards specific goals, in a more efficient and sustainable manner

Detecting parent of origin and dominant QTL in a two-generation commercial poultry pedigree using variance component methodology

<p>Abstract</p> <p>Introduction</p> <p>Variance component QTL methodology was used to analyse three candidate regions on chicken chromosomes 1, 4 and 5 for dominant and parent-of-origin QTL effects. Data were available for bodyweight and conformation score measured at 40 days from a two-generation commercial broiler dam line. One hundred dams were nested in 46 sires with phenotypes and genotypes on 2708 offspring. Linear models were constructed to simultaneously estimate fixed, polygenic and QTL effects. Different genetic models were compared using likelihood ratio test statistics derived from the comparison of full with reduced or null models. Empirical thresholds were derived by permutation analysis.</p> <p>Results</p> <p>Dominant QTL were found for bodyweight on chicken chromosome 4 and for bodyweight and conformation score on chicken chromosome 5. Suggestive evidence for a maternally expressed QTL for bodyweight and conformation score was found on chromosome 1 in a region corresponding to orthologous imprinted regions in the human and mouse.</p> <p>Conclusion</p> <p>Initial results suggest that variance component analysis can be applied within commercial populations for the direct detection of segregating dominant and parent of origin effects.</p

Metabolic Profiling of an Echinostoma caproni Infection in the Mouse for Biomarker Discovery

Consumption of raw fish and other freshwater products can lead to unpleasant worm infections. Indeed, such worm infections are of growing public health and veterinary concern, but they are often neglected, partially explained by the difficulty of accurate diagnosis. In the present study we infected 12 mice with an intestinal worm (i.e., Echinostoma caproni) and collected blood, stool, and urine samples 7 times between 1 and 33 days after the infection. At the same time points, blood, stool, and urine were also sampled from 12 uninfected mice. These biofluid samples were examined with a spectrometer and data were analyzed with a multivariate approach. We observed important differences between the infected and the uninfected control animals. For example, we found an increased level of branched chain amino acids in the stool of infected mice and subsequent depletion in blood plasma. Additionally, we observed changes related to a disturbed intestinal bacterial composition, particularly in urine and stool. The combination of results from the three types of biofluids gave the most comprehensive characterization of an E. caproni infection in the mouse. Urine would be the biofluid of choice for diagnosis of an infection because the ease of sample collection and the high number and extent of changed metabolites

A multi-component flood risk assessment in the Maresme coast (NW Mediterranean)

Coastal regions are the areas most threatened by natural hazards, with floods being the most frequent and significant threat in terms of their induced impacts, and therefore, any management scheme requires their evaluation. In coastal areas, flooding is a hazard associated with various processes acting at different scales: coastal storms, flash floods, and sea level rise (SLR). In order to address the problem as a whole, this study presents a methodology to undertake a preliminary integrated risk assessment that determines the magnitude of the different flood processes (flash flood, marine storm, SLR) and their associated consequences, taking into account their temporal and spatial scales. The risk is quantified using specific indicators to assess the magnitude of the hazard (for each component) and the consequences in a common scale. This allows for a robust comparison of the spatial risk distribution along the coast in order to identify both the areas at greatest risk and the risk components that have the greatest impact. This methodology is applied on the Maresme coast (NW Mediterranean, Spain), which can be considered representative of developed areas of the Spanish Mediterranean coast. The results obtained characterise this coastline as an area of relatively low overall risk, although some hot spots have been identified with high-risk values, with flash flooding being the principal risk process

SARS-CoV Pathogenesis Is Regulated by a STAT1 Dependent but a Type I, II and III Interferon Receptor Independent Mechanism

Severe acute respiratory syndrome coronavirus (SARS-CoV) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. The virus-host interactions that governed development of these acute end stage lung diseases and death are unknown. To address this question, we evaluated the role of innate immune signaling in protection from human (Urbani) and a recombinant mouse adapted SARS-CoV, designated rMA15. In contrast to most models of viral pathogenesis, infection of type I, type II or type III interferon knockout mice (129 background) with either Urbani or MA15 viruses resulted in clinical disease outcomes, including transient weight loss, denuding bronchiolitis and alveolar inflammation and recovery, identical to that seen in infection of wildtype mice. This suggests that type I, II and III interferon signaling play minor roles in regulating SARS pathogenesis in mouse models. In contrast, infection of STAT1−/− mice resulted in severe disease, high virus titer, extensive pulmonary lesions and 100% mortality by day 9 and 30 post-infection with rMA15 or Urbani viruses, respectively. Non-lethal in BALB/c mice, Urbani SARS-CoV infection in STAT1−/− mice caused disseminated infection involving the liver, spleen and other tissues after day 9. These findings demonstrated that SARS-CoV pathogenesis is regulated by a STAT1 dependent but type I, II and III interferon receptor independent, mechanism. In contrast to a well documented role in innate immunity, we propose that STAT1 also protects mice via its role as an antagonist of unrestrained cell proliferation

SnoRNA Snord116 (Pwcr1/MBII-85) Deletion Causes Growth Deficiency and Hyperphagia in Mice

Prader-Willi syndrome (PWS) is the leading genetic cause of obesity. After initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if intake is not restricted. Short stature with abnormal growth hormone secretion, hypogonadism, cognitive impairment, anxiety and behavior problems are other features. PWS is caused by lack of expression of imprinted genes in a ∼4 mb region of chromosome band 15q11.2. Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. To test this hypothesis, we created a ∼150 kb deletion of the >40 copies of Snord116 (Pwcr1/MBII-85) in C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation

Shearwater Foraging in the Southern Ocean: The Roles of Prey Availability and Winds

Background Sooty (Puffinus griseus) and short-tailed (P. tenuirostris) shearwaters are abundant seabirds that range widely across global oceans. Understanding the foraging ecology of these species in the Southern Ocean is important for monitoring and ecosystem conservation and management. Methodology/Principal Findings Tracking data from sooty and short-tailed shearwaters from three regions of New Zealand and Australia were combined with at-sea observations of shearwaters in the Southern Ocean, physical oceanography, near-surface copepod distributions, pelagic trawl data, and synoptic near-surface winds. Shearwaters from all three regions foraged in the Polar Front zone, and showed particular overlap in the region around 140°E. Short-tailed shearwaters from South Australia also foraged in Antarctic waters south of the Polar Front. The spatial distribution of shearwater foraging effort in the Polar Front zone was matched by patterns in large-scale upwelling, primary production, and abundances of copepods and myctophid fish. Oceanic winds were found to be broad determinants of foraging distribution, and of the flight paths taken by the birds on long foraging trips to Antarctic waters. Conclusions/Significance The shearwaters displayed foraging site fidelity and overlap of foraging habitat between species and populations that may enhance their utility as indicators of Southern Ocean ecosystems. The results highlight the importance of upwellings due to interactions of the Antarctic Circumpolar Current with large-scale bottom topography, and the corresponding localised increases in the productivity of the Polar Front ecosystem