Obesity and cage environment modulate metabolism in the Zucker rat: a multiple biological matrix approach to characterizing metabolic phenomena

Obesity and its comorbidities are increasing worldwide imposing a heavy socioeconomic burden. The effects of obesity on the metabolic profiles of tissues (liver, kidney, pancreas), urine, and the systemic circulation were investigated in the Zucker rat model using 1H NMR spectroscopy coupled to multivariate statistical analysis. The metabolic profiles of the obese ( fa/ fa) animals were clearly differentiated from the two phenotypically lean phenotypes, ((+/+) and ( fa/+)) within each biological compartment studied, and across all matrices combined. No significant differences were observed between the metabolic profiles of the genotypically distinct lean strains. Obese Zucker rats were characterized by higher relative concentrations of blood lipid species, cross-compartmental amino acids (particularly BCAAs), urinary and liver metabolites relating to the TCA cycle and glucose metabolism; and lower amounts of urinary gut microbial-host cometabolites, and intermatrix metabolites associated with creatine metabolism. Further to this, the obese Zucker rat metabotype was defined by significant metabolic alterations relating to disruptions in the metabolism of choline across all compartments analyzed. The cage environment was found to have a significant effect on urinary metabolites related to gut-microbial metabolism, with additional cage-microenvironment trends also observed in liver, kidney, and pancreas. This study emphasizes the value in metabotyping multiple biological matrices simultaneously to gain a better understanding of systemic perturbations in metabolism, and also underscores the need for control or evaluation of cage environment when designing and interpreting data from metabonomic studies in animal models

Age and Microenvironment Outweigh Genetic Influence on the Zucker Rat Microbiome

Animal models are invaluable tools which allow us to investigate the microbiome-host dialogue. However, experimental design introduces biases in the data that we collect, also potentially leading to biased conclusions. With obesity at pandemic levels animal models of this disease have been developed; we investigated the role of experimental design on one such rodent model. We used 454 pyrosequencing to profile the faecal bacteria of obese (n = 6) and lean (homozygous n = 6; heterozygous n = 6) Zucker rats over a 10 week period, maintained in mixed-genotype cages, to further understand the relationships between the composition of the intestinal bacteria and age, obesity progression, genetic background and cage environment. Phylogenetic and taxon-based univariate and multivariate analyses (non-metric multidimensional scaling, principal component analysis) showed that age was the most significant source of variation in the composition of the faecal microbiota. Second to this, cage environment was found to clearly impact the composition of the faecal microbiota, with samples from animals from within the same cage showing high community structure concordance, but large differences seen between cages. Importantly, the genetically induced obese phenotype was not found to impact the faecal bacterial profiles. These findings demonstrate that the age and local environmental cage variables were driving the composition of the faecal bacteria and were more deterministically important than the host genotype. These findings have major implications for understanding the significance of functional metagenomic data in experimental studies and beg the question; what is being measured in animal experiments in which different strains are housed separately, nature or nurture

VLT FORS2 comparative transmission spectroscopy: Detection of Na in the atmosphere of WASP-39b from the ground

We present transmission spectroscopy of the warm Saturn-mass exoplanet WASP-39b made with the Very Large Telescope FOcal Reducer and Spectrograph (FORS2) across the wavelength range 411–810 nm. The transit depth is measured with a typical precision of 240 parts per million (ppm) in wavelength bins of 10 nm on a V = 12.1 mag star. We detect the sodium absorption feature (3.2σ) and find evidence of potassium. The ground-based transmission spectrum is consistent with Hubble Space Telescope (HST) optical spectroscopy, supporting the interpretation that WASP-39b has a largely clear atmosphere. Our results demonstrate the great potential of the recently upgraded FORS2 spectrograph for optical transmission spectroscopy, with which we obtained HST-quality light curves from the ground

Paracetamol metabolism, hepatotoxicity, biomarkers and therapeutic interventions: a perspective

After over 60 years of therapeutic use in the UK, paracetamol (acetaminophen, N-acetyl-p-aminophenol, APAP) remains the subject of considerable research into both its mode of action and toxicity. The pharmacological properties of APAP are the focus of some activity, with the role of the metabolite N-arachidonoylaminophenol (AM404) still a topic of debate. However, that the hepatotoxicity of APAP results from the production of the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI/NABQI) that can deplete glutathione, react with cellular macromolecules, and initiate cell death, is now beyond dispute. The disruption of cellular pathways that results from the production of NAPQI provides a source of potential biomarkers of the severity of the damage. Research in this area has provided new diagnostic markers such as the microRNA miR-122 as well as mechanistic biomarkers associated with apoptosis, mitochondrial dysfunction, inflammation and tissue regeneration. Additionally, biomarkers of, and systems biology models for, glutathione depletion have been developed. Furthermore, there have been significant advances in determining the role of both the innate immune system and genetic factors that might predispose individuals to APAP-mediated toxicity. This perspective highlights some of the progress in current APAP-related research

Evaluation of a standard provision versus an autonomy promotive exercise referral programme: rationale and study design

Background The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials. Recent empirical evidence in health care and physical activity promotion contexts provides a foundation for testing the utility of a Self Determination Theory (SDT) -based exercise referral consultation. Methods/Design Design: An exploratory cluster randomised controlled trial comparing standard provision exercise on prescription with a Self Determination Theory-based (SDT) exercise on prescription intervention. Participants: 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008. The 13 exercise on prescription sites in Birmingham were randomised to current practice (n=7) or to the SDT-based intervention (n=6). Outcomes measured at 3 and 6-months: Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall; physical health: blood pressure and weight; health status measured using the Dartmouth CO-OP charts; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score; motivation and processes of change: perceptions of autonomy support from the advisor, satisfaction of the needs for competence, autonomy, and relatedness via physical activity, and motivational regulations for exercise. Discussion This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a standard programme and will test the underlying SDT-based process model (perceived autonomy support, need satisfaction, motivation regulations, outcomes) via structural equation modelling. Trial registration The trial is registered as Current Controlled trials ISRCTN07682833

Evidence for a pervasive 'idling-mode' activity template in flying and pedestrian insects

This is the final version. Available on open access from the Royal Society via the DOI in this recordUnderstanding the complex movement patterns of animals in natural environments is a key objective of 'movement ecology'. Complexity results from behavioural responses to external stimuli but can also arise spontaneously in their absence. Drawing on theoretical arguments about decision-making circuitry, we predict that the spontaneous patterns will be scale-free and universal, being independent of taxon and mode of locomotion. To test this hypothesis, we examined the activity patterns of the European honeybee, and multiple species of noctuid moth, tethered to flight mills and exposed to minimal external cues. We also reanalysed pre-existing data for Drosophila flies walking in featureless environments. Across these species, we found evidence of common scale-invariant properties in their movement patterns; pause and movement durations were typically power law distributed over a range of scales and characterized by exponents close to 3/2. Our analyses are suggestive of the presence of a pervasive scale-invariant template for locomotion which, when acted on by environmental cues, produces the movements with characteristic scales observed in nature. Our results indicate that scale-finite complexity as embodied, for instance, in correlated random walk models, may be the result of environmental cues overriding innate behaviour, and that scale-free movements may be intrinsic and not limited to 'blind' foragers as previously thought.Rothamsted research receives grant aided support from the Biotechnology and Biological Sciences Research Council. S.W. was funded jointly by a grant from BBSRC, Defra, NERC, the Scottish Government and the Wellcome Trust, under the Insect Pollinators Initiative (grant nos. BB/I00097/1). A.J.P. was funded by a BBSRC Doctoral Training Partnership in Food Security awarded to K.W. and J.W.C. H.B.C.J. was funded by a BBSRC Quota studentship awarded to J.W.C. and J.K.

School Violence Among a Nationally Representative Sample of Adolescents in Chile

Background: School violence is widely acknowledged as a public health problem with considerable consequences on student learning and social development. There are also a wide range of health consequences. A large share of previous research on school violence has focused on populations in the global north, with significant gaps in the state of knowledge in the world's emerging economies. To this end, the present study provides an examination of correlates for school-based violence in Chile using a nationally representative cohort.Methods: Six independent variables were considered (age, sex, physical activity, sedentary life style, bullying victimization, food insecurity) within a logistic regression model to ascertain the strength and direction of associations with physical fighting.Results: Among the surveyed students, ~13.08% reported being involved in two or more physical fights during the twelve month recall period. Males were significantly over represented among those reporting being involved in a fight OR 2.91 (CI = 1.98–4.27). Those who reported experiencing food insecurity were 5.29 (CI = 1.43–19.50) times more likely to have been involved in a physical fight. Students who reported being bullied were 2.41 (CI = 1.67–3.47) times more likely to have been involved in physical fights. While age provided protection from involvement in physical fights with an adjusted odds ratio of 0.91 (CI = 0.84–0.98).Conclusion: Consistent with previous research, our results suggest that the use of school-based interventions that target multiple risk behaviors may be helpful in reducing rates of physical fighting.</p

Wildlife Crime: The application of forensic geoscience to assist with criminal investigations

Wildlife crime is a growing problem in many rural areas. However, it can often be difficult to determine exactly what had happened and provide evidential Court material, especially where evidence is ephemeral. This paper presents a case study where a badger sett had been illegally filled and evidence was rapidly required to support a prosecution before it was either destroyed by the suspect/further badger activities or eroded by weather/time. A topographic surface survey was undertaken, quantifying the number and spatial position of sett entrances, as well as which had been filled by a slurry material. A ground penetrating radar survey was also undertaken to quantify how much tunnels were filled. Study results evidenced five sett tunnels were filled out of twelve observed. The slurry fill material was not being observed elsewhere on the surface. GPR survey data evidenced ~1m -5 m of slurry fill in tunnels. A subsequent report was forwarded to the CPS as evidential material. Study implications suggest the importance of rapid geoscience surveys to assist Police Forces to both gain scientific evidence for prosecutions and to deter future wildlife crime

Leibniz, Acosmism, and Incompossibility

Leibniz claims that God acts in the best possible way, and that this includes creating exactly one world. But worlds are aggregates, and aggregates have a low degree of reality or metaphysical perfection, perhaps none at all. This is Leibniz’s tendency toward acosmism, or the view that there this no such thing as creation-as-a-whole. Many interpreters reconcile Leibniz’s acosmist tendency with the high value of worlds by proposing that God sums the value of each substance created, so that the best world is just the world with the most substances. I call this way of determining the value of a world the Additive Theory of Value (ATV), and argue that it leads to the current and insoluble form of the problem of incompossibility. To avoid the problem, I read “possible worlds” in “God chooses the best of all possible worlds” as referring to God’s ideas of worlds. These ideas, though built up from essences, are themselves unities and so well suited to be the value bearers that Leibniz’s theodicy requires. They have their own value, thanks to their unity, and that unity is not preserved when more essences are added