Enhancing energy and glucose metabolism by disrupting triglyceride synthesis: Lessons from mice lacking DGAT1

Although the ability to make triglycerides is essential for normal physiology, excess accumulation of triglycerides results in obesity and is associated with insulin resistance. Inhibition of triglyceride synthesis, therefore, may represent a feasible strategy for the treatment of obesity and type 2 diabetes. Acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) is one of two DGAT enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 have increased energy expenditure and insulin sensitivity and are protected against diet-induced obesity and glucose intolerance. These metabolic effects of DGAT1 deficiency result in part from the altered secretion of adipocyte-derived factors. Studies of DGAT1-deficient mice have helped to provide insights into the mechanisms by which cellular lipid metabolism modulates systemic carbohydrate and insulin metabolism, and a better understanding of how DGAT1 deficiency enhances energy expenditure and insulin sensitivity may identify additional targets or strategies for the treatment of obesity and type 2 diabetes

Simulation of an Optional Strategy in the Prisoner's Dilemma in Spatial and Non-spatial Environments

This paper presents research comparing the effects of different environments on the outcome of an extended Prisoner's Dilemma, in which agents have the option to abstain from playing the game. We consider three different pure strategies: cooperation, defection and abstinence. We adopt an evolutionary game theoretic approach and consider two different environments: the first which imposes no spatial constraints and the second in which agents are placed on a lattice grid. We analyse the performance of the three strategies as we vary the loner's payoff in both structured and unstructured environments. Furthermore we also present the results of simulations which identify scenarios in which cooperative clusters of agents emerge and persist in both environments.Comment: 12 pages, 8 figures. International Conference on the Simulation of Adaptive Behavio

Terpyridyl Complexes as Antimalarial Agents

Anumber of transition metals and their terpyridyl complexes have been evaluated for antimalarial activity on the strain 3D7. The metals, ligands and complexes were each in turn investigated for their efficacy. All activities were in the sub-micromolar range (0.1–1 μM). Their modes of action were compared with that of chloroquine to discover whether or not they were capable of inhibiting haemozoin formation. The data indicate that efficacy could be a result of several mechanisms and that speciation of the metal complex and the manner in which the agents are added to the parasitic broth have a profound effect on the activity of the agents. We believe that our study offers a template by which other researchers should approach their experiments using transition metal complex agents.KEYWORDS Antimalarial agents, terpyridyl and transition metals

Postnatal checks and primary care consultations in the year following childbirth: an observational cohort study of 309573 women in the UK, 2006-2016

Objective To describe women’s uptake of postnatal checks and primary care consultations in the year following childbirth. Design Observational cohort study using electronic health records. Setting UK primary care. Participants Women aged 16–49 years who had given birth to a single live infant recorded in The Health Improvement Network (THIN) primary care database in 2006–2016. Main outcome measures Postnatal checks and direct consultations in the year following childbirth. Results We examined 1 427 710 consultations in 309 573 women who gave birth to 241 662 children in 2006–2016. Of these women, 78.7% (243 516) had a consultation at the time of the postnatal check, but only 56.2% (174 061) had a structured postnatal check documented. Teenage women (aged 16–19 years) were 12% less likely to have a postnatal check compared with those aged 30–35 years (incidence rate ratio (IRR) 0.88, 95% CI 0.85 to 0.91) and those living in the most deprived versus least deprived areas were 10% less likely (IRR 0.90, 95% CI 0.88 to 0.92). Women consulted on average 4.8 times per woman per year and 293 049 women (94.7%) had at least one direct consultation in the year after childbirth. Consultation rates were higher for those with a caesarean delivery (7.7 per woman per year, 95% CI 7.7 to 7.8). Consultation rates peaked during weeks 5–10 following birth (11.8 consultations/100 women) coinciding with the postnatal check. Conclusions Two in 10 women did not have a consultation at the time of the postnatal check and four in 10 women have no record of receiving a structured postnatal check within the first 10 weeks after giving birth. Teenagers and those from the most deprived areas are among the least likely to have a check. We estimate up to 350 400 women per year in the UK may be missing these opportunities for timely health promotion and to have important health needs identified following childbirth

Apparent mass of small children: Experimental measurements

A test facility and protocol were developed for measuring the seated, vertical, whole-body vibration response of small children of less than 18 kg in mass over the frequency range from 1 to 45 Hz. The facility and protocol adhered to the human vibration testing guidelines of BS7085 and to current codes of ethics for research involving children. Additional procedures were also developed which are not currently defined in the guidelines, including the integral involvement of the parents and steps taken to maximize child happiness. Eight children were tested at amplitudes of 0.8 and 1.2 m/s2 using band-limited, Gaussian, white noise acceleration signals defined over the frequency interval from 1 to 50 Hz. Driving point apparent mass modulus and phase curves were determined for all eight children at both test amplitudes. All results presented a single, principal, anti-resonance, and were similar to data reported for primates and for adult humans seated in an automotive posture which provided backrest support. The mean frequency of the apparent mass peak was 6.25 Hz for the small children, as compared to values between 6.5 - 8.5 Hz for small primates and values between 6.5 - 8.6 Hz for adults seated with backrest support. The peak value of the mean, normalized, apparent mass was 1.54 for the children, which compares to values from 1.19 to 1.45 reported in the literature for small primates and 1.28 for adults seated with backrest support. ISO standard 5982, which specifies a mean, normalized, apparent mass modulus peak of 1.50 at a frequency of 4.0 Hz for adults seated without backrest support, provides significant differences

In Vivo Assessment of Arsenic Bioavailability in Rice and Its Significance for Human Health Risk Assessment

BACKGROUND: Millions of people worldwide consume arsenic-contaminated rice; however, little is known about the uptake and bioavailability of arsenic species after arsenic-contaminated rice ingestion. OBJECTIVES: In this study, we assessed arsenic speciation in greenhouse-grown and supermarket-bought rice, and determined arsenic bioavailability in cooked rice using an in vivo swine model. RESULTS: In supermarket-bought rice, arsenic was present entirely in the inorganic form compared to greenhouse-grown rice (using irrigation water contaminated with sodium arsenate), where most (~ 86%) arsenic was present as dimethylarsinic acid (organic arsenic). Because of the low absolute bioavailability of dimethylarsinic acid and the high proportion of dimethylarsinic acid in greenhouse-grown rice, only 33 ± 3% (mean ± SD) of the total rice-bound arsenic was bioavailable. Conversely, in supermarket-bought rice cooked in water contaminated with sodium arsenate, arsenic was present entirely in the inorganic form, and bioavailability was high (89 ± 9%). CONCLUSIONS: These results indicate that arsenic bioavailability in rice is highly dependent on arsenic speciation, which in turn can vary depending on rice cultivar, arsenic in irrigation water, and the presence and nature of arsenic speciation in cooking water. Arsenic speciation and bioavailability are therefore critical parameters for reducing uncertainties when estimating exposure from the consumption of rice grown and cooked using arsenic-contaminated water

Film support and the challenge of ‘sustainability’: on wing design, wax and feathers, and bolts from the blue

In recognition of the importance of film in generating both economic and cultural value, the UK Labour government set up a new agency – the United Kingdom Film Council (UKFC) – in 2000 with a remit to build a sustainable film industry. But, reflecting a plethora of differing expectations in relation to the purposes behind public support for film, the UKFC's agenda shifted and broadened over the organisation's lifetime (2000–11). Apparently unconvinced by the UKFC's achievements, the Coalition government which came to power in May 2010 announced the Council's abolition and reassigned its responsibilities as part of a general cost-cutting strategy. Based on original empirical research, this article examines how the UKFC's sense of strategic direction was determined, how and why the balance of objectives it pursued changed over time and what these shifts tell us about the nature of film policy and the challenges facing bodies that are charged with enacting it in the twenty-first century