Fat and carbohydrate intake over three generations modify growth, metabolism and cardiovascular phenotype in female mice in an age-related manner

Environmental challenges such as a high fat diet during pregnancy can induce changes in offspring growth, metabolism and cardiovascular function. However, challenges that are sustained over several generations can induce progressive compensatory metabolic adjustments in young adults. It is not known if such effects persist during ageing. We investigated whether diets with different fat and carbohydrate contents over three generations modifies markers of ageing. Female C57BL/6 F0 mice were fed diets containing 5% or 21% fat (w/w) throughout pregnancy and lactation. Female offspring were fed the same diet as their dams until the F3 generation. In each generation, body weight, 24-hour food intake were recorded weekly, and plasma metabolites were measured by colorimetric assays, blood pressure by tail cuff plethysmography and vasoconstriction by myography on postnatal day 90 or 456. There was little effect of diet or generation on phenotypic markers in day 90 adults. There was a significant increase in whole body, liver and heart weight with ageing (d456) in the F3 21% fat group compared to the F1 and F3 5% groups. Fasting plasma glucose concentration was significantly increased with ageing in the 5% group in the F3 generation and in the 21% group in both generations. There was a significant effect of diet and generation on ex-vivo vasoconstriction in ageing females. Differences in dietary fat may induce metabolic compensation in young adults that persist over three generations. However, such compensatory effects decline during ageing

The open source guild: creating more sustainable enterprise?

© 2017, © Emerald Publishing Limited. Purpose: The purpose of this paper is to report on an action research project with two emergent micro-businesses that explored how their business model connected with the principles of open source. Design/methodology/approach: The authors first gained initial qualitative data to establish the core values of each micro-business, which the authors then explored in the context of open source and business models in two design workshops with each organisation. Findings: The authors developed the open source guild business model, which has the elements of: building a focal micro-business with resources secured through the guild, promoting learning and development through apprenticeship, promoting shared values through a commons of experience and capturing value by protecting key intellectual property. Research limitations/implications: This research was undertaken with two emergent micro-businesses in the North West of England. Further research will be needed to establish the wider applicability of the open source guild model. Practical implications: The open source guild model can be a mechanism for an emergent micro-business to create a community around their values and grow their business without conventional external investment of resources. Originality/value: This research contributes to the literature on business models based on open source and how these models can be sustainable in terms of the quadruple bottom line, which extends the triple bottom line to include personal values and meaning

Agents in decentralised information ecosystems: the DIET approach

The complexity of the current global information infrastructure requires novel means of understanding and exploiting the dynamics of information. One means may be through the concept of an information ecosystem. An information ecosystem is analo gous to a natural ecosystem in which there are flo ws of materials and energy analo gous to information flow between many interacting individuals. This paper describes a multi-agent platform, DIET (Decentralised Information Ecosystem Technologies) that can be used to implement open, robust, adaptive and scalable ecosystem-inspired systems. We describe the design principles of the DIET software architecture, and present a simple example application based upon it. We go on to consider how the DIET system can be used to develop information brokering agents, and how these can contribute to the implementation of economic interactions between agents, as well as identifying some open questions relating to research in these areas. In this way we show the capacity of the DIET system to support applications using information agents.Future and Emerging Technologies arm of the IST Programme of the European Union, under the FET Proactive Initiative – Universal Information Ecosystems (FET, 1999), through project DIET (IST -1999-10088), BTexaCT Intelligent Systems Laboratory for stimulating discussion and comment

Progressive, Transgenerational Changes in Offspring Phenotype and Epigenotype following Nutritional Transition

Induction of altered phenotypes during development in response to environmental input involves epigenetic changes. Phenotypic traits can be passed between generations by a variety of mechanisms, including direct transmission of epigenetic states or by induction of epigenetic marks de novo in each generation. To distinguish between these possibilities we measured epigenetic marks over four generations in rats exposed to a sustained environmental challenge. Dietary energy was increased by 25% at conception in F0 female rats and maintained at this level to generation F3. F0 dams showed higher pregnancy weight gain, but lower weight gain and food intake during lactation than F1 and F2 dams. On gestational day 8, fasting plasma glucose concentration was higher and β-hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPARα and carnitine palmitoyl transferase-1 mRNA expression. PEPCK mRNA expression was inversely related to the methylation of specific CpG dinucleotides in its promoter. DNA methyltransferase (Dnmt) 3a2, but not Dnmt1 or Dnmt3b, expression increased and methylation of its promoter decreased from F1 to F3 generations. These data suggest that the regulation of energy metabolism during pregnancy and lactation within a generation is influenced by the maternal phenotype in the preceding generation and the environment during the current pregnancy. The transgenerational effects on phenotype were associated with altered DNA methylation of specific genes in a manner consistent with induction de novo of epigenetic marks in each generation

Vascular Dysfunction Induced in Offspring by Maternal Dietary Fat Involves Altered Arterial Polyunsaturated Fatty Acid Biosynthesis

Nutrition during development affects risk of future cardiovascular disease. Relatively little is known about whether the amount and type of fat in the maternal diet affect vascular function in the offspring. To investigate this, pregnant and lactating rats were fed either 7%(w/w) or 21%(w/w) fat enriched in either18:2n-6, trans fatty acids, saturated fatty acids, or fish oil. Their offspring were fed 4%(w/w) soybean oil from weaning until day 77. Type and amount of maternal dietary fat altered acetylcholine (ACh)-mediated vaso-relaxation in offspring aortae and mesenteric arteries, contingent on sex. Amount, but not type, of maternal dietary fat altered phenylephrine (Pe)-induced vasoconstriction in these arteries. Maternal 21% fat diet decreased 20:4n-6 concentration in offspring aortae. We investigated the role of Δ6 and Δ5 desaturases, showing that their inhibition in aortae and mesenteric arteries reduced vasoconstriction, but not vaso-relaxation, and the synthesis of specific pro-constriction eicosanoids. Removal of the aortic endothelium did not alter the effect of inhibition of Δ6 and Δ5 desaturases on Pe-mediated vasoconstriction. Thus arterial smooth muscle 20:4n-6 biosynthesis de novo appears to be important for Pe-mediated vasoconstriction. Next we studied genes encoding these desaturases, finding that maternal 21% fat reduced Fads2 mRNA expression and increased Fads1 in offspring aortae, indicating dysregulation of 20:4n-6 biosynthesis. Methylation at CpG −394 bp 5′ to the Fads2 transcription start site predicted its expression. This locus was hypermethylated in offspring of dams fed 21% fat. Pe treatment of aortae for 10 minutes increased Fads2, but not Fads1, mRNA expression (76%; P<0.05). This suggests that Fads2 may be an immediate early gene in the response of aortae to Pe. Thus both amount and type of maternal dietary fat induce altered regulation of vascular tone in offspring though differential effects on vaso-relaxation, and persistent changes in vasoconstriction via epigenetic processes controlling arterial polyunsaturated fatty acid biosynthesis

The legacies of coercion and the challenges of contingency: Mozambican unions in difficult times

Although insecure work may be found everywhere, the general lack of secure work in emerging economies is a particularly striking feature of the contemporary condition, undermining the continued viability of the labour movement in such countries. Yet, this topic is rarely tackled directly in African studies or business history journals. The two key questions addressed in this paper are, first, to what extent does the labour movement’s past define their present and future, and second, what are the challenges and opportunities affecting their ability to mobilise workers, influence government and effectively tackle employment security? This article details how in Mozambique, unions’ ability to mobilise has been affected by: the post-colonial, post-conflict and post-socialist historical context; the resulting legacies of regional and racial discrimination; international imperatives for liberalisation and privatisation; challenging relationships with the country’s African neighbours; and high levels of informal sector work. In order to remain viable, key imperatives include: effectively influencing national government, engaging internationally and working with organisations representing informal sector workers

Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.

BACKGROUND: Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial. PURPOSE: To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending pound5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants. METHODS: Single blind controlled trials with allocation concealment. INTERVENTIONS: Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with pound5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures. RESULTS: Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6-4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference -0.2 (95% CI -0.6-0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4-6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7-5.2). LIMITATIONS: There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic. CONCLUSION: Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a pound5 reimbursement for participants' time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265-273. http://ctj.sagepub.com

A novel form of a pointing device

This paper presents a novel approach for man machine interaction applying real time computer vision techniques

Supplementation with n-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells

BACKGROUND: Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans.METHODS AND RESULTS: We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5' regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (&gt;10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (&gt;10%) 1/12 ELOVL5 CpGs in men. OO altered (&gt;6%) 8/22 FADS2 CpGs and (&gt;3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (&gt;5%) 3/22 FADS2 CpGs and 2/12 (&gt;3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts.CONCLUSIONS: These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function