Adipokines have a role to play in the treatment of metabolic disease

Editoria

Effect of n-3 fatty acids on the antitumour effects of cytotoxic drugs

Background: n-3 fatty acids are increasingly being administered to cancer patients for the treatment of cachexia, and it is thus important to know of any potential interactions with ongoing cytotoxic drug therapy. Materials and methods: For this reason eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were administered to mice bearing the cachexia-inducing MAC16 colon adenocarcinoma, and the effect of epothilone, gemcitabine, 5-fluorouracil and cyclophosphamide on tumour growth and body weight determined. Results: Epothilone alone had a minimal effect on tumour growth rate, but this was potentiated by DHA, while for 5-fluorouracil and cyclophosphamide tumour growth inhibition was enhanced by EPA. The antitumour effect of gemcitabine was not altered by either fatty acid. EPA arrested the development of cachexia, while DHA had no effect and the same was true for their effect on tumour growth rate. The anticachectic effect of EPA was only seen in combination with 5-fluorouracil. Conclusion: These results suggest that n-3 fatty acids do not interfere with the action of chemotherapy and may potentiate the effect of certain agents

Attenuation of skeletal muscle atrophy in cancer cachexia by d-myo-inositol 1,2,6-triphosphate

PURPOSE: To determine the effectiveness of the polyanionic, metal binding agent D-myo-inositol-1,2,6-triphosphate (alpha trinositol, AT), and its hexanoyl ester (HAT), in tissue wasting in cancer cachexia. METHODS: The anti-cachexic effect was evaluated in the MAC16 tumour model. RESULTS: Both AT and HAT attenuated the loss of body weight through an increase in the nonfat carcass mass due to an increase in protein synthesis and a decrease in protein degradation in skeletal muscle. The decrease in protein degradation was associated with a decrease in activity of the ubiquitin-proteasome proteolytic pathway and caspase-3 and -8. Protein synthesis was increased due to attenuation of the elevated autophosphorylation of double-stranded RNA-dependent protein kinase, and of eukaryotic initiation factor 2alpha together with hyperphosphorylation of eIF4E-binding protein 1 and decreased phosphorylation of eukaryotic elongation factor 2. In vitro, AT completely attenuated the protein degradation in murine myotubes induced by both proteolysis-inducing factor and angiotensin II. CONCLUSION: These results show that AT is a novel therapeutic agent with the potential to alleviate muscle wasting in cancer patients

A tri-dimensional approach for auditing brand loyalty

Over the past twenty years brand loyalty has been an important topic for both marketing practitioners and academics. While practitioners have produced proprietary brand loyalty audit models, there has been little academic research to make transparent the methodology that underpins these audits and to enable practitioners to understand, develop and conduct their own audits. In this paper, we propose a framework for a brand loyalty audit that uses a tri-dimensional approach to brand loyalty, which includes behavioural loyalty and the two components of attitudinal loyalty: emotional and cognitive loyalty. In allowing for different levels and intensity of brand loyalty, this tri-dimensional approach is important from a managerial perspective. It means that loyalty strategies that arise from a brand audit can be made more effective by targeting the market segments that demonstrate the most appropriate combination of brand loyalty components. We propose a matrix with three dimensions (emotional, cognitive and behavioural loyalty) and two levels (high and low loyalty) to facilitate a brand loyalty audit. To demonstrate this matrix, we use the example of financial services, in particular a rewards-based credit card

Canopy nitrogen, carbon assimilation, and albedo in temperate and boreal forests: Functional relations and potential climate feedbacks

The availability of nitrogen represents a key constraint on carbon cycling in terrestrial ecosystems, and it is largely in this capacity that the role of N in the Earth\u27s climate system has been considered. Despite this, few studies have included continuous variation in plant N status as a driver of broad-scale carbon cycle analyses. This is partly because of uncertainties in how leaf-level physiological relationships scale to whole ecosystems and because methods for regional to continental detection of plant N concentrations have yet to be developed. Here, we show that ecosystem CO2 uptake capacity in temperate and boreal forests scales directly with whole-canopy N concentrations, mirroring a leaf-level trend that has been observed for woody plants worldwide. We further show that both CO2 uptake capacity and canopy N concentration are strongly and positively correlated with shortwave surface albedo. These results suggest that N plays an additional, and overlooked, role in the climate system via its influence on vegetation reflectivity and shortwave surface energy exchange. We also demonstrate that much of the spatial variation in canopy N can be detected by using broad-band satellite sensors, offering a means through which these findings can be applied toward improved application of coupled carbon cycle–climate models

The effects of climatic fluctuations and extreme events on running water ecosystems

Most research on the effects of environmental change in freshwaters has focused on incremental changes in average conditions, rather than fluctuations or extreme events such as heatwaves, cold snaps, droughts, floods or wildfires, which may have even more profound consequences. Such events are commonly predicted to increase in frequency, intensity and duration with global climate change, with many systems being exposed to conditions with no recent historical precedent. We propose a mechanistic framework for predicting potential impacts of environmental fluctuations on running water ecosystems by scaling up effects of fluctuations from individuals to entire ecosystems. This framework requires integration of four key components: effects of the environment on individual metabolism, metabolic and biomechanical constraints on fluctuating species interactions, assembly dynamics of local food webs and mapping the dynamics of the meta-community onto ecosystem function. We illustrate the framework by developing a mathematical model of environmental fluctuations on dynamically assembling food webs. We highlight (currently limited) empirical evidence for emerging insights and theoretical predictions. For example, widely supported predictions about the effects of environmental fluctuations are: high vulnerability of species with high per capita metabolic demands such as large-bodied ones at the top of food webs; simplification of food web network structure and impaired energetic transfer efficiency; reduced resilience and top-down relative to bottom-up regulation of food web and ecosystem processes. We conclude by identifying key questions and challenges that need to be addressed to develop more accurate and predictive bio-assessments of the effects of fluctuations, and implications of fluctuations for management practices in an increasingly uncertain world

Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome).

We report an allelic series of eight mutations in GATA2 underlying Emberger syndrome, an autosomal dominant primary lymphedema associated with a predisposition to acute myeloid leukemia. GATA2 is a transcription factor that plays an essential role in gene regulation during vascular development and hematopoietic differentiation. Our findings indicate that haploinsufficiency of GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in this syndrome

SNR 1E 0102.2-7219 as an X-ray calibration standard in the 0.5−1.0 keV bandpass and its application to the CCD instruments aboard Chandra , Suzaku , Swift and XMM-Newton

Context. The flight calibration of the spectral response of charge-coupled device (CCD) instruments below 1.5 keV is difficult in general because of the lack of strong lines in the on-board calibration sources typically available. This calibration is also a function of time due to the effects of radiation damage on the CCDs and/or the accumulation of a contamination layer on the filters or CCDs. Aims. We desire a simple comparison of the absolute effective areas of the current generation of CCD instruments onboard the following observatories: Chandra ACIS-S3, XMM-Newton (EPIC-MOS and EPIC-pn), Suzaku XIS, and Swift XRT and a straightforward comparison of the time-dependent response of these instruments across their respective mission lifetimes. Methods. We have been using 1E 0102.2-7219, the brightest supernova remnant in the Small Magellanic Cloud, to evaluate and modify the response models of these instruments. 1E 0102.2-7219 has strong lines of O, Ne, and Mg below 1.5 keV and little or no Fe emission to complicate the spectrum. The spectrum of 1E 0102.2-7219 has been well-characterized using the RGS gratings instrument on XMM-Newton and the HETG gratings instrument on Chandra. As part of the activities of the International Astronomical Consortium for High Energy Calibration (IACHEC), we have developed a standard spectral model for 1E 0102.2-7219 and fit this model to the spectra extracted from the CCD instruments. The model is empirical in that it includes Gaussians for the identified lines, an absorption component in the Galaxy, another absorption component in the SMC, and two thermal continuum components with different temperatures. In our fits, the model is highly constrained in that only the normalizations of the four brightest lines/line complexes (the O vii Heα triplet, O viii Lyα line, the Ne ix Heα triplet, and the Ne x Lyα line) and an overall normalization are allowed to vary, while all other components are fixed. We adopted this approach to provide a straightforward comparison of the measured line fluxes at these four energies. We have examined these measured line fluxes as a function of time for each instrument after applying the most recent calibrations that account for the time-dependent response of each instrument. Results. We performed our effective area comparison with representative, early mission data when the radiation damage and contamination layers were at a minimum, except for the XMM-Newton EPIC-pn instrument which is stable in time. We found that the measured fluxes of the O vii Heαr line, the O viii Lyα line, the Ne ix Heαr line, and the Ne x Lyα line generally agree to within ±10% for all instruments, with 38 of our 48 fitted normalizations within ± 10% of the IACHEC model value. We then fit all available observations of 1E 0102.2-7219 for the CCD instruments close to the on-axis position to characterize the time dependence in the 0.5−1.0 keV band. We present the measured line normalizations as a function of time for each CCD instrument so that the users may estimate the uncertainty in their measured line fluxes for the epoch of their observations

Finding meaning: HIV self-management and wellbeing among people taking antiretroviral therapy in Uganda

© 2016 Russell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original author and source are credited. The health of people living with HIV (PLWH) and the sustained success of antiretroviral therapy (ART) programmes depends on PLWH's motivation and ability to self-manage the condition over the long term, including adherence to drugs on a daily basis. PLWH's selfmanagement of HIV and their wellbeing are likely to be interrelated. Successful self-management sustains wellbeing, and wellbeing is likely to motivate continued self-management. Detailed research is lacking on PLWH's self-management processes on ART in resourcelimited settings. This paper presents findings from a study of PLWH's self-management and wellbeing in Wakiso District, Uganda. Thirty-eight PLWH (20 women, 18 men) were purposefully selected at ART facilities run by the government and by The AIDS Support Organisation in and around Entebbe. Two in-depth interviews were completed with each participant over three or four visits. Many were struggling economically, however the recovery of health and hope on ART had enhanced wellbeing and motivated self-management. The majority were managing their condition well across three broad domains of self-management. First, they had mobilised resources, notably through good relationships with health workers. Advice and counselling had helped them to reconceptualise their condition and situation more positively and see hope for the future, motivating their work to self-manage. Many had also developed a new network of support through contacts they had developed at the ART clinic. Second, they had acquired knowledge and skills to manage their health, a useful framework to manage their condition and to live their life. Third, participants were psychologically adjusting to their condition and their new 'self': They saw HIV as a normal disease, were coping with stigma and had regained self-esteem, and were finding meaning in life. Our study demonstrates the centrality of social relationships and other nonmedical aspects of wellbeing for self-management which ART programmes might explore further and encourage

Meta-Milgram:An Empirical Synthesis of the Obedience Experiments

Milgram's famous experiment contained 23 small-sample conditions that elicited striking variations in obedient responding. A synthesis of these diverse conditions could clarify the factors that influence obedience in the Milgram paradigm. We assembled data from the 21 conditions (N = 740) in which obedience involved progression to maximum voltage (overall rate 43.6%) and coded these conditions on 14 properties pertaining to the learner, the teacher, the experimenter, the learner-teacher relation, the experimenter-teacher relation, and the experimental setting. Logistic regression analysis indicated that eight factors influenced the likelihood that teachers continued to the 450 volt shock: the experimenter's directiveness, legitimacy, and consistency; group pressure on the teacher to disobey; the indirectness, proximity, and intimacy of the relation between teacher and learner; and the distance between the teacher and the experimenter. Implications are discussed