A key role for leukemia inhibitory factor in C26 cancer cachexia

Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling, and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-κB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. LIF was elevated in C26 conditioned medium (CM), but IL-6, OSM, TNFα, and myostatin were not. A LIF-blocking antibody abolished C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and myotube atrophy but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together, these data support an important role of LIF-JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia.R01 AR060217 - NIAMS NIH HHS; UL1 TR000157 - NCATS NIH HHS; UL1-TR000157 - NCATS NIH HHShttp://www.jbc.org/content/290/32/19976.full.pdf?sid=936d126d-814b-4f54-961d-0e98caa31314Published versio

Free-Roaming Dogs in Developing Countries: The Benefits of Capture, Neuter, and Return Programs

This chapter provides an overview of animal welfare and public health problems associated with free-roaming dog populations and strategies to resolve these problems. Placing CNR programs in the context of earlier dog and rabies control methods, the chapter explores CNR’s potential to overcome some of the shortcomings of earlier approaches and to improve animal welfare, reduce dog population growth, and prevent the spread of rabies and other canine-transmitted diseases. Constraints and current debates on current implementation of CNR programs are also examined

Proceedings from the National Technology Assessment Workshop on Animal Assisted Programs for Youth At Risk

Workshop held December 6-7, 2007 in Baltimore, Maryland Co-sponsored by Humane Society of the United States and Center for Prevention of Youth Violence of the Johns Hopkins University Bloomberg School of Public Health with support from the Laura J. Niles Foundationhttps://www.wellbeingintlstudiesrepository.org/ebooks/1014/thumbnail.jp

Ethical and compliance-competence evaluation: a key element of sound corporate governance

Motivated by the ongoing post-Enron refocusing on corporate governance and the shift by the Financial Services Authority (FSA) in the UK to promoting compliance- competence within the financial services sector, this paper demonstrates how template analysis can be used as a tool for evaluating compliance-competence. Focusing on the ethical dimension of compliance-competence, we illustrate how this can be subjectively appraised. We propose that this evaluation technique could be utilised as a starting point in informing senior management of corporate governance issues and be used to monitor and demonstrate key compliance and ethical aspects of an institution to external stakeholders and regulators

Disentangling bulk polymers from adsorbed polymers using the quartz crystal microbalance

At sufficient adhesion energy, polymers may adsorb irreversibly at an interface, with many adhesion sites per polymer and significant changes in their conformation. In addition to irreversibly adsorbed polymers there may be reversibly adsorbed polymers, which are in dynamic equilibrium with bulk polymers, and which have fewer adhesion sites per polymer and less significant conformational changes. In this work, we simultaneously determine the viscoelasticity of irreversibly adsorbed polymers, reversibly adsorbed polymers, and bulk polymers. To this end, we combine hydrodynamic modelling with quartz crystal microbalance-dissipation (QCM-D) measurements involving an adsorbing target surface and a non-adsorbing, i.e., passivated surface. We apply the method to polyethylene glycol adsorption at the water–silica interface. The results demonstrate that the viscoelasticity of the reversibly adsorbed polymers is similar to that of the bulk polymers, whereas the irreversibly adsorbed polymers are less elastic. This is the first approach to decouple these viscoelastic contributions, which provides a new analytical tool to quantify the kinetics and conformation of reversibly adsorbed polymers, shedding light on polymer dynamics near interfaces

An Audit of Political Behavior Research

What are the most important concepts in the political behavior literature? Have experiments supplanted surveys as the dominant method in political behavior research? What role does the American National Election Studies (ANES) play in this literature? We utilize a content analysis of over 1,100 quantitative articles on American mass political behavior published between 1980 and 2009 to address these questions. We then supplement this with a second sample of articles published between 2010 and 2018. Four key takeaways are apparent. First, the agenda of this literature is heavily skewed toward understanding voting to a relative lack of attention to specific policy attitudes and other topics. Second, experiments are ascendant, but are far from displacing surveys, and particularly the ANES. Third, while important changes to this agenda have occurred over time, it remains much the same in 2018 as it was in 1980. Fourth, the centrality of the ANES seems to stem from its time-series component. In the end, we conclude that the ANES is a critical investment for the scientific community and a main driver of political behavior research

Accumulating exercise and postprandial health in adolescents

ArticleCopyright © 2015 Published by Elsevier Inc.Purpose: To examine the influence of exercise intensity on postprandial health outcomes in adolescents when exercise is accumulated throughout the day. Methods: 19 adolescents (9 male, 13.7 ± 0.4 y) completed three 1-day trials in a randomised order: 1) rest (CON); or four bouts of 2) 2 x 1 min cycling at 90% peak power with 75 s recovery (high-intensity interval exercise; HIIE); or 3) cycling at 90% of the gas exchange threshold (moderate-intensity exercise; MIE), which was work-matched to HIIE. Each bout was separated by 2 hours. Participants consumed a high fat milkshake for breakfast and lunch. Postprandial triacylglycerol (TAG), glucose, systolic blood pressure (SBP) and fat oxidation were assessed throughout the day. Results: There was no effect of trial on total area under the curve (TAUC) for TAG (P=0.87). TAUC-glucose was lower in HIIE compared to CON (P=0.03, ES=0.42) and MIE (P=0.04, ES=0.41), with no difference between MIE and CON (P=0.89, ES=0.04). Postprandial SBP was lower in HIIE compared to CON (P=0.04, ES=0.50) and MIE (P=0.04, ES=0.40), but not different between MIE and CON (P=0.52, ES=0.11). Resting fat oxidation was increased in HIIE compared to CON (P=0.01, ES=0.74) and MIE (P=0.05, ES=0.51), with no difference between MIE and CON (P=0.37, ES=0.24). Conclusion: Neither exercise trial attenuated postprandial lipaemia. However, accumulating brief bouts of HIIE, but not MIE, reduced postprandial plasma glucose and SBP, and increased resting fat oxidation in adolescent boys and girls. The intensity of accumulated exercise may therefore have important implications for health outcomes in youth.Sport and Health Sciences Research Committee, College of Life and Environmental Sciences, University of Exeter

Lookup tables to compute high energy cosmic ray induced atmospheric ionization and changes in atmospheric chemistry

A variety of events such as gamma-ray bursts and supernovae may expose the Earth to an increased flux of high-energy cosmic rays, with potentially important effects on the biosphere. Existing atmospheric chemistry software does not have the capability of incorporating the effects of substantial cosmic ray flux above 10 GeV . An atmospheric code, the NASA-Goddard Space Flight Center two-dimensional (latitude, altitude) time-dependent atmospheric model (NGSFC), is used to study atmospheric chemistry changes. Using CORSIKA, we have created tables that can be used to compute high energy cosmic ray (10 GeV - 1 PeV) induced atmospheric ionization and also, with the use of the NGSFC code, can be used to simulate the resulting atmospheric chemistry changes. We discuss the tables, their uses, weaknesses, and strengths.Comment: In press: Journal of Cosmology and Astroparticle Physics. 6 figures, 3 tables, two associated data files. Major revisions, including results of a greatly expanded computation, clarification and updated references. In the future we will expand the table to at least EeV levels

Comparability of surrogate and self-reported information on melanoma risk factors.

Surrogate reports by patients about their relatives, and vice versa, are potentially of great use in studies of the genetic and environmental causes of the familial aggregation of cancer. To assess the quality of such information in a family study of melanoma aetiology in Queensland, Australia, the authors compared surrogate reports with self-reports of standard melanoma risk factors obtained by mailed self-administered questionnaire. There was moderate agreement between surrogate reports provided by the cases and relatives' self-reports for questions on ability to tan (polychoric correlation coefficient (pc) = 0.60), skin colour (pc = 0.57), average propensity to burn (pc = 0.56), and hair colour at age 21 (kappa coefficient = 0.55), although relatives in the extreme risk factor categories were misclassified by surrogates at least half of the time. Agreement was lower for questions on degree of moliness (pc = 0.45), tendency to acute sunburn (pc = 0.42), and number of episodes of painful sunburn (pc = 0.23). The quality of relatives' surrogate reports about cases was similar to that of cases' surrogate reports about relatives. Cases who reported a family history of melanoma provided better surrogate information than did cases who indicated no family history, and female cases provided better surrogate reports than did males. Cases were better able to report for their parents and children than for their siblings. The authors conclude that when the use of surrogate reports of melanoma risk factors is unavoidable, results should be interpreted cautiously in the light of potentially high rates of misclassification. In particular, surrogate reports appear to be a comparatively poor measure of self-assessment of number of moles, the strongest known phenotypic indicator of melanoma risk, and may bias comparisons between families with and without a history of melanoma