Impaired Inhibitory Control in Recreational Cocaine Users

Chronic use of cocaine is associated with impairment in response inhibition but it is an open question whether and to which degree findings from chronic users generalize to the upcoming type of recreational users. This study compared the ability to inhibit and execute behavioral responses in adult recreational users and in a cocaine-free-matched sample controlled for age, race, gender distribution, level of intelligence, and alcohol consumption. Response inhibition and response execution were measured by a stop-signal paradigm. Results show that users and non users are comparable in terms of response execution but users need significantly more time to inhibit responses to stop-signals than non users. Interestingly, the magnitude of the inhibitory deficit was positively correlated with the individuals lifetime cocaine exposure suggesting that the magnitude of the impairment is proportional to the degree of cocaine consumed

Entrepreneurs' exit and paths to retirement : theoretical and empirical considerations

The number of ageing entrepreneurs in micro- and small-sized companies is rapidly increasing in Finland and other European Union countries. Over half a million jobs, in over one hundred thousand companies within the EU, are lost annually due to unsuccessful, predominantly retirement-related transfers of businesses. This challenge coincides with EU Grand Challenges and has been highlighted in the Entrepreneurship 2020 Action Plan (European Commission 2013). It has been estimated that in Finland, some 8000 jobs are lost yearly due to the ageing of entrepreneurs. Therefore, entrepreneur ageing has implications not only for the ageing individual but also for the company and the society at large. As entrepreneurs age it becomes more essential for them to start planning when and how they transition into retirement. While they may experience several exits and subsequent re-entries into working life via buying or starting new companies, exiting ones entrepreneurial career due to old age retirement differs from exits that occur earlier during the career. In this chapter, we provide a short overview of the entrepreneur retirement and exit literature from an age perspective. Furthermore, we present a theoretical conceptualization which combines entrepreneur retirement process with exit theories. This will enable scholars to better understand the retirement process, including decision-making, transitioning, and adjustment to retirement. We also provide empirical evidence using data collected among Finnish entrepreneurs in 2012 and 2015, where we outline the types of exits and assess several factors, including age, in association with exit intentions.fi=vertaisarvioitu|en=peerReviewed

Suppression of Ribosomal Function Triggers Innate Immune Signaling through Activation of the NLRP3 Inflammasome

Some inflammatory stimuli trigger activation of the NLRP3 inflammasome by inducing efflux of cellular potassium. Loss of cellular potassium is known to potently suppress protein synthesis, leading us to test whether the inhibition of protein synthesis itself serves as an activating signal for the NLRP3 inflammasome. Murine bone marrow-derived macrophages, either primed by LPS or unprimed, were exposed to a panel of inhibitors of ribosomal function: ricin, cycloheximide, puromycin, pactamycin, and anisomycin. Macrophages were also exposed to nigericin, ATP, monosodium urate (MSU), and poly I:C. Synthesis of pro-IL-ß and release of IL-1ß from cells in response to these agents was detected by immunoblotting and ELISA. Release of intracellular potassium was measured by mass spectrometry. Inhibition of translation by each of the tested translation inhibitors led to processing of IL-1ß, which was released from cells. Processing and release of IL-1ß was reduced or absent from cells deficient in NLRP3, ASC, or caspase-1, demonstrating the role of the NLRP3 inflammasome. Despite the inability of these inhibitors to trigger efflux of intracellular potassium, the addition of high extracellular potassium suppressed activation of the NLRP3 inflammasome. MSU and double-stranded RNA, which are known to activate the NLRP3 inflammasome, also substantially inhibited protein translation, supporting a close association between inhibition of translation and inflammasome activation. These data demonstrate that translational inhibition itself constitutes a heretofore-unrecognized mechanism underlying IL-1ß dependent inflammatory signaling and that other physical, chemical, or pathogen-associated agents that impair translation may lead to IL-1ß-dependent inflammation through activation of the NLRP3 inflammasome. For agents that inhibit translation through decreased cellular potassium, the application of high extracellular potassium restores protein translation and suppresses activation of the NLRP inflammasome. For agents that inhibit translation through mechanisms that do not involve loss of potassium, high extracellular potassium suppresses IL-1ß processing through a mechanism that remains undefined

Sport for development and global public health issues:A case study of National Sports Associations

Sport is widely recognised for the contribution it can make to international development goals. More specifically, the value of sport as a tool for development gained its impetus through the HIV/AIDS pandemic in sub-Saharan Africa. The institutionalized relationship between sport and development has mainly focussed on sport-for-development (SfD) non-governmental organisations (NGOs). This study proposed to examine the response of National Sports Associations (NSAs) towards the multisectoral approach for HIV/AIDS prevention in Zambia. The study draws on lessons learnt from how NSAs within a resource-scarce or low-income country responded to a health pandemic. While public health was previously a state and health sector preserve, the impact of HIV/AIDS pandemic influenced not only the way that a pandemic is managed but also other public health issues. A case study approach was adopted comprising of three National Sports Associations (NSAs) as units of analysis. The study utilised semi-structured interviews, documentary analysis and field observations to gain perspectives on how each NSA mainstreamed and implemented work-based health programmes. Using governance and policy network theories, the paper discusses each NSAs’ role in the governance and implementation of a multisectoral approach to a health pandemic. The findings identified lack of engagement of sports agencies at strategic decision-making level, marginalisation of sport by other sectors, and variations in implementation patterns among sports agencies. Further findings indicate that lack of resources among government sport agencies or departments limited their involvement with other state or non-state actors in strategic level meetings or health policy networks. Resource-scarce conditions placed limitations on the political steer of state actors while non-state actors with foreign resources attracted collaboration from other public health policy networks

A quantitative estimation of the global translational activity in logarithmically growing yeast cells.

BACKGROUND: Translation of messenger mRNAs makes significant contributions to the control of gene expression in all eukaryotes. Because translational control often involves fractional changes in translational activity, good quantitative descriptions of translational activity will be required to achieve a comprehensive understanding of this aspect of biology. Data on translational activity are difficult to generate experimentally under physiological conditions, however, translational activity as a parameter is in principle accessible through published genome-wide datasets. RESULTS: An examination of the accuracy of genome-wide expression datasets generated for Saccharomyces cerevisiae shows that the available datasets suffer from large random errors within studies as well as systematic shifts in reported values between studies, which make predictions of translational activity at the level of individual genes relatively inaccurate. In contrast, predictions of cell-wide translational activity are possible from such datasets with higher accuracy, and current datasets predict a production rate of about 13,000 proteins per haploid cell per second under fast growth conditions. This prediction is shown to be consistent with independently derived kinetic information on nucleotide exchange reactions that occur during translation, and on the ribosomal content of yeast cells. CONCLUSIONS: This study highlights some of the limitations in published genome-wide expression datasets, but also demonstrates a novel use for such datasets in examining global properties of cells. The global translational activity of yeast cells predicted in this study is a useful benchmark against which biochemical data on individual translation factor activities can be interpreted