Computational and transcriptional evidence for microRNAs in the honey bee genome

A total of 68 non-redundant candidate honey bee miRNAs were identified computationally; several of them appear to have previously unrecognized orthologs in the Drosophila genome. Several miRNAs showed caste- or age-related differences in transcript abundance and are likely to be involved in regulating honey bee development

Non-Equilibrium Social Science and Policy

Between 2011 and 2014 the European Non-Equilibrium Social Science Project (NESS) investigated the place of equilibrium in the social sciences and policy. Orthodox economics is based on an equilibrium view of how the economy functions and does not offer a complete description of how the world operates. However, mainstream economics is not an empty box. Its fundamental insight, that people respond to incentives, may be the only universal law of behaviour in the social sciences. Only economics has used equilibrium as a primary driver of system behaviour, but economics has become much more empirical at the microlevel over the past two decades. This is due to two factors: advances in statistical theory enabling better estimates of policy consequences at the microlevel, and the rise of behavioural economics which looks at how people, firms and governments really do behave in practice. In this context, this chapter briefly reviews the contributions of this book across the social sciences and ends with a discussion of the research themes that act as a roadmap for further research. These include: realistic models of agent behaviour; multilevel systems; policy informatics; narratives and decision making under uncertainty; and validation of agent-based complex systems models

The p53 codon 72 proline allele is endowed with enhanced cell-death inducing potential in cancer cells exposed to hypoxia

The preferential retention of the arginine allele at the p53 codon 72 locus is commonly observed in tumours from arginine/proline heterozygotes. Considering that cancer cells are harboured in a hypoxic environment in vivo, we here tested the hypothesis that the p53 codon 72 proline allele confers a survival disadvantage in presence of hypoxia. Here, we show that the transient transfection of the proline allele in p53 null cancer cells exposed to low oxygen tension or to the hypoxia-mimetic drug Desferoxamine induces a higher amount of cell death than the arginine allele. Accordingly, proline allele transiently transfected cell lines express lower levels of hypoxia pro-survival genes (HIF-1α, carbonic anhydrase IX, vascular endothelial growth factor, heme oxygenase-I, hepatocyte growth factor receptor, vascular endothelial growth factor receptor 2), compared to those transiently transfected with the arginine allele. Further, we report that the exposure of the arginine/proline heterozygote MCF-7 breast cancer cell line to cytotoxic concentration of Desferoxamine for several weeks, gives raise to hypoxia-resistant clones, carrying the arginine, but not the proline allele. These data indicate that the p53 codon 72 proline allele is less permissive for the growth of cancer cells in a hypoxic environment, and suggest that the preferential retention of the arginine allele in the tumour tissues of arginine/proline heterozygous patients may depend upon its lowered capacity to induce cell death in a hypoxic tumour environment

Global Systems Science and Policy

The vision of Global Systems Science (GSS) is to provide scientific evidence and means to engage into a reflective dialogue to support policy-making and public action and to enable civil society to collectively engage in societal action in response to global challenges like climate change, urbanisation, or social inclusion. GSS has four elements: policy and its implementation, the science of complex systems, policy informatics, and citizen engagement. It aims to give policy makers and citizens a better understanding of the possible behaviours of complex social systems. Policy informatics helps generate and evaluate policy options with computer-based tools and the abundance of data available today. The results they generate are made accessible to everybody—policymakers, citizens—through intuitive user interfaces, animations, visual analytics, gaming, social media, and so on. Examples of Global Systems include epidemics, finance, cities, the Internet, trade systems and more. GSS addresses the question of policies having desirable outcomes, not necessarily optimal outcomes. The underpinning idea of GSS is not to precisely predict but to establish possible and desirable futures and their likelihood. Solving policy problems is a process, often needing the requirements, constraints, and lines of action to be revisited and modified, until the problem is ‘satisficed’, i.e. an acceptable compromise is found between competing objectives and constraints. Thus policy problems and their solutions coevolve much as in a design process. Policy and societal action is as much about attempts to understand objective facts as it is about the narratives that guide our actions. GSS tries to reconcile these apparently contradictory modes of operations. GSS thus provides policy makers and society guidance on their course of action rather than proposing (illusionary) optimal solutions

Decrease in shunt volume in patients with cryptogenic stroke and patent foramen ovale

<p>Abstract</p> <p>Background</p> <p>In patients with patent foramen ovale (PFO) there is evidence supporting the hypothesis of a change in right-to-left shunt (RLS) over time. Proven, this could have implications for the care of patients with PFO and a history of stroke. The following study addressed this hypothesis in a cohort of patients with stroke and PFO.</p> <p>Methods</p> <p>The RLS volume assessed during hospitalisation for stroke (index event/T0) was compared with the RLS volume on follow-up (T1) (median time between T0 and T1 was 10 months). In 102 patients with a history of stroke and PFO the RLS volume was re-assessed on follow-up using contrast-enhanced transcranial Doppler/duplex (ce-TCD) ultrasound. A change in RLS volume was defined as a difference of ≥20 microembolic signals (MES) or no evidence of RLS during ce-TCD ultrasound on follow-up.</p> <p>Results</p> <p>There was evidence of a marked reduction in RLS volume in 31/102 patients; in 14/31 patients a PFO was no longer detectable. An index event classified as cryptogenic stroke (P < 0.001; OD = 39.2, 95% confidence interval 6.0 to 258.2) and the time interval to the follow-up visit (P = 0.03) were independently associated with a change in RLS volume over time.</p> <p>Conclusions</p> <p>RLS volume across a PFO decreases over time, especially in patients with cryptogenic stroke. These may determine the development of new strategies for the management in the secondary stroke prevention.</p

Investigation of Association between PFO Complicated by Cryptogenic Stroke and a Common Variant of the Cardiac Transcription Factor GATA4

Patent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke

Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry

OBJECTIVES: This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. METHODS: RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. RESULTS: Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. CONCLUSION: Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies