Communicating climate knowledge proxies, processes, politics

This forum article is the product of interdisciplinary discussion at a conference on climate histories held inCambridge, United Kingdom, in early 2011, with the specific aim of building a network around the issue of communicating cultural knowledge of environmental change. The lead articles, by Kirsten Hastrup as an anthropologist and Simon Schaffer as a historian of science, highlight the role of agents and proxies. These are followed by five interdisciplinary commentaries, which engage with the lead articles through new ethnographic material, and a set of shorter commentaries by leading scholars of different disciplines. Finally, the lead authors respond to the discussion. In this debate, climate change does not emerge as a single preformed "problem." Rather, different climate knowledges appear as products of particular networks and agencies. Just as the identification of proxies creates agents (ice, mountains, informants) by inserting them into new networks, we hope that these cross-disciplinary exchanges will produce further conversations and new approaches to action. © 2012 by The Wenner-Gren Foundation for Anthropological Research

Complementary activation of peripheral natural killer cell immunity in nasopharyngeal carcinoma

NK cells and αβ- and γδ-CTL play important roles in cellular immunity against tumors. We previously demonstrated that NPC patients have a quantitative and qualitative deficit in γδ-CTL and EBV-specific αβ-CTL when compared to normal subjects and NPC long-term survivors. In this study we report further observations of a complementary activation of peripheral NK cells in NPC patients. The NK cells in these patients, compared to those of healthy subjects and NPC survivors, were preferentially activated in response to the stimulation of myeloma cell line XG-7 and expanded in the presence of exogenous IL-2. The production of IFN-γ was lowest in the patient group, whereas IL-12, IL-15 and TNF-α were produced in higher levels in patients than in the donors and survivors. The cytolytic effect of the NK cells against NPC cells in the patient group was also higher than that of the donors and survivors. Furthermore, the patients at later stages of NPC had lower γδ-CTL activity but higher NK cytotoxicity towards NPC targets, with higher production of IL-12, IL-15 and TNF-α but lower production of IFN-γ than in patients at earlier stages. This might be part of a triggered compensatory re-activation of the innate immunity, believed to be mediated through various cytokines and chemokines when adaptive T cell immunity is breached. Together, these data suggest complementary roles of innate and adaptive immune response in tumor immunity where NK cells, γδ- and αβ-CTL compensate for the deficits of one another at different stages of tumor invasion. © 2006 Japanese Cancer Association.published_or_final_versio

Protocol for the insight study: a randomised controlled trial of single-dose tocilizumab in patients with depression and low-grade inflammation.

INTRODUCTION: Observational studies indicate a potentially causal role for interleukin 6 (IL-6), a proinflammatory cytokine, in pathogenesis of depression, but interventional studies based on patients with depression have not been conducted. Tocilizumab, anti-inflammatory drug, is a humanised monoclonal antibody that inhibits IL-6 signalling and is licensed in the UK for treatment of rheumatoid arthritis. The main objectives of this study are to test whether IL-6 contributes to the pathogenesis of depression and to examine potential mechanisms by which IL-6 affects mood and cognition. A secondary objective is to compare depressed participants with and without evidence of low-grade systemic inflammation. METHODS AND ANALYSIS: This is a proof-of-concept, randomised, parallel-group, double-blind, placebo-controlled clinical trial. Approximately 50 participants with International Classification of Diseases 10th revision (ICD-10) diagnosis of depression who have evidence of low-grade inflammation, defined as serum high-sensitivity C reactive protein (hs-CRP) level ≥3 mg/L, will receive either a single intravenous infusion of tocilizumab or normal saline. Blood samples, behavioural and cognitive measures will be collected at baseline and after infusion around day 7, 14 and 28. The primary outcome is somatic symptoms score around day 14 postinfusion. In addition, approximately, 50 depressed participants without low-grade inflammation (serum hs-CRP level <3 mg/L) will complete the same baseline assessments as the randomised cohort. ETHICS AND DISSEMINATION: The study has been approved by the South Central-Oxford B Research Ethics Committee (REC) (Reference: 18/SC/0118). Study findings will be published in peer-review journals. Findings will be also disseminated by conference/departmental presentations and by social and traditional media. TRIAL REGISTRATION NUMBER: ISRCTN16942542; Pre-results

Impaired cognitive plasticity and goal-directed control in adolescent obsessive-compulsive disorder.

BACKGROUND: Youths with obsessive-compulsive disorder (OCD) experience severe distress and impaired functioning at school and at home. Critical cognitive domains for daily functioning and academic success are learning, memory, cognitive flexibility and goal-directed behavioural control. Performance in these important domains among teenagers with OCD was therefore investigated in this study. METHODS: A total of 36 youths with OCD and 36 healthy comparison subjects completed two memory tasks: Pattern Recognition Memory (PRM) and Paired Associates Learning (PAL); as well as the Intra-Extra Dimensional Set Shift (IED) task to quantitatively gauge learning as well as cognitive flexibility. A subset of 30 participants of each group also completed a Differential-Outcome Effect (DOE) task followed by a Slips-of-Action Task, designed to assess the balance of goal-directed and habitual behavioural control. RESULTS: Adolescent OCD patients showed a significant learning and memory impairment. Compared with healthy comparison subjects, they made more errors on PRM and PAL and in the first stages of IED involving discrimination and reversal learning. Patients were also slower to learn about contingencies in the DOE task and were less sensitive to outcome devaluation, suggesting an impairment in goal-directed control. CONCLUSIONS: This study advances the characterization of juvenile OCD. Patients demonstrated impairments in all learning and memory tasks. We also provide the first experimental evidence of impaired goal-directed control and lack of cognitive plasticity early in the development of OCD. The extent to which the impairments in these cognitive domains impact academic performance and symptom development warrants further investigation.This work was funded by a Wellcome Trust Grant (grant number 089589/Z/09/Z) awarded to TW Robbins, BJ Everitt, AC Roberts, JW Dalley, and BJ Sahakian, and a Wellcome Trust Senior Investigator Award (104631/Z/14/Z) to TW Robbins. The research was conducted in the Behavioural and Clinical Neuroscience Institute, which is supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354). J Gottwald was supported by a BCNI MRC PhD studentship and St John’s College, Cambridge

Sources and characteristics of summertime organic aerosol in the Colorado Front Range: perspective from measurements and WRF-Chem modeling

Abstract. The evolution of organic aerosols (OAs) and their precursors in the boundary layer (BL) of the Colorado Front Range during the Front Range Air Pollution and Photochemistry Éxperiment (FRAPPÉ, July–August 2014) was analyzed by in situ measurements and chemical transport modeling. Measurements indicated significant production of secondary OA (SOA), with enhancement ratio of OA with respect to carbon monoxide (CO) reaching 0.085±0.003 µg m−3 ppbv−1. At background mixing ratios of CO, up to  ∼  1.8 µg m−3 background OA was observed, suggesting significant non-combustion contribution to OA in the Front Range. The mean concentration of OA in plumes with a high influence of oil and natural gas (O&amp;G) emissions was  ∼  40 % higher than in urban-influenced plumes. Positive matrix factorization (PMF) confirmed a dominant contribution of secondary, oxygenated OA (OOA) in the boundary layer instead of fresh, hydrocarbon-like OA (HOA). Combinations of primary OA (POA) volatility assumptions, aging of semi-volatile species, and different emission estimates from the O&amp;G sector were used in the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) simulation scenarios. The assumption of semi-volatile POA resulted in greater than a factor of 10 lower POA concentrations compared to PMF-resolved HOA. Including top-down modified O&amp;G emissions resulted in substantially better agreements in modeled ethane, toluene, hydroxyl radical, and ozone compared to measurements in the high-O&amp;G-influenced plumes. By including emissions from the O&amp;G sector using the top-down approach, it was estimated that the O&amp;G sector contributed to  &lt;  5 % of total OA, but up to 38 % of anthropogenic SOA (aSOA) in the region. The best agreement between the measured and simulated median OA was achieved by limiting the extent of biogenic hydrocarbon aging and consequently biogenic SOA (bSOA) production. Despite a lower production of bSOA in this scenario, contribution of bSOA to total SOA remained high at 40–54 %. Future studies aiming at a better emissions characterization of POA and intermediate-volatility organic compounds (IVOCs) from the O&amp;G sector are valuable

Single Nucleotide Polymorphism Typing of Mycobacterium ulcerans Reveals Focal Transmission of Buruli Ulcer in a Highly Endemic Region of Ghana

Buruli ulcer (BU) is an emerging necrotizing disease of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. While proximity to stagnant or slow flowing water bodies is a risk factor for acquiring BU, the epidemiology and mode of M. ulcerans transmission is poorly understood. Here we have used high-throughput DNA sequencing and comparisons of the genomes of seven M. ulcerans isolates that appeared monomorphic by existing typing methods. We identified a limited number of single nucleotide polymorphisms (SNPs) and developed a real-time PCR SNP typing method based on these differences. We then investigated clinical isolates of M. ulcerans on which we had detailed information concerning patient location and time of diagnosis. Within the Densu river basin of Ghana we observed dominance of one clonal complex and local clustering of some of the variants belonging to this complex. These results reveal focal transmission and demonstrate, that micro-epidemiological analyses by SNP typing has great potential to help us understand how M. ulcerans is transmitted

SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation

Macrophages exhibit a spectrum of activation states ranging from classical to alternative activation1. Alternatively, activated macrophages are involved in diverse pathophysiological processes such as confining tissue parasites2, improving insulin sensitivity3 or promoting an immune tolerant microenvironment that facilitates tumour growth and metastasis4. Recently, the role of metabolism regulating macrophage function has come into focus as both the classical and alternative activation programmes require specific regulated metabolic reprogramming5. While most of the studies regarding immunometabolism have focussed on the catabolic pathways activated to provide energy, little is known about the anabolic pathways mediating macrophage alternative activation. In this study, we show that the anabolic transcription factor sterol regulatory element binding protein 1 (SREBP1) is activated in response to the canonical Th2 cytokine interleukin 4 (IL-4) to trigger the de novo lipogenesis (DNL) programme, as a necessary step for macrophage alternative activation. Mechanistically, DNL consumes NADPH, partitioning it away from cellular antioxidant defences and raising ROS levels. ROS serves as a second messenger, signalling sufficient DNL, and promoting macrophage alternative activation. The pathophysiological relevance of this mechanism is validated by showing that SREBP1/DNL is essential for macrophage alternative activation in vivo in a helminth infection model.This work was supported by the British Heart Foundation (RG/18/7/33636), the MRC (MC_UU_00014/2) and the FP7 MITIN (223450). K.P. was a recipient of a fellowship from the Wellcome Trust. A.N.J.M. and E.J. are supported by the Wellcome Trust (100963/Z/13/Z) and the MRC (U105178805). J.L. is a recipient fellowship of the British Heart Foundation. A.D. was a Marie-Curie Early-Stage Researcher supported by the European Union’s Horizon 2020 research and innovation programme (675585 Marie-Curie ITN ‘SymBioSys’) to J.S.-R. A.K. is supported by the Wellcome Trust (106260/Z/14/Z) and an ERC award (648889). P.F. is supported by the Science Foundation Ireland (10/IN.1/B3004). The IMS Genomics and Transcriptomics and Histology cores (B.M.-A., B.Y.H.L. and M.K.M.) are funded by the UK MRC Metabolic Disease Unit (MRC_MC_UU_12012/5) and a Wellcome Trust Strategic Award (100574/Z/12/Z). The Disease Model Core is part of the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/5) and Wellcome Trust Strategic Award (100574/Z/12/Z)

Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

The Copenhagen Diagnosis: Updating the World on the Latest Climate Science

The Copenhagen Diagnosis is a summary of the global warming peer reviewed science since 2007. Produced by a team of 26 scientists led by the University of New South Wales Climate Research Centre, the Diagnosis convincingly proves that the effects of global warming have gotten worse in the last three years. It is a timely update to the UN’s Intercontinental Panel on Climate Change 2007 Fourth Assessment document (IPCC AR4). The report places the blame for the century long temperature increase on human factors and says the turning point ";must come soon";. If we are to limit warming to 2 degrees above pre-industrial values, global emissions must peak by 2020 at the latest and then decline rapidly. The scientists warned that waiting for higher levels of scientific certainty could mean that some tipping points will be crossed before they are recognized. By 2050 we will effectively need to be in a post-carbon economy if we are to avoid unlivable temperatures