Re-organisation of the cytoskeleton during developmental programmed cell death in Picea abies embryos

Cell and tissue patterning in plant embryo development is well documented. Moreover, it has recently been shown that successful embryogenesis is reliant on programmed cell death (PCD). The cytoskeleton governs cell morphogenesis. However, surprisingly little is known about the role of the cytoskeleton in plant embryogenesis and associated PCD. We have used the gymnosperm, Picea abies , somatic embryogenesis model system to address this question. Formation of the apical-basal embryonic pattern in P. abies proceeds through the establishment of three major cell types: the meristematic cells of the embryonal mass on one pole and the terminally differentiated suspensor cells on the other, separated by the embryonal tube cells. The organisation of microtubules and F-actin changes successively from the embryonal mass towards the distal end of the embryo suspensor. The microtubule arrays appear normal in the embryonal mass cells, but the microtubule network is partially disorganised in the embryonal tube cells and the microtubules disrupted in the suspensor cells. In the same embryos, the microtubule-associated protein, MAP-65, is bound only to organised microtubules. In contrast, in a developmentally arrested cell line, which is incapable of normal embryonic pattern formation, MAP-65 does not bind the cortical microtubules and we suggest that this is a criterion for proembryogenic masses (PEMs) to passage into early embryogeny. In embryos, the organisation of F-actin gradually changes from a fine network in the embryonal mass cells to thick cables in the suspensor cells in which the microtubule network is completely degraded. F-actin de-polymerisation drugs abolish normal embryonic pattern formation and associated PCD in the suspensor, strongly suggesting that the actin network is vital in this PCD pathway.

Peer effects in UK adolescent substance use: Never mind the classmates?

This article estimates peer influences on the alcohol, tobacco and cannabis use of UK adolescents. We present evidence of large, positive and statistically significant peer effects in all three behaviours when classmates are taken as the reference group. We also find large, positive and statistically significant associations between own substance use and friends' substance use. When both reference groups are considered simultaneously, the influence of classmates either disappears or is much reduced, whereas the association between own and friends' behaviours does not change. The suggestion is that classmate behaviour is primarily relevant only inasmuch as it proxies for friends' behaviour.

Climate Change, national politics and grassroots action: an introduction

Climate change continues to dominate academic work within green/environmental politics. Indeed, there appears to be almost an inverse relationship between the lack of political leadership on tackling climate change and the growth in ever more sophisticated academic analyses of this complex and multifaceted problem. There is an increasing disjunction between the growth in our knowledge and understanding of the ethical, political, economic, sociological, cultural, and psychological aspects of climate change and the lack of political achievement in putting in place clear and binding targets, an agreed decarbonisation roadmap, and associated regulatory and policy instruments with enforcement. This gap might be taken as evidence that we do not need more reports on climate change. To quote that most unlikely of green politicians, Arnold Schwarzenegger, former Governor of California: ‘The debate is over. We know the science. We see the threat. And we know that the time for action is now’ (California Energy Commission 2007, p. 1). This special issue focuses on a variety of ways in which climate change is conceptualised in normative political and ethical theory, and addressed in policy and regulations.

Anniversaries

The hundredth anniversary of the outbreak of the First World War is only the first of a large number of major European historical anniversaries that will occur in the coming four years. Other twentieth-century anniversaries include that of the Russian Revolution and the Easter Uprising; notable corollaries from earlier centuries include the Battle of Bannockburn, the Hanoverian succession, the Battle of Waterloo and, perhaps most significant of all, the five hundredth anniversary of the Lutheran Reformation. Rather than commission special issues or other features to tie in to individual anniversaries centred on or relevant to German history in a manner which repeats unthinkingly the conventions of scholarly and popular culture, the editors elected to reflect more fundamentally on what might be at stake in major anniversaries for professional scholars of history. In anticipation of the major wave of scholarly and popular publications, commemorative activities and memory conflicts that each of these will generate, and in order to reflect upon the dynamics of German history, memory and commemoration in a more overtly comparative context, the editors invited a number of scholars working on different national histories to reflect on the possibilities and potential pitfalls such anniversaries offer to historians who tie their work in to such moments. They are Jörg Arnold (Nottingham), Thomas A. Brady (Berkeley), Fearghal McGarry (Queen’s University, Belfast), Tim Grady (Chester) and Dan Healey (St Antony’s College, Oxford). The questions were posed by the editors.

Biomass-derived Oxymethylene Ethers as Diesel Additives: A Thermodynamic Analysis

Conversion of biomass for production of liquid fuels can help in reducing the greenhouse gas (GHG) emissions which are predominantly generated by combustion of fossil fuels. Adding oxymethylene ethers (OMEs) in conventional diesel fuel has the potential to reduce soot formation during the combustion in a diesel engine. OMEs are downstream products of syngas, which can be generated by the gasification of biomass. In this research, a thermodynamic analysis has been conducted through development of data intensive process models of all the unit operations involved in production of OMEs from biomass. Based on the developed model, the key process parameters affecting the OMEs production including equivalence ratio, H2/CO ratio, and extra water flow rate were identified. This was followed by development of an optimal process design for high OMEs production. It was found that for a fluidized bed gasifier with heat capacity of 28 MW, the conditions for highest OMEs production are at an air amount of 317 tonne/day, at H2/CO ratio of 2.1, and without extra water injection. At this level, the total OMEs production is 55 tonne/day (13 tonne/day OME3 and 9 tonne/day OME4). This model would further be used in a techno-economic assessment study of the whole biomass conversion chain to determine the most attractive pathways.

Clinical trial designs for rare diseases: Studies developed and discussed by the International Rare Cancers Initiative

BACKGROUND: The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research.

SETTINGS: The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional--usually randomized--clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed.

RESULTS: The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design.

INTERPRETATION: Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases.

The Climate of War: Violence, Warfare and Climatic Reductionism

National security agencies and other interested parties now often regard conflict as the inevitable consequence of climate change. This inclination to reduce war to the vicissitudes of climate is not new however. Here I examine some of the earlier ways in which violence was attributed to climatic conditions, particularly in the United States, and trace links between these older advocates of climatic determinism and the recent writings of those insisting that climate change will usher in a grim world of chronic warfare. It ends by drawing attention to the writings of some critics who are troubled by the ease with which climatic reductionism is capturing the public imagination.

EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients

BACKGROUND: Cetuximab has shown significant clinical activity in metastatic colon cancer. However, cetuximab-containing neoadjuvant chemoradiation has not been shown to improve tumor response in locally advanced rectal cancer patients in recent phase I/II trials. We evaluated functional germline polymorphisms of genes involved in epidermal growth factor receptor pathway, angiogenesis, antibody-dependent cell-mediated cytotoxicity, DNA repair, and drug metabolism, for their potential role as molecular predictors for clinical outcome in locally advanced rectal cancer patients treated with preoperative cetuximab-based chemoradiation.

METHODS: 130 patients (74 men and 56 women) with locally advanced rectal cancer (4 with stage II, 109 with stage III, and 15 with stage IV, 2 unknown) who were enrolled in phase I/II clinical trials treated with cetuximab-based chemoradiation in European cancer centers were included. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor samples and genotyping was done by using PCR-RFLP assays. Fisher's exact test was used to examine associations between polymorphisms and complete pathologic response (pCR) that was determined by a modified Dworak classification system (grade III vs. grade IV: complete response).

RESULTS: Patients with the epidermal growth factor (EGF) 61 G/G genotype had pCR of 45% (5/11), compared with 21% (11/53) in patients heterozygous, and 2% (1/54) in patients homozygous for the A/A allele (P < 0.001). In addition, this association between EGF 61 G allele and pCR remained significant (P = 0.019) in the 59 patients with wild-type KRAS.

CONCLUSION: This study suggested EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer.

Biomass-derived oxymethylene ethers as diesel additives: A techno-economic assessment

Conversion of agricultural biomass such as wood chips, wheat straw and forest residue for the production of fuels can help in reducing GHG emissions since they are considered as nearly carbon neutral. Around the world there is a significant amount of forest and agricultural-biomass available which could be used for the production of liquid fuels that can be blended with the petroleum-based diesel. Oxymethylene ethers (OMEs) can be derived from biomass via gasification, water-gas shift reaction and methanol production. The addition of OMEs to conventional diesel fuel has great potential to reduce soot formation during the combustion in diesel engines. Unlike methanol and dimethyl ether (DMM) which can also reduce soot formation, the physical properties of OMEs allow the use in modern diesel engines without significant change of the engines infrastructure. In this study, a detailed and data intensive process simulation model was developed to simulate all the unit operations involved in the production of OMEs from biomass. The unit operation considered include biomass drying, gasification, gas cleaning, water gas shift reaction, methanol production and OMEs synthesis. The simulation results were then utilized to conduct a detailed techno-economic assessment study of the whole biomass conversion chain to determine the most attractive pathways for OMEs production. Our recent study shows that the key parameters affecting the OMEs production are equivalence ratio, H2/CO ratio and optimal air flow. Overall, the cost of production ($/liter) of OMEs from different biomass feedstock in Alberta will be determined