Antithrombotic actions of statins involve PECAM-1 signalling

Statins are widely prescribed cholesterol-lowering drugs that are a first-line treatment for coronary artery disease and atherosclerosis, reducing the incidence of thrombotic events such as myocardial infarction and stroke. Statins have been shown to reduce platelet activation, although the mechanism(s) through which this occurs is unclear. Since several of the characteristic effects of statins on platelets are shared with those elicited by the inhibitory platelet adhesion receptor PECAM-1, we investigated a potential connection between the influence of statins on platelet function and PECAM-1 signalling. Statins were found to inhibit a range of platelet functional responses and thrombus formation in vitro and in vivo. Notably, these effects of statins on platelet function in vitro and in vivo were diminished in PECAM-1-/- platelets. Activation of PECAM-1 signalling results in its tyrosine phosphorylation, the recruitment and activation of tyrosine phosphatase SHP-2, the subsequent binding of phosphoinositol 3-kinase (PI3-K) and diminished PI3-K signalling. Statins resulted in the stimulation of these events, leading to the inhibition of Akt activation. Together, these data provides evidence for a fundamental role of PECAM-1 in the inhibitory effects of statins on platelet activation, which may explain some of the pleiotropic actions of these drugs.

Participatory scenarios as a tool to link science and policy on food security under climate change in East Africa

How effective are multi-stakeholder scenarios building processes to bring diverse actors together and create a policy-making tool to support sustainable development and promote food security in the developing world under climate change? The effectiveness of a participatory scenario development process highlights the importance of ‘boundary work’ that links actors and organizations involved in generating knowledge on the one hand, and practitioners and policymakers who take actions based on that knowledge on the other. This study reports on the application of criteria for effective boundary work to a multi-stakeholder scenarios process in East Africa that brought together a range of regional agriculture and food systems actors. This analysis has enabled us to evaluate the extent to which these scenarios were seen by the different actors as credible, legitimate and salient, and thus more likely to be useful. The analysis has shown gaps and opportunities for improvement on these criteria, such as the quantification of scenarios, attention to translating and communicating the results through various channels and new approaches to enable a more inclusive and diverse group of participants. We conclude that applying boundary work criteria to multi-stakeholder scenarios processes can do much to increase the likelihood of developing sustainable development and food security policies that are more appropriate.

Options for support to agriculture and food security under climate change

Agriculture and food security are key sectors for intervention under climate change. Agricultural production is highly vulnerable even to 2C (low-end) predictions for global mean temperatures in 2100, with major implications for rural poverty and for both rural and urban food security. Agriculture also presents untapped opportunities for mitigation, given the large land area under crops and rangeland, and the additional mitigation potential of aquaculture. This paper presents a summary of current knowledge on options to support farmers, particularly smallholder farmers, in achieving food security through agriculture under climate change. Actions towards adaptation fall into two broad overlapping areas: (1) accelerated adaptation to progressive climate change over decadal time scales, for example integrated packages of technology, agronomy and policy options for farmers and food systems, and (2) better management of agricultural risks associated with increasing climate variability and extreme events, for example improved climate information services and safety nets. Maximization of agriculture’s mitigation potential will require investments in technological innovation and agricultural intensification linked to increased efficiency of inputs, and creation of incentives and monitoring systems that are inclusive of smallholder farmers. Food systems faced with climate change need urgent, broad-based action in spite of uncertainties.

A Guide to Office Clerical Time Standards

A Guide to Office Clerical Time Standards is an instructional performance piece based on a corporate manual from 1960. The pamphlet is focused on the time necessary for the accomplishment of minute labour procedures in the office, from the depressing and releasing of typewriter keys to the opening and closing of filing cabinet drawers. In the performance, seven costumed performers represent the different levels of management and employment while performing the actions described in the guide, accompanied by a live musical score. There has been much discussion of the changes to work in the west following the decline of post-Fordist service sector jobs. These increasingly emphasise the specificity of employees’ knowledge and cognitive skill. However, this greater flexibility and creativity at work has been accompanied by an opposite trajectory. The proletarisation of white collar work has given rise to more bureaucracy, target assessment and control for workers in previously looser creative professions, from academia to the arts. The midcentury office is the meeting point of these cultures, where the assembly line efficiency management of the factory meets the quantifying control of the knowledge economy. A Guide to Office Clerical Time Standards explores the survival of one regime into its successor following the lines of combined and uneven development that have turned the emancipatory promise of immaterial labour into the perma-temp hell of the cognitariat. The movement is accompanied by a score of guitar, bass and drums, the componenets of the rock ‘n’ roll music that rose from the car factories of the motor city and the cotton fields of the southern states to represent the same junction of expression and control.

Aluminium and breast cancer: sources of exposure, tissue measurements and mechanisms of toxicological actions on breast biology

This review examines recent evidence linking exposure to aluminium with the aetiology of breast cancer. The human population is exposed to aluminium throughout daily life including through diet, application of antiperspirants, use of antacids and vaccination. Aluminium has now been measured in a range of human breast structures at higher levels than in blood serum and experimental evidence suggests that the tissue concentrations measured have the potential to adversely influence breast epithelial cells including generation of genomic instability, induction of anchorage-independent proliferation and interference in oestrogen action. The presence of aluminium in the human breast may also alter the breast microenvironment causing disruption to iron metabolism, oxidative damage to cellular components, inflammatory responses and alterations to the motility of cells. The main research need is now to investigate whether the concentrations of aluminium measured in the human breast can lead in vivo to any of the effects observed in cells in vitro and this would be aided by the identification of biomarkers specific for aluminium action.

Cities’ low carbon plans in an ‘age of austerity’: an analysis of UK local authority actions, attitudes and responses

Background: Cities play a significant role globally in creating carbon emissions but, as centers of major population, innovation and social practice, they also offer important opportunities to tackle climate change. The new challenges faced by cities in an ‘age of austerity’ and decentralist agendas present substantial challenges for coordinated multilevel governance. Results: Based on research carried out in 2011–2012, this paper examines the attitudes and responses of sustainability and climate change officers in UK cities that have prepared low carbon and climate change plans, in the context of these challenges. Using a conceptual framework that analyses ‘awareness’, ‘analysis’ and ‘actions��� (in the context of spending cuts and a new ‘decentralized’ policy agenda) this research suggests that progress on low-carbon futures for cities continues to be fragmented, with increased funding constraints, short-termism and lack of leadership acting as key barriers to progress. Conclusion: Recent UK national policies (including localism, austerity measures and new economic incentives) have not only created further uncertainties, but also scope for cities’ local innovation through policy leverage and self-governing actions.

Housing or property? The dynamics of housing policy and property principles in the right to buy

This paper examines the interplay and tension between housing law and policy and property law, in the specific context of the right to buy (RTB). It focuses on funding arrangements between the RTB tenant and another party. It first examines how courts determine the parties' respective entitlements in the home, highlighting the difficulty of categorising, under traditional property law principles, a contribution in the form of the statutory discount conferred on the RTB tenant. Secondly, it considers possible exploitation of the RTB scheme, both at the macro level of exploitation of the policy underpinning the legislation and, at the micro level, of exploitation of the tenant. The measures contained in the Housing Act 2004 intended to curb exploitation of the RTB are analysed to determine what can be considered to be legitimate and illegitimate uses of the scheme. It is argued that, despite the government's implicit approval, certain funding arrangements by non-resident relatives fail to give effect to the spirit of the scheme.

Destructive behaviours and leadership: the source of the shift from a functional to dysfunctional workplace?

Destructive leadership behaviour often results in damage to the organisations that the individual is entrusted to lead. Although accurately pinpointing the type of destructive behaviour is difficult, this article seeks to offer suggestions as to why leaders spiral into such unattractive behaviour. After reviewing the literature, this paper highlights four drivers for destructive ways that people act based on detailed qualitative scenarios that involve how those who experienced such behaviour reacted and felt. The study reveals a noticeable human experience from which nobody can escape, and offers understanding of the study participants’ experiences. Out of respect to the participants, the authors keep their identity anonomous. We drew our subjects from a cross-section of organisations that function internationally within one area of the manufacturing industry. The article presents a model comprising two dimensions: 1) the leader’s attitude to the organisation he or she leads and 2) adequacy of his or her leadership capabilities. The models offer us understanding of the drivers of the destructive actions that the leader exhibits. Understanding allows us to provide managers with tactical methods to protect them against destructive behaviour and help them lessen the worst aspects of destructive behaviour in both their colleagues and themselves.

Contribution of insect pollinators to crop yield and quality varies with agricultural intensification

Background: Up to 75% of crop species benefit at least to some degree from animal pollination for fruit or seed set and yield. However, basic information on the level of pollinator dependence and pollinator contribution to yield is lacking for many crops. Even less is known about how insect pollination affects crop quality. Given that habitat loss and agricultural intensification are known to decrease pollinator richness and abundance, there is a need to assess the consequences for different components of crop production. Methods: We used pollination exclusion on flowers or inflorescences on a whole plant basis to assess the contribution of insect pollination to crop yield and quality in four flowering crops (spring oilseed rape, field bean, strawberry, and buckwheat) located in four regions of Europe. For each crop, we recorded abundance and species richness of flower visiting insects in ten fields located along a gradient fromsimple to heterogeneous landscapes. Results: Insect pollination enhanced average crop yield between 18 and 71% depending on the crop. Yield quality was also enhanced in most crops. For instance, oilseed rape had higher oil and lower chlorophyll contents when adequately pollinated, the proportion of empty seeds decreased in buckwheat, and strawberries’ commercial grade improved; however, we did not find higher nitrogen content in open pollinated field beans. Complex landscapes had a higher overall species richness of wild pollinators across crops, but visitation rates were only higher in complex landscapes for some crops. On the contrary, the overall yield was consistently enhanced by higher visitation rates, but not by higher pollinator richness. Discussion. For the four crops in this study, there is clear benefit delivered by pollinators on yield quantity and/or quality, but it is not maximized under current agricultural intensification. Honeybees, the most abundant pollinator, might partially compensate the loss of wild pollinators in some areas, but our results suggest the need of landscape-scale actions to enhance wild pollinator populations.

A niche-based framework to assess current monitoring of European forest birds and guide indicator species' selection

Concern that European forest biodiversity is depleted and declining has provoked widespread efforts to improve management practices. To gauge the success of these actions, appropriate monitoring of forest ecosystems is paramount. Multi-species indicators are frequently used to assess the state of biodiversity and its response to implemented management, but generally applicable and objective methodologies for species' selection are lacking. Here we use a niche-based approach, underpinned by coarse quantification of species' resource use, to objectively select species for inclusion in a pan-European forest bird indicator. We identify both the minimum number of species required to deliver full resource coverage and the most sensitive species' combination, and explore the trade-off between two key characteristics, sensitivity and redundancy, associated with indicators comprising different numbers of species. We compare our indicator to an existing forest bird indicator selected on the basis of expert opinion and show it is more representative of the wider community. We also present alternative indicators for regional and forest type specific monitoring and show that species' choice can have a significant impact on the indicator and consequent projections about the state of the biodiversity it represents. Furthermore, by comparing indicator sets drawn from currently monitored species and the full forest bird community, we identify gaps in the coverage of the current monitoring scheme. We believe that adopting this niche-based framework for species' selection supports the objective development of multi-species indicators and that it has good potential to be extended to a range of habitats and taxa.

Polyphenols, glucosinolates, dietary fibre and colon cancer: Understanding the potential of specific types of fruit and vegetables to reduce bowel cancer progression

Colorectal cancer is the third most prevalent cancer worldwide and the most common diet-related cancer, influenced by diets rich in red meat, low in plant foods and high in saturated fats. Observational studies have shown that fruit and vegetable intake may reduce colorectal cancer risks, although the precise bioactive components remain unclear. This review will outline the evidence for the role of polyphenols, glucosinolates and fibres against cancer progression in the gastrointestinal tract. Those bioactive compounds are considered protective agents against colon cancer, with evidence taken from epidemiological, human clinical, animal and in vitro studies. Various mechanisms of action have been postulated, such as the potential of polyphenols and glucosinolates to inhibit cancer cell growth and the actions of insoluble fibres as prebiotics and the evidence for these actions are detailed within. In addition, recent evidence suggests that polyphenols also have the potential to shift the gut ecology in a beneficial manner. Such actions of both fibre and polyphenols in the gastrointestinal tract and through interaction with gut epithelial cells may act in an additive manner to help explain why certain fruits and vegetables, but not all, act to differing extents to inhibit cancer incidence and progression. Indeed, a focus on the individual actions of such fruit and vegetable components, in particular polyphenols, glucosinolates and fibres is necessary to help explain which components are active in reducing gastrointestinal cancer risk.

Operational active fire mapping and burnt area identification applicable to Mexican Nature Protection Areas using MODIS and NOAA-AVHRR direct readout data

Since 1999, the National Commission for the Knowledge and Use of the Biodiversity (CONABIO) in Mexico has been developing and managing the “Operational program for the detection of hot-spots using remote sensing techniques”. This program uses images from the MODerate resolution Imaging Spectroradiometer (MODIS) onboard the Terra and Aqua satellites and from the Advanced Very High Resolution Radiometer of the National Oceanic and Atmospheric Administration (NOAA-AVHRR), which are operationally received through the Direct Readout station (DR) at CONABIO. This allows the near-real time monitoring of fire events in Mexico and Central America. In addition to the detection of active fires, the location of hot spots are classified with respect to vegetation types, accessibility, and risk to Nature Protection Areas (NPA). Besides the fast detection of fires, further analysis is necessary due to the considerable effects of forest fires on biodiversity and human life. This fire impact assessment is crucial to support the needs of resource managers and policy makers for adequate fire recovery and restoration actions. CONABIO attempts to meet these requirements, providing post-fire assessment products as part of the management system in particular for satellite-based burnt area mapping. This paper provides an overview of the main components of the operational system and will present an outlook to future activities and system improvements, especially the development of a burnt area product. A special focus will also be placed on the fire occurrence within NPAs of Mexico

Military targeting in the context of self-defence actions

In order to bring conceptual clarity to a particular dimension of the relationship between the jus ad bellum and the jus in bello regimes, this article explores the independent sources of a military targeting rule in both branches of international law. The aim is not to displace the jus in bello as the ‘lead’ regime on how targeting decisions must be made, or to undermine the traditional separation between these regimes. Rather, conceptual light is shed on a sometimes assumed but generally neglected dimension of the jus ad bellum’s necessity and proportionality criteria that may, in limited circumstances, have significance for our understanding of human protection during war, by covering possible gaps in the jus in bello targeting rules.

The Article 51 reporting requirement for self-defense actions

This article examines one legal criterion for the exercise of the right of self-defense that has been significantly overlooked by commentators: the so-called “reporting requirement.” Article 51 of the United Nations (UN) Charter provides, inter alia, that “[m]easures taken by members in the exercise of this right of self-defense shall be immediately reported to the Security Council.” Although the requirement to report all self-defense actions to the Council is clearly set out in Article 51, the Charter offers no further guidance with regard to this obligation. Reference to the practice of states since the UN’s inception in 1945 is therefore essential to understanding the scope and nature of the reporting requirement. As such, this article is underpinned by an extensive original dataset of reporting practice covering the period from January 1, 1998 to December 31, 2013. We know from Article 51 that states “shall” report, but do they, and—if so—in what manner? What are the various implications of reporting, of failing to report, and of the way in which states report? How are reports used, and by whom? Most importantly, this article questions the ultimate value of states reporting their self-defense actions to the Security Council in modern interstate relations.

Pharmacological actions of nobiletin in the modulation of platelet function

Background and Purpose The discovery that flavonoids are capable of inhibiting platelet function has led to their investigation as potential antithrombotic agents. However, despite the range of studies on the antiplatelet properties of flavonoids, little is known about the mechanisms by which flavonoids inhibit platelet function. In this study, we aimed to explore the pharmacological effects of a polymethoxy flavonoid, nobiletin in the modulation of platelet function. Experimental Approach The ability of nobiletin to modulate platelet function was explored by using a range of in vitro and in vivo experimental approaches. Aggregation, dense granule secretion and spreading assays were performed using washed platelets. The fibrinogen binding, α-granule secretion and calcium mobilisation assays were performed using platelet-rich plasma and whole blood was used in impedance aggregometry and thrombus formation experiments. The effect of nobiletin in vivo was assessed by measuring tail bleeding time using C57BL/6 mice. Key Results Nobiletin was shown to supress a range of well-established activatory mechanisms, including platelet aggregation, granule secretion, integrin modulation, calcium mobilisation and thrombus formation. Nobiletin was shown to extend bleeding time in mice and reduce the phosphorylation of Akt and PLCγ2 within the collagen receptor (GPVI) - stimulated pathway, in addition to increasing the levels of cGMP and phosphorylation of VASP, a protein whose activity is associated with inhibitory cyclic nucleotide signalling. Conclusions and Implications This study provides insight into the underlying molecular mechanisms through which nobiletin modulates haemostasis and thrombus formation. Therefore nobiletin may represent a potential antithrombotic agent of dietary origins.