New Knowledge from Old: In silico discovery of novel protein domains in Streptomyces coelicolor

BACKGROUND: Streptomyces coelicolor has long been considered a remarkable bacterium with a complex life-cycle, ubiquitous environmental distribution, linear chromosomes and plasmids, and a huge range of pharmaceutically useful secondary metabolites. Completion of the genome sequence demonstrated that this diversity carried through to the genetic level, with over 7000 genes identified. We sought to expand our understanding of this organism at the molecular level through identification and annotation of novel protein domains. Protein domains are the evolutionary conserved units from which proteins are formed. RESULTS: Two automated methods were employed to rapidly generate an optimised set of targets, which were subsequently analysed manually. A final set of 37 domains or structural repeats, represented 204 times in the genome, was developed. Using these families enabled us to correlate items of information from many different resources. Several immediately enhance our understanding both of S. coelicolor and also general bacterial molecular mechanisms, including cell wall biosynthesis regulation and streptomycete telomere maintenance. DISCUSSION: Delineation of protein domain families enables detailed analysis of protein function, as well as identification of likely regions or residues of particular interest. Hence this kind of prior approach can increase the rate of discovery in the laboratory. Furthermore we demonstrate that using this type of in silico method it is possible to fairly rapidly generate new biological information from previously uncorrelated data

The MG Rover closure and policy response: an evaluation of the Task Force model in the UK

In recent years there have been a number of high-profile plant closures in the UK. In several cases, the policy response has included setting up a task force to deal with the impacts of the closure. It can be hypothesised that task force involving multi-level working across territorial boundaries and tiers of government is crucial to devising a policy response tailored to people's needs and to ensuring success in dealing with the immediate impacts of a closure. This suggests that leadership, and vision, partnership working and community engagement, and delivery of high quality services are important. This paper looks at the case of the MG Rover closure in 2005, to examine the extent to which the policy response to the closure at the national, regional and local levels dealt effectively with the immediate impacts of the closure, and the lessons that can be learned from the experience. Such lessons are of particular relevance given the closure of the LDV van plant in Birmingham in 2009 and more broadly – such as in the case of the downsizing of the Opel operation in Europe following its takeover by Magna

Plant closures and taskforce responses:an analysis of the impact of and policy response to MG Rover in Birmingham

This paper explores the socio-economic impacts and associated policy responses to the collapse of MG Rover at Longbridge in Birmingham. Critically, it attempts to move beyond a ‘standard’ taskforce narrative that emphasizes the role of the regional response. While recognizing that significant policy ‘successes’ were indeed evident at the regional level in anticipating and responding to the crisis, a wider perspective is required that situates this taskforce response in (1) a fuller understanding of labour market precariousness (that in turn mitigates some of its policy ‘successes’), and (2) more local perspectives that highlight the local impacts of closure, the role of the neighbourhood level officials and the third sector in mediating these. Taking this broader perspective suggests that longer-term, workers face a precarious situation and the need for policies to create and sustain ‘good quality’ jobs remains paramount. Adding in more local perspectives, a key lesson from the Longbridge experience for dealing with closures more generally is that the public policy responses must be: multidimensional in that they transcend narrow sector-based concerns and addresses broader spatial impacts; inclusive in that they build on a broad coalition of economic and social stakeholders; and long-term in that they acknowledge that adaptation takes many years. If anything, the Birmingham Longbridge experience demonstrates the difficulty of achieving such responses in the context of crisis where action is imperative and deliberation a luxury

Estimating a Path through a Map of Decision Making

Studies of the evolution of collective behavior consider the payoffs of individual versus social learning. We have previously proposed that the relative magnitude of social versus individual learning could be compared against the transparency of payoff, also known as the “transparency” of the decision, through a heuristic, two-dimensional map. Moving from west to east, the estimated strength of social influence increases. As the decision maker proceeds from south to north, transparency of choice increases, and it becomes easier to identify the best choice itself and/or the best social role model from whom to learn (depending on position on east–west axis). Here we show how to parameterize the functions that underlie the map, how to estimate these functions, and thus how to describe estimated paths through the map. We develop estimation methods on artificial data sets and discuss real-world applications such as modeling changes in health decisions

Risks to biodiversity from temperature overshoot pathways

Temperature overshoot pathways entail exceeding a specified global warming level (e.g. 1.5°C or 2°C) followed by a decline in warming, achieved through anthropogenically enhanced CO2 removal from the atmosphere. However, risks to biodiversity from temperature overshoot pathways are poorly described. Here, we explore biodiversity risks from overshoot by synthesizing existing knowledge and quantifying the dynamics of exposure and de-exposure to potentially dangerous temperatures for more than 30 000 species for a 2°C overshoot scenario. Our results suggest that climate risk to biodiversity from temperature overshoot pathways will arrive suddenly, but decrease only gradually. Peak exposure for biodiversity occurs around the same time as peak global warming, but the rate of de-exposure lags behind the temperature decline. While the global overshoot period lasts around 60 years, the duration of elevated exposure of marine and terrestrial biodiversity is substantially longer (around 100 and 130 years, respectively), with some ecological communities never returning to pre-overshoot exposure levels. Key biodiversity impacts may be irreversible and reliance on widespread CO2 removal to reduce warming poses additional risks to biodiversity through altered land use. Avoiding any temperature overshoot must be a priority for reducing biodiversity risks from climate change, followed by limiting the magnitude and duration of any overshoot. More integrated models that include direct and indirect impacts from overshoot are needed to inform policy. This article is part of the theme issue 'Ecological complexity and the biosphere: the next 30 years'

How Do Ultra‐Low Frequency Waves Access the Inner Magnetosphere During Geomagnetic Storms?

Wave‐particle interactions play a key role in radiation belt dynamics. Traditionally, ultra‐low frequency (ULF) wave‐particle interaction is parameterized statistically by a small number of controlling factors for given solar wind driving conditions or geomagnetic activity levels. Here we investigate solar wind driving of ULF wave power and the role of the magnetosphere in screening that power from penetrating deep into the inner magnetosphere. We demonstrate that during enhanced ring current intensity, the Alfvén continuum plummets, allowing lower frequency waves to penetrate deeper into the magnetosphere than during quiet periods. With this penetration, ULF wave power is able to accumulate closer to the Earth than characterized by statistical models. During periods of enhanced solar wind driving such as coronal mass ejection driven storms, where ring current intensities maximize, the observed penetration provides a simple physics‐based reason for why storm time ULF wave power is different compared to nonstorm time waves

Subglacial lakes and hydrology across the Ellsworth Subglacial Highlands, West Antarctica

Subglacial water plays an important role in ice sheet dynamics and stability. Subglacial lakes are often located at the onset of ice streams and have been hypothesised to enhance ice flow downstream by lubricating the ice–bed interface. The most recent subglacial-lake inventory of Antarctica mapped nearly 400 lakes, of which ∼ 14 % are found in West Antarctica. Despite the potential importance of subglacial water for ice dynamics, there is a lack of detailed subglacial-water characterisation in West Antarctica. Using radio-echo sounding data, we analyse the ice–bed interface to detect subglacial lakes. We report 33 previously uncharted subglacial lakes and present a systematic analysis of their physical properties. This represents a ∼ 40 % increase in subglacial lakes in West Antarctica. Additionally, a new digital elevation model of basal topography of the Ellsworth Subglacial Highlands was built and used to create a hydropotential model to simulate the subglacial hydrological network. This allows us to characterise basal hydrology, determine subglacial water catchments and assess their connectivity. We show that the simulated subglacial hydrological catchments of the Rutford Ice Stream, Pine Island Glacier and Thwaites Glacier do not correspond to their ice surface catchments

Phosphodiesterase isozyme inhibition and the potentiation by Zaprinast of endothelium-derived relaxing factor and guanylate cyclase stimulating agents in vascular smooth muscle

ABSTRAC

Participative decision making and the sharing of benefits: laws, ethics, and data protection for building extended global communities

Transdisciplinary and cross-cultural cooperation and collaboration are needed to build extended, densely interconnected information resources. These are the prerequisites for the successful implementation and execution of, for example, an ambitious monitoring framework accompanying the post-2020 Global Biodiversity Framework (GBF) of the Convention on Biological Diversity (CBD; SCBD 2021). Data infrastructures that meet the requirements and preferences of concerned communities can focus and attract community involvement, thereby promoting participatory decision making and the sharing of benefits. Community acceptance, in turn, drives the development of the data resources and data use. Earlier this year, the alliance for biodiversity knowledge (2021a) conducted forum-based consultations seeking community input on designing the next generation of digital specimen representations and consequently enhanced infrastructures. The multitudes of connections that arise from extending the digital specimen representations through linkages in all “directions” will form a powerful network of information for research and application. Yet, with the power of an extended, accessible data network comes the responsibility to protect sensitive information (e.g., the locations of threatened populations, culturally context-sensitive traditional knowledge, or businesses’ fundamental data and infrastructure assets). In addition, existing legislation regulates access and the fair and equitable sharing of benefits. Current negotiations on ‘Digital Sequence Information’ under the CBD suggest such obligations might increase and become more complex in the context of extensible information networks. For example, in the case of data and resources funded by taxpayers in the EU, such access should follow the general principle of being “as open as possible; as closed as is legally necessary” (cp. EC 2016). At the same time, the international regulations of the CBD Nagoya Protocol (SCBD 2011) need to be taken into account. Summarizing main outcomes from the consultation discussions in the forum thread “Meeting legal/regulatory, ethical and sensitive data obligations” (alliance for biodiversity knowledge 2021b), we propose a framework of ten guidelines and functionalities to achieve community building and drive application: Substantially contribute to the conservation and protection of biodiversity (cp. EC 2020). Use language that is CBD conformant. Show the importance of the digital and extensible specimen infrastructure for the continuing design and implementation of the post-2020 GBF, as well as the mobilisation and aggregation of data for its monitoring elements and indicators. Strive to openly publish as much data and metadata as possible online. Establish a powerful and well-thought-out layer of user and data access management, ensuring security of ‘sensitive data’. Encrypt data and metadata where necessary at the level of an individual specimen or digital object; provide access via digital cryptographic keys. Link obligations, rights and cultural information regarding use to the digital key (e.g. CARE principles (Carroll et al. 2020), Local Context-labels (Local Contexts 2021), licenses, permits, use and loan agreements, etc.). Implement a transactional system that records every transaction. Amplify workforce capacity across the digital realm, its work areas and workflows. Do no harm (EC 2020): Reduce the social and ecological footprint of the implementation, aiming for a long-term sustainable infrastructure across its life-cycle, including development, implementation and management stages. Balancing the needs for open access, as well as protection, accountability and sustainability, the framework is designed to function as a robust interface between the (research) infrastructure implementing the extensible network of digital specimen representations, and the myriad of applications and operations in the real world. With the legal, ethical and data protection layers of the framework in place, the infrastructure will provide legal clarity and security for data providers and users, specifically in the context of access and benefit sharing under the CBD and its Nagoya Protocol. Forming layers of protection, the characteristics and functionalities of the framework are envisioned to be flexible and finely-grained, adjustable to fulfill the needs and preferences of a wide range of stakeholders and communities, while remaining focused on the protection and rights of the natural world. Respecting different value systems and national policies, the framework is expected to allow a divergence of views to coexist and balance differing interests. Thus, the infrastructure of the digital extensible specimen network is fair and equitable to many providers and users. This foundation has the capacity and potential to bring together the diverse global communities using, managing and protecting biodiversity