The British Lower Palaeolithic of the early Middle Pleistocene

The archaeology of Britain during the early Middle Pleistocene (MIS 19–12) is represented by a number of key sites across eastern and southern England. These sites include Pakefield, Happisburgh 1, High Lodge, Warren Hill, Waverley Wood, Boxgrove, Kent's Cavern, and Westbury-sub-Mendip, alongside a ‘background scatter’ lithic record associated with the principal river systems (Bytham, pre-diversion Thames, and Solent) and raised beaches (Westbourne–Arundel). Hominin behaviour can be characterised in terms of: preferences for temperate or cool temperate climates and open/woodland mosaic habitats (indicated by mammalian fauna, mollusca, insects, and sediments); a biface-dominated material culture characterised by technological diversity, although with accompanying evidence for distinctive core and flake (Pakefield) and flake tool (High Lodge) assemblages; probable direct hunting-based subsistence strategies (with a focus upon large mammal fauna); and generally locally-focused spatial and landscape behaviours (principally indicated by raw material sources data), although with some evidence of dynamic, mobile and structured technological systems. The British data continues to support a ‘modified short chronology’ to the north of the Alps and the Pyrenees, with highly sporadic evidence for a hominin presence prior to 500–600 ka, although the ages of key assemblages are subject to ongoing debates regarding the chronology of the Bytham river terraces and the early Middle Pleistocene glaciations of East Anglia.

Private investment in the countryside: an assessment of the role of new houses and estates in sustaining the rural economy and environment

The British countryside has been shaped and sustained over the years by the establishment of landed estates. Some of our best known, and now most protected, landmarks derive from this tradition by which money, that was often sourced from outside the rural economy, was invested in land. Whilst there was some reversal in this trend during the last century, there is again a widespread desire among people of means to invest in new country property. Paragraph 3.21 of Planning Policy Guidance Note 7: The Countryside - Environmental Quality and Economic and Social Development was introduced in 1997 as a means of perpetuating the historic tradition of innovation in the countryside through the construction of fine individual houses in landscaped grounds. That it was considered necessary to use a special provision of this kind reflects the prevailing presumption of planning authorities against allowing private residential development in open countryside. The Government is currently reviewing rural planning policy and is focusing on higher density housing, affordable homes and the use of brownfield sites. There is an underlying conception that individual private house developments contribute nothing and are seen as the least attractive option for most development sites. The purpose of paragraph 3.21 lies outside the government’s priorities and its particular provisions may therefore be excluded in forthcoming ‘policy statements’. This paper seeks to examine the role of private investors wishing to build new houses in the countryside, and the impact that that might have on local economies. It explores the interpretation placed on PPG7 through an investigation of appeal sites, and concludes by making recommendations for the review process, including the retention of some form of exceptions policy for new build houses.

Impact of gut passage and mucus secretion by the earthworm Lumbricus terrestris on mobility and speciation of arsenic in contaminated soil

Earthworms inhabiting arsenic contaminated soils may accelerate the leaching of As into surface and ground waters. We carried out three experiments to determine the impact of passage of As contaminated soil (1150 mgAs kg−1) through the gut of the earthworm Lumbricus terrestris on the mobility and speciation of As and the effects of earthworm mucus on As mobility. The concentration of water soluble As in soil increased (from 1.6 to 18 mg kg−1) after passage through the earthworm gut. Casts that were aged for 56 days still contained more than nine times greater water soluble As than bulk earthworm inhabited soil. Changes were due to increases in As(V) mobility, with no change in As(III). Dilute mucus extracts reduced As mobility through the formation of As-amino acid-iron oxide ternary complexes. More concentrated mucus extracts increased As mobility. These changes, together with those due to the passage through the gut, were due to increases in pH, phosphate and soluble organic carbon. The mobilisation of As from contaminated soils in the environment by cast production and mucus secretion may allow for accelerated leaching or uptake into biota which is underestimated when bulk soil samples are analysed and the influence of soil biota ignored.

Producing leisure spaces out of thin air: the case of the Countryside Stewardship Scheme

This paper examines the growing dysfunction between the apparently increasing significance of diverse leisure practices in the countryside and the largely unchanging official response towards them. Although there is recognition in the recent rural White Paper (DOE and MAFF, 1995) that access is essential to enjoying the countryside, the construction of this term is dubious, since paid access agreements, based on producer requirements, are favoured over any form of demand-driven freedom to roam. Using the Countryside Stewardship Scheme (CSS) as an example of the incentive structure developed to promote this policy, the paper applies Plato's simulacrum as a reading of how this process is being utilised to underpin the dominant rights associated with rural property interests. In particular, the paper makes the point that rather than representing the corollary of a market situation, as its supporters claim, the CSS involves government grant for the eclectic provision of short term licences over ground which remains unmapped as anything other than its continued agricultural use. In concluding, the paper asserts that rather than representing an increase in the availability of leisure sites in the countryside, the CSS and other schemes represent a diversion from the wider and deeper socio-cultural process of continued wealth and power redistribution.

Automatic prediction of functional site regions in low-resolution protein structures

World-wide structural genomics initiatives are rapidly accumulating structures for which limited functional information is available. Additionally, state-of-the art structural prediction programs are now capable of generating at least low resolution structural models of target proteins. Accurate detection and classification of functional sites within both solved and modelled protein structures therefore represents an important challenge. We present a fully automatic site detection method, FuncSite, that uses neural network classifiers to predict the location and type of functionally important sites in protein structures. The method is designed primarily to require only backbone residue positions without the need for specific side-chain atoms to be present. In order to highlight effective site detection in low resolution structural models FuncSite was used to screen model proteins generated using mGenTHREADER on a set of newly released structures. We found effective metal site detection even for moderate quality protein models illustrating the robustness of the method.

Staphylococcal extracellular adherence protein induces platelet activation by stimulation of thiol isomerases

OBJECTIVE: Staphylococcus aureus can induce platelet aggregation. The rapidity and degree of this correlates with the severity of disseminated intravascular coagulation, and depends on platelet peptidoglycans. Surface-located thiol isomerases play an important role in platelet activation. The staphylococcal extracellular adherence protein (Eap) functions as an adhesin for host plasma proteins. Therefore we tested the effect of Eap on platelets. METHODS AND RESULTS: We found a strong stimulation of the platelet-surface thiol isomerases protein disulfide isomerase, endoplasmic reticulum stress proteins 57 and 72 by Eap. Eap induced thiol isomerase-dependent glycoprotein IIb/IIIa activation, granule secretion, and platelet aggregation. Treatment of platelets with thiol blockers, bacitracin, and anti-protein disulfide isomerase antibody inhibited Eap-induced platelet activation. The effect of Eap on platelets and protein disulfide isomerase activity was completely blocked by glycosaminoglycans. Inhibition by the hydrophobic probe bis(1-anilinonaphthalene 8-sulfonate) suggested the involvement of hydrophobic sites in protein disulfide isomerase and platelet activation by Eap. CONCLUSIONS: In the present study, we found an additional and yet unknown mechanism of platelet activation by a bacterial adhesin, involving stimulation of thiol isomerases. The thiol isomerase stimulatory and prothrombotic features of a microbial secreted protein are probably not restricted to S aureus and Eap. Because many microorganisms are coated with amyloidogenic proteins, it is likely that the observed mechanism is a more general one.

Natal nest locations of the Asian house rat (Rattus tanezumi) in lowland rice–coconut cropping systems: a coconut penthouse or rice bunds with water frontage?

CONTEXT. Rattus tanezumi is a serious crop pest within the island of Luzon, Philippines. In intensive flood-irrigated rice field ecosystems of Luzon, female R. tanezumi are known to primarily nest within the tillers of ripening rice fields and along the banks of irrigation canals. The nesting habits of R. tanezumi in complex rice–coconut cropping systems are unknown. AIMS. To identify the natal nest locations of R. tanezumi females in rice–coconut systems of the Sierra Madre Biodiversity Corridor (SMBC), Luzon, during the main breeding season to develop a management strategy that specifically targets their nesting habitat. METHODS. When rice was at the booting to ripening stage, cage-traps were placed in rice fields adjacent to coconut habitat. Thirty breeding adult R. tanezumi females were fitted with radio-collars and successfully tracked to their nest sites. KEY RESULTS. Most R. tanezumi nests (66.7%) were located in coconut groves, five nests (16.7%) were located in rice fields and five nests (16.7%) were located on the rice field edge. All nests were located above ground level and seven nests were located in coconut tree crowns. The median distance of nest sites to the nearest rice field was 22.5m. Most nest site locations had good cover of ground vegetation and understorey vegetation, but low canopy cover. Only one nest location had an understorey vegetation height of less than 20 cm. CONCLUSIONS. In the coastal lowland rice–coconut cropping systems of the SMBC, female R. tanezumi showed a preference for nesting in adjacent coconut groves. This is contrary to previous studies in intensive flood-irrigated rice ecosystems of Luzon, where the species nests mainly in the banks of irrigation canals. It is important to understand rodent breeding ecology in a specific ecosystem before implementing appropriate management strategies. IMPLICATIONS. In lowland rice–coconut cropping systems, coconut groves adjacent to rice fields should be targeted for the 20 management of R. tanezumi nest sites during the main breeding season as part of an integrated ecologically based approach to rodent pest management.

Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of Parkinson's disease (PD). LRRK2 contains a Ras of complex proteins (ROC) domain that may act as a GTPase to regulate its protein kinase activity. The structure of ROC and the mechanism(s) by which it regulates kinase activity are not known. Here, we report the crystal structure of the LRRK2 ROC domain in complex with GDP-Mg2+ at 2.0-Å resolution. The structure displays a dimeric fold generated by extensive domain-swapping, resulting in a pair of active sites constructed with essential functional groups contributed from both monomers. Two PD-associated pathogenic residues, R1441 and I1371, are located at the interface of two monomers and provide exquisite interactions to stabilize the ROC dimer. The structure demonstrates that loss of stabilizing forces in the ROC dimer is likely related to decreased GTPase activity resulting from mutations at these sites. Our data suggest that the ROC domain may regulate LRRK2 kinase activity as a dimer, possibly via the C-terminal of ROC (COR) domain as a molecular hinge. The structure of the LRRK2 ROC domain also represents a signature from a previously undescribed class of GTPases from complex proteins and results may provide a unique molecular target for therapeutics in PD.

A study into the accuracy of using meteorological wind data to estimate turbine generation output

Meteorological (met) station data is used as the basis for a number of influential studies into the impacts of the variability of renewable resources. Real turbine output data is not often easy to acquire, whereas meteorological wind data, supplied at a standardised height of 10 m, is widely available. This data can be extrapolated to a standard turbine height using the wind profile power law and used to simulate the hypothetical power output of a turbine. Utilising a number of met sites in such a manner can develop a model of future wind generation output. However, the accuracy of this extrapolation is strongly dependent on the choice of the wind shear exponent alpha. This paper investigates the accuracy of the simulated generation output compared to reality using a wind farm in North Rhins, Scotland and a nearby met station in West Freugh. The results show that while a single annual average value for alpha may be selected to accurately represent the long term energy generation from a simulated wind farm, there are significant differences between simulation and reality on an hourly power generation basis, with implications for understanding the impact of variability of renewables on short timescales, particularly system balancing and the way that conventional generation may be asked to respond to a high level of variable renewable generation on the grid in the future.

Agonist-induced endocytosis of rat somatostatin receptor 1

Somatostatin-receptor 1 (sst1) is an autoreceptor in the central nervous system that regulates the release of somatostatin. Sst1 is present intracellularly and at the cell surface. To investigate sst1 trafficking, rat sst1 tagged with epitope was expressed in rat insulinoma cells 1046-38 (RIN-1046-38) and tracked by antibody labeling. Confocal microscopic analysis revealed colocalization of intracellularly localized rat sst1-human simplex virus (HSV) with Rab5a-green fluorescent protein and Rab11a-green fluorescent protein, indicating the distribution of the receptor in endocytotic and recycling organelles. Somatostatin-14 induced internalization of cell surface receptors and reduction of binding sites on the cell surface. It also stimulated recruitment of intracellular sst1-HSV to the plasma membrane. Confocal analysis of sst1-HSV revealed that the receptor was initially transported within superficial vesicles. Prolonged stimulation of the cells with the peptide agonist induced intracellular accumulation of somatostatin-14. Because the number of cell surface binding sites did not change during prolonged stimulation, somatostatin-14 was internalized through a dynamic process of continuous endocytosis, recycling, and recruitment of intracellularly present sst1-HSV. Accumulated somatostatin-14 bypassed degradation via the endosomal-lysosomal route and was instead rapidly released as intact and biologically active somatostatin-14. Our results show for the first time that sst1 mediates a dynamic process of endocytosis, recycling, and re-endocytosis of its cognate ligand.

Stock measurement and regeneration policy approaches to ‘hardcore’ brownfield sites: England and Japan compared

This paper discusses key contextual differences and similarities in a comparative study on brownfield regeneration in England and Japan. Over the last decade, the regeneration of large-scale ‘flagship’ projects has been a primary focus in England, and previous research has discussed policy issues and key barriers at these sites. However, further research is required to explore specific barriers associated with problematic ‘hardcore’ sites suffering from long-term dereliction due to site-specific obstacles such as contamination and fragmented ownership. In comparison with England, brownfield regeneration is a relatively new urban agenda in Japan. Japan has less experience in terms of promoting redevelopment of brownfield sites at national level and the specific issues of ‘hardcore’ sites have been under-researched. The paper reviews and highlights important issues in comparing the definitions, national policy frameworks and the current stock of brownfields.

Phosphorylation of the voltage-gated potassium channel Kv2.1 by AMP-activated protein kinase regulates membrane excitability

Firing of action potentials in excitable cells accelerates ATP turnover. The voltage-gated potassium channel Kv2.1 regulates action potential frequency in central neurons, whereas the ubiquitous cellular energy sensor AMP-activated protein kinase (AMPK) is activated by ATP depletion and protects cells by switching off energy-consuming processes. We show that treatment of HEK293 cells expressing Kv2.1 with the AMPK activator A-769662 caused hyperpolarizing shifts in the current-voltage relationship for channel activation and inactivation. We identified two sites (S440 and S537) directly phosphorylated on Kv2.1 by AMPK and, using phosphospecific antibodies and quantitative mass spectrometry, show that phosphorylation of both sites increased in A-769662-treated cells. Effects of A-769662 were abolished in cells expressing Kv2.1 with S440A but not with S537A substitutions, suggesting that phosphorylation of S440 was responsible for these effects. Identical shifts in voltage gating were observed after introducing into cells, via the patch pipette, recombinant AMPK rendered active but phosphatase-resistant by thiophosphorylation. Ionomycin caused changes in Kv2.1 gating very similar to those caused by A-769662 but acted via a different mechanism involving Kv2.1 dephosphorylation. In cultured rat hippocampal neurons, A-769662 caused hyperpolarizing shifts in voltage gating similar to those in HEK293 cells, effects that were abolished by intracellular dialysis with Kv2.1 antibodies. When active thiophosphorylated AMPK was introduced into cultured neurons via the patch pipette, a progressive, time-dependent decrease in the frequency of evoked action potentials was observed. Our results suggest that activation of AMPK in neurons during conditions of metabolic stress exerts a protective role by reducing neuronal excitability and thus conserving energy.

An analysis of the UK development industry's role in brownfield regeneration

Purpose – This study aims to provide a review of brownfield policy and the emerging sustainable development agenda in the UK, and to examine the development industry’s (both commercial and residential) role and attitudes towards brownfield regeneration and contaminated land. Design/methodology/approach – The paper analyses results from a two-stage survey of commercial and residential developers carried out in mid-2004, underpinned by structured interviews with 11 developers. Findings – The results suggest that housebuilding on brownfield is no longer the preserve of specialists, and is now widespread throughout the industry in the UK. The redevelopment of contaminated sites for residential use could be threatened by the impact of the EU Landfill Directive. The findings also suggest that developers are not averse to developing on contaminated sites, although post-remediation stigma remains an issue. The market for warranties and insurance continues to evolve. Research limitations/implications – The survey is based on a sample which represents nearly 30 per cent of UK volume housebuilding. Although the response in the smaller developer groups was relatively under-represented, non-response bias was not found to be a significant issue. More research is needed to assess the way in which developers approach brownfield regeneration at a local level. Practical implications – The research suggests that clearer Government guidance in the UK is needed on how to integrate concepts of sustainability in brownfield development and that EU policy, which has been introduced for laudable aims, is creating tensions within the development industry. There may be an emphasis towards greenfield development in the future, as the implications of the Barker review are felt. Originality/value – This is a national survey of developers’ attitudes towards brownfield development in the UK, following the Barker Review, and highlights key issues in UK and EU policy layers. Keywords Brownfield sites, Contamination Paper type Research paper

In situ preservation of wetland heritage: hydrological and chemical change in the burial environment of the Somerset Levels, UK.

In Situ preservation is a core strategy for the conservation and management of waterlogged remains at wetland sites. Inorganic and organic remains can, however, quickly become degraded, or lost entirely, as a result of chemical or hydrological changes. Monitoring is therefore crucial in identifying baseline data for a site, the extent of spatial and or temporal variability, and in evaluating the potential impacts of these variables on current and future In Situ preservation potential. Since August 2009, monthly monitoring has taken place at the internationally important Iron Age site of Glastonbury Lake Village in the Somerset Levels, UK. A spatial, stratigraphic, and analytical approach to the analysis of sediment horizons and monitoring of groundwater chemistry, redox potential, water table depth and soil moisture (using TDR) was used to characterize the site. Significant spatial and temporal variability has been identified, with results from water-table monitoring and some initial chemical analysis from Glastonbury presented here. It appears that during dry periods parts of this site are at risk from desiccation. Analysis of the chemical data, in addition to integrating the results from the other parameters, is ongoing, with the aim of clarifying the risk to the entire site.

Simulating the interannual variability of major dust storms on Mars using variable lifting thresholds

The redistribution of a finite amount of martian surface dust during global dust storms and in the intervening periods has been modelled in a dust lifting version of the UK Mars General Circulation Model. When using a constant, uniform threshold in the model’s wind stress lifting parameterisation and assuming an unlimited supply of surface dust, multiannual simulations displayed some variability in dust lifting activity from year to year, arising from internal variability manifested in surface wind stress, but dust storms were limited in size and formed within a relatively short seasonal window. Lifting thresholds were then allowed to vary at each model gridpoint, dependent on the rates of emission or deposition of dust. This enhanced interannual variability in dust storm magnitude and timing, such that model storms covered most of the observed ranges in size and initiation date within a single multiannual simulation. Peak storm magnitude in a given year was primarily determined by the availability of surface dust at a number of key sites in the southern hemisphere. The observed global dust storm (GDS) frequency of roughly one in every 3 years was approximately reproduced, but the model failed to generate these GDSs spontaneously in the southern hemisphere, where they have typically been observed to initiate. After several years of simulation, the surface threshold field—a proxy for net change in surface dust density—showed good qualitative agreement with the observed pattern of martian surface dust cover. The model produced a net northward cross-equatorial dust mass flux, which necessitated the addition of an artificial threshold decrease rate in order to allow the continued generation of dust storms over the course of a multiannual simulation. At standard model resolution, for the southward mass flux due to cross-equatorial flushing storms to offset the northward flux due to GDSs on a timescale of ∼3 years would require an increase in the former by a factor of 3–4. Results at higher model resolution and uncertainties in dust vertical profiles mean that quasi-periodic redistribution of dust on such a timescale nevertheless appears to be a plausible explanation for the observed GDS frequency.