Pseudogene rescue: an adaptive mechanism of codon reassignment

Alterations to the genetic code – codon reassignments – have occurred many times in life’s history, despite the fact that genomes are coadapted to their genetic codes and therefore alterations are likely to be maladaptive. A potential mechanism for adaptive codon reassignment, which could trigger either a temporary period of codon ambiguity or a permanent genetic code change, is the reactivation of a pseudogene by a nonsense suppressor mutant transfer RNA. I examine the population genetics of each stage of this process and find that pseudogene rescue is plausible and also readily explains some features of extant variability in genetic codes.

The loss of Normandy and the invention of Terre Normannorum, 1204

The conquest of Normandy by Philip Augustus of France effectively ended the ‘Anglo-Norman’ realm created in 1066, forcing cross-Channel landholders to choose between their English and their Norman estates. The best source for the resulting tenurial upheaval in England is the Rotulus de valore terrarum Normannorum, a list of seized properties and their former holders, and this article seeks to expand our understanding of the impact of the loss of Normandy through a detailed analysis of this document. First, it demonstrates that the compilation of the roll can be divided into two distinct stages, the first containing valuations taken before royal justices in June 1204 and enrolled before the end of July, and the second consisting of returns to orders for the valuation of particular properties issued during the summer and autumn, as part of the process by which these estates were committed to new holders. Second, study of the roll and other documentary sources permits a better understanding of the order for the seizure of the lands of those who had remained in Normandy, the text of which does not survive. This establishes that this royal order was issued in late May 1204 and, further, that it enjoined the temporary seizure rather than the permanent confiscation of these lands. Moreover, the seizure was not retrospective and covers a specific window of time in 1204. On the one hand, this means that the roll is far from a comprehensive record of terre Normannorum. On the other hand, it is possible to correlate the identities of those Anglo-Norman landholders whose English estates were seized with the military progress of the French king through the duchy in May and June and thus shed new light on the campaign of 1204. Third, the article considers the initial management of the seized estates and highlights the fact that, when making arrangements for the these lands, John was primarily concerned to maintain his freedom of manoeuvre, since he was not prepared to accept that Normandy had been lost for good.

A 'Kimberley protest': diamond mining, export sanctions, and poverty in Awatia, Ghana

The temporary suspension of diamond exports in Ghana in 2006 and 2007 is arguably the most significant move to address mounting criticisms of the Kimberley Process Certification Scheme (KPCS), an international initiative aimed at stemming the flow of rough diamonds used to finance wars. The ban, which took effect in November 2006, was much praised, particularly in civil society circles, where it continues to be seen as a genuine effort to prevent the smuggling of ‘conflict diamonds’. At the time, Ghana was accused of harbouring stones originating from rebel-held territories in neighbouring Côte d’Ivoire. No evidence was found in support of the case that it was a repository for ‘conflict diamonds’, however, and exports resumed early in March 2007. This article examines the context for the accusations of Ghana’s implication in the smuggling of illicit diamonds, and draws on recent fieldwork to explain how the suspension has affected Akwatia, the country’s main diamondiferous area. The actions taken raise important questions about how suspected violators – particularly smaller diamond-producing nations – of the KPCS should be handled, and underscore how global compacts can have a host of negative repercussions at the village level.

Advances in mucoadhesion and mucoadhesive polymers

Mucoadhesion is the ability of materials to adhere to mucosal membranes in the human body and provide a temporary retention. This property has been widely used to develop polymeric dosage forms for buccal, oral, nasal, ocular and vaginal drug delivery. Excellent mucoadhesive properties are typical for hydrophilic polymers possessing charged groups and/or non-ionic functional groups capable of forming hydrogen bonds with mucosal surfaces. This feature article considers recent advances in the study of mucoadhesion and mucoadhesive polymers. It provides an overview on the structure of mucosal membranes, properties of mucus gels and the nature of mucoadhesion. It describes the most common methods to evaluate mucoadhesive properties of various dosage forms and discusses the main classes of mucoadhesives.

Real estate in the mixed-asset portfolio: the question of consistency

The recent poor performance of the equity market in the UK has meant that real estate is increasingly been seen as an attractive addition to the mixed-asset portfolio. However, determining whether the good return enjoyed by real estate is a temporary or long-term phenomenon is a question that remains largely unanswered. In other words, there is little or no evidence to indicate whether real estate should play a consistent role in the mixed-asset portfolio over short- and long-term investment horizons. Consistency in this context refers to the ability of an asset to maintain a positive allocation in an efficient portfolio over different holding periods. Such consistency is a desirable trait for any investment, but takes on particular significance when real estate is considered, as the asset class is generally perceived to be a long-term investment due to illiquidity. From an institutional investor’s perspective, it is therefore crucial to determine whether real estate can be reasonably expected to maintain a consistent allocation in the mixed-asset portfolio in both the short and long run and at what percentage. To address the question of consistency the allocation of real estate in the mixed-asset portfolio was calculated over different holding periods varying from 5- to 25-years.

African language books for children: issues for authors

Growing interest in bilingual education in sub-Saharan Africa has highlighted an urgent need for reading material in African languages. In this paper, we focus on authors, one of several groups of stakeholders with responsibility for meeting this demand. We address three main issues: the nature and extent of African language publishing for children; the challenges for authors; and the available support. Our analysis is based on interviews and focus group discussions with publishers, authors, translators, educationalists, and representatives of book promotion organisations from nine African countries and documentary data on children's books in African languages in South Africa. Although there is evidence of a growing interest in producing books in local languages, the number of titles is constrained by funding. The challenges for authors include the need to understand the ingredients for successful children's books and for the sensitivity necessary to negotiate the linguistic challenges associated with a newly emergent genre in African languages. Support, in the form of competitions and workshops, relies on external funding and expertise and offers only temporary solutions. We finish with suggestions for more sustainable ways forward.

Investigating the phytotoxicity of the graminicide fluazifop-P-butyl against native UK wildflower species

BACKGROUND: The selective graminicide fluazifop-P-butyl is used for the control of grass weeds in dicotyledonous crops, and commonly applied in amenity areas to reduce grass productivity and promote wildflower establishment. However, evidence suggests that fluazifop-P-butylmight also have phytotoxic effects on somenon-target plants. This study investigates the effects of fluazifop-P-butyl on the emergence, phytotoxicity and above-ground biomass of nine perennial wildflower species and two grass species, following pre- and post-emergent applications at half, full and double label rates in a series of glasshouse experiments. RESULTS: While pre- and post-emergent applications of fluazifop-P-butyl caused reductions in seedling emergence and increased phytotoxicity on native wildflower and grass species, these effects were temporary for the majority of wildflower species tested, and generally only occurred at the double application rate. No differences in biomass were observed at any of the rates, suggesting good selectivity and no long-term effects of fluazifop-P-butyl application on the wildflower species from either pre-emergent or post-emergent applications. CONCLUSION: These results have direct relevance to the management of amenity areas for biodiversity, as they confirm the suitability of these wildflower species for inclusion in seed mixtures where fluazifop-P-butyl is to be applied to control grass productivity.

Early–Middle Holocene vegetation history, climate change and human activities at Lago Riane (Ligurian Apennines, NW Italy)

The radiocarbon-dated palaeoecological study of Lago Riane (Ligurian Apennines, NW Italy) presented here forms part of a wider investigation into the relationships between Holocene vegetation succession, climate change and human activities in the northern Apennines. The record of vegetation history from Lago Riane indicates that, since the end of the last glaciation, climate change and prehistoric human activities, combined with several local factors, have strongly influenced the pattern and timing of natural vegetation succession. The pollen record indicates an important change in vegetation cover at Lago Riane at ~8500–8200 cal. years b.p., coincident with a well-known period of rapid climate change. At ~6100 cal. years b.p., Fagus woodland colonised Lago Riane during a period of climate change and expansion of Late Neolithic human activities in the upland zone of Liguria. A marked decline in Abies woodland, and the expansion of Fagus woodland, at ~4700 cal. years b.p., coincided with further archaeological evidence for pastoralism in the mountains of Liguria during the Copper Age. At ~3900–3600 cal. years b.p. (Early to Middle Bronze Age transition), a temporary expansion of woodland at Lago Riane has been provisionally attributed to a decline in human pressure on the environment during a period of short-term climate change

The determination of total nitrogen and total phosphorus concentrations in freshwaters from land use, stock headage and population data: testing of a model for use in conservation and water quality management

1. Nutrient concentrations (particularly N and P) determine the extent to which water bodies are or may become eutrophic. Direct determination of nutrient content on a wide scale is labour intensive but the main sources of N and P are well known. This paper describes and tests an export coefficient model for prediction of total N and total P from: (i) land use, stock headage and human population; (ii) the export rates of N and P from these sources; and (iii) the river discharge. Such a model might be used to forecast the effects of changes in land use in the future and to hindcast past water quality to establish comparative or baseline states for the monitoring of change. 2. The model has been calibrated against observed data for 1988 and validated against sets of observed data for a sequence of earlier years in ten British catchments varying from uplands through rolling, fertile lowlands to the flat topography of East Anglia. 3. The model predicted total N and total P concentrations with high precision (95% of the variance in observed data explained). It has been used in two forms: the first on a specific catchment basis; the second for a larger natural region which contains the catchment with the assumption that all catchments within that region will be similar. Both models gave similar results with little loss of precision in the latter case. This implies that it will be possible to describe the overall pattern of nutrient export in the UK with only a fraction of the effort needed to carry out the calculations for each individual water body. 4. Comparison between land use, stock headage, population numbers and nutrient export for the ten catchments in the pre-war year of 1931, and for 1970 and 1988 show that there has been a substantial loss of rough grazing to fertilized temporary and permanent grasslands, an increase in the hectarage devoted to arable, consistent increases in the stocking of cattle and sheep and a marked movement of humans to these rural catchments. 5. All of these trends have increased the flows of nutrients with more than a doubling of both total N and total P loads during the period. On average in these rural catchments, stock wastes have been the greatest contributors to both N and P exports, with cultivation the next most important source of N and people of P. Ratios of N to P were high in 1931 and remain little changed so that, in these catchments, phosphorus continues to be the nutrient most likely to control algal crops in standing waters supplied by the rivers studied.

The Natural History of Slapton Ley Nature Reserve XVIII: nitrogen and phosphorus losses from the catchment - an export coefficient modelling approach

Nitrogen and phosphorus losses from the catchment of Slapton Ley, a small coastal lake in SW England, were calculated using an adaptation of a model developed by Jorgensen (1980). A detailed survey of the catchment revealed that its land use is dominated by both permanent and temporary grassland (respectively 38 and 32% of its total area), and that the remainder is made up of the cultivation of cereals and field vegetables, and market gardening. Livestock numbers in the catchment constitute ca. 6600 head of cattle, 10,000 sheep, 590 pigs, 1700 poultry and 58 horses. The permanent human population of the area is ca. 2000, served by two small gravity-fed sewage treatment works (STWs). Inputs to, and losses from, farmland in the catchment were computed using Jorgensen’s model, and coefficients derived from the data of Cooke (1976), Gostick (1982), Rast and Lee (1983) and Vollenweider (1968). Allowing for outputs from STWs, the total annual external load of N and P upon Slapton Ley is 160 t (35 kg ha-1) a-1 N, and 4.8 t (1.05 kg ha-1) a-1 P. Accordingly to Vollenweider (1968, 1975), such loadings exceed OECD permissible level by a factor of ca. 50 in the case of N, and ca. 5 in that of P. In order to reduce nutrient loads, attention would need to be paid to both STW and agricultural sources.

Military competition and the emergence of nationalism: putting the logic of political survival into historical context

This essay aims to make a contribution to the conversation between IR and nationalism literatures by considering a particular question: What is the relationship between interstate military competition and the emergence of nationalism as a potent force in world politics? The conventional wisdom among international security scholars, especially neorealists, holds that nationalism can be more or less treated like a “technology” that allowed states to extract significant resources as well as manpower from their respective populations. This paper underlines some of the problems involved with this perspective and pushes forward an interpretation that is based on the logic of political survival. I argue that nationalism’s emergence as a powerful force in world politics followed from the “mutation” and absorption of the universalistic/cosmopolitan republican ideas that gained temporary primacy in Europe during the eighteenth century into particularistic nationalist ideologies. This transformation, in turn, can be best explained by the French Revolution’s dramatic impacts on rulers’ political survival calculi vis-à-vis both interstate and domestic political challenges. The analysis offered in this essay contributes to our understanding of the relationship between IR and nationalism while also highlighting the potential value of the political survival framework for exploring macrohistorical puzzles.

Time development of small disturbances to plane Couette Flow

The question of linear sheared-disturbance evolution in constant-shear parallel flow is here reexamined with regard to the temporary-amplification phenomenon noted first by Orr in 1907. The results apply directly to Rossby waves on a beta-plane, and are also relevant to the Eady model of baroclinic instability. It is shown that an isotropic initial distribution of standing waves maintains a constant energy level throughout the shearing process, the amplification of some waves being precisely balanced by the decay of the others. An expression is obtained for the energy of a distribution of disturbances whose wavevectors lie within a given angular wedge and an upper bound derived. It is concluded that the case for ubiquitous amplification made in recent studies may have been somewhat overstated: while carefully-chosen individual Fourier components can amplify considerably before they decay. a general distribution will tend to exhibit little or no amplification.

Endocannabinoids, FOXO and the metabolic syndrome: redox, function and tipping point--the view from two systems

The endocannabinoid system (ECS) was only 'discovered' in the 1990s. Since then, many new ligands have been identified, as well as many new intracellular targets--ranging from the PPARs, to mitochondria, to lipid rafts. It was thought that blocking the CB-1 receptor might reverse obesity and the metabolic syndrome. This was based on the idea that the ECS was dysfunctional in these conditions. This has met with limited success. The reason may be that the ECS is a homeostatic system, which integrates energy seeking and storage behaviour with resistance to oxidative stress. It could be viewed as having thrifty actions. Thriftiness is an innate property of life, which is programmed to a set point by both environment and genetics, resulting in an epigenotype perfectly adapted to its environment. This thrifty set point can be modulated by hormetic stimuli, such as exercise, cold and plant micronutrients. We have proposed that the physiological and protective insulin resistance that underlies thriftiness encapsulates something called 'redox thriftiness', whereby insulin resistance is determined by the ability to resist oxidative stress. Modern man has removed most hormetic stimuli and replaced them with a calorific sedentary lifestyle, leading to increased risk of metabolic inflexibility. We suggest that there is a tipping point where lipotoxicity in adipose and hepatic cells induces mild inflammation, which switches thrifty insulin resistance to inflammation-driven insulin resistance. To understand this, we propose that the metabolic syndrome could be seen from the viewpoint of the ECS, the mitochondrion and the FOXO group of transcription factors. FOXO has many thrifty actions, including increasing insulin resistance and appetite, suppressing oxidative stress and shifting the organism towards using fatty acids. In concert with factors such as PGC-1, they also modify mitochondrial function and biogenesis. Hence, the ECS and FOXO may interact at many points; one of which may be via intracellular redox signalling. As cannabinoids have been shown to modulate reactive oxygen species production, it is possible that they can upregulate anti-oxidant defences. This suggests they may have an 'endohormetic' signalling function. The tipping point into the metabolic syndrome may be the result of a chronic lack of hormetic stimuli (in particular, physical activity), and thus, stimulus for PGC-1, with a resultant reduction in mitochondrial function and a reduced lipid capacitance. This, in the context of a positive calorie environment, will result in increased visceral adipose tissue volume, abnormal ectopic fat content and systemic inflammation. This would worsen the inflammatory-driven pathological insulin resistance and inability to deal with lipids. The resultant oxidative stress may therefore drive a compensatory anti-oxidative response epitomised by the ECS and FOXO. Thus, although blocking the ECS (e.g. via rimonabant) may induce temporary weight loss, it may compromise long-term stress resistance. Clues about how to modulate the system more safely are emerging from observations that some polyphenols, such as resveratrol and possibly, some phytocannabinoids, can modulate mitochondrial function and might improve resistance to a modern lifestyle.

Evolution and change in the serviced office sector: a decade later

With particular reference to its role in the corporate real estate supply chain, this paper focuses on how the serviced office sector in the UK has evolved and changed over the last decade. A qualitative research approach involving 21 semi-structured interviews with corporate clients of serviced office operators was used to address a number of issues regarding the perceptions of users of serviced offices. It is concluded that the serviced office sector has become an established sector of the UK’s commercial real estate market providing an essential product for many corporate organisations. The serviced office sector has been relatively nimble and a range of operational models have emerged. It was found that corporate organisations use serviced office space and services in order to align workforce change with portfolio change, to transfer risk, for short-term project space, as temporary overflow space, to pilot a new location, to become familiar with a specific geographical marketplace or simply to gain an initial presence in an area.

Protection of dried probiotic bacteria from bile using bile adsorbent resins

Enteric coated oral tablets or capsules can deliver dried live cells directly into the intestine. Previously, we found that a live attenuated bacterial vaccine acquired sensitivity to intestinal bile when dried, raising the possibility that although gastric acid can be bypassed, significant loss of viability might occur on release from an enteric coated oral formulations. Here we demonstrate that some food-grade lyophilised preparations of Lactobacillus casei and Lactobacillus salivarius also show temporary bile sensitivity that can be rapidly reversed by rehydration. To protect dried bacterial cells from temporary bile sensitivity, we propose using bile acid adsorbing resins, such as cholestyramine, which are bile acid binding agents, historically used to lower cholesterol levels. Vcaps™ HPMC capsules alone provided up to 830-fold protection from bile. The inclusion of 50% w/w cholestyramine in Vcaps™ HPMC capsules resulted in release of up to 1700-fold more live Lactobacillus casei into simulated intestinal fluid containing 1% bile, when compared to dried cells added directly to bile. We conclude that delivery of dried live probiotic organisms to the intestine may be improved by providing protection from bile by addition of bile adsorbing resins and the use of HPMC capsules.