BbgIV is an important Bifidobacterium β-galactosidase for the synthesis of prebiotic galactooligosaccharides at high temperatures

The individual contribution of four β-galactosidases present in Bifidobacterium bifidum NCIMB 41171 towards galactooligosaccharides (GOS) synthesis was investigated. Although the β-galactosidase activity of the whole cells significantly decreased as a function of temperature (40 to 75 °C), GOS yield was at its maximum at 65 °C. Native-PAGE electrophoresis of the whole cells showed that the contribution of BbgIII and BbgIV towards GOS synthesis increased as the temperature increased. Moreover, BbgIII and BbgIV were found to be more temperature stable and to produce a higher GOS yield than BbgI and BbgII, when used in their free form. The GOS yield using BbgIV was 54.8 % (% of total carbohydrates) and 63.9 % (% lactose converted to GOS) at 65 °C from 43 % w/w lactose. It was shown that BbgIV is the most important β-galactosidase in B. bifidum NCIMB 41171 and can be used for GOS synthesis at elevated temperatures.

Modelling of the natural chlorine cycling in a coniferous stand: implications for chlorine-36 behaviour in a contaminated forest environment

Considered as one of the most available radionuclide in soileplant system, 36Cl is of potential concern for long-term management of radioactive wastes, due to its high mobility and its long half-life. To evaluate the risk of dispersion and accumulation of 36Cl in the biosphere as a consequence of a potential contamination, there is a need for an appropriate understanding of the chlorine cycling dynamics in the ecosystems. To date, a small number of studies have investigated the chlorine transfer in the ecosystem including the transformation of chloride to organic chlorine but, to our knowledge, none have modelled this cycle. In this study, a model involving inorganic as well as organic pools in soils has been developed and parameterised to describe the biogeochemical fate of chlorine in a pine forest. The model has been evaluated for stable chlorine by performing a range of sensitivity analyses and by comparing the simulated to the observed values. Finally a range of contamination scenarios, which differ in terms of external supply, exposure time and source, has been simulated to estimate the possible accumulation of 36Cl within the different compartments of the coniferous stand. The sensitivity study supports the relevancy of the model and its compartments, and has highlighted the chlorine transfers affecting the most the residence time of chlorine in the stand. Compared to observations, the model simulates realistic values for the chlorine content within the different forest compartments. For both atmospheric and underground contamination scenarios most of the chlorine can be found in its organic form in the soil. However, in case of an underground source, about two times less chlorine accumulates in the system and proportionally more chlorine leaves the system through drainage than through volatilisation.

Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with Autism

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato–thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto–striato–parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto–striato–cerebellar dysregulation in ASD.

The state estimation of flow demands in gas networks from sparse pressure telemetry

This paper presents novel observer-based techniques for the estimation of flow demands in gas networks, from sparse pressure telemetry. A completely observable model is explored, constructed by incorporating difference equations that assume the flow demands are steady. Since the flow demands usually vary slowly with time, this is a reasonable approximation. Two techniques for constructing robust observers are employed: robust eigenstructure assignment and singular value assignment. These techniques help to reduce the effects of the system approximation. Modelling error may be further reduced by making use of known profiles for the flow demands. The theory is extended to deal successfully with the problem of measurement bias. The pressure measurements available are subject to constant biases which degrade the flow demand estimates, and such biases need to be estimated. This is achieved by constructing a further model variation that incorporates the biases into an augmented state vector, but now includes information about the flow demand profiles in a new form.

It was never good world sence minister must have wyves”: clerical celibacy, clerical marriage, and anticlericalism in Reformation England

The impact of the Reformation was felt strongly in the nature and character of the priesthood, and in the function and reputation of the priest. A shift in the understanding of the priesthood was one of the most tangible manifestations of doctrinal change, evident in the physical arrangement of the church, in the language of the liturgy, and in the relaxation of the discipline of celibacy, which had for centuries bound priests in the Latin tradition to a life of perpetual continence. Clerical celibacy, and accusations of clerical incontinence, featured prominently in evangelical criticisms of the Catholic church and priesthood, which made a good deal of polemical capital out of the perceived relationship of the priest and the efficacy of his sacred function. Citing St Paul, Protestant polemicists presented clerical marriage as the only, and appropriate remedy, for priestly immorality. But did the advent of a married priesthood create more problems than it solved? The polemical certainties that informed evangelical writing on sacerdotal celibacy did not guarantee the immediate acceptance of a married priesthood, and the vocabulary that had been used to denounce clergy who failed in their obligation to celibacy was all too readily turned against the married clergy. The anti-clerical lexicon, and its usage, remained remarkably static despite the substantial doctrinal and practical challenges posed to the traditional model of priesthood by the Protestant Reformation.

The evolution of innovation capability in multinational enterprise subsidiaries: dual network embeddedness and the divergence of subsidiary specialisation in Taiwan

This paper examines how innovation-related capabilities for production, design and marketing develop at the subsidiary level within multinational enterprises (MNEs). We focus on how subsidiary autonomy and changing opportunities to access internal (MNE) and external (host country) sources of capability contribute in a combined way to the accumulation of specialist capabilities in five Taiwan-based MNE subsidiaries in the semiconductor industry. Longitudinal analysis shows how the accumulation process is subject to discontinuities, as functional divisions are (re)opened and closed during the lifetime of the subsidiary. A composite set of innovation output measures also shows significant variations in within-function levels of capability across our sample. We conclude that subsidiary specialisation and unique subsidiary-specific advantages have evolved in a way that is strongly influenced by the above factors.

Lipoma preferred partner is a mechanosensitive protein regulated by nitric oxide in the heart

Adaptor proteins play an important role in signaling pathways by providing a platform on which many other proteins can interact. Malfunction or mislocalization of these proteins may play a role in the development of disease. Lipoma preferred partner (LPP) is a nucleocytoplasmic shuttling adaptor protein. Previous work shows that LPP plays a role in the function of smooth muscle cells and in atherosclerosis. In this study we wanted to determine whether LPP has a role in the myocardium. LPP expression increased by 56% in hearts from pressure overload aortic-banded rats (p < 0.05 n = 4), but not after myocardial infarction, suggesting hemodynamic load regulates its expression. In vitro, LPP expression was 87% higher in cardiac fibroblasts than myocytes (p < 0.05 n = 3). LPP expression was downregulated in the absence of the actin cytoskeleton but not when microtubules were disassembled. We mechanically stretched cardiac fibroblasts using the Flexcell 4000 for 48 h (1 Hz, 5% maximum strain), which decreased total LPP total expression and membrane localization in subcellular fractions (p < 0.05, n = 5). However, L-NAME, an inhibitor of nitric oxide synthase (NOS), significantly upregulated LPP expression. These findings suggest that LPP is regulated by a complex interplay between NO and mechanical cues and may play a role in heart failure induced by increased hemodynamic load.

Prehistoric activity in Peterstone Great Wharf Palaeochannels: field survey 2005-6

This is an interim report on research carried out at the intertidal site of Peterstone Great Wharf, located on the Wentlooge Levels, c. 7 km east of Cardiff. The project is the first detailed survey and excavation of a site originally recorded in 1996-7 as part of a larger survey of the intertidal zone from Cardiff to the Second Severn Crossing. The 1997 survey produced important evidence for prehistoric human activity preserved within four palaeochannels. Significant erosion has taken place since then. A new survey of the foreshore has identified additional palaeochannels not seen in 1997 which form part of a more complex system of inter-cutting channels, many containing wood structures including short lines of timbers on the channel edge. Artefacts include a wooden axe handle, antler artefacts, an animal bone assemblage and some pottery of Beaker and Bronze Age date. The finds are thought to derive from a nearby, possibly eroded, settlement. The channels have trapped artefacts and preserved evidence of a range of activities, including what are interpreted as possible boat landings and fishing structures.

Cyborgs in space

Practical realisation of Cyborgs opens up significant new opportunities in many fields. In particular when it comes to space travel many of the limitations faced by humans, in stand-alone form, are transposed by the adoption of a cyborg persona. In this article a look is taken at different types of Brain-Computer interface which can be employed to realise Cyborgs, biology-technology hybrids. e approach taken is a practical one with applications in mind, although some wider implications are also considered. In particular results from experiments are discussed in terms of their meaning and application possibilities. e article is written from the perspective of scientific experimentation opening up realistic possibilities to be faced in the future rather than giving conclusive comments on the technologies employed. Human implantation and the merger of biology and technology are though important elements.

Connexin40 regulates platelet function

The presence of multiple connexins was recently demonstrated in platelets, with notable expression of Cx37. Studies with Cx37-deficient mice and connexin inhibitors established roles for hemichannels and gap junctions in platelet function. It was uncertain, however, whether Cx37 functions alone or in collaboration with other family members through heteromeric interactions in regulation of platelet function. Here we report the presence and functions of an additional platelet connexin, Cx40. Inhibition of Cx40 in human platelets or its deletion in mice reduces platelet aggregation, fibrinogen binding, granule secretion and clot retraction. The effects of the Cx37 inhibitor 37,43Gap27 on Cx40-/- mouse platelets and of the Cx40 inhibitor 40Gap27 on Cx37-/- mouse platelets revealed that each connexin is able to function independently. Inhibition or deletion of Cx40 reduces haemostatic responses in mice, indicating the physiological importance of this protein in platelets. We conclude that multiple connexins are involved in regulating platelet function, thereby contributing to haemostasis and thrombosis.

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.

Corticospinal tract integrity and lesion volume play different roles in chronic hemiparesis and its improvement through motor practice

Background. Initial evidence suggests that the integrity of the ipsilesional corticospinal tract (CST) after stroke is strongly related to motor function in the chronic state but not the treatment gain induced by motor rehabilitation. Objective. We examined the association of motor status and treatment benefit by testing patients with a wide range of severity of hemiparesis of the left and right upper extremity. Method. Diffusion tensor imaging was performed in 22 patients beyond 12 months after onset of stroke with severe to moderate hemiparesis. Motor function was tested before and after 2 weeks of modified constraint-induced movement therapy. Results. CST integrity, but not lesion volume, correlated with the motor ability measures of the Wolf Motor Function Test and the Motor Activity Log. No differences were found between left and right hemiparesis. Motor performance improved significantly with the treatment regime, and did so equally for patients with left and right arm paresis. However, treatment benefit was not associated with either CST integrity or lesion volume. Conclusion. CST integrity correlated best in this small trial with chronic long-term status but not treatment-induced improvements. The CST may play a different role in the mechanisms mediating long-term outcome compared to those underlying practice-induced gains after a chronic plateau in motor function.

Risk allocation in a public–private partnership: a case study of construction and operation of kindergartens in Kazakhstan

In Kazakhstan, a transitional nation in Central Asia, the development of public–private partnerships (PPPs) is at its early stage and increasingly of strategic importance. This case study investigates risk allocation in an ongoing project: the construction and operation of 11 kindergartens in the city of Karaganda in the concession form for 14 years. Drawing on a conceptual framework of effective risk allocation, the study identifies principal PPP risks, provides a critical assessment of how and in what way each partner bears a certain risk, highlights the reasons underpinning risk allocation decisions and delineates the lessons learned. The findings show that the government has effectively transferred most risks to the private sector partner, whilst both partners share the demand risk of childcare services and the project default risk. The strong elements of risk allocation include clear assignment of parties’ responsibilities, streamlined financing schemes and incentives to complete the main project phases on time. However, risk allocation has missed an opportunity to create incentives for service quality improvements and take advantage of economies of scale. The most controversial element of risk allocation, as the study finds, is a revenue stream that an operator is supposed to receive from the provision of services unrelated to childcare, as neither partner is able to mitigate this revenue risk. The article concludes that in the kindergartens’ PPP, the government has achieved almost complete transfer of risks to the private sector partner. However, the costs of transfer are extensive government financial outlays that seriously compromise the PPP value for money.

The global effect of follicle-stimulating hormone and tumour necrosis factor α on gene expression in cultured bovine ovarian granulosa cells

Background Oocytes mature in ovarian follicles surrounded by granulosa cells. During follicle growth, granulosa cells replicate and secrete hormones, particularly steroids close to ovulation. However, most follicles cease growing and undergo atresia or regression instead of ovulating. To investigate the effects of stimulatory (follicle-stimulating hormone; FSH) and inhibitory (tumour necrosis factor alpha; TNFα) factors on the granulosa cell transcriptome, bovine ovaries were obtained from a local abattoir and pools of granulosa cells were cultured in vitro for six days under defined serum-free conditions with treatments present on days 3–6. Initially dose–response experiments (n = 4) were performed to determine the optimal concentrations of FSH (0.33 ng/ml) and TNFα (10 ng/ml) to be used for the microarray experiments. For array experiments cells were cultured under control conditions, with FSH, with TNFα, or with FSH plus TNFα (n = 4 per group) and RNA was harvested for microarray analyses. Results Statistical analysis showed primary clustering of the arrays into two groups, control/FSH and TNFα/TNFα plus FSH. The effect of TNFα on gene expression dominated that of FSH, with substantially more genes differentially regulated, and the pathways and genes regulated by TNFα being similar to those of FSH plus TNFα treatment. TNFα treatment reduced the endocrine activity of granulosa cells with reductions in expression of FST, INHA, INBA and AMH. The top-ranked canonical pathways and GO biological terms for the TNFα treatments included antigen presentation, inflammatory response and other pathways indicative of innate immune function and fibrosis. The two most significant networks also reflect this, containing molecules which are present in the canonical pathways of hepatic fibrosis/hepatic stellate cell activation and transforming growth factor β signalling, and these were up regulated. Upstream regulator analyses also predicted TNF, interferons γ and β1 and interleukin 1β. Conclusions In vitro, the transcriptome of granulosa cells responded minimally to FSH compared with the response to TNFα. The response to TNFα indicated an active process akin to tissue remodelling as would occur upon atresia. Additionally there was reduction in endocrine function and induction of an inflammatory response to TNFα that displays features similar to immune cells.

Disability [sport] and discourse: stories within the Paralympic legacy

This paper aims to encourage critical reflection on what are key and pressing social and political issues surrounding the Paralympics Games. The focus of the paper is personal narratives of six current elite Paralympic athletes who have participated in at least one Paralympic Games. In response to critical stimuli presented in the form of five ‘unfinished stories’, the self-reflexive, personal, compelling narrative reflections of these individuals were (re)presented for each of the stories as a composite narrative. The stories expose questions over fear, despair, freedom, hope, love, oppression, hatred, hurt, terror, (in)equality, peace, performance and impairment. To really learn from London and reflect for Rio, we need academic work that can understand sport, sporting bodies and physical activity as important ‘sites’ through which social forces, discourses, institutions and processes congregate, congeal and are contested in a manner that contributes to the shaping of human relations, subjectivities, and experiences in particular, contextually contingent ways.