Gap junctions and connexin hemichannels in the regulation of haemostasis and thrombosis

Platelets are involved in the maintenance of haemostasis but their inappropriate activation leads to thrombosis, a principal trigger for heart attack and ischemic stroke. Although platelets circulate in isolation, upon activation they accumulate or aggregate together to form a thrombus, where they function in a coordinated manner to prevent loss of blood and control wound repair. Recent reports indicate that the stability and functions of a thrombus are maintained through sustained, contact dependent signalling between platelets. Given the role of gap junctions in the coordination of tissue responses, it was hypothesized that gap junctions may be present within a thrombus and mediate intercellular communication between platelets. Therefore studies were performed to explore the presence and functions of connexins in platelets. In this brief review, the roles of hemichannels and gap junctions in the control of thrombosis and haemostasis and the future directions for this research will be discussed.

Efficient masking of corrosion and fission products such as Ni(II) and Pd(II) in the presence of the minor actinide Am(III) using hydrophilic anionic or cationic bis-triazines

Water soluble anionic and cationic bis-triazine ligands are able to suppress (mask) the extraction of corrosion and fission products such as Ni(II) and Pd(II) that are found in PUREX raffinates. Thus it is possible to separate these elements from the minor actinide Am(III). Although some masking agents have previously been developed that retard the extraction of Pd(II), this is the first time a masking agent has been developed for Ni(II).

On the threshold of adulthood: a new approach for the use of maturation indicators to assess puberty in adolescents from medieval England

Objectives: This study provides the first large scale analysis of the age at which adolescents in medieval England entered and completed the pubertal growth spurt. This new method has implications for expanding our knowledge of adolescent maturation across different time periods and regions. Methods: In total, 994 adolescent skeletons (10-25 years) from four urban sites in medieval England (AD 900-1550) were analysed for evidence of pubertal stage using new osteological techniques developed from the clinical literature (i.e. hamate hook development, CVM, canine mineralisation, iliac crest ossification, radial fusion). Results: Adolescents began puberty at a similar age to modern children at around 10-12 years, but the onset of menarche in girls was delayed by up to 3 years, occurring around 15 for most in the study sample and 17 years for females living in London. Modern European males usually complete their maturation by 16-18 years; medieval males took longer with the deceleration stage of the growth spurt extending as late as 21 years. Conclusions: This research provides the first attempt to directly assess the age of pubertal development in adolescents during the tenth to seventeenth centuries. Poor diet, infections, and physical exertion may have contributed to delayed development in the medieval adolescents, particularly for those living in the city of London. This study sheds new light on the nature of adolescence in the medieval period, highlighting an extended period of physical and social transition.

Microphase separation induced in the melt of Pluronic copolymers by blending with a hydrogen bonding urea–urethane end-capped supramolecular polymer

Blending with a hydrogen-bonding supramolecular polymer is shown to be a successful novel strategy to induce microphase-separation in the melt of a Pluronic polyether block copolymer. The supramolecular polymer is a polybutadiene derivative with urea–urethane end caps. Microphase separation is analysed using small-angle X-ray scattering and its influence on the macroscopic rheological properties is analysed. FTIR spectroscopy provides a detailed picture of the inter-molecular interactions between the polymer chains that induces conformational changes leading to microphase separation.

The interaction of moist convection and mid-level dry air in the advance of the onset of the Indian monsoon

The advance of the onset of the Indian monsoon is here explained in terms of a balance between the low-level monsoon flow and an over-running intrusion of mid-tropospheric dry air. The monsoon advances, over a period of about 6 weeks, from the south of the country to the northwest. Given that the low-level monsoon winds are westerly or southwesterly, and the midlevel winds northwesterly, the monsoon onset propagates upwind relative to midlevel flow, and perpendicular to the low-level flow, and is not directly caused by moisture flux toward the northwest. Lacking a conceptual model for the advance means that it has been hard to understand and correct known biases in weather and climate prediction models. The mid-level northwesterlies form a wedge of dry air that is deep in the far northwest of India and over-runs the monsoon flow. The dry layer is moistened from below by shallow cumulus and congestus clouds, so that the profile becomes much closer to moist adiabatic, and the dry layer is much shallower in the vertical, toward the southeast of India. The profiles associated with this dry air show how the most favourable environment for deep convection occurs in the south, and onset occurs here first. As the onset advances across India, the advection of moisture from the Arabian Sea becomes stronger, and the mid-level dry air is increasingly moistened from below. This increased moistening makes the wedge of dry air shallower throughout its horizontal extent, and forces the northern limit of moist convection to move toward the northwest. Wetting of the land surface by rainfall will further reinforce the north-westward progression, by sustaining the supply of boundary layer moisture and shallow cumulus. The local advance of the monsoon onset is coincident with weakening of the mid-level northwesterlies, and therefore weakened mid-level dry advection.

Molecular insights of p47phox phosphorylation dynamics in the regulation of NADPH oxidase activation and superoxide production

Phagocyte superoxide production by a multicomponent NADPH oxidase is important in host defense against microbial invasion. However inappropriate NADPH oxidase activation causes inflammation. Endothelial cells express NADPH oxidase and endothelial oxidative stress due to prolonged NADPH oxidase activation predisposes many diseases. Discovering the mechanism of NADPH oxidase activation is essential for developing novel treatment of these diseases. The p47phox is a key regulatory subunit of NADPH oxidase; however, due to the lack of full protein structural information, the mechanistic insight of p47phox phosphorylation in NADPH oxidase activation remains incomplete. Based on crystal structures of three functional domains, we generated a computational structural model of the full p47phox protein. Using a combination of in silico phosphorylation, molecular dynamics simulation and protein/protein docking, we discovered that the C-terminal tail of p47phox is critical for stabilizing its autoinhibited structure. Ser-379 phosphorylation disrupts H-bonds that link the C-terminal tail to the autoinhibitory region (AIR) and the tandem Src homology 3 (SH3) domains, allowing the AIR to undergo phosphorylation to expose the SH3 pocket for p22phox binding. These findings were confirmed by site-directed mutagenesis and gene transfection of p47phox_/_ coronary microvascular cells. Compared with wild-type p47phoxcDNAtransfected cells, the single mutation of S379A completely blocked p47phox membrane translocation, binding to p22phox and endothelial O2 . production in response to acute stimulation of PKC. p47phox C-terminal tail plays a key role in stabilizing intramolecular interactions at rest. Ser-379 phosphorylation is a molecular switch which initiates p47phox conformational changes and NADPH oxidase-dependent superoxide production by cells.

Distribution of lipids in the grain of wheat (cv Hereward) determined by lipidomic analysis of milling and pearling fractions

Lipidomic analyses of milling and pearling fractions from wheat grain were carried out to determine differences in composition which could relate to the spatial distribution of lipids in the grain. Free fatty acids and triacylglycerols were major components in all fractions, but the relative contents of polar lipids varied, particularly lysophosphatidyl choline and digalactosyldiglyceride, which were enriched in flour fractions. By contrast, minor phospholipids were enriched in bran and offal fractions. The most abundant fatty acids in the analysed acyl lipids were C16:0 and C18:2 and their combinations, including C36:4 and C34:2. Phospholipids and galactolipids have been reported to have beneficial properties for bread making, while free fatty acids and triacylglycerols are considered detrimental. The subtle differences in the compositions of fractions determined in the present study could therefore underpin the production of flour fractions with optimised compositions for different end uses.

Winckelmann in the perspective of Altertumswissenschaft: Christian Gottlob Heyne and Friedrich August Wolf

Winckelmann's writings hold an interest for modern classical studies which is not restricted to the subfield of classical archaeology. Considered in terms of methodology, his writings dramatise problems and questions which attend any attempt to provide a comprehensive account of ancient culture and society. The Geschichte der Kunst des Alterthums provided an influential model of what such a reconstruction might look like in a period when classical philology was undergoing a significant reconfiguration as „Alterthums-Wissenschaft" at the hands of scholars such as Christian Gottlob Heyne and Friedrich August Wolf. Investigation of their critical responses to Winckelmann’s works aims to contribute to understanding both of the early reception of his works and of questions which are still relevant today. Im Rahmen der modernen Altertumswissenschaften kommt den Werken Winckelmanns eine Bedeutung zu, die nicht auf den Bereich der Klassischen Archäologie beschränkt ist. Methodologisch betrachtet, dramatisieren seine Schriften Probleme und Fragen, die jedem Versuch einer umfassenden, erklärenden Rekonstruktion der antiken Kultur und Gesellschaft zugrunde liegen. Die Geschichte der Kunst des Alterthums hat ein einflussreiches Modell dafür geliefert, was eine solche Rekonstruktion in einer Zeit leisten konnte, in der die klassische Philologie einer erheblichen Umstrukturierung als „Alterthums-Wissenschaft“ durch Gelehrte wie Christian Gottlob Heyne und Friedrich August Wolf unterzogen wurde. Die vorliegende Untersuchung ihrer kritischen Reaktionen auf Winckelmanns Schriften soll dazu beitragen, sowohl die frühe Rezeption seines Werkes als auch Fragestellungen, die heute noch aktuell sind, besser zu verstehen.

The role of evaporating showers in the transfer of sting-jet momentum to the surface

The most damaging winds in a severe extratropical cyclone often occur just ahead of the evaporating ends of cloud filaments emanating from the so-called cloud head. These winds are associated with low-level jets (LLJs), sometimes occurring just above the boundary layer. The question then arises as to how the high momentum is transferred to the surface. An opportunity to address this question arose when the severe ‘St Jude's Day’ windstorm travelled across southern England on 28 October 2013. We have carried out a mesoanalysis of a network of 1 min resolution automatic weather stations and high-resolution Doppler radar scans from the sensitive S-band Chilbolton Advanced Meteorological Radar (CAMRa), along with satellite and radar network imagery and numerical weather prediction products. We show that, although the damaging winds occurred in a relatively dry region of the cyclone, there was evidence within the LLJ of abundant precipitation residues from shallow convective clouds that were evaporating in a localized region of descent. We find that pockets of high momentum were transported towards the surface by the few remaining actively precipitating convective clouds within the LLJ and also by precipitation-free convection in the boundary layer that was able to entrain evaporatively cooled air from the LLJ. The boundary-layer convection was organized in along-wind rolls separated by 500 to about 3000 m, the spacing varying according to the vertical extent of the convection. The spacing was greatest where the strongest winds penetrated to the surface. A run with a medium-resolution version of the Weather Research and Forecasting (WRF) model was able to reproduce the properties of the observed LLJ. It confirmed the LLJ to be a sting jet, which descended over the leading edge of a weaker cold-conveyor-belt jet.

The effectiveness of protected areas in the conservation of species with changing geographical ranges

A cornerstone of conservation is the designation and management of protected areas (PAs): locations often under conservation management containing species of conservation concern, where some development and other detrimental influences are prevented or mitigated. However, the value of PAs for conserving biodiversity in the long term has been questioned given that species are changing their distributions in response to climatic change. There is a concern that PAs may become climatically unsuitable for those species that they were designated to protect, and may not be located appropriately to receive newly-colonizing species for which the climate is improving. In the present study, we analyze fine-scale distribution data from detailed resurveys of seven butterfly and 11 bird species in Great Britain aiming to examine any effect of PA designation in preventing extinctions and promoting colonizations. We found a positive effect of PA designation on species' persistence at trailing-edge warm range margins, although with a decreased magnitude at higher latitudes and altitudes. In addition, colonizations by range expanding species were more likely to occur on PAs even after altitude and latitude were taken into account. PAs will therefore remain an important strategy for conservation. The potential for PA management to mitigate the effects of climatic change for retracting species deserves further investigation.

Planning in the face of ‘deep divisions’: a view from Beirut, Lebanon

This article discusses planning in the global South-East while focusing on the specific context of social divides, political turmoil and conflict situations. The article proposes a five-way framework based on political science and planning to theory to analyse such contexts. The article explores the case of Beirut, Lebanon that has undergone several episodes of internal and external conflicts resulting in a society splintered along sectarianism. Three Two case studies of open urban spaces and their public activities are analysed using the five-way framework The discussion indicates how economic liberalism that is prevalent in countries of the South-East, along with place-based identities, interest-based identities, consensus orientated processes and institutionalism might facilitate a cultivation of deep values away from a narrowly constructed identity. The article argues that planners should understand the options for positive action that aim to bridge deep divisions and suggests that the five-way framework provides a reference for contextualising in different ways to suit particular contexts. Therefore, the framework is not necessarily restricted to the South-East but could be applicable to any context which manifests deep divisions.

Can milk proteins be a useful tool in the management of cardiometabolic health? An updated review of human intervention trials

The prevalence of cardiometabolic diseases is a significant public health burden worldwide. Emerging evidence supports the inverse association between greater dairy consumption and reduced risk of cardiometabolic diseases. Dairy proteins may have in important role in the favourable impact of dairy on human health such as blood pressure (BP) control, blood lipid and glucose control. The purpose of this review is to update and critically evaluate the evidence on the impacts of casein and whey protein in relation to metabolic function. Evidence from acute clinical studies assessing postprandial responses to milk protein ingestion suggests benefits on vascular function independent of BP, as well as improvement in glycaemic homeostasis. Chronic interventions have been less conclusive, with some showing benefits and others indicating a lack of improvement in vascular function. During chronic consumption BP appears to be lowered and both dyslipidaemia and hyperglacaemia seems to be controlled. Limited number of trials investigated the effects of dairy proteins on oxidative stress and inflammation. The beneficial changes in cardiometabolic homeostasis are likely mediated through improvements in insulin resistance, however to gain more detailed understanding on the underlying mechanism of milk proteins warrants further research. The incorporation of meals enriched with dairy protein in the habitual diet may result in the beneficial effects on cardiometabolic health. Nevertheless, future well-designed, controlled studies are needed to investigate the relative effects of both casein and whey protein on BP, vascular function, glucose homeostasis and inflammation.

An idealized study of coupled atmosphere-ocean 4D-Var in the presence of model error

Atmosphere only and ocean only variational data assimilation (DA) schemes are able to use window lengths that are optimal for the error growth rate, non-linearity and observation density of the respective systems. Typical window lengths are 6-12 hours for the atmosphere and 2-10 days for the ocean. However, in the implementation of coupled DA schemes it has been necessary to match the window length of the ocean to that of the atmosphere, which may potentially sacrifice the accuracy of the ocean analysis in order to provide a more balanced coupled state. This paper investigates how extending the window length in the presence of model error affects both the analysis of the coupled state and the initialized forecast when using coupled DA with differing degrees of coupling. Results are illustrated using an idealized single column model of the coupled atmosphere-ocean system. It is found that the analysis error from an uncoupled DA scheme can be smaller than that from a coupled analysis at the initial time, due to faster error growth in the coupled system. However, this does not necessarily lead to a more accurate forecast due to imbalances in the coupled state. Instead coupled DA is more able to update the initial state to reduce the impact of the model error on the accuracy of the forecast. The effect of model error is potentially most detrimental in the weakly coupled formulation due to the inconsistency between the coupled model used in the outer loop and uncoupled models used in the inner loop.

Evaluation of thermal simulation of households in the metropolitan region of So Paulo, Brazil

This paper aims at assessing the performance of a program of thermal simulation (Arquitrop) in different households in the city of Sao Paulo, Brazil. The households were selected for the Wheezing Project which followed up children under 2 years old to monitor the occurrence of respiratory diseases. The results show that in all three study households there is a good approximation between the observed and the simulated indoor temperatures. It was also observed a fairly consistent and realistic behavior between the simulated indoor and the outdoor temperatures, describing the Arquitrop model as an efficient estimator and good representative of the thermal behavior of households in the city of Sao Paulo. The worst simulation is linked to the poorest type of construction. This may be explained by the bad quality of the construction, which the Architrop could not simulate adequately.

Nutritional information of meals supplied by companies, participating in the workers` meal program in Sao Paulo, Brazil

Objective. To compare the nutritional value of meals provided by companies participating in the Workers` Meal Program in the city of Sao Paulo, Brazil, to the nutritional recommendations and guidelines established by the Ministry of Health for the Brazilian population. Methods. The 72 companies studied were grouped according to economic sector (industrial, services, or commerce), size (micro, small, medium, or large), meal preparation modality (prepared on-site by the company itself, on-site by a hired caterer, or off-site by a hired caterer), and supervision by a dietitian (yes or no). The per capita amount of food was determined based on the lunch, dinner, and supper menus for three days. The nutritional value of the meals was defined by the amount of calories, carbohydrates, protein, total fat, polyunsaturated fat, saturated fat, trans fat, sugars, cholesterol, and fruits and vegetables. Results. Most of the menus were deficient in the number of fruits and vegetables (63.9%) and amount of polyunsaturated fat (83.3%), but high in total fat (47.2%) and cholesterol (62.5%). Group 2, composed of mostly medium and large companies, supervised by a dietician, belonging to the industrial and/or service sectors, and using a hired caterer, on averaged served meals with higher calorie content (P < 0.001), higher percentage of polyunsaturated fat (P < 0.001), more cholesterol (P = 0.015), and more fruits and vegetables (P < 0.001) than Group 1, which was composed of micro and small companies from the commercial sector, that prepare the meals themselves on-site, and are not supervised by a dietitian. Regarding the nutrition guidelines set for the Brazilian population, Group 2 meals were better in terms of fruit and vegetable servings (P < 0.001). Group I meals were better in terms of cholesterol content (P = 0.05). Conclusions. More specific action is required targeting company officers and managers in charge of food and nutrition services, especially in companies without dietitian supervision.