AMM15: a new high-resolution NEMO configuration for operational simulation of the European north-west shelf

This paper describes the next-generation ocean forecast model for the European north-west shelf, which will become the basis of operational forecasts in 2018. This new system will provide a step change in resolution and therefore our ability to represent small-scale processes. The new model has a resolution of 1.5 km compared with a grid spacing of 7 km in the current operational system. AMM15 (Atlantic Margin Model, 1.5 km) is introduced as a new regional configuration of NEMO v3.6. Here we describe the technical details behind this configuration, with modifications appropriate for the new high-resolution domain. Results from a 30-year non-assimilative run using the AMM15 domain demonstrate the ability of this model to represent the mean state and variability of the region. Overall, there is an improvement in the representation of the mean state across the region, suggesting similar improvements may be seen in the future operational system. However, the reduction in seasonal bias is greater off-shelf than on-shelf. In the North Sea, biases are largely unchanged. Since there has been no change to the vertical resolution or parameterization schemes, performance improvements are not expected in regions where stratification is dominated by vertical processes rather than advection. This highlights the fact that increased horizontal resolution will not lead to domain-wide improvements. Further work is needed to target bias reduction across the north-west shelf region

Substantial metabolic activity of human brown adipose tissue during warm conditions and cold-induced lipolysis of local triglycerides

Current understanding of in vivo human brown adipose tissue (BAT) physiology is limited by a reliance on positron emission tomography (PET)/computed tomography (CT) scanning, which has measured exogenous glucose and fatty acid uptake but not quantified endogenous substrate utilization by BAT. Six lean, healthy men underwent 18fluorodeoxyglucose-PET/CT scanning to localize BAT so microdialysis catheters could be inserted in supraclavicular BAT under CT guidance and in abdominal subcutaneous white adipose tissue (WAT). Arterial and dialysate samples were collected during warm (∼25°C) and cold exposure (∼17°C), and blood flow was measured by 133xenon washout. During warm conditions, there was increased glucose uptake and lactate release and decreased glycerol release by BAT compared with WAT. Cold exposure increased blood flow, glycerol release, and glucose and glutamate uptake only by BAT. This novel use of microdialysis reveals that human BAT is metabolically active during warm conditions. BAT activation substantially increases local lipolysis but also utilization of other substrates such as glutamate

X-ray crystallographic study of DNA duplex cross-linking: simultaneous binding to two d(CGTACG)(2) molecules by a bis(9-aminoacridine-4-carboxamide) derivative

Acridine-4-carboxamides form a class of known DNA mono-intercalating agents that exhibit cytotoxic activity against tumour cell lines due to their ability to inhibit topoisomerases. Previous studies of bis-acridine derivatives have yielded equivocal results regarding the minimum length of linker necessary between the two acridine chromophores to allow bis-intercalation of duplex DNA. We report here the 1.7 angstrom resolution X-ray crystal structure of a six-carbon-linked bis(acridine-4-carboxamide) ligand bound to d(CGTACG)(2) molecules by non-covalent duplex cross-linking. The asymmetric unit consists of one DNA duplex containing an intercalated acridine-4-carboxamide chromophore at each of the two CG steps. The other half of each ligand is bound to another DNA molecule in a symmetry-related manner, with the alkyl linker threading through the minor grooves. The two crystallographically independent ligand molecules adopt distinct side chain interactions, forming hydrogen bonds to either O6 or N7 on the major groove face of guanine, in contrast to the semi-disordered state of mono-intercalators bound to the same DNA molecule. The complex described here provides the first structural evidence for the non-covalent cross-linking of DNA by a small molecule ligand and suggests a possible explanation for the inconsistent behaviour of six-carbon linked bis-acridines in previous assays of DNA bis-intercalation

Heligmosomoides bakeri: a model for exploring the biology and genetics of resistance to chronic gastrointestinal nematode infections

The intestinal nematode Heligmosomoides bakeri has undergone 2 name changes during the last 4 decades. Originally, the name conferred on the organism in the early 20th century was Nematospiroides dubius, but this was dropped in favour of Heligmosomoides polygyrus, and then more recently H. bakeri, to distinguish it from a closely related parasite commonly found in wood mice in Europe. H. bakeri typically causes long-lasting infections in mice and in this respect it has been an invaluable laboratory model of chronic intestinal nematode infections. Resistance to H. bakeri is a dominant trait and is controlled by genes both within and outside the MHC. More recently, a significant QTL has been identified on chromosome 1, although the identity of the underlying genes is not yet known. Other QTL for resistance traits and for the accompanying immune responses were also defined, indicating that resistance to H. bakeri is a highly polygenic phenomenon. Hence marker-assisted breeding programmes aiming to improve resistance to GI nematodes in breeds of domestic livestock will need to be highly selective, focussing on genes that confer the greatest proportion of overall genetic resistance, whilst leaving livestock well-equipped genetically to cope with other types of pathogens and preserving important production traits

Endothelial cells and angiogenesis in the horse in health and disease—A review

The cardiovascular system is the first functional organ in the embryo, and its blood vessels form a widespread conductive network within the organism. Blood vessels develop de novo, by the differentiation of endothelial progenitor cells (vasculogenesis) or by angiogenesis, which is the formation of new blood vessels from existing ones. This review presents an overview of the current knowledge on physiological and pathological angiogenesis in the horse including studies on equine endothelial cells. Principal study fields in equine angiogenesis research were identified: equine endothelial progenitor cells; equine endothelial cells and angiogenesis (heterogeneity, markers and assessment); endothelial regulatory molecules in equine angiogenesis; angiogenesis research in equine reproduction (ovary, uterus, placenta and conceptus, testis); angiogenesis research in pathological conditions (tumours, ocular pathologies, equine wound healing, musculoskeletal system and laminitis). The review also includes a table that summarizes in vitro studies on equine endothelial cells, either describing the isolation procedure or using previously isolated endothelial cells. A particular challenge of the review was that results published are fragmentary and sometimes even contradictory, raising more questions than they answer. In conclusion, angiogenesis is a major factor in several diseases frequently occurring in horses, but relatively few studies focus on angiogenesis in the horse. The challenge for the future is therefore to continue exploring new therapeutic angiogenesis strategies for horses to fill in the missing pieces of the puzzle

Potential impacts of climate change on the primary production of regional seas: A comparative analysis of five European seas

Regional seas are potentially highly vulnerable to climate change, yet are the most directly societally important regions of the marine environment. The combination of widely varying conditions of mixing, forcing, geography (coastline and bathymetry) and exposure to the open-ocean makes these seas subject to a wide range of physical processes that mediates how large scale climate change impacts on these seas’ ecosystems. In this paper we explore the response of five regional sea areas to potential future climate change, acting via atmospheric, oceanic and terrestrial vectors. These include the Barents Sea, Black Sea, Baltic Sea, North Sea, Celtic Seas, and are contrasted with a region of the Northeast Atlantic. Our aim is to elucidate the controlling dynamical processes and how these vary between and within these seas. We focus on primary production and consider the potential climatic impacts on: long term changes in elemental budgets, seasonal and mesoscale processes that control phytoplankton’s exposure to light and nutrients, and briefly direct temperature response. We draw examples from the MEECE FP7 project and five regional model systems each using a common global Earth System Model as forcing. We consider a common analysis approach, and additional sensitivity experiments. Comparing projections for the end of the 21st century with mean present day conditions, these simulations generally show an increase in seasonal and permanent stratification (where present). However, the first order (low- and mid-latitude) effect in the open ocean projections of increased permanent stratification leading to reduced nutrient levels, and so to reduced primary production, is largely absent, except in the NE Atlantic. Even in the two highly stratified, deep water seas we consider (Black and Baltic Seas) the increase in stratification is not seen as a first order control on primary production. Instead, results show a highly heterogeneous picture of positive and negative change arising from complex combinations of multiple physical drivers, including changes in mixing, circulation and temperature, which act both locally and non-locally through advection