Role of persistent CMV infection in configuring T cell immunity in the elderly

Ageing is associated with declines in many physiological parameters, including multiple immune system functions. The rate of acceleration of the frequency of death due to cardiovascular disease or cancer seems to increase with age from middle age up to around 80 years, plateauing thereafter. Mortality due to infectious disease, however, does not plateau, but continues to accelerate indefinitely. The elderly commonly possess oligoclonal expansions of T cells, especially of CD8 cells, which, surprisingly, are often associated with cytomegalovirus (CMV) seropositivity. This in turn is associated with many of the same phenotypic and functional alterations to T cell immunity that have been suggested as biomarkers of immune system aging. Thus, the manner in which CMV and the host immune system interact is critical in determining the "age" of specific immunity. We may therefore consider immunosenescence in some respects as an infectious state. This implies that interventions aimed at the pathogen may improve the organ system affected. Hence, CMV-directed anti-virals or vaccination may have beneficial effects on immunity in later life

Understanding anisotropy and architecture in ice-templated biopolymer scaffolds.

Biopolymer scaffolds have great therapeutic potential within tissue engineering due to their large interconnected porosity and biocompatibility. Using an ice-templated technique, where collagen is concentrated into a porous network by ice nucleation and growth, scaffolds with anisotropic pore architecture can be created, mimicking natural tissues like cardiac muscle and bone. This paper describes a systematic set of experiments undertaken to understand the effect of local temperatures on architecture in ice-templated biopolymer scaffolds. The scaffolds within this study were at least 10mm in all dimensions, making them applicable to critical sized defects for biomedical applications. It was found that monitoring the local freezing behavior within the slurry was critical to predicting scaffold structure. Aligned porosity was produced only in parts of the slurry volume which were above the equilibrium freezing temperature (0°C) at the time when nucleation first occurs in the sample as a whole. Thus, to create anisotropic scaffolds, local slurry cooling rates must be sufficiently different to ensure that the equilibrium freezing temperature is not reached throughout the slurry at nucleation. This principal was valid over a range of collagen slurries, demonstrating that by monitoring the temperature within slurry during freezing, scaffold anisotropy with ice-templated scaffolds can be predicted.The authors gratefully acknowledge the financial supp ort of the Gates Cambridge Trust, the Newton Trust, and ERC Advanced Grant 320598 3D-E. A.H. holds a Daphne Jackson Fellowship funded by the University of Cambridge.This is a pre-print of an article which received final publication in Materials Science and Engineering: C Volume 37, 1 April 2014, Pages 141–147. The version offered here does not reflect changes resulting from peer-review. The version of record is available at http://www.sciencedirect.com/science/article/pii/S0928493114000101

Ionic solutes impact collagen scaffold bioactivity.

The structure of ice-templated collagen scaffolds is sensitive to many factors. By adding 0.5 wt% of sodium chloride or sucrose to collagen slurries, scaffold structure could be tuned through changes in ice growth kinetics and interactions of the solute and collagen. With ionic solutes (sodium chloride) the entanglements of the collagen molecule decreased, leading to fibrous scaffolds with increased pore size and decreased attachment of chondrocytes. With non-ionic solutes (sucrose) ice growth was slowed, leading to significantly reduced pore size and up-regulated cell attachment. This highlights the large changes in structure and biological function stimulated by solutes in ice-templating systems.The authors gratefully acknowledge the financial support of the Gates Cambridge Trust, the Newton Trust, NIHR, and ERC Advanced Grant 320598 3D-E. A.H. holds a Daphne Jackson Fellowship funded by the University of Cambridge. Also, the authors thank Dr. S. Butler for help with the rheological measurements.This is the accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10856-015-5457-8

Molecular ND Band Spectroscopy in the Divertor Region of Nitrogen Seeded JET Discharges

In this contribution we present OES measurements in the JET tokamak of the deuterated NH (ND) radical and the correlation between results of those experiments and measurement of ammonia production. The observation region covers most of the divertor and its outer throat. Measurements are performed in different magnetic configurations. The results include temporal and spatial dependence of the molecular emission intensity and study of the emission band shape (vibrational and rotational temperatures) during different JET pulses, with or without nitrogen seeding. Results are a step towards the understanding of nitrogen-containing molecule creation and destruction in the divertor plasmaEURATOM 63305

Altering crystal growth and annealing in ice-templated scaffolds.

The potential applications of ice-templating porous materials are constantly expanding, especially as scaffolds for tissue engineering. Ice-templating, a process utilizing ice nucleation and growth within an aqueous solution, consists of a cooling stage (before ice nucleation) and a freezing stage (during ice formation). While heat release during cooling can change scaffold isotropy, the freezing stage, where ice crystals grow and anneal, determines the final size of scaffold features. To investigate the path of heat flow within collagen slurries during solidification, a series of ice-templating molds were designed with varying the contact area with the heat sink, in the form of the freeze drier shelf. Contact with the heat sink was found to be critical in determining the efficiency of the release of latent heat within the perspex molds. Isotropic collagen scaffolds were produced with pores which ranged from 90 μm up to 180 μm as the contact area decreased. In addition, low-temperature ice annealing was observed within the structures. After 20 h at -30 °C, conditions which mimic storage prior to lyophilization, scaffold architecture was observed to coarsen significantly. In future, ice-templating molds should consider not only heat conduction during the cooling phase of solidification, but the effects of heat flow during ice growth and annealing.The authors gratefully acknowledge the financial support of the Gates Cambridge Trust, the Newton Trust, and ERC Advanced Grant 320598 3D-E. A.H. held a Daphne Jackson Fellowship funded by the University of Cambridge.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10853-015-9343-

Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States

Background: Studies have suggested that CMV infection may influence cardiovascular disease (CVD) risk and mortality. However, there have been no large-scale examinations of these relationships among demographically diverse populations. The inflammatory marker C-reactive protein (CRP) is also linked with CVD outcomes and mortality and may play an important role in the pathway between CMV and mortality. We utilized a U.S. nationally representative study to examine whether CMV infection is associated with all-cause and CVD-related mortality. We also assessed whether CRP level mediated or modified these relationships. Methodology/Principal Findings: Data come from subjects ≥25 years of age who were tested for CMV and CRP level and were eligible for mortality follow-up on December 31st, 2006 (N = 14153) in the National Health and Nutrition Examination Survey (NHANES) III (1988-1994). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and CVD-related mortality by CMV serostatus. After adjusting for multiple confounders, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41). The association between CMV and CVD-related mortality did not achieve statistical significance after confounder adjustment. CRP did not mediate these associations. However, CMV seropositive individuals with high CRP levels showed a 30.1% higher risk for all-cause mortality and 29.5% higher risk for CVD-related mortality compared to CMV seropositive individuals with low CRP levels. Conclusions/Significance: CMV was associated with a significant increased risk for all-cause mortality and CMV seropositive subjects who also had high CRP levels were at substantially higher risk for both for all-cause and CVD-related mortality than subjects with low CRP levels. Future work should target the mechanisms by which CMV infection and low-level inflammation interact to yield significant impact on mortality

Is there variety × isolate interaction in the polygenic quantitative resistance of carrot to Alternaria dauci ?

Horizontal and polygenic resistance is race-nonspecific and, therefore, more durable, unlike vertical resistance, which is race-specific and unstable. However, this division is perhaps not so obvious since some cultivar × isolate interactions have already been observed for plant species with partial resistance. Carrot is known to be partially resistant to Alternaria dauci, but it is relevant for breeders to study cultivar × isolate interactions in order to develop durable resistant varieties. For this purpose, 12 highly diverse carrot genotypes and one segregating population were inoculated in a tunnel or in a glass house with 11 isolates of A. dauci that also represented a high diversity in terms of geographical origin, aggressiveness and genetic diversity. Disease severity values were assessed three times in the tunnel in a one-year experiment (2002) and twice in the glass house in an experiment over two consecutive years (2011 and 2012). The interaction of isolate with genotype was non-significant in the tunnel, and the same result was obtained in the glasshouse for both years of study except for the first scoring date in 2011, suggesting that the partial resistance of carrot to A. dauci is probably mainly explained by major QTLs that confer resistance to a large number of isolates and, potentially, some minor isolate-specific QTLs as well

Overview of Phosphorus Effect in Molybdenum-Based Hydrotreating Catalysts Supported on Ordered Mesoporous Siliceous Materials

This chapter presents an overview of the literature on the effect of phosphorus modification of ordered mesoporous silica (OMS) such as MCM-41, HMS, SBA-15, and SBA-16 to be used as supports for hydrotreating catalysts based on transition metal sulfides (TMS). The influence of the support modification with variable quantities of phosphorus on the performance for hydrodesulfurization (HDS) and hydrodenitrogenation (HDN) reactions is outlined and discussed considering the changes in the structural and textural properties (SBET), acidity, reducibility, etc., of the substrate brought about by phosphorus incorporation