Does metabolic reprogramming underpin age-associated changes in T cell phenotype and function?

T cells are required for an effective adaptive immune response. The principal function of T cells is to promote efficient removal of foreign material by identifying and mounting a specific response to nonself. A decline in T cell function in aging is thought to contribute to reduced response to infection and vaccination and an increase in autoimmunity. This may in part be due to the age-related decrease in naïve CD4+ T cells and increase in antigen-experienced CD4+ T cells, loss of redox homeostasis, and impaired metabolic switching. Switching between subsets is triggered by the integration of extracellular signals sensed through surface receptors and the activation of discrete intracellular metabolic pathways. This article explores how metabolic programming and loss of redox homeostasis during aging may contribute to age-associated changes in T cell phenotype and function. © 2014 Elsevier Inc

Phenolic profile and content of sorghum grains under different irrigation managements

Sorghum grain is widely consumed in Sub-Saharan Africa and Asia, as a staple food due to its adaptation to harsh environments. The impact of irrigation regime: full irrigation (100%); deficit irrigation (50%); and severe deficit irrigation (25%) on phenolic profile and content of six sorghum grain genotypes was investigated by high performance liquid chromatography coupled with diode array detection and electrospray ionization mass spectrometry (HPLC-DAD-ESI-MS). A total of 25 individual polyphenols were unequivocally or tentatively identified. Compared to the colored-grain genotypes, the white grained sorghum var. Liberty had a simpler polyphenol profile. The concentrations of the sorghum-specific 3-deoxyanthocyanidins luteolinidin and apigeninidin, were higher under deficit irrigation compared to the other two regimes in all genotypes. These findings will be valuable for the selection of sorghum genotypes for grain production as human food under water deficit conditions, since polyphenol levels can affect the grain's nutritional value and health properties

Engineering Antibodies to Enhance Activity and Increase Half-life

Background: HIV/AIDS remains one of the most serious current threats to global public health. Although anti-HIV drugs have been effective among the wealthiest populations, a vaccine and/or new methods to prevent infections are needed lo control HIV globally. Strategies to combat HIV-1 require structural knowledge of how antibodies recognize HIV envelope proteins and how the immune system eliminates viruses. Until recently, only a small number of broadly neutralizing antibodies against HIV-1 had been characterized, and the immunological basis for their breadth and potency remains poorly understood. However. it was recently demonstrated that antibodies could be engineered to greatly enhance their breadth and potency (Diskin et al., Science 2011). Unfortunately, this and other engineering efforts have resulted in a decrease in antibody half-life in mouse and non-human primate models. This decrease in half-life correlates with an increase in reactivity to a variety of antigens, termed polyreactivity. Methods: In order to make better targets for passive delivery therapies, we are working to increase the half-life of antibodies while maintaining their breadth and potency using a variety of computational and structured-based techniques. One technique involves reducing the spatial aggregation propensity, in which an algorithm finds dynamically exposed hydrophobic patches on the surlace of proteins (Chemansetty et al., PNAS 2009). To this end, we have constructed several mutations in regions that have been predicted to have high aggregation propensities, and have tested them for polyreactivity and potency in neutralization assays. Results: Initial results show that these novel reagents have reduced polyreactivily, yet they still maintain their potency in in vitro neutralization assays. Conclusions: We are currently pursuing in vivo experiments in mice to further understand the relationship between antibody potency, polyreactivity, and half-life

Band gap reduction in GaNSb alloys due to the anion mismatch

The structural and optoelectronic properties in GaNxSb1–x alloys (0<=x<0.02) grown by molecular-beam epitaxy on both GaSb substrates and AlSb buffer layers on GaAs substrates are investigated. High-resolution x-ray diffraction (XRD) and reciprocal space mapping indicate that the GaNxSb1–x epilayers are of high crystalline quality and the alloy composition is found to be independent of substrate, for identical growth conditions. The band gap of the GaNSb alloys is found to decrease with increasing nitrogen content from absorption spectroscopy. Strain-induced band-gap shifts, Moss-Burstein effects, and band renormalization were ruled out by XRD and Hall measurements. The band-gap reduction is solely due to the substitution of dilute amounts of highly electronegative nitrogen for antimony, and is greater than observed in GaNAs with the same N content

Testing the Gaussianity of the COBE-DMR data with spherical wavelets

We investigate the Gaussianity of the 4-year COBE-DMR data (in HEALPix pixelisation) using an analysis based on spherical Haar wavelets. We use all the pixels lying outside the Galactic cut and compute the skewness, kurtosis and scale-scale correlation spectra for the wavelet coefficients at each scale. We also take into account the sensitivity of the method to the orientation of the input signal. We find a detection of non-Gaussianity at $> 99$ per cent level in just one of our statistics. Taking into account the total number of statistics computed, we estimate that the probability of obtaining such a detection by chance for an underlying Gaussian field is 0.69. Therefore, we conclude that the spherical wavelet technique shows no strong evidence of non-Gaussianity in the COBE-DMR data.Comment: latex file 7 pages, 6 figures, submitted to MNRA

Causality - Complexity - Consistency: Can Space-Time Be Based on Logic and Computation?

The difficulty of explaining non-local correlations in a fixed causal structure sheds new light on the old debate on whether space and time are to be seen as fundamental. Refraining from assuming space-time as given a priori has a number of consequences. First, the usual definitions of randomness depend on a causal structure and turn meaningless. So motivated, we propose an intrinsic, physically motivated measure for the randomness of a string of bits: its length minus its normalized work value, a quantity we closely relate to its Kolmogorov complexity (the length of the shortest program making a universal Turing machine output this string). We test this alternative concept of randomness for the example of non-local correlations, and we end up with a reasoning that leads to similar conclusions as in, but is conceptually more direct than, the probabilistic view since only the outcomes of measurements that can actually all be carried out together are put into relation to each other. In the same context-free spirit, we connect the logical reversibility of an evolution to the second law of thermodynamics and the arrow of time. Refining this, we end up with a speculation on the emergence of a space-time structure on bit strings in terms of data-compressibility relations. Finally, we show that logical consistency, by which we replace the abandoned causality, it strictly weaker a constraint than the latter in the multi-party case.Comment: 17 pages, 16 figures, small correction

Faraday-cage-assisted etching of suspended gallium nitride nanostructures

We have developed an inductively coupled plasma etching technique using a Faraday cage to create suspended gallium-nitride devices in a single step. The angle of the Faraday cage, gas mix, and chamber condition define the angle of the etch and the cross-sectional profile, which can feature undercut angles of up to 45°. We fabricate singly- and doubly-clamped cantilevers of a triangular cross section and show that they can support single optical modes in the telecom C-band

Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ

Differences in lipid metabolism associate with age-related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids (FAs) initiate pro-inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age-associated changes in individual FAs in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FAs by gas chromatography in 26 healthy younger individuals (age 50 years). Linear mixed models were used to explore the association between circulating FAs, age and cytokines. We showed that plasma saturated, poly- and mono-unsaturated FAs increase with age. Circulating TNF-α and IL-6 concentrations increased with age, whereas IL-10 and TGF-β1 concentrations decreased. Oxidation of MitoSOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FAs, indicative of their metabolic relationships. Higher levels of the saturated FAs C18:0 and C24:0 were associated with lower TGF-β1 concentrations, and higher C16:0 were associated with higher TNF-α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro-inflammatory cytokines in response to phorbol myristate acetate-induced differentiation through ceramide-dependent inhibition of PPARγ activity. Conversely, C18:1 primed a pro-resolving macrophage which was PPARγ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti-inflammatory macrophages through metabolic reprogramming

Continental threat: How many common carp (Cyprinus carpio) are there in Australia?

Common carp (Cyprinus carpio) are one of the world's most destructive vertebrate pests. In Australia, they dominate many aquatic ecosystems causing a severe threat to aquatic plants, invertebrates, water quality, native fish and social amenity. The Australian Government is considering release of cyprinid herpesvirus-3 (CyHV-3) as a control measure and consequently a robust, continental-scale estimate of the carp population and biomass is essential to inform planning and risk management. Here, we pioneer a novel model-based approach to provide the first estimate of carp density (no/ha) and biomass density (kg/ha) at river reach/waterbody, basin and continental scales. We built a spatial layer of rivers and waterbodies, classified aquatic habitats and calculated the area of each throughout the range of carp in Australia. We then developed a database of fishery-independent electrofishing catch-per-unit-effort (CPUE) for habitat types, containing catch information for 574,145 carp caught at 4831 sites. Eastern Australia accounted for 96% of carp biomass and 92% of the total available wetted habitat area (16,686 km2) was occupied. To correct these data for variable detection efficiencies, we used existing electrofishing data and undertook additional field experiments to establish relationships between relative and absolute abundances. We then scaled-up site-based estimates to habitat types to generate continental estimates. The number of carp was estimated at 199.2 M (95%Crl: 106 M to 357.6 M) for an ‘average’ hydrological scenario and 357.5 M (95%Crl: 178.9 M to 685.1 M) for a ‘wet’ hydrological scenario. In eastern Australia, these numbers correspond with biomasses of 205,774 t (95%Crl: 117,532–356,482 t) (average scenario) and 368,357 t (95%Crl: 184,234–705,630 t) (wet scenario). At a continental scale the total biomass was estimated at 215,456 t for an ‘average’ hydrological scenario. Perennial lowland rivers had the highest CPUE and greatest biomass density (up to 826 kg/ha) and the modelled biomass exceeded a density-impact threshold of 80–100 kg/ha in 54% of wetlands and 97% of stream area in large lowland rivers. The continental-scale biomass estimates provide a baseline for focusing national conservation strategies to reduce carp populations below thresholds needed to restore aquatic ecosystems at a range of spatial scales