Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study

Abstract Background In patients infected with human immunodeficiency virus 1 (HIV-1) neuropathic symptoms may develop within weeks of starting combination antiretroviral therapy (cART). This timing coincides with the occurrence of immune reconstitution inflammatory syndrome. Our objective was to investigate the longitudinal association of plasma cytokine and soluble receptor concentrations with incident neuropathic symptoms within 12 weeks of starting programme-based cART in a nested case-control study. Methods One hundred and twenty adults without neuropathic symptoms and about to initiate cART were followed longitudinally for 24 weeks after cART initiation. Subjects were examined for peripheral neuropathy at baseline (pre-cART) and 2-, 4-, 12- and 24 weeks thereafter. Individuals developing neuropathic symptoms within 12 weeks of starting cART were matched in a nested case-control design with those remaining symptom-free for at least 24 weeks. Plasma was collected at each visit. Cytokines and soluble receptors were quantified using multiplex immunometric assays. Results Incident neuropathic symptoms occurred in 32 (27%) individuals within 12 weeks of starting cART for the first time. Cytokine concentrations increased at 2 weeks, irrespective of symptom-status, returning to baseline concentrations at 12 weeks. Compared to the control group, the symptomatic group had higher baseline levels of interleukin-1 receptor (IL-1R)-antagonist. The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12. Ratios of pro-inflammatory- vs anti-inflammatory cytokines were higher for TNF-alpha/IL-4 (p = 0.022) and interferon-gamma/IL-10 (p = 0.044) in those developing symptoms. After 24 weeks of cART, the symptomatic group showed higher CD4+ counts (p = 0.002). Conclusions The initiation of cART in previously treatment naïve individuals was associated with a cytokine 'burst’ between 2- and 4 weeks compared with pre-cART levels. Individuals developing neuropathic symptoms within 12 weeks of starting cART showed evidence of altered cytokine concentrations even prior to initiating cART, most notably higher circulating IL-1R-antagonist levels, and altered ratios of “pain-associated” cytokine and soluble receptors shortly after cART initiation

Spectral characteristics of propylitic alteration minerals as a vectoring tool for porphyry copper deposits

publisher: Elsevier articletitle: Spectral characteristics of propylitic alteration minerals as a vectoring tool for porphyry copper deposits journaltitle: Journal of Geochemical Exploration articlelink: http://dx.doi.org/10.1016/j.gexplo.2017.10.019 content_type: article copyright: © 2017 Elsevier B.V. All rights reserved.© 2017 Elsevier B.V. All rights reserved. The attached document is the authors’ final submitted version of the journal article. You are advised to consult the publisher’s version if you wish to cite from it

Re-Os dating of pyrite confirms an early diagenetic onset and extended duration of mineralization in the Irish Zn-Pb ore field

0000-0002-7706-6003The Irish Midlands region contains one of the world’s largest hydrothermal Zn-Pb ore districts, but uncertainty exists in the timing of mineralization relative to host rock ages. Consequently, genetic models for ore formation are poorly constrained and remain controversial. Here we use Re-Os geochronology to show that ore-stage pyrite from the Lisheen deposit formed at 346.6 ± 3.0 Ma, shortly after host rock deposition. Pyrite from the Silvermines deposit returns an age of 334.0 ± 6.1 Ma, indicating that at least some mineralization occurred during later burial. These age determinations show that the much younger paleomagnetic ages reported for the Irish Zn-Pb deposits reflect remagnetization during the Variscan orogeny, a process that we suggest affects paleomagnetic dating more widely. The Re-Os ages overlap with the ages of lower Carboniferous volcanic rocks in the Midlands, which are the product of magmatism that has been invoked as the driving force for hydrothermal activity. The relatively low initial Os ratios for both Lisheen (0.253 ± 0.045) and Silvermines (0.453 ± 0.006) are compatible with derivation of Os from these magmas, or from the Caledonian basement that underlies the ore deposits.This journal is published under the terms of Green Open Access. Authors may post a copy of the accepted (i.e., post-peer review) version of their paper (https://doi.org/10.1130/G36296.1) in a repository of their choice or to their personal website after the relevant embargo period has passed. The embargo period will be 12 months from formal online publication

Establishment of Enabling Technology for Manufacture of Selected Types of Continental and Speciality Cheeses

End of Project ReportThe objectives in the project were the development of the science and technology for speciality cheese manufacture, identification and overcoming of the technical constraints to the manufacture of soft speciality cheeses in Ireland and the development of Moorepark Technology Limited (MTL) pilot plant as an integrated, flexible pre-commercial manufacturing platform with which to evaluate the market for speciality cheese.Department of Agriculture, Food and the Marin

Charactersing a holographic modal phase mask for the detection of ocular aberrations

This is the final version of the article. Available from Society of Photo-optical Instrumentation Engineers (SPIE) via the DOI in this record.The accurate measurement of the double-pass ocular wave front has been shown to have a broad range of applications from LASIK surgery to adaptively corrected retinal imaging. The ocular wave front can be accurately described by a small number of Zernike circle polynomials. The modal wave front sensor was first proposed by Neil et al. and allows the coefficients of the individual Zernike modes to be measured directly. Typically the aberrations measured with the modal sensor are smaller than those seen in the ocular wave front. In this work, we investigated a technique for adapting a modal phase mask for the sensing of the ocular wave front. This involved extending the dynamic range of the sensor by increasing the pinhole size to 2.4mm and optimising the mask bias to 0.75λ. This was found to decrease the RMS error by up to a factor of three for eye-like aberrations with amplitudes up to 0.2μm. For aberrations taken from a sample of real-eye measurements a 20% decrease in the RMS error was observed

Chlorite and epidote mineral chemistry in porphyry ore systems: a case study of the Northparkes district, NSW, Australia

Propylitic alteration, characterized by the occurrence of chlorite and epidote, is typically the most extensive and peripheral alteration facies developed around porphyry ore deposits. However, exploration within this alteration domain is particularly challenging, commonly owing to weak or nonexistent whole-rock geochemical gradients and the fact that similar assemblages can be developed in other geologic settings, particularly during low-grade metamorphism. We document and interpret systematic spatial trends in the chemistry of chlorite and epidote from propylitic alteration around the E48 and E26 porphyry Cu-Au deposits of the Northparkes district, New South Wales, Australia. These trends vary as a function of both distance from hydrothermal centers and alteration paragenesis. The spatial trends identified in porphyry-related chlorite and epidote at Northparkes include (1) a deposit-proximal increase in Ti, As, Sb, and V in epidote and Ti in chlorite, (2) a deposit-distal increase in Co and Li in chlorite and Ba in epidote, and (3) a pronounced halo around deposits in which Mn and Zn in chlorite, as well as Mn, Zn, Pb, and Mg in epidote, are elevated. Chlorite Al/Si ratios and epidote Al/Fe ratios may show behavior similar to that of Mn-Zn or may simply decrease outward, and V and Ni concentrations in chlorite are lowest in the peak Mn-Zn zone. In comparison to porphyry-related samples, chlorite from the regional metamorphic assemblage in the district contains far higher concentrations of Li, Ca, Ba, Pb, and Cu but much less Ti. Similarly, metamorphic epidote contains higher concentrations of Sr, Pb, As, and Sb but less Bi and Ti. These chlorite and epidote compositional trends are the net result of fluid-mineral partitioning under variable physicochemical conditions within a porphyry magmatic-hydrothermal system. They are most easily explained by the contribution of spent magmatic-derived ore fluid(s) into the propylitic domain. It is envisaged that such fluids experience progressive cooling and reduction in fs2 during outward infiltration into surrounding country rocks, with their pH controlled by the extent of rock-buffering experienced along the fluid pathway

A Dietary Sugarcane-Derived Polyphenol Mix Reduces the Negative Effects of Cyclic Heat Exposure on Growth Performance, Blood Gas Status, and Meat Quality in Broiler Chickens

Heat stress (HS) compromises growth performance and meat quality of broiler chickens by interrupting lipid and protein metabolism, resulting in increased oxidative damages. The experiment attempted to investigate whether dietary polyphenols (Polygain (POL)) could ameliorate the aforementioned adverse effects of HS on performance and meat quality. One hundred and twenty one day-old-male chicks were allocated to two temperature conditions, thermoneutral (TN) or HS, and fed with either a control diet (CON) or the CON plus four different doses of POL (2, 4, 6 and 10 g/kg). Heat stress caused respiratory alkalosis as evidenced by increased rectal temperature (p < 0.001) and respiration rate (p < 0.001) due to increased blood pH (p < 0.001). Heat stress decreased final body weight (p = 0.061) and breast muscle water content (p = 0.013) while POL improved both (p = 0.002 and p = 0.003, respectively). Heat stress amplified muscle damages, indicated by increased thiobarbituric acid reactive substances (p < 0.001) and reduced myofibril fragmentation index (p = 0.006) whereas POL improved both (p = 0.037 and p = 0.092, respectively). Heat stress impaired meat tenderness (p < 0.001) while POL improved it (p = 0.003). In conclusion, HS impaired growth performance and meat quality whereas POL ameliorated these responses in a dose-dependent manner, and effects of POL were evident under both temperature conditions

First In human study of a novel biased apelin receptor ligand, MM54, a G-alpha(i) agonist/beta-arrestin antagonist

Introduction: The peptide apelin acts via G proteins to cause beneficial vasodilation and potent positive inotropy to ameliorate pulmonary arterial hypertension in humans and animal models. Apelin is internalised via β-arrestin. In contrast, with loss of endogenous apelin, its receptor acts as a mechanosensor, stimulating β-arrestin to induce detrimental cardiac hypertrophy. Our aim was to characterise the action of our apelin ligand, MM54 that in cell based assays blocks β-arrestin but activates the Gαi protein pathway, in this first in human study. Method: Competition binding in human heart (n=3) used [I125] [Pyr1]apelin-13 (0.1nmol/L). β-arrestin recruitment, receptor internalization and forskolin-induced cAMP inhibition were measured in CHO-K1 cells expressing human apelin receptor. Forearm blood flow was measured in 9 volunteers using venous occlusion plethysmography at baseline and at 4 incremental doses (1, 10, 30, 100 nmol/min) of MM54, each for eight minutes. The Aellig hand vein technique was used to measure the effect of 3 incremental doses (3, 30, 300 nmol/min) of MM54 for 15 min on veins pre-constricted with noradrenaline in 6 individuals compared with 8 controls. Data are mean+SEM, n≥3. Results: MM54 had an affinity of pKi = 6.50±0.03. In β-arrestin (pKB 6.93±0.15) and receptor internalization assays (pKB 5.89±0.06) MM54 was an antagonist, but activated the G protein pathway (pD2±SEM 5.86+0.23). At the highest concentration (100 nmol/min), MM54 caused a significant absolute increase in forearm blood flow compared to control arm, representing a 76 % change from baseline (P<0.01, ANOVA with repeated measures with Dunnett’s post hoc analysis on untransformed data). In the hand vein, MM54 caused a significant concentration dependent dilatation in veins over the concentration range tested, with the highest dose causing 57% reversal (P<0.01). Conclusion: At the cellular level, the results suggest MM54 induced a different conformation in the receptor compared with the native peptide apelin, resulting in a biased profile of activating the G protein pathway but blocking β-arrestin. In agreement in clinical studies, in both the arterial and venous circulation, MM54 induced vasodilatation that is thought to be mediated by the G protein pathway

Influence of buttermilk powder or buttermilk addition on phospholipid content, chemical and bio-chemical composition and bacterial viability in Cheddar style-cheese

peer-reviewedThe effect of buttermilk powder addition post-curd formation or buttermilk addition to cheese milk on total and individual phospholipid content, chemical composition, enzyme activity, microbial populations and microstructure within Cheddar-style cheese was investigated. Buttermilk or buttermilk powder addition resulted in significant increases in total phospholipid content and their distribution throughout the cheese matrix. Addition of 10% buttermilk powder resulted in higher phospholipid content, moisture, pH and salt in moisture levels, and lower fat, fat in dry matter, L. helveticus and non-starter bacteria levels in cheeses. Buttermilk powder inclusion resulted in lower pH 4.6/Soluble Nitrogen (SN) levels and significantly lower free amino acid levels in 10% buttermilk powder cheeses. Buttermilk addition provided a more porous cheese microstructure with greater fat globule coalescence and increased free fat pools, while also increasing moisture and decreasing protein, fat and pH levels. Addition of buttermilk in liquid or powdered form offers potential for new cheeses with associated health benefits

Porphyry Indicator Minerals (PIMS) and Porphyry Vectoring and Fertility Tools (PVFTS) – Indicators of Mineralization Styles and Recorders of Hypogene Geochemical Dispersion Halos

In the past decade, significant research efforts have been devoted to mineral chemistry studies to assist porphyry exploration. These activities can be divided into two major fields of research: (1) porphyry indicator minerals (PIMS), which aims to identify the presence of, or potential for, porphyry-style mineralization based on the chemistry of magmatic minerals such as plagioclase, zircon and apatite, or resistate hydrothermal minerals such as magnetite; and (2) porphyry vectoring and fertility tools (PVFTS), which use the chemical compositions of hydrothermal minerals such as epidote, chlorite and alunite to predict the likely direction and distance to mineralized centres, and the potential metal endowment of a mineral district. This new generation of exploration tools has been enabled by advances in laser ablation-inductively coupled plasma mass spectrometry, short wave length infrared data acquisition and data processing, and the increased availability of microanalytical techniques such as cathodoluminescence. PVFTS and PIMS show considerable promise for porphyry exploration, and are starting to be applied to the diversity of environments that host porphyry and epithermal deposits around the circum-Pacific region. Industry has consistently supported development of these tools, in the case of PVFTS encouraged by several successful “blind tests” where deposit centres have successfully been predicted from distal propylitic settings. Industry adoption is steadily increasing but is restrained by a lack of the necessary analytical equipment and expertise in commercial laboratories.Item freely available with no apparent Creative Commons License or copyright statement. The attached file is the published pdf