Validation of Differentially Expressed Immune Biomarkers in Latent and Active Tuberculosis by Real-Time PCR

Tuberculosis (TB) remains a major global threat and diagnosis of active TB ((ATB) both extra-pulmonary (EPTB), pulmonary (PTB)) and latent TB (LTBI) infection remains challenging, particularly in high-burden countries which still rely heavily on conventional methods. Although molecular diagnostic methods are available, e.g., Cepheid GeneXpert, they are not universally available in all high TB burden countries. There is intense focus on immune biomarkers for use in TB diagnosis, which could provide alternative low-cost, rapid diagnostic solutions. In our previous gene expression studies, we identified peripheral blood leukocyte (PBL) mRNA biomarkers in a non-human primate TB aerosol-challenge model. Here, we describe a study to further validate select mRNA biomarkers from this prior study in new cohorts of patients and controls, as a prerequisite for further development. Whole blood mRNA was purified from ATB patients recruited in the UK and India, LTBI and two groups of controls from the UK (i) a low TB incidence region (CNTRLA) and (ii) individuals variably-domiciled in the UK and Asia ((CNTRLB), the latter TB high incidence regions). Seventy-two mRNA biomarker gene targets were analyzed by qPCR using the Roche Lightcycler 480 qPCR platform and data analyzed using GeneSpring™ 14.9 bioinformatics software. Differential expression of fifty-three biomarkers was confirmed between MTB infected, LTBI groups and controls, seventeen of which were significant using analysis of variance (ANOVA): CALCOCO2, CD52, GBP1, GBP2, GBP5, HLA-B, IFIT3, IFITM3, IRF1, LOC400759 (GBP1P1), NCF1C, PF4V1, SAMD9L, S100A11, TAF10, TAPBP, and TRIM25. These were analyzed using receiver operating characteristic (ROC) curve analysis. Single biomarkers and biomarker combinations were further assessed using simple arithmetic algorithms. Minimal combination biomarker panels were delineated for primary diagnosis of ATB (both PTB and EPTB), LTBI and identifying LTBI individuals at high risk of progression which showed good performance characteristics. These were assessed for suitability for progression against the standards for new TB diagnostic tests delineated in the published World Health Organization (WHO) technology product profiles (TPPs)

NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide Association Study from the CHARGE Consortium

Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity

Low temperature synthesis and hcaracterization of Ag2S1-x Tez(O<x<1)

A low-temperature route for the synthesis of Ag2S,Ag2Te and their solid solutions Ag2S1-xTex(0 less-than-or-equal-to x less-than-or-equal-to 1) is reported. Ag2S is prepared by the direct addition of silver nitrate solution to thiourea, while Ag2Te is prepared by reacting silver nitrate solution with tellurium in nitric acid and subsequently reducing it with hydrazine hydrate. The solid solutions of Ag2S and Ag2Te are obtained by the addition of nitrate solutions of silver and tellurium to thiourea followed by its reduction with hydrazine hydrate. The method enables the synthesis of low-temperature crystalline phase of Ag2S1-xTex solid solutions. The powder X-ray diffraction studies suggest that the solid solutions of compositions x < 0.3 have a phase akin to alpha-Ag2S and those with compositions x > 0.6 are similar to alpha-Ag2Te. In the intermediate range of compositions (x = 0.4 and 0.5), the solid solutions are found to be mixtures of alpha-Ag2S and alpha-Ag2Te phases which transform totally to alpha-Ag2S phase on prolonged annealing at about 473 K

Pes study of spin-state transitions in d6 transition metal complexes and oxides

Transitions from the low-to the high-spin state in Fe2+ and Co3+ compounds have been examined by X-ray and UV photoelectron spectroscopy. It has been shown that the core-level bands in XPES, in particular the metal 3s band, as well as the valence bands, are diagnosis in the study of spin-state transitions

Nanoscale Ag–Pd and Cu–Pd alloys

Nanoparticles of Ag-Pd and Gu-Pd alloys with diameters in the 5-40 nm range have been prepared over the entire range of compositions, by employing the heterogeneous reaction of dry methanol or ethanol with intimate mixtures of AgNO3+PdOx and CuOx+PdOx, respectively. The nanoscale alloys have been characterized by energy-dispersive Xray (EDX) analysis, transmission electron microscopy (TEM) and X-ray diffraction (XRD). All the alloy particles possess the fee structure and can be obtained in bulk quantities

Electrochemical studies of cobalt hydroxide-an additive for nickel electrodes

The electrochemical behavior of chemically precipitated cobalt hydroxide is studied by cyclic voltammetry and galvanostatic charge/discharge cycling. When cycled in the potential range between the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER), the electrode undergoes two pairs of reactions. The pair of current peaks close to the OER is attributed to quasi-reversible oxidation of $Co(OH)_2$ to CoOOH, whereas the pair of current peaks close to the HER is due to quasi-reversible reduction of $Co(OH)_2$ to Co. The peak current values of both reactions do not show dependence on alkali concentration. Possible mechanisms are proposed for the reactions, in which the diffusion of dissolved $Co(OH)_2$ prior to the electron-transfer step is considered to be the rate-determining step. Considering the fact that the $Co(OH)_2/CoOOH$ and $Co(OH)_2/Co$ reactions are separated by a potential difference of about 1.2 V, a galvanic cell is constructed by using two $Co(OH)_2$ electrodes in 6 M KOH. On charging, the positive electrode attained a stable potential of about 0.4 V versus Hg/HgO, $OH^−$ and the negative electrode attained a stable potential of about −0.8 V versus Hg/HgO, $OH^−$, thus resulting in an open circuit cell voltage of about 1.2 V. By discharging the cell, a capacity of $15 mA h g^{−1}$ of $Co(OH)_2$ is obtained over about 15 charge/discharge cycles. The charged electrodes are analyzed by powder XRD and IR spectroscopy and the presence of Co and CoOOH in the negative and positive electrodes, respectively, is confirmed. Although the cell is not commercially viable, the concept of a "double hydroxide" is demonstrated akin to the "double sulfate" principle of lead-acid batteries. It is expected that $Ni(OH)_2$, which is isostructural to $Co(OH)_2$, may also show a similar behavior

Effects of incorporation of Cu and Ag in Pd on electrochemical oxidation of methanol in alkaline solution

Pd fine particles were prepared by heterogeneous reaction of PdOx with dry methanol as well as by the NaBH4 reduction method. The former method was found to give Pd nanoparticles (similar to 5 nm). Similarly f.c.c. structured, single phase nanoparticles of alloy compositions Pd0.8Cu0.2, Pd0.5Cu0.5, Pd0.8Ag0.2 and Pd0.5Ag0.5 were prepared by the heterogeneous reaction of dry methanol with intimate mixtures of PdOx + CuOx and PdOx + AgNO3. The electrochemical properties of the porous unsupported electrodes, prepared from these materials, in alkaline solutions, were investigated by cyclic voltammetry and steady-state polarization measurements. Various processes taking place during potential scanning in the presence and absence of methanol in 6 M KOH solution are discussed. Steady-state polarization data indicate that the methanol oxidation reaction (MOR) activity decreases with incorporation of Cu and Ag into the Pd lattice. The extent of decrease in the MOR activity is less for Cu addition than for Ag addition

Synthesis and characterization of nano-MnO2 for electrochemical supercapacitor studies

Nanostructured MnO2 was synthesized at ambient condition by reduction of potassium permanganate with aniline. Powder X-ray diffraction, thermal analysis (thermogravimetric and differential thermal analysis), Brunauer-Emmett-Teller surface area, and infrared spectroscopy studies were carried out for physical and chemical characterization. The as-prepared MnO2 was amorphous and contained particles of 5-10 nm diameter. Upon annealing at temperatures >400°C, the amorphous MnO2 attained crystalline α-phase with a concomitant change in morphology. A gradual conversion of nanoparticles to nanorods is evident from scanning electron microscopy and transmission electron microscopy (TEM) studies. High-resolution TEM images suggested that nanoparticles and nanorods grow in different crystallographic planes. Capacitance behavior was studied by cyclic voltammetry and galvanostatic charge-discharge cycling in a potential range from -0.2 to 1.0 V vs SCE in 0.1 M sodium sulfate solution. Specific capacitance of about 250 F g-1 was obtained at a current density of 0.5 mA cm-2(0.8 A g-1)

Microwave synthesis and electrochemical properties of LiCo1−xMxO2LiCo_{1-x}M_xO_2 (M = Al and Mg) cathodes for Li-ion rechargeable batteries

Single phase $LiCo_{1-x}M_xO_2$ (M = Al and Mg) cathode materials for Li-ion batteries are synthesized by microwave dielectric heating with a reaction time less than 20 min. Aluminium forms solid solutions up to a composition of x = 0.5 and magnesium up to x = 0.2. Lattice constants are found to vary with the composition. The compounds are electrochemically active with good discharge capacity

A note on overpotential dependence of AC impedance data

Charge-transfer resistance [R-ct = (d eta/di)(eta=0)] and Tafel plots of current density (i) versus overpotential (eta) data are generally known to yield values of the energy-transfer coeffficient (alpha) and exchange current density (i(o)) of an electrochemical reaction. In the present investigation, the resistance (d eta/di)(eta not equal 0) that could be calculated by differentiating a wide range of i - eta curves was also shown to provide the values of alpha and i(o), by plotting ln(d eta/di)(eta not equal 0) against eta. Since alpha and i(o) could also be evaluated directly from the experimental DC polarization data, the procedure was not of significant importance.. Nevertheless, it was considered important in evaluating alpha and i(o) from AC impedance data, because the procedure was based on data analysis, which was much simpler than that reported in the literature. A cobalt electrode prepared from fine metal powder was used in 1 M KOH electrolyte and the hydrogen evolution reaction was studied by AC impedance at several potentials. The resistance values measured from the complex plane impedance diagram were plotted against the potential, and the values of alpha and i(o) were evaluated