Urine peptidomic biomarkers for diagnosis of patients with systematic lupus erythematosus

Background: Systematic lupus erythematosus (SLE) is characterized with various complications which can cause serious organ damage in the human body. Despite the significant improvements in disease management of SLE patients, the non-invasive diagnosis is entirely missing. In this study, we used urinary peptidomic biomarkers for early diagnosis of disease onset to improve patient risk stratification, vital for effective drug treatment. Methods: Urine samples from patients with SLE, lupus nephritis (LN) and healthy controls (HCs) were analyzed using capillary electrophoresis coupled to mass spectrometry (CE-MS) for state-of-the-art biomarker discovery. Results: A biomarker panel made up of 65 urinary peptides was developed that accurately discriminated SLE without renal involvement from HC patients. The performance of the SLE-specific panel was validated in a multicentric independent cohort consisting of patients without SLE but with different renal disease and LN. This resulted in an area under the receiver operating characteristic (ROC) curve (AUC) of 0.80 (p < 0.0001, 95% confidence interval (CI) 0.65–0.90) corresponding to a sensitivity and a specificity of 83% and 73%, respectively. Based on the end terminal amino acid sequences of the biomarker peptides, an in silico methodology was used to identify the proteases that were up or down-regulated. This identified matrix metalloproteinases (MMPs) as being mainly responsible for the peptides fragmentation. Conclusions: A laboratory-based urine test was successfully established for early diagnosis of SLE patients. Our approach determined the activity of several proteases and provided novel molecular information that could potentially influence treatment efficacy

Halogens in pore water of peat bogs – the role of peat decomposition and dissolved organic matter

Halogens are strongly enriched in peat and peatlands and such they are one of their largest active terrestrial reservoir. The enrichment of halogens in peat is mainly attributed to the formation of organohalogens and climatically controlled humification processes. However, little is known about release of halogens from the peat substrate and the distribution of halogens in the peat pore water. In this study we have investigated the distribution of chlorine, bromine and iodine in pore water of three pristine peat bogs located in the Magellanic Moorlands, southern Chile. Peat pore waters were collected using a sipping technique, which allows in situ sampling down to a depth greater than 6m. Halogens and halogen species in pore water were determined by ion-chromatography (IC) (chlorine) and IC-ICP-MS (bromine and iodine). Results show that halogen concentrations in pore water are 15–30 times higher than in rainwater. Mean concentrations of chlorine, bromine and iodine in pore water were 7–15 mg l^−1, 56–123 μg l^−1, and 10–20 μg l^−1, which correspond to mean proportions of 10–15%, 1–2.3% and 0.5–2.2% of total concentrations in peat, respectively. Organobromine and organoiodine were the predominant species in pore waters, whereas chlorine in pore water was mostly chloride. Advection and diffusion of halogens were found to be generally low and halogen concentrations appear to reflect release from the peat substrate. Release of bromine and iodine from peat depend on the degree of peat degradation, whereas this relationship is weak for chlorine. Relatively higher release of bromine and iodine was observed in less degraded peat sections, where the release of dissolved organic carbon (DOC) was also the most intensive. It has been concluded that the release of halogenated dissolved organic matter (DOM) is the predominant mechanism of iodine and bromine release from peat

Epithermal Neutron Beam Interference with Cardiac Pacemakers

Peer reviewe

Circadian Organization in Hemimetabolous Insects

The circadian system of hemimetabolous insects is reviewed in respect to the locus of the circadian clock and multioscillatory organization. Because of relatively easy access to the nervous system, the neuronal organization of the clock system in hemimetabolous insects has been studied, yielding identification of the compound eye as the major photoreceptor for entrainment and the optic lobe for the circadian clock locus. The clock site within the optic lobe is inconsistent among reported species; in cockroaches the lobula was previously thought to be a most likely clock locus but accessory medulla is recently stressed to be a clock center, while more distal part of the optic lobe including the lamina and the outer medulla area for the cricket. Identification of the clock cells needs further critical studies. Although each optic lobe clock seems functionally identical, in respect to photic entrainment and generation of the rhythm, the bilaterally paired clocks form a functional unit. They interact to produce a stable time structure within individual insects by exchanging photic and temporal information through neural pathways, in which serotonin and pigment-dispersing factor (PDF) are involved as chemical messengers. The mutual interaction also plays an important role in seasonal adaptation of the rhythm

Mining ancient microbiomes using selective enrichment of damaged DNA molecules

The identification of bona fide microbial taxa in microbiomes derived from ancient and historical samples is complicated by the unavoidable mixture between DNA from ante- and post-mortem microbial colonizers. One possibility to distinguish between these sources of microbial DNA is querying for the presence of age-associated degradation patterns typical of ancient DNA (aDNA). The presence of uracils, resulting from cytosine deamination, has been detected ubiquitously in aDNA retrieved from diverse sources, and used as an authentication criterion. Here, we employ a library preparation method that separates molecules that carry uracils from those that do not for a set of samples that includes Neandertal remains, herbarium specimens and archaeological plant remains

Shear stress fluctuations in the granular liquid and solid phases

We report on experimentally observed shear stress fluctuations in both granular solid and fluid states, showing that they are non-Gaussian at low shear rates, reflecting the predominance of correlated structures (force chains) in the solidlike phase, which also exhibit finite rigidity to shear. Peaks in the rigidity and the stress distribution's skewness indicate that a change to the force-bearing mechanism occurs at the transition to fluid behaviour, which, it is shown, can be predicted from the behaviour of the stress at lower shear rates. In the fluid state stress is Gaussian distributed, suggesting that the central limit theorem holds. The fibre bundle model with random load sharing effectively reproduces the stress distribution at the yield point and also exhibits the exponential stress distribution anticipated from extant work on stress propagation in granular materials.Comment: 11 pages, 3 figures, latex. Replacement adds journal reference and addresses referee comment

Bestimmung von Uran-232 und Folgeprodukten in bestrahlten Uran-Thorium-Kernbrennstoffen

Aliquots from radiochemically separated and purified uranium fractions of solutions from irradiated nuclear fuels containing uranium and thorium have been measuredwith the aid of $\gamma$-spectrometry and $\alpha$-spectrometry. Obtained values for the atomic ratios of $^{232}$U to $^{233}$U and of $^{232}$U to the total uranium amounts are given

The filamentation instability driven by warm electron beams: Statistics and electric field generation

The filamentation instability of counterpropagating symmetric beams of electrons is examined with 1D and 2D particle-in-cell (PIC) simulations, which are oriented orthogonally to the beam velocity vector. The beams are uniform, warm and their relative speed is mildly relativistic. The dynamics of the filaments is examined in 2D and it is confirmed that their characteristic size increases linearly in time. Currents orthogonal to the beam velocity vector are driven through the magnetic and electric fields in the simulation plane. The fields are tied to the filament boundaries and the scale size of the flow-aligned and the perpendicular currents are thus equal. It is confirmed that the electrostatic and the magnetic forces are equally important, when the filamentation instability saturates in 1D. Their balance is apparently the saturation mechanism of the filamentation instability for our initial conditions. The electric force is relatively weaker but not negligible in the 2D simulation, where the electron temperature is set higher to reduce the computational cost. The magnetic pressure gradient is the principal source of the electrostatic field, when and after the instability saturates in the 1D simulation and in the 2D simulation.Comment: 10 pages, 6 figures, accepted by the Plasma Physics and Controlled Fusion (Special Issue EPS 2009

Clustering and Non-Gaussian Behavior in Granular Matter

We investigate the properties of a model of granular matter consisting of $N$ Brownian particles on a line subject to inelastic mutual collisions. This model displays a genuine thermodynamic limit for the mean values of the energy and the energy dissipation. When the typical relaxation time $\tau$ associated with the Brownian process is small compared with the mean collision time $\tau_c$ the spatial density is nearly homogeneous and the velocity probability distribution is gaussian. In the opposite limit $\tau \gg \tau_c$ one has strong spatial clustering, with a fractal distribution of particles, and the velocity probability distribution strongly deviates from the gaussian one.Comment: 4 pages including 3 eps figures, LaTex, added references, corrected typos, minimally changed contents and abstract, to published in Phys.Rev.Lett. (tentatively on 28th of October, 1998

Iodine speciation in rain, snow and aerosols and possible transfer of organically bound iodine species from aerosol to droplet phases

International audienceIodine oxides, such as iodate, should theoretically be the only stable sink species for iodine in the troposphere. However, field observations have increasingly found very little iodate and significant amounts of iodide and organically bound iodine in precipitation and aerosols. The aim of this study was to investigate iodine speciation, including the organic fraction, in rain, snow, and aerosols in an attempt to further clarify aqueous phase iodine chemistry. Diurnal aerosol samples were taken with a 5 stage cascade impactor and a virtual impactor (PM2.5) from the Mace Head research station, Ireland, during summer 2006. Rain was collected from Australia, New Zealand, Patagonia, Germany, Ireland, and Switzerland while snow was obtained from Greenland, Germany, Switzerland, and New Zealand. All samples were analysed for total iodine by inductively coupled plasma mass spectrometry (ICP-MS) and speciation was determined by coupling an ion chromatography unit to the ICP-MS. Total iodine in the aerosols from Mace Head gave a median concentration of 50 pmol m?3 of which the majority was associated with the organic fraction (median day: 91±7%, night: 94±6% of total iodine). Iodide exhibited higher concentrations than iodate (median 5% vs. 0.8% of total iodine), and displayed significant enrichment during the day compared to the night. Interestingly, up to 5 additional, presumably anionic organic peaks were observed in all IC-ICP-MS chromatograms, composing up to 15% of the total iodine. Organically bound iodine was also the dominant fraction in all rain and snow samples, with lesser amounts of iodide and iodate (iodate was particularly low in snow). Two of the same unidentified peaks found in aerosols were also observed in precipitation from both Southern and Northern Hemispheres, suggesting that these species are transferred from the aerosol phase into precipitation. It is suggested that organo-I is formed by reactions between HOI and organic matter derived from the ocean surface layer. This may then photolytically decompose to give iodide and the unidentified species. The data in this study show that iodine oxides are the least abundant species in rain, snow, and aerosols and therefore considerably more effort is required on aqueous phase iodine chemistry for a holistic understanding of the iodine cycle