Calciphylaxis following kidney transplantation: a case report

Introduction: Calciphylaxis occurring after kidney transplantation is rare and rarely reported. It results in chronic non-healing wounds and is associated with a poor prognosis and is often fatal. We present a case of proximal lower limb calciphylaxis that occurred early after kidney transplantation. The patient had no classic associated risk factors. He had previously had a total parathyroidectomy but had normal serum calcium-phosphate product and parathyroid hormone levels. The clinical outcome of this case was favorable and highlights some fundamental issues relating to management. Case prsentation: A 70-year-old British Caucasian man with end-stage renal failure secondary to IgA nephropathy presented six months post kidney transplantation with cutaneous calciphylaxis lesions involving the medial aspect of the thigh bilaterally. Conclusion: To the best of our knowledge, this is the first reported case of rapid onset cutaneous calciphylaxis occurring soon after kidney transplantation that was associated with a favorable outcome. Cutaneous calciphylaxis lesions should be promptly managed with meticulous wound care, antimicrobial therapy and the correction of calcium-phosphate product where indicated

Protein farnesyltransferase and protein prenylation in Plasmodium falciparum

Comparison of the malaria parasite and mammalian protein prenyltransferases and their cellular substrates is important for establishing this enzyme as a target for developing antimalarial agents. Nineteen heptapeptides differing only in their carboxyl-terminal amino acid were tested as alternative substrates of partially purified Plasmodium falciparum protein farnesyltransferase. Only NRSCAIM and NRSCAIQ serve as substrates, with NRSCAIM being the best. Peptidomimetics, FTI-276 and GGTI-287, inhibit the transferase with IC50 values of 1 and 32 nm, respectively. Incubation of P. falciparum-infected erythrocytes with [H-3]farnesol labels 50- and 22-28-kDa proteins, whereas [H-3]geranylgeraniol labels only 22-28-kDa proteins. The 50-kDa protein is shown to be farnesylated, whereas the 22-28-kDa proteins are geranylgeranylated, irrespective of the labeling prenol. Protein labeling is inhibited more than 50% by either 5 mum FTI-277 or GGTI-298. The same concentration of inhibitors also inhibits parasite growth from the ring stage by 50%, decreases expression of prenylated proteins as measured with prenyl-specific antibody, and inhibits parasite differentiation beyond the trophozoite stage. Furthermore, differentiation specific prenylation of P. falciparum proteins is demonstrated. Protein labeling is detected predominantly during the trophozoite to schizont and schizont to ring transitions. These results demonstrate unique properties of protein prenylation in P. falciparum: a limited specificity of the farnesyltransferase for peptide substrates compared with mammalian enzymes, the ability to use farnesol to label both farnesyl and geranylgeranyl moieties on proteins, differentiation specific protein prenylation, and the ability of peptidomimetic prenyltransferase inhibitors to block parasite differentiation

Polyurea-Functionalized Multiwalled Carbon Nanotubes

An in situ polycondensation approach was applied to functionalize multiwalled carbon nanotubes (MWNTs), resulting in various linear or hyperbranched polycondensed polymers [e.g., polyureas, polyurethanes, and poly(urea-urethane)-bonded carbon nanotubes]. The quantity of the grafted polymer can be easily controlled by the feed ratio of monomers. As a typical example, the polyurea-functionalized MWNTs were measured and characterized in detail. The oxidized MWNTs (MWNT-COOH) were converted into acyl chloride-functionalized MWNTs (MWNT-COCl) by reaction with neat thionyl chloride (SOCl2). MWNT-COCl was reacted with excess 1,6-diaminohexane, affording amino-functionalized MWNTs (MWNT-NH2). In the presence of MWNT-NH2, the polyurea was covalently coated onto the surfaces of the nanotube by in situ polycondensation of diisocyanate [e.g., 4,4‘-methylenebis(phenylisocyanate)] and 1,6-diaminohexane, followed by the removal of free polymer via repeated filtering and solvent washing. The coated polyurea content can be controlled to some extent by adjusting the feed ratio of the isocyanato and amino groups. The structure and morphology of the resulting nanocomposites were characterized by FTIR, NMR, Raman, confocal Raman, TEM, EDS, and SEM measurements. The polyurea-coated MWNTs showed interesting self-assembled flat- or flowerlike morphologies in the solid state. The signals corresponding to that of the D and G bands of the carbon nanotubes were strongly attenuated after polyurea was chemically tethered to the MWNT surfaces. Comparative experiments showed that the grafted polymer species and structures have a strong effect on the Raman signals of polymer-functionalized MWNTs

Revised Stellar Properties of Kepler Targets for the Q1-17 (DR25) Transit Detection Run

The determination of exoplanet properties and occurrence rates using Kepler data critically depends on our knowledge of the fundamental properties (such as temperature, radius and mass) of the observed stars. We present revised stellar properties for 197,096 Kepler targets observed between Quarters 1-17 (Q1-17), which were used for the final transiting planet search run by the Kepler Mission (Data Release 25, DR25). Similar to the Q1--16 catalog by Huber et al. the classifications are based on conditioning published atmospheric parameters on a grid of Dartmouth isochrones, with significant improvements in the adopted methodology and over 29,000 new sources for temperatures, surface gravities or metallicities. In addition to fundamental stellar properties the new catalog also includes distances and extinctions, and we provide posterior samples for each stellar parameter of each star. Typical uncertainties are ~27% in radius, ~17% in mass, and ~51% in density, which is somewhat smaller than previous catalogs due to the larger number of improved logg constraints and the inclusion of isochrone weighting when deriving stellar posterior distributions. On average, the catalog includes a significantly larger number of evolved solar-type stars, with an increase of 43.5% in the number of subgiants. We discuss the overall changes of radii and masses of Kepler targets as a function of spectral type, with particular focus on exoplanet host stars.Comment: 19 pages, 13 figures. ApJS in pres

Integrated approach on heat transfer and inactivation kinetics of microorganisms on the surface of foods during heat treatments: Software development

The objective of this work was to create a software application (Bugdeath 1.0) for the simulation of inactivation kinetics of microorganisms on the surface of foods, during dry and wet pasteurisation treatments. The program was developed under the Real Basic 5.2 application, and it is a user-friendly tool. It integrates heat transfer phenomena and microbial inactivation under constant and time-varying temperature conditions. On the basis of the selection of a heating regime of the medium, the program predicts the food surface temperature and the change in microbial load during the process. Input data and simulated values can be visualised in graphics or data tables. Printing, exporting and saving file options are also available. Bugdeath 1.0 includes also a useful database of foods (beef and potato) and related thermal properties, microorganisms (Salmonella and Listeria monocytogenes) and corresponding inactivation kinetic parameters. This software can be coupled to an apparatus developed under the scope of the European Project BUGDEATH (QLRT-2001-01415), which was conceived to provide repeatable surface temperature-time treatments on food samples. The program has also a great potential for research and industrial applications

Mapping the Human Memory B Cell and Serum Neutralizing Antibody Responses to Dengue Virus Serotype 4 Infection and Vaccination

ABSTRACT The four dengue virus (DENV) serotypes are mosquito-borne flaviviruses responsible for dengue fever and dengue hemorrhagic fever. People exposed to DENV develop antibodies (Abs) that strongly neutralize the serotype responsible for infection. Historically, infection with DENV serotype 4 (DENV4) has been less common and less studied than infections with the other three serotypes. However, DENV4 has been responsible for recent large and sustained epidemics in Asia and Latin America. The neutralizing antibody responses and the epitopes targeted against DENV4 have not been characterized in human infection. In this study, we mapped and characterized epitopes on DENV4 recognized by neutralizing antibodies in people previously exposed to DENV4 infections or to a live attenuated DENV4 vaccine. To study the fine specificity of DENV4 neutralizing human antibodies, B cells from two people exposed to DENV4 were immortalized and screened to identify DENV-specific clones. Two human monoclonal antibodies (MAbs) that neutralized DENV4 were isolated, and their epitopes were finely mapped using recombinant viruses and alanine scan mutation array techniques. Both antibodies bound to quaternary structure epitopes near the hinge region between envelope protein domain I (EDI) and EDII. In parallel, to characterize the serum neutralizing antibody responses, convalescence-phase serum samples from people previously exposed to primary DENV4 natural infections or a monovalent DENV4 vaccine were analyzed. Natural infection and vaccination also induced serum-neutralizing antibodies that targeted similar epitope domains at the EDI/II hinge region. These studies defined a target of neutralizing antigenic site on DENV4 targeted by human antibodies following natural infection or vaccination. IMPORTANCE The four serotypes of dengue virus are the causative agents of dengue fever and dengue hemorrhagic fever. People exposed to primary DENV infections develop long-term neutralizing antibody responses, but these principally recognize only the infecting serotype. An effective vaccine against dengue should elicit long-lasting protective antibody responses to all four serotypes simultaneously. We and others have defined antigenic sites on the envelope (E) protein of viruses of dengue virus serotypes 1, 2, and 3 targeted by human neutralizing antibodies. The epitopes on DENV4 E protein targeted by the human neutralizing antibodies and the mechanisms of serotype 4 neutralization are poorly understood. Here, we report the properties of human antibodies that neutralize dengue virus serotype 4. People exposed to serotype 4 infections or a live attenuated serotype 4 vaccine developed neutralizing antibodies that bound to similar sites on the viral E protein. These studies have provided a foundation for developing and evaluating DENV4 vaccines

Interaction and observation, categorically

This paper proposes to use dialgebras to specify the semantics of interactive systems in a natural way. Dialgebras are a conservative extension of coalgebras. In this categorical model, from the point of view that we provide, the notions of observation and interaction are separate features. This is useful, for example, in the specification of process equivalences, which are obtained as kernels of the homomorphisms of dialgebras. As an example we present the asynchronous semantics of the CCS.Comment: In Proceedings ICE 2011, arXiv:1108.014

Kepler-432: a red giant interacting with one of its two long period giant planets

We report the discovery of Kepler-432b, a giant planet ($M_b = 5.41^{+0.32}_{-0.18} M_{\rm Jup}, R_b = 1.145^{+0.036}_{-0.039} R_{\rm Jup}$) transiting an evolved star $(M_\star = 1.32^{+0.10}_{-0.07} M_\odot, R_\star = 4.06^{+0.12}_{-0.08} R_\odot)$ with an orbital period of $P_b = 52.501129^{+0.000067}_{-0.000053}$ days. Radial velocities (RVs) reveal that Kepler-432b orbits its parent star with an eccentricity of $e = 0.5134^{+0.0098}_{-0.0089}$, which we also measure independently with asterodensity profiling (AP; $e=0.507^{+0.039}_{-0.114}$), thereby confirming the validity of AP on this particular evolved star. The well-determined planetary properties and unusually large mass also make this planet an important benchmark for theoretical models of super-Jupiter formation. Long-term RV monitoring detected the presence of a non-transiting outer planet (Kepler-432c; $M_c \sin{i_c} = 2.43^{+0.22}_{-0.24} M_{\rm Jup}, P_c = 406.2^{+3.9}_{-2.5}$ days), and adaptive optics imaging revealed a nearby (0\farcs87), faint companion (Kepler-432B) that is a physically bound M dwarf. The host star exhibits high signal-to-noise asteroseismic oscillations, which enable precise measurements of the stellar mass, radius and age. Analysis of the rotational splitting of the oscillation modes additionally reveals the stellar spin axis to be nearly edge-on, which suggests that the stellar spin is likely well-aligned with the orbit of the transiting planet. Despite its long period, the obliquity of the 52.5-day orbit may have been shaped by star-planet interaction in a manner similar to hot Jupiter systems, and we present observational and theoretical evidence to support this scenario. Finally, as a short-period outlier among giant planets orbiting giant stars, study of Kepler-432b may help explain the distribution of massive planets orbiting giant stars interior to 1 AU.Comment: 22 pages, 19 figures, 5 tables. Accepted to ApJ on Jan 24, 2015 (submitted Nov 11, 2014). Updated with minor changes to match published versio

Choline Regulates SOX4 through miR-129-5p and Modifies H3K27me3 in the Developing Cortex

Choline availability regulates neural progenitor cell proliferation and differentiation in the developing cerebral cortex. Here, we investigated the molecular mechanism underlying this process and demonstrated that choline regulates the transcription factor SOX4 in neural progenitor cells. Specifically, we found that low choline intake during neurogenesis reduces SOX4 protein levels, causing the downregulation of EZH2, a histone methyltransferase. Importantly, we demonstrate that low choline is not involved in SOX4 protein degradation rate and established that protein reduction is caused by aberrant expression of a microRNA (miR-129-5p). To confirm the role of miR-129-5p, we conducted gain-of-function and loss-of-function assays in neural progenitor cells and demonstrated that directly altering miR-129-5p levels could affect SOX4 protein levels. We also observed that the reduction in SOX4 and EZH2 led to decreased global levels of H3K27me3 in the developing cortex, contributing to reduced proliferation and precocious differentiation. For the first time, to our knowledge, we demonstrate that a nutrient, choline, regulates a master transcription factor and its downstream targets, providing a novel insight into the role of choline in brain development