Electron impact excitation of S-like iron

Energy levels and radiative rates for transitions among the lowest 48 fine-structure levels belonging to the (1s(2) 2s(2) 2p (6)) 3s (2)3p (4) , 3s3p(5), 3s (2)3p (3) 3d and 3p(6) configurations of Fe xi have been calculated using the fully relativistic grasp code. Additionally, collision strengths for transitions among these levels have also been computed using the Dirac Atomic R-matrix Code (darc) of Norrington & Grant. Radiative rates and oscillator strengths are tabulated for all allowed transitions among the 48 fine-structure levels, while collision strengths are reported at three energies above thresholds, i.e. 8, 16 and 24 Ryd for a few representative transitions. Furthermore, excitation rates have been calculated in a wide electron temperature range below 5 x 10(6) K, and the contribution of resonances has been included in the threshold regions. Comparisons are made with the earlier available theoretical and experimental rates, and it is concluded that the experimental rates are overestimated by up to a factor of 2.

Gamma ray-induced bystander effect in tumour glioblastoma cells: a specific study on cell survival, cytokine release and cytokine receptors.

Recent experimental evidence has challenged the paradigm according to which radiation traversal through the nucleus of a cell is a prerequisite for producing genetic changes or biological responses. Thus, unexposed cells in the vicinity of directly irradiated cells or recipient cells of medium from irradiated cultures can also be affected. The aim of the present study was to evaluate, by means of the medium transfer technique, whether interleukin-8 and its receptor (CXCR1) may play a role in the bystander effect after gamma irradiation of T98G cells in vitro. In fact the cell specificity in inducing the bystander effect and in receiving the secreted signals that has been described suggests that not only the ability to release the cytokines but also the receptor profiles are likely to modulate the cell responses and the final outcome. The dose and time dependence of the cytokine release into the medium, quantified using an enzyme linked immunosorbent assay, showed that radiation causes alteration in the release of interleukin-8 from exposed cells in a dose-independent but time-dependent manner. The relative receptor expression was also affected in exposed and bystander cells.

A role of cellular prion protein in programming T-cell cytokine responses in disease.

The cellular prion protein (PrPC) is widely expressed in neural and non-neural tissues, but its function is unknown. Elucidation of the part played by PrPC in adaptive immunity has been a particular conundrum: increased expression of cell surface PrPC has been documented during T-cell activation, yet the functional significance of this activation remains unclear, with conflicting data on the effects of Prnp gene knockout on various parameters of T-cell immunity. We show here that Prnp mRNA is highly inducible within 8–24 h of T-cell activation, with surface protein levels rising from 24 h. When measured in parallel with CD69 and CD25, PrPC is a late activation antigen. Consistent with its up-regulation being a late activation event, PrP deletion did not alter T-cell-antigen presenting cell conjugate formation. Most important, activated PrP0/0 T cells demonstrated much reduced induction of several T helper (Th) 1, Th2, and Th17 cytokines, whereas others, such as TNF- and IL-9, were unaffected. These changes were investigated in the context of an autoimmune model and a bacterial challenge model. In experimental autoimmune encephalomyelitis, PrP-knockout mice showed enhanced disease in the face of reduced IL-17 responses. In a streptococcal sepsis model, this constrained cytokine program was associated with poorer local control of infection, although with reduced bacteremia. The findings indicate that PrPC is a potentially important molecule influencing T-cell activation and effector function.

The human prion protein residue 129 polymorphism lies within a cluster of epitopes for T cell recognition.

T cell immune responses to central nervous system-derived and other self-antigens are commonly described in both healthy and autoimmune individuals. However, in the case of the human prion protein (PrP), it has been argued that immunologic tolerance is uncommonly robust. Although development of an effective vaccine for prion disease requires breaking of tolerance to PrP, the extent of immune tolerance to PrP and the identity of immunodominant regions of the protein have not previously been determined in humans. We analyzed PrP T cell epitopes both by using a predictive algorithm and by measuring functional immune responses from healthy donors. Interestingly, clusters of epitopes were focused around the area of the polymorphic residue 129, previously identified as an indicator of susceptibility to prion disease, and in the C-terminal region. Moreover, responses were seen to PrP peptide 121-134 containing methionine at position 129, whereas PrP 121-134 [129V] was not immunogenic. The residue 129 polymorphism was also associated with distinct patterns of cytokine response: PrP 128-141 [129M] inducing IL-4 and IL-6 production, which was not seen in response to PrP 128-141 [129V]. Our data suggest that the immunogenic regions of human PrP lie between residue 107 and the C-terminus and that, like with many other central nervous system antigens, healthy individuals carry responses to PrP within the T cell repertoire and yet do not experience deleterious autoimmune reactions.

Branching ratios of x-ray photons from dielectronic recombination processes in H-like titanium ions

In dielectronic recombination of hydrogenlike ions an intermediate doubly excited heliumlike ion is formed. Since the K shell is empty, both excited electrons can decay sequentially to the ground state. In this paper we analyze the x-ray radiation emitted from doubly and singly excited heliumlike titanium ions produced inside the Tokyo electron beam ion trap. Theoretical population densities of the singly excited states after the first transition and the transition probabilities of these states into the ground state were also calculated. This allowed theoretical branching ratios to be determined for each manifold. These branching ratios are compared to the experimentally obtained x-ray distribution by fitting across the relevant peak using a convolution of the theoretically obtained resonance strengths and energies. By taking into account 2E1 transitions which are not observed in the experiment, the measured and calculated ratios agree well. This method provides a valuable insight into the transition dynamics of excited highly charged ions.

First dielectronic recombination measurements with H-like uranium

In this report we show first results on dielectronic recombination (DR) measurements with H-like uranium U91+. The experiments were conducted at the heavy ion storage ring ESR of GSI. The electron cooler of the ESR was used as a target for free electrons. Stochastic pre-cooling of the stored ion beam was employed in order to accomplish high-energy resolution at the necessary high electron-ion collision energies of more than 64 keV. For the DR of U91+ this novel technique enabled us to measure for the first time the KLL-DR process and even to resolve the individual j-j' fine structure components of the KLjLj' resonances. The experimental data are compared with fully relativistic Multi-Configuration Dirac-Fock (DR-MCDF) calculations. (c) 2006 Elsevier Ltd. All rights reserved.

Expedited Solid-Phase Synthesis of Fluorescently Labeled and Biotinylated Aminoalkane Diphenyl Phosphonate Affinity Probes for Chymotrypsin- and Elastase-Like Serine Proteases

In this study, we report on a novel, expedited solid-phase approach for the synthesis of biotinylated and fluorescently tagged irreversible affinity based probes for the chymotrypsin and elastase-like serine proteases. The novel solid-phase biotinylation or fluorescent labeling of the aminoalkane diphenyl phosphonate warhead using commercially available Biotin-PEG-NovaTag or EDANS NovaTag resin permits rapid, facile synthesis of these reagents. We demonstrate the kinetic evaluation and utilization of a number of these irreversible inactivators for chymotrypsin-like (chymotrypsin/human cathepsin G) and elastase-like serine proteases. Encouragingly, these compounds display comparable potency against their target proteases as their N-benzyloxycarbonyl (Cbz)-protected parent compounds, from which they were derived, and function as efficient active site-directed inactivators of their target proteases. We subsequently applied the biotinylated reagents for the sensitive detection of protease species via Western blot, showing that the inactivation of the protease was specifically mediated through the active site serine. Furthermore, we also demonstrate the successful detection of serine protease species with the fluorescently labeled derivatives “in-gel”, thus avoiding the need for downstream Western blotting. Finally, we also show the utility of biotinylated and pegylated affinity probes for the isolation/enrichment of serine protease species, via capture with immobilized streptavidin, and their subsequent identification via de novo sequencing. Given their selectivity of action against the serine proteases, we believe that these reagents can be exploited for the direct, rapid, and selective identification of these enzymes from biological milieu containing multiple protease subclasses.

Effects of antidiabetic drugs on dipeptidyl peptidase IV activity: Nateglinide is an inhibitor of DPP IV and augments the antidiabetic activity of glucagon-like peptide-1

Dipeptidyl peptidase IV (DPP IV) is the primary inactivator of glucoregulatory incretin hormones. This has lead to development of DPP IV inhibitors as a new class of agents for the treatment of type 2 diabetes. Recent reports indicate that other antidiabetic drugs, such as metformin, may also have inhibitory effects on DPP IV activity. In this investigation we show that high concentrations of several antidiabetic drug classes, namely thiazolidinediones, sulphonylureas, meglitinides and morphilinoguanides can inhibit DPP IV The strongest inhibitor nateglinide, the insulin-releasing meglitinide was effective at low therapeutically relevant concentrations as low as 25 mu mol/l. Nateglinide also prevented the degradation of glucagon-like peptide-1 (GLP-1) by DPP IV in a time and concentration-dependent manner. In vitro nateglinide and GLP-1 effects on insulin release were additive. In vivo nateglinide improved the glucose-lowering and insulin-releasing activity of GLP-1 in obese-diabetic ob/ob mice. This was accompanied by significantly enhanced circulating concentrations of active GLP-1(7-36)amide and lower levels of DPP IV activity. Nateglinide similarly benefited the glucose and insulin responses to feeding in ob/ob mice and such actions were abolished by coadministration of exendin(9-39) and (Pro(3))GIP to block incretin hormone action. These data indicate that the use of nateglinide as a prandial insulin-releasing agent may partly rely on inhibition of GLP-1 degradation as well as beta-cell K-ATP channel inhibition. (C) 2007 Elsevier B.V. All rights reserved.