Measurement of the complete nuclide production and kinetic energies of the system 136Xe + hydrogen at 1 GeV per nucleon

We present an extensive overview of production cross sections and kinetic energies for the complete set of nuclides formed in the spallation of 136Xe by protons at the incident energy of 1 GeV per nucleon. The measurement was performed in inverse kinematics at the FRagment Separator (GSI, Darmstadt). Slightly below the Businaro-Gallone point, 136Xe is the stable nuclide with the largest neutron excess. The kinematic data and cross sections collected in this work for the full nuclide production are a general benchmark for modelling the spallation process in a neutron-rich nuclear system, where fission is characterised by predominantly mass-asymmetric splits.Comment: 18 pages, 14 figure

Fission and cluster decay of 76^{76}Sr nucleus in the ground-state and formed in heavy-ion reactions

Calculations for fission and cluster decay of $^{76}Sr$ are presented for this nucleus to be in its ground-state or formed as an excited compound system in heavy-ion reactions. The predicted mass distribution, for the dynamical collective mass transfer process assumed for fission of $^{76}Sr$, is clearly asymmetric, favouring $\alpha$-nuclei. Cluster decay is studied within a preformed cluster model, both for ground-state to ground-state decays and from excited compound system to the ground-state(s) or excited states(s) of the fragments.Comment: 14 pages LaTeX, 5 Figures available upon request Submitted to Phys. Rev.

Molecular Determinants of S100B Oligomer Formation

Background: S100B is a dimeric protein that can form tetramers, hexamers and higher order oligomers. These forms have been suggested to play a role in RAGE activation. Methodology/Principal Findings: Oligomerization was found to require a low molecular weight trigger/cofactor and could not be detected for highly pure dimer, irrespective of handling. Imidazol was identified as a substance that can serve this role. Oligomerization is dependent on both the imidazol concentration and pH, with optima around 90 mM imidazol and pH 7, respectively. No oligomerization was observed above pH 8, thus the protonated form of imidazol is the active species in promoting assembly of dimers to higher species. However, disulfide bonds are not involved and the process is independent of redox potential. The process was also found to be independent of whether Ca 2+ is bound to the protein or not. Tetramers that are purified from dimers and imidazol by gel filtration are kinetically stable, but dissociate into dimers upon heating. Dimers do not revert to tetramer and higher oligomer unless imidazol is again added. Both tetramers and hexamers bind the target peptide from p53 with retained stoichiometry of one peptide per S100B monomer, and with high affinity (lgK = 7.360.2 and 7.260.2, respectively in 10 mM BisTris, 5 mM CaCl 2, pH 7.0), which is less than one order of magnitude reduced compared to dimer under the same buffer conditions. Conclusion/Significance: S100B oligomerization requires protonated imidazol as a trigger/cofactor. Oligomers ar

Heat shock proteins in chronic kidney disease

Heat shock proteins (HSP) form a heterogenous, evolutionarily conserved group of molecules with high sequence homology. They mainly act as intracellular chaperones, protecting the protein structure and folding under stress conditions. The extracellular HSP, released in the course of damage or necrosis, play a pivotal role in the innate and adaptive immune responses. They also take part in many pathological processes. The aim of this review is to update the recent developments in the field of HSP in chronic kidney disease (CKD), in regard to three different aspects. The first is the assessment of the role of HSP, either positive or deleterious, in the pathogenesis of CKD and the possibilities to influence its progression. The second is the impact of dialysis, being a potentially modifiable stressor, on HSP and the attempt to assess the value of these proteins as the biocompatibility markers. The last area is that of kidney transplantation and the potential role of HSP in the induction of the immune tolerance in kidney recipients

S100A14 Stimulates Cell Proliferation and Induces Cell Apoptosis at Different Concentrations via Receptor for Advanced Glycation End Products (RAGE)

S100A14 is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effects on different types of cells. However, exact extracellular roles of S100A14 have not been clarified yet. Here we investigated the effects of S100A14 on esophageal squamous cell carcinoma (ESCC) cell lines. Results demonstrated that low doses of extracellular S100A14 stimulate cell proliferation and promote survival in KYSE180 cells through activating ERK1/2 MAPK and NF-κB signaling pathways. Immunoprecipitation assay showed that S100A14 binds to receptor for advanced glycation end products (RAGE) in KYSE180 cells. Inhibition of RAGE signaling by different approaches including siRNA for RAGE, overexpression of a dominant-negative RAGE construct or a RAGE antagonist peptide (AmphP) significantly blocked S100A14-induced effects, suggesting that S100A14 acts via RAGE ligation. Furthermore, mutation of the N-EF hand of S100A14 (E39A, E45A) virtually reduced 10 µg/ml S100A14-induced cell proliferation and ERK1/2 activation. However, high dose (80 µg/ml) of S100A14 causes apoptosis via the mitochondrial pathway with activation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase. High dose S100A14 induces cell apoptosis is partially in a RAGE-dependent manner. This is the first study to demonstrate that S100A14 binds to RAGE and stimulates RAGE-dependent signaling cascades, promoting cell proliferation or triggering cell apoptosis at different doses

Light Nuclides Produced in the Proton-Induced Spallation of 238U at 1 GeV

The production of light and intermediate-mass nuclides formed in the reaction 1H+238U at 1 GeV was measured at the Fragment Separator (FRS) at GSI, Darmstadt. The experiment was performed in inverse kinematics, shooting a 1 A GeV 238U beam on a thin liquid-hydrogen target. 254 isotopes of all elements in the range from Z=7 to Z=37 were unambiguously identified, and the velocity distributions of the produced nuclides were determined with high precision. The results show that the nuclides are produced in a very asymmetric binary decay of heavy nuclei originating from the spallation of uranium. All the features of the produced nuclides merge with the characteristics of the fission products as their mass increases.Comment: 40 pages, 16 figures, 3 table

Matrix metalloproteinases (MMP-2,9) and their tissue inhibitors (TIMP-1,2) as novel markers of stress response and atherogenesis in children with chronic kidney disease (CKD) on conservative treatment

The system of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may play a key role in atherogenesis of chronic kidney disease (CKD) patients by its impact on matrix accumulation. Connections with inflammation, stress, or endothelial dysfunction are also probable. However, the data on correlations between these parameters in CKD patients are scarce in adults and absent in children. The aim of our study was to evaluate serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2, as well as their correlations with markers of stress response (Hsp90-α, anti-Hsp60), endothelial dysfunction (sE-selectin), and inflammation (high-sensitivity C-reactive protein) in CKD children treated conservatively. Thirty-seven patients were divided into two groups according to the CKD stage (gr.CKDI, 19 children with CKD stages 2–3; gr.CKDII, 18 subjects with CKD stages 4–5). Twenty-four age-matched healthy subjects served as controls. Serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, Hsp90-α, anti-Hsp60, and sE-selectin were assessed by ELISA. Median values of MMP-2, MMP-9, TIMP-1, and TIMP-2 were significantly higher in all CKD children vs. controls and were increased in patients with CKD stages 4–5 vs. CKD stages 2–3. Hsp90-α, anti-Hsp60, sE-selectin, and glomerular filtration rate predicted the values of MMPs and TIMPs. Chronic kidney disease in children is characterized by MMP/TIMP system dysfunction, aggravated by the progression of renal failure. Correlations between examined parameters, heat shock proteins, and markers of endothelial damage suggest the possibility of MMP/TIMP application as indicators of stress response and atherogenesis in children with CKD on conservative treatment

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Macrophage polarization by the microenvironment of atherosclerotic plaques

Macrophages are key cellular mediators of innate immunity: they are positionally and transcriptionally programmed to respond to pathogens and environmental challenges. When activated by inflammatory signals in their microenvironment they develop into functionally and phenotypically distinct polarized subpopulations: classically activated macrophages, M1, characterized by cytotoxix/proinflammatory activity; alternatively activated macrophages, M2, characterized by anti-inflammatory/wound repair activity. M1 pro-inflammatory macrophages drive atherosclerotic plaques progression towards instability, cap fragilization and rupture. Our study provide new informations about the role exherted by IL-23 and its receptor in human carotid atherosclerotic plaque progression. We show the presence of IL-23 immunoreactivity, mRNA and protein in macrophages infiltrating human carotid atherosclerotic plaques. Our immunohistochemical analysis demonstrated a strong IL-23 immunoreactivity within the inflammatory infiltrate at the shoulder of the plaques, and at the level of cells lining the fibrous cap. FISH analysis confirmed the expression of IL-23 detected by immunohistochemistry. Immunofluorescence, followed by FISH analysis, showed that cells positive for IL-23 mRNA bind anti-CD68 mAb, thus indicating that these cells belong to the macrophage components of the inflammatory infiltrate. This result was further confirmed by double labelling experiments. IL-23 immunoreactivity was detected within the fibrous layer and co-localized with cells belonging to the monocyte-macrophage lineage as shown by their strong CD68- and CD14-related reaction. Clusters of double-positive cells were found at the border of the plaque, as well as in the subendothelial space. Immunohistochemistry and immunofluorescence showed a strong immunoreactivity for IL-23R at the level of inflammatory mononuclear cells accumulated within the plaque. In vitro, only M1 pro-inflammatory, but not M2 anti-inflammatory macrophages produced IL-23, upon stimulation with zymosan or bacterial lipopolysaccharide. Our results suggests that a hyperactive and highly pathogenic IL-23-IL-23R system drives chronic inflammation in atherosclerosis, while the presence of IL-23 proximal to the fibrous cap may contribute to the atherosclerotic plaque instability