Formation of 4-hydroxynonenal and further aldehydic mediators of inflammation during bromotrichlorornethane treatment of rat liver cells

Bromotrichloromethane (CBrCl3) treatment is a model for studies on molecular mechanisms of haloalkane toxicity with some advantages compared with CCl4 treatment. The formation of 4-hydroxynonenal and similar aldehydic products of lipid peroxidation, which play a role as mediators of inflammatory processes, was clearly demonstrated in rat hepatocytes treated with CBrCl3. It may be assumed that haloalkane toxicity is connected with the biological effects of those inflammation mediatory aldehydic compounds

Serum Concentrations of F2-Isoprostanes and 4-Hydroxynonenal in Hemodialysis Patients in Relation to Inflammation and Renal Anemia

Background: Patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) are apparently exposed to enhanced oxidative stress and to inflammation. It was the aim of this study to characterize the state of systemic oxidative stress of ESRD patients before and following HD using highly specific biomarkers, F2-isoprostanes and 4-hydroxynonenal (HNE). Furthermore the question should be answered, if there are associations between inflammation and systemic oxidative stress and/or between systemic oxidative stress and renal anemia, which is more or less typical for HD patients.Patients and methods: Concentrations of F2-isoprostanes, 4- HNE, CRP as marker of inflammation, and hemoglobin were measured in serum samples of patients with ESRD before and after HD and of healthy control persons for comparison. Total (esterified plus free) F2-isoprostanes were quantified by highly sensitive gas chromatography/mass spectrometry technique, HNE by thin layer chromatography and HPLC/UV detection, CRP by immunoturbidimetry and hemoglobin by clinico-chemical routine assay.Results: 1. HD patients showed significantly higher serum concentrations of F2-isoprostanes and HNE than healthy human control subjects. 2. Total (esterified plus free) F2-isoprostane levels before HD were not significantly different from those after HD, whereas HNE levels were significantly decreased in patients after HD. 3. F2-isoprostane concentrations in HD patients correlated with the levels of CRP, whereas HNE concentrations inversely correlated with the content of hemoglobin.Conclusion: Both, F2-isoprostanes and HNE serum concentrations are useful oxidative stress parameters in ESRD patients undergoing HD. Whereas HNE strongly correlates with the severity of renal anemia, leading to left heart insufficiency, F2-isoprostanes (sum of free plus esterified) highly correlate with the degree of inflammation

Simple relations among E2 matrix elements of low-lying collective states

A method is developed to derive simple relations among the reduced matrix elements of the quadrupole operator between low-lying collective states. As an example, the fourth order scalars of Q are considered. The accuracy and validity of the proposed relations is checked for the ECQF Hamiltonian of the IBM-1 in the whole parameter space of the Casten triangle. Furthermore these relations are successfully tested for low-lying collective states in nuclei for which all relevant data is available.Comment: 12 pages, 1 figure, RevTeX preprint-styl

Singular Character of Critical Points in Nuclei

The concept of critical points in nuclear phase transitional regions is discussed from the standpoints of Q-invariants, simple observables and wave function entropy. It is shown that these critical points very closely coincide with the turning points of the discussed quantities, establishing the singular character of these points in nuclear phase transition regions between vibrational and rotational nuclei, with a finite number of particles.Comment: 12 pages, 7 figures, elsart, revised version, considerable changes and addition

Proteome Profile of Myelin in the Zebrafish Brain

The velocity of nerve conduction along vertebrate axons depends on their ensheathment with myelin. Myelin membranes comprise specialized proteins well characterized in mice. Much less is known about the protein composition of myelin in non-mammalian species. Here, we assess the proteome of myelin biochemically purified from the brains of adult zebrafish (Danio rerio), considering its increasing popularity as model organism for myelin biology. Combining gel-based and gel-free proteomic approaches, we identified > 1,000 proteins in purified zebrafish myelin, including all known constituents. By mass spectrometric quantification, the predominant Ig-CAM myelin protein zero (MPZ/P0), myelin basic protein (MBP), and the short-chain dehydrogenase 36K constitute 12%, 8%, and 6% of the total myelin protein, respectively. Comparison with previously established mRNA-abundance profiles shows that expression of many myelin-related transcripts coincides with the maturation of zebrafish oligodendrocytes. Zebrafish myelin comprises several proteins that are not present in mice, including 36K, CLDNK, and ZWI. However, a surprisingly large number of ortholog proteins is present in myelin of both species, indicating partial evolutionary preservation of its constituents. Yet, the relative abundance of CNS myelin proteins can differ markedly as exemplified by the complement inhibitor CD59 that constitutes 5% of the total zebrafish myelin protein but is a low-abundant myelin component in mice. Using novel transgenic reporter constructs and cryo-immuno electron microscopy, we confirm the incorporation of CD59 into myelin sheaths. These data provide the first proteome resource of zebrafish CNS myelin and demonstrate both similarities and heterogeneity of myelin composition between teleost fish and rodents

Conservation and divergence of myelin proteome and oligodendrocyte transcriptome profiles between humans and mice

Human myelin disorders are commonly studied in mouse models. Since both clades evolutionarily diverged approximately 85 million years ago, it is critical to know to what extent the myelin protein composition has remained similar. Here, we use quantitative proteomics to analyze myelin purified from human white matter and find that the relative abundance of the structural myelin proteins PLP, MBP, CNP, and SEPTIN8 correlates well with that in C57Bl/6N mice. Conversely, multiple other proteins were identified exclusively or predominantly in human or mouse myelin. This is exemplified by peripheral myelin protein 2 (PMP2), which was specific to human central nervous system myelin, while tetraspanin-2 (TSPAN2) and connexin-29 (CX29/GJC3) were confined to mouse myelin. Assessing published scRNA-seq-datasets, human and mouse oligodendrocytes display well-correlating transcriptome profiles but divergent expression of distinct genes, including Pmp2, Tspan2, and Gjc3. A searchable web interface is accessible via www.mpinat.mpg.de/myelin. Species-dependent diversity of oligodendroglial mRNA expression and myelin protein composition can be informative when translating from mouse models to humans

Progressive axonopathy when oligodendrocytes lack the myelin protein CMTM5

Oligodendrocytes facilitate rapid impulse propagation along the axons they myelinate and support their long-term integrity. However, the functional relevance of many myelin proteins has remained unknown. Here, we find that expression of the tetraspan-transmembrane protein CMTM5 (chemokine-like factor-like MARVEL-transmembrane domain containing protein 5) is highly enriched in oligodendrocytes and central nervous system (CNS) myelin. Genetic disruption of the Cmtm5 gene in oligodendrocytes of mice does not impair the development or ultrastructure of CNS myelin. However, oligodendroglial Cmtm5 deficiency causes an early-onset progressive axonopathy, which we also observe in global and tamoxifen-induced oligodendroglial Cmtm5 mutants. Presence of the WldS mutation ameliorates the axonopathy, implying a Wallerian degeneration-like pathomechanism. These results indicate that CMTM5 is involved in the function of oligodendrocytes to maintain axonal integrity rather than myelin biogenesis

Transition Rates between Mixed Symmetry States: First Measurement in 94Mo

The nucleus 94Mo was investigated using a powerful combination of gamma-singles photon scattering experiments and gamma-gamma-coincidence studies following the beta-decay of 94mTc. The data survey short-lived J^pi=1+,2+ states and include branching ratios, E2/M1 mixing ratios, lifetimes, and transition strengths. The mixed-symmetry (MS) 1+ scissors mode and the 2+ MS state are identified from M1 strengths. A gamma transition between MS states was observed and its rate was measured. Nine M1 and E2 strengths involving MS states agree with the O(6) limit of the interacting boson model-2 using the proton boson E2 charge as the only free parameter.Comment: 9 pages, 3 PostScript figures included, ReVTeX, accepted for publication in Physical Review Letters, tentatively scheduled for August 9, 199

Peter Eckl: Research on the Pro-/Antioxidant Balance

Peter Maria ECKL started his scientific career in the late 1970s at the Paris-Lodron University of Salzburg working in the field of radiation research [...