Cerebral pathology in immunodeficient gnotobiotic laboratory mice

Gnotobiotic autoimmunity prone, antigen presentation, T lymphocyte receptor gene knockout mice show cerebral pathology in the form of meningitis, venous blood statis with subarachnoid hemorrhages and massive hemosiderin deposits. A more or less severe hydrocephalus was present in all animals examined. In all cases except the CD1-/- animals, the pineal gland was considerably reduced in mass. Only in the latter strain was a strong pineal hypertrophy in the form of a benign tumor present in ca. 50 % of the animals. A possible sequence of events leading to hydrocephalus is discussed. Endogenous vertically transmitted facultative pathogens, active in the immunocompromised animals, probably play a primary etiological role. The results show that caution is needed in planning immunobiological studies on the B10.PL and B10.PL-derived mice, and possibly other strains not examined for possible neuropathological changes

Multidirectional changes in parameters related to sulfur metabolism in frog tissues exposed to heavy metal-related stress

The investigations showed changes of the cystathionine $\gamma$ -lyase (CTH), 3-mercaptopyruvate sulfurtransferase (MPST) and rhodanese (TST) activity and gene expression in the brain, heart, liver, kidney, skeletal muscles and testes in frogs Pelophylax ridibundus, Xenopus laevis and Xenopus tropicalis in response to Pb$^{2+}$, Hg$^{2+}$ and Cd$^{2+}$ stress. The results were analyzed jointly w ith changes in the expression of selected antioxidant enzymes (cytoplasmic and mitochondrial superoxide dismutase, glutathione peroxidase, catalase and thioredoxin reducatase) and with the level of malondialdehyde (a product of lipid peroxidation). The obtained results allowed for confirming the role of sulfurtransferases in the antioxidant protection of tissues exposed to heavy metal ions. Our results revealed different transcriptional responses of the investigated tissues to each of the examined heavy metals. The CTH, MPST and TST genes might be regarded as heavy metal stress-responsive. The CTH gene expression up-regulation w as confirmed in the liver (Pb$^{2+}$, Hg$^{2+}$, Cd$^{2+}$) and skeletal muscle (Hg$^{2+}$), MPST in the brain (Pb$^{2+}$ , Hg$^{2+}$), kidney (Pb$^{2+}$, Cd$^{2+}$ ), skeletal muscle (Pb$^{2+}$, Hg$^{2+}$,Cd$^{2+}$) and TST in the brain (Pb$^{2+}$) and kidney (Pb$^{2+}$, Hg$^{2+}$, Cd$^{2+}$ ). Lead, mercury and cadmium toxicity was demonstrated to affect the glutathione (GSH) and cysteine levels, the concentration ratio of reduced to oxidized glutathione ([GSH]/[GSSG]) and the level of sulfane sulfur-containing compounds, which in case of enhanced reactive oxygen species generation can reveal their antioxidative properties. The present report is the first to widely describe the role of the sulfane sulfur/H$_{2}$S generating enzymes and the cysteine/glutathione system in Pb$^{2+}$, Hg$^{2+}$ and Cd$^{2+}$ stress in various frog tissues, and to explore the mechanisms mediating heavy metal-related stress

The glial Gomori-positive material is sulfane sulpfur.

The Gomori-positive glia are periventricular astrocytes with abundant cytoplasmic granular material, predominantly occupying a periventricular site in the brain. These granular inclusions are strongly stained with chrome hematoxylin in the Gomori's method as well as exhibit red autofluorescence and non-enzymatic peroxidase activity. The glial Gomori-positive material (GGPM) granules are positive in the performic acid Alcian blue method indicating the presence of protein-bound sulfur, what has been shown by our previous studies. The number of cells containing glial Gomori-positive granules dropped after administration of cyanide and increased under the influence of sulfane sulfur donor (diallyl disulfide). This suggests, that sulfur of these granules is a sulfane sulfur, possibly in the form of protein-bound cysteine persulfide. Sulfane sulfur is labile, reactive sulfur atom covalently bound to another sulfur atom. In this paper we present evidence that GGPM exhibit affinity to cyanolysis and its stainability in Gomori's method is due to the presence of protein-bound sulfane sulfur. The biological role of the Gomori-positive glia connected with protective properties of sulfane sulfur has been discussed

The effect of Aspirin on Gomori-positive glia in mouse brain

Aspirin (acetylsalicylic acid, ASA) treatment resulted in a significant decrease in the amount of the sulfur-rich Gomori-positive material present in the cytoplasm of periventricular glia. It also caused the accumulation of the Gomori-positive neurosecretory material in the supraoptic and paraventricular nuclei and, most pronounced, in the neurosecretory axons of the paraventricular- and supraoptic-neurophypophysial tract

AtEAF1 is a potential platform protein for Arabidopsis NuA4 acetyltransferase complex.

BACKGROUND: Histone acetyltransferase complex NuA4 and histone variant exchanging complex SWR1 are two chromatin modifying complexes which act cooperatively in yeast and share some intriguing structural similarities. Protein subunits of NuA4 and SWR1-C are highly conserved across eukaryotes, but form different multiprotein arrangements. For example, the human TIP60-p400 complex consists of homologues of both yeast NuA4 and SWR1-C subunits, combining subunits necessary for histone acetylation and histone variant exchange. It is currently not known what protein complexes are formed by the plant homologues of NuA4 and SWR1-C subunits. RESULTS: We report on the identification and molecular characterization of AtEAF1, a new subunit of Arabidopsis NuA4 complex which shows many similarities to the platform protein of the yeast NuA4 complex. AtEAF1 copurifies with Arabidopsis homologues of NuA4 and SWR1-C subunits ARP4 and SWC4 and interacts physically with AtYAF9A and AtYAF9B, homologues of the YAF9 subunit. Plants carrying a T-DNA insertion in one of the genes encoding AtEAF1 showed decreased FLC expression and early flowering, similarly to Atyaf9 mutants. Chromatin immunoprecipitation analyses of the single mutant Ateaf1b-2 and artificial miRNA knock-down Ateaf1 lines showed decreased levels of H4K5 acetylation in the promoter regions of major flowering regulator genes, further supporting the role of AtEAF1 as a subunit of the plant NuA4 complex. CONCLUSIONS: Growing evidence suggests that the molecular functions of the NuA4 and SWR1 complexes are conserved in plants and contribute significantly to plant development and physiology. Our work provides evidence for the existence of a yeast-like EAF1 platform protein in A. thaliana, filling an important gap in the knowledge about the subunit organization of the plant NuA4 complex

NuA4 and H2A.Z control environmental responses and autotrophic growth in Arabidopsis.

Nucleosomal acetyltransferase of H4 (NuA4) is an essential transcriptional coactivator in eukaryotes, but remains poorly characterized in plants. Here, we describe Arabidopsis homologs of the NuA4 scaffold proteins Enhancer of Polycomb-Like 1 (AtEPL1) and Esa1-Associated Factor 1 (AtEAF1). Loss of AtEAF1 results in inhibition of growth and chloroplast development. These effects are stronger in the Atepl1 mutant and are further enhanced by loss of Golden2-Like (GLK) transcription factors, suggesting that NuA4 activates nuclear plastid genes alongside GLK. We demonstrate that AtEPL1 is necessary for nucleosomal acetylation of histones H4 and H2A.Z by NuA4 in vitro. These chromatin marks are diminished genome-wide in Atepl1, while another active chromatin mark, H3K9 acetylation (H3K9ac), is locally enhanced. Expression of many chloroplast-related genes depends on NuA4, as they are downregulated with loss of H4ac and H2A.Zac. Finally, we demonstrate that NuA4 promotes H2A.Z deposition and by doing so prevents spurious activation of stress response genes