DNA damage induced by a chromium(III) Schiff base complex is reversible under physiological condition

[Cr(naphen)(H2O)(2)]+, where naphen is 1,2-bis(naphthylideneamino)ethane having the basic salen moiety, has been characterized structurally. [Cr(naphen)(H2O)(2)]+, which has an extended aromatic system and binds with calf thymus DNA (CT DNA) intercalatively, has been found to promote DNA cleavage in the presence of biological reductant such as ascorbate and oxidant like hydrogen peroxide. Results of electron paramagnetic resonance (EPR) experiments suggest involvement of hydroxyl radicals in the oxidative cleavage of DNA in the presence of the Cr(III) complex and hydrogen peroxide. The cell viability study on nicked DNA by [Cr(naphen)(H2O)(2)]+ has shown that the damage brought about to DNA could be repaired by Escherichia coli DNA repair enzymes.     

Mineral contents of Aloe vera leaf gel and their role on streptozotocin-induced diabetic rats

The role of some inorganic elements like vanadium, zinc, sodium, potassium, calcium, copper, manganese, and traces of chromium in the improvement of impaired glucose tolerance and their indirect role in the management of diabetes mellitus are being increasingly recognized. In traditional methods, medicinal plants are being used, which contain both organic and inorganic constituents. In the present study, an attempt has been made to analyze the inorganic elements present in Aloe vera leat gel and their role on diabetes-related biochemical alterations in experimental rats. Special emphasis was given to the inorganic parts by carefully preparing ash of the leaf gel. The results clearly indicate the presence of several hypoglycemic-activity-possessing elements in the gel. The ash treatment also resulted in hypoglycemic action. In conclusion, the presence of various inorganic trace elements in the gel might account for the hypoglycemic nature of the plant.     

Plasmodium falciparum: characterization of a late asexual stage golgi protein containing both ankyrin and DHHC domains

Proteins containing the DHHC motif have been shown to function as palmitoyl transferases. The palmitoylation of proteins has been shown to play an important role in the trafficking of proteins to the proper subcellular location. Herein, we describe a protein containing both ankyrin domains and a DHHC domain that is present in the Golgi of late schizonts of P. falciparum. The timing of expression as well as the location of this protein suggests that it may play an important role in the sorting of proteins to the apical organelles during the development of the asexual stage of the parasite.     

Epistatic suppression of systemic lupus erythematosus: fine mapping of Sles1 to less than 1 mb

Sle is a susceptibility locus for systemic autoimmunity derived from the lupus-prone NZM2410 mouse. The New Zealand White-derived suppressive modifier Sles1 was identified as a specific modifier of Sle1 and prevents the development of IgG anti-chromatin autoantibodies mediated by Sle1 on the C57BL/6 (B6) background. Fine mapping of Sles1 with truncated congenic intervals localizes it to a approximately 956-kb segment of mouse chromosome 17. Sles1 completely abrogates the development of activated T and B cell populations in B6.Sle1. Despite this suppression of the Sle1-mediated cell surface activation phenotypes, B6.Sle1 Sles1 splenic B cells still exhibit intrinsic ERK phosphorylation. Classic genetic complementation tests using the nonautoimmmune 129/SvJ mouse suggests that this strain possesses a Sles1 allele complementary to that of New Zealand White, as evidenced by the lack of glomerulonephritis, splenomegaly, and antinuclear autoantibody production seen in (129 x B6.Sle1 Sles1)F(1)s. These findings localize and characterize the suppressive properties of Sles1 and implicate 129 as a useful strain for aiding in the identification of this elusive epistatic modifier gene.     

Gene expression intensity shapes evolutionary rates of the proteins encoded by the vertebrate genome

Natural selection leaves its footprints on protein-coding sequences by modulating their silent and replacement evolutionary rates. In highly expressed genes in invertebrates, these footprints are seen in the higher codon usage bias and lower synonymous divergence. In mammals, the highly expressed genes have a shorter gene length in the genome and the breadth of expression is known to constrain the rate of protein evolution. Here we have examined how the rates of evolution of proteins encoded by the vertebrate genomes are modulated by the amount (intensity) of gene expression. To understand how natural selection operates on proteins that appear to have arisen in earlier and later phases of animal evolution, we have contrasted patterns of mouse proteins that have homologs in invertebrate and protist genomes (Precambrian genes) with those that do not have such detectable homologs (vertebrate-specific genes). We find that the intensity of gene expression relates inversely to the rate of protein sequence evolution on a genomic scale. The most highly expressed genes actually show the lowest total number of substitutions per polypeptide, consistent with cumulative effects of purifying selection on individual amino acid replacements. Precambrian genes exhibit a more pronounced difference in protein evolutionary rates (up to three times) between the genes with high and low expression levels as compared to the vertebrate-specific genes, which appears to be due to the narrower breadth of expression of the vertebrate-specific genes. These results provide insights into the differential relationship and effect of the increasing complexity of animal body form on evolutionary rates of proteins.     

The thrH gene product of Pseudomonas aeruginosa is a dual activity enzyme with a novel phosphoserine:homoserine phosphotransferase activity

The thrH gene product of Pseudomonas aeruginosa has been shown to complement both homoserine kinase (thrB gene product) and phosphoserine phosphatase (serB gene product) activities in vivo. Sequence comparison has revealed that ThrH is related to phosphoserine phosphatases (PSP, EC 3.1.3.3) and belongs to the l-2-haloacid dehalogenase-like protein superfamily. We have solved the crystal structures of ThrH in the apoform and in complex with a bound product phosphate. The structure confirms an overall fold similar to that of PSP. Most of the catalytic residues of PSP are also conserved in ThrH, suggesting that similar catalytic mechanisms are used by both enzymes. Spectrophotometry-based in vitro assays show that ThrH is indeed a phosphoserine phosphatase with a K(m) of 0.207 mm and k(cat) of 13.4 min(-1), comparable with those of other PSPs. More interestingly, using high pressure liquid chromatography-based assays, we have demonstrated that ThrH is able to further transfer the phosphoryl group to homoserine using phosphoserine as the phosphoryl group donor, indicating that ThrH has a novel phosphoserine:homoserine phosphotransferase activity.     

Monomeric recombinant TCR ligand reduces relapse rate and severity of experimental autoimmune encephalomyelitis in SJL/J mice through cytokine switch

Our previous studies demonstrated that oligomeric recombinant TCR ligands (RTL) can treat clinical signs of experimental autoimmune encephalomyelitis (EAE) and induce long-term T cell tolerance against encephalitogenic peptides. In the current study, we produced a monomeric I-A(s)/PLP 139-151 peptide construct (RTL401) suitable for use in SJL/J mice that develop relapsing disease after injection of PLP 139-151 peptide in CFA. RTL401 given i.v. or s.c. but not empty RTL400 or free PLP 139-151 peptide prevented relapses and significantly reduced clinical severity of EAE induced by PLP 139-151 peptide in SJL/J or (C57BL/6 x SJL)F(1) mice, but did not inhibit EAE induced by PLP 178-191 or MBP 84-104 peptides in SJL/J mice, or MOG 35-55 peptide in (C57BL/6 x SJL/J)F(1) mice. RTL treatment of EAE caused stable or enhanced T cell proliferation and secretion of IL-10 in the periphery, but reduced secretion of inflammatory cytokines and chemokines. In CNS, there was a modest reduction of inflammatory cells, reduced expression of very late activation Ag-4, lymphocyte function-associated Ag-1, and inflammatory cytokines, chemokines, and chemokine receptors, but enhanced expression of Th2-related factors, IL-10, TGF-beta3, and CCR3. These results suggest that monomeric RTL therapy induces a cytokine switch that curbs the encephalitogenic potential of PLP 139-151-specific T cells without fully preventing their entry into CNS, wherein they reduce the severity of inflammation. This mechanism differs from that observed using oligomeric RTL therapy in other EAE models. These results strongly support the clinical application of this novel class of peptide/MHC class II constructs in patients with multiple sclerosis who have focused T cell responses to known encephalitogenic myelin peptides.