Successful immunotherapy with matrix metalloproteinase-derived peptides in adjuvant arthritis depends on the timing of peptide administration

We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development of such therapies.     

Structural and functional importance of first-shell metal ligands in the binuclear manganese cluster of arginase I

Arginase is a binuclear manganese metalloenzyme that hydrolyzes l-arginine to form l-ornithine and urea. The three-dimensional structures of D128E, D128N, D232A, D232C, D234E, H101N, and H101E arginases I have been determined by X-ray crystallographic methods to elucidate the roles of the first-shell metal ligands in the stability and catalytic activity of the enzyme. This work represents the first structure-based dissection of the binuclear manganese cluster using site-directed mutagenesis and X-ray crystallography. Substitution of the metal ligands compromises the catalytic activity of the enzyme, either by the loss or disruption of the metal cluster or the nucleophilic metal-bridging hydroxide ion. However, the substitution of the metal ligands or the reduction of Mn(2+)(A) or Mn(2+)(B) occupancy does not compromise enzyme-substrate affinity as reflected by K(M), which remains relatively invariant across this series of arginase variants. This implicates a nonmetal binding site for substrate l-arginine in the precatalytic Michaelis complex, as proposed based on analysis of the native enzyme structure (Kanyo, Z. F., Scolnick, L. R., Ash, D. E., and Christianson, D. W. (1996) Nature 383, 554-557).     

Unforeseen consequences of IL-12 expression in the eye of GFAP-IL12 transgenic mice following herpes simplex virus type 1 infection

Transgenic mice expressing interleukin-12 (IL-12) under the glial fibrillary acidic protein (GFAP) promoter were evaluated for their sensitivity to herpes simplex virus type 1 (HSV-1) infection of the cornea. There was a modest but significant decrease in the infiltration of mononuclear cells in the cornea of the GFAP-IL12 transgenic mice compared to the wild-type controls during the acute stage of infection. However, during the latent stage of infection (i.e., day 30 postinfection) GFAP-IL12 transgenic mice had significantly more infiltrating cells in the corneal stroma compared to the wild-type controls. The infiltration was exacerbated by depleting transgenic mice of either CD4(+) or CD8(+) cells at the time of infection. In addition, infiltration of mononuclear cells was associated with the expression of transforming growth factor-beta (TGF-beta) by cells in the cornea. Consistent with increases in tissue associated TGF-beta was the presence of anterior subcapsular cataracts in the GFAP-IL12 transgenic mice. Although the GFAP-IL12 transgenic mice are highly resistant to HSV-1 infection in the eye, this resistance is not related to local expression of TGF-beta1 per se because transgenic mice expressing TGF-beta1 driven by the lens-specific alphaA-crystallin promoter succumb to HSV-1 infection at a similar rate as wild-type controls.     

How season of grazing and herbivore selectivity influence monsoon tall-grass communities of northern Australia

Abstract. The hypothesis that season of defoliation and herbivore selectivity may be as important as level of use in determining plant community response to grazing was tested in a monsoon grassland in northern Australia. Plots, dominated by the tussock grasses Themeda triandra and Chrysopogon fallax, were grazed by cattle at low, medium and high rates of utilization in either the early wet, late wet or dry seasons. Effects of grazing on species composition were greatest in the early wet season when high rates of utilization significantly reduced the proportion and occurrence of Themeda and increased the proportion of forbs. Grazing in the dry season had no significant effect on composition. At medium and high levels of utilization in the early wet season, the pasture responded negatively to defoliation, only partially compensating for plant tissue lost to herbivory. The negative response to defoliation carried over to the next wet season when these same medium and high-grazing treatments produced only 80 % and 60 % growth, respectively, of that in treatments grazed at low levels of utilization or those grazed during the dry season. The frequency of Themeda was still lower, and that of annual grasses and non-leguminous forbs higher, in plots that had been grazed at a high rate of utilization for just eight weeks in the early wet season two years previously. Species richness and diversity were also significantly affected by this grazing disturbance. If species composition is to be maintained in these grasslands then stocking rates must be set at low levels to cope with the combined effect of undercompensation in response to defoliation in the wet season and strong dietary preferences for grazing sensitive species.     

GTfold: Enabling parallel RNA secondary structure prediction on multi-core desktops

ABSTRACT: BACKGROUND: Accurate and efficient RNA secondary structure prediction remains an important open problem in computational molecular biology. Historically, advances in computing technology have enabled faster and more accurate RNA secondary structure predictions. Previous parallelized prediction programs achieved significant improvements in runtime, but their implementations were not portable from niche high-performance computers or easily accessible to most RNA researchers. With the increasing prevalence of multi-core desktop machines, a new parallel prediction program is needed to take full advantage of today's computing technology. FINDINGS: We present here the first implementation of RNA secondary structure prediction by thermodynamic optimization for modern multi-core computers. We show that GTfold predicts secondary structure in less time than UNAfold and RNAfold, without sacrificing accuracy, on machines with four or more cores. CONCLUSIONS: GTfold supports advances in RNA structural biology by reducing the timescales for secondary structure prediction. The difference will be particularly valuable to researchers working with lengthy RNA sequences, such as RNA viral genomes.     

Phylogenetic analysis of the tenascin gene family: evidence of origin early in the chordate lineage

Background  

Tenascins are a family of glycoproteins found primarily in the extracellular matrix of embryos where they help to regulate cell proliferation, adhesion and migration. In order to learn more about their origins and relationships to each other, as well as to clarify the nomenclature used to describe them, the tenascin genes of the urochordate Ciona intestinalis, the pufferfish Tetraodon nigroviridis and Takifugu rubripes and the frog Xenopus tropicalis were identified and their gene organization and predicted protein products compared with the previously characterized tenascins of amniotes.     

A novel surface protein of Trichomonas vaginalis is regulated independently by low iron and contact with vaginal epithelial cells

Background  

Trichomonosis caused by Trichomonas vaginalis is the number one, non-viral sexually transmitted disease (STD) that affects more than 250 million people worldwide. Immunoglobulin A (IgA) has been implicated in resistance to mucosal infections by pathogens. No reports are available of IgA-reactive proteins and the role, if any, of this class of antibody in the control of this STD. The availability of an IgA monoclonal antibody (mAb) immunoreactive to trichomonads by whole cell (WC)-ELISA prompted us to characterize the IgA-reactive protein of T. vaginalis.