Genetic determinants of acute inflammation regulate Salmonella infection and modulate Slc11a1 gene (formerly Nramp1) effects in selected mouse lines

Two lines of mice selected to produce maximal (AIRmax) or minimal (AIRmin) acute inflammatory reactions (AIR) differ in their susceptibility to infection by Salmonella enterica serotype Typhimurium (S. Typhimurium). The LD(50) for AIRmax mice is 1000 times higher than that observed for AIRmin mice, and higher frequencies of Slc11a1 alleles (known to confer either resistance (R) or high susceptibility (S) to S. Typhimurium) were consistently found in AIRmax and AIRmin mouse lines, respectively. In order to evaluate the effect of the quantitative trait loci (QTL) segregated in AIRmax and AIRmin mice on Slc11a1 dependent susceptibility to S. Typhimurium, the R and S alleles were fixed in homozygosity in AIRmax and AIRmin backgrounds by genotype assisted breedings. These new lines were named AIRmax(RR), AIRmax(SS), AIRmin(RR), and AIRmin(SS). Acute inflammation of Slc11a1(RR) animals was more severe in comparison to their Slc11a1(SS) counterparts, implicating Slc11a1 (or other linked genes) in AIR regulation. The LD(50) of S. Typhimurium was 800-times higher for AIRmax(SS) than for AIRmin(SS), demonstrating that AIR QTL can act as modifiers of the Slc11a1(SS) susceptibility gene. Four microsatellite markers for S. Typhimurium susceptibility QTL described in other mouse lines showed specific allele fixation in AIRmax or AIRmin mice, suggesting that these chromosomal regions also segregate with inflammatory phenotypes.     

The oxidant/antioxidant network: role of melatonin

Melatonin is now known to be a multifaceted free radical scavenger and antioxidant. It detoxifies a variety of free radicals and reactive oxygen intermediates including the hydroxyl radical, peroxynitrite anion, singlet oxygen and nitric oxide. Additionally, it reportedly stimulates several antioxidative enzymes including glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and superoxide dismutase; conversely, it inhibits a prooxidative enzyme, nitric oxide synthase. Melatonin also crosses all morphophysiological barriers, e.g., the blood-brain barrier, placenta, and distributes throughout the cell; these features increase the efficacy of melatonin as an antioxidant. Melatonin has been shown to markedly protect both membrane lipids and nuclear DNA from oxidative damage. In every experimental model in which melatonin has been tested, it has been found to resist macromolecular damage and the associated dysfunction associated with free radicals.     

Model of oxygen transport and metabolism predicts effect of hyperoxia on canine muscle oxygen uptake dynamics.

Previous studies have shown that increased oxygen delivery, via increased convection or arterial oxygen content, does not speed the dynamics of oxygen uptake, Vo(2m), in dog muscle electrically stimulated at a submaximal metabolic rate. However, the dynamics of transport and metabolic processes that occur within working muscle in situ is typically unavailable in this experimental setting. To investigate factors affecting Vo(2m) dynamics at contraction onset, we combined dynamic experimental data across working muscle with a mechanistic model of oxygen transport and metabolism in muscle. The model is based on dynamic mass balances for O(2), ATP, and PCr. Model equations account for changes in cellular ATPase, oxidative phosphorylation, and creatine kinase fluxes in skeletal muscle during exercise, and cellular respiration depends on [ADP] and [O(2)]. Model simulations were conducted at different levels of arterial oxygen content and blood flow to quantify the effects of convection and diffusion of oxygen on the regulation of cellular respiration during step transitions from rest to isometric contraction in dog gastrocnemius muscle. Simulations of arteriovenous O(2) differences and (.)Vo(2m) dynamics were successfully compared with experimental data (Grassi B, Gladden LB, Samaja M, Stary CM, Hogan MC. J Appl Physiol 85: 1394-1403, 1998; and Grassi B, Gladden LB, Stary CM, Wagner PD, Hogan MC. J Appl Physiol 85: 1404-1412, 1998), thus demonstrating the validity of the model, as well as its predictive capability. The main findings of this study are: 1) the estimated dynamic response of oxygen utilization at contraction onset in muscle is faster than that of oxygen uptake; and 2) hyperoxia does not accelerate the dynamics of diffusion and consequently muscle oxygen uptake at contraction onset due to the hyperoxia-induced increase in oxygen stores. These in silico derived results cannot be obtained from experimental observations alone.     

Analysis of HLA expression in human tumor tissues

Cancer cells can be detected and destroyed by cytotoxic T lymphocytes in many experimental tumor systems, and--as has been well-documented--in some human tumors. In humans however, most diagnosed tumors are not eliminated by T cells but grow steadily, invading and metastasizing until the host is destroyed. Evidence is accumulating that progressive tumor growth occurs not because the immune system is defective or deteriorated, but because the cancer cell is capable of developing a variety of strategies to escape immune recognition. In addition, cancer cells acquire new biological properties to generate invasive capacity in order to migrate and colonize new tissues. Major histocompatibility complex (MHC) antigens are molecules that are specialized in communicating with the T cell receptor and natural killer (NK) cell ligands. With the former, they use the interaction with peptides derived from processed cellular and exogenous proteins to monitor self and non-self status. With the latter, they determine the degree of activation and killing capacity of NK cells by interacting with NK receptors. Any change in the MHC profile of tumor cells (including classical and nonclassical MHC molecules) may therefore have a profound influence on the immune recognition and immune rejection of cancer cells. We have reviewed the data from our laboratory and other groups, and have presented a standardized procedure for analyzing the MHC profile of human tumors with special emphasis on the quality and laboratory use of the material obtained from microdissected tumor samples. Appropriate tissue processing is of particular relevance, since it is not possible to obtain tumor cell lines from most patients. Oncologists require rapid information on the MHC profile of the tumor if gene therapy is envisaged to restore normal MHC class I gene expression.     

Introgression of 1Dx5+1Dy10 into Tritordeum

The uses of hexaploid tritordeum as a crop for human consumption require improvement of its bread-making quality. For this purpose chromosome 1D of bread wheat with the Glu-D1 allele encoding for high-molecular-weight glutenin subunits Dx5+Dy10 was introgressed into tritordeum. Different primary tritordeums were crossed with wheats carrying subunits Dx5+Dy10. The hybrids were backcrossed to tritordeum and seeds for the next backcross (or selfing) were selected for the presence of chromosome 1D using SDS-PAGE. Forty two chromosome plants carrying subunits Dx5+Dy10 were obtained after two backcrosses and selfing. Chromosome characterization of these plants using fluorescence in situ hybridisation (FISH) proved that either chromosome substitution 1H(ch)/1D or 1A/1D had been obtained. A homozygous plant with a translocation of the entire 1DL arm to 1H(ch)S was also obtained. The complete chromosome substitution lines have better agronomic characteristics than the lines with translocations.     

5H-furan-2-ones from fungal cultures of Aporpium caryae

Four furanones 1-4 with an unusual skeleton containing an acetylene unit, named aporpinones, were isolated from the culture of the basidiomycete Aporpium caryae and their structures were elucidated by spectroscopic methods. Compounds 3 and 4 showed weak to moderate antibacterial activity against Bacillus subtilis, Staphylococcus aureus and Escherichia coli.     

Ecological affinity and current distribution of primates (Cebidae) in Campeche, Mexico

We carried out surveys realized field work from March to September 2000 to get the current distribution of Cebids in the state of Campeche, Mexico. Based on interviews and direct observations. We defined the distribution of Ateles geoffroyi yucatanensis and Alouatta pigra and we documented the first time localities where Allouata palliata is found in the state. We made distributional maps of each species using vegetation overlays from Inventario Nacional Forestal (Inv For) and each point documented during fieldwork. We presented the distribution of species according to confiability of the verified or expected data. Using the attributes table of Inv For, we calculated the areas of distribution which were 22,735 km2 for Alouatta sp. and 18,501 km2 for A. g. yucatanensis. We also presented the area occupied by each species according to vegetation types and the relative proportion of these vegetation types in the state. We confirmed the ability of Alouatta sp. to survive in disturbed environments produced by habitat fragmentation, and the affinity of A. g. yucatanesis to well preserved habitats.     

Distribution and abundance of Caiman crocodilus in the Caño Negro National Wild Life Refuge, Costa Rica

The distribution and abundance of a population of Caiman crocodilus fuscus were estimated by monthly counting of eye-shines at night, from February 1999 to March 2000 in six transects of Río Frío in the Ca?o Negro National Refuge (RNVSCN), Northern Costa Rica. March was the month with the greatest abundance of caimans observed. The visible fraction of the population (PV2 index) fluctuated between 42.59% to 54.71% during the wet season and 35.49% to 53.93% in the dry season. The transects of river with greater abundance of caimans were Terrón-Sabogal and Sabogal-Playuela. Significant differences were determined in the abundance of caimans between transects, except the transects Entrada San Sebastían-Las Cubas and Las Cubas-Entrada Ca?o Los Patos and Entrada Ca?o Los Patos-Terrón and Boca Sabogal-Playuela. The population of estimated brown caiman in this study was 2283.48 +/- 313.5. The statistical analysis by seasons did not show significant differences in the number of caimans observed. Estimated mean number of caimans per km of river was 74.36/km for 30.7 km of habitat. The results of this study indicated that the fluctuation in population density during the seasons is attributable to local movements.