Galectin-3 and soluble fibrinogen act in concert to modulate neutrophil activation and survival: involvement of alternative MAPK pathways

Galectin-3 (Gal-3), a member of a family of highly conserved carbohydrate-binding proteins, has recently emerged as a novel cellular modulator at inflammatory foci. Here we investigated the effects of Gal-3 on central effector functions of human neutrophils, including phagocytosis, exocytosis of secretory granules, and survival. We examined the effects of Gal-3 alone or in combination with soluble fibrinogen (sFbg), an extracellular mediator that plays a key role during the early phase of the inflammatory response through binding to integrin receptors. In addition we evaluated the intracellular signals triggered by these mediators in human neutrophils. Human neutrophils incubated with recombinant Gal-3 alone increased their phagocytic activity and CD66 surface expression. In contrast to the known antiapoptotic effect of Gal-3 on many cellular types, Gal-3 enhanced PMN apoptotic rate. Preincubation with Gal-3 primed neutrophils to the effects of sFbg, resulting in a synergistic action on degranulation. On the other hand, Gal-3 and sFbg had opposite effects on PMN survival, and the simultaneous action of both agonists partially counteracted the proapoptotic effects of Gal-3. In addition, although sFbg induced its effects through the activation of the ERKs, Gal-3 led to p38 phosphorylation. Disruption of this signaling pathway abrogated Gal-3-mediated modulation of neutrophil degranulation, phagocytosis, and apoptosis. Together, our results support the notion that Gal-3 and sFbg are two physiological mediators present at inflammatory sites that activate different components of the MAPK pathway and could be acting in concert to modulate the functionality and life span of neutrophils.     

Inhibitory and excitatory effects of iodobenzene on the antennal benzoic acid receptor cells of the female silk moth Bombyx mori L

As shown in single-sensillum recordings, iodobenzene has a bimodal effect on the receptor cell tuned to benzoic acid (BA) of the female silk moth Bombyx mori. Exposure to iodobenzene causes an inhibition of the response to BA. With stimulation by iodobenzene alone, a reduction of basic nerve impulse firing during exposure is followed by a transient post-stimulus excitation (rebound). We suggest that inhibition suppresses excitation during exposure but fades afterwards more rapidly than excitation. Due to the spatial equivalence of the iodine and the acid residue, these effects might indicate opposing interactions of iodobenzene with the specific site for the key compound BA. This is supported by the fact that substitutions by smaller halogens are less effective in both inhibition and rebound. The inhibitory effect but not the rebound with iodobenzene alone was also observed in receptor cells tuned to key compounds other than benzoic acid, e.g. in the cell most sensitive to 2,6-dimethyl-5-heptene-2-ol (DMH-cell) occurring in the same sensillum as the BA-cell, or in the bombykol- and bombykal-cells of the male. At least in these cells the inhibitory effect might reflect the action of iodobenzene on a general site, e.g. the lipid matrix of the plasma membrane of the receptor cells.     

The reinfection threshold

Thresholds in transmission are responsible for critical changes in infectious disease epidemiology. The epidemic threshold indicates whether infection invades a totally susceptible population. The reinfection threshold indicates whether self-sustained transmission occurs in a population that has developed a degree of partial immunity to the pathogen (by previous infection or vaccination). In models that combine susceptible and partially immune individuals, the reinfection threshold is technically not a bifurcation of equilibria as correctly pointed out by Breban and Blower. However, we show that a branch of equilibria to a reinfection submodel bifurcates from the disease-free equilibrium as transmission crosses this threshold. Consequently, the full model indicates that levels of infection increase by two orders of magnitude and the effect of mass vaccination becomes negligible as transmission increases across the reinfection threshold.     

Virus isolates during acute and chronic human immunodeficiency virus type 1 infection show distinct patterns of sensitivity to entry inhibitors

We studied the effect of entry inhibitors on 58 virus isolates derived during acute and chronic infection to validate these inhibitors in vitro and to probe whether viruses at early and chronic disease stages exhibit general differences in the interaction with entry receptors. We included members of all types of inhibitors currently identified: (i) agents that block gp120 binding to CD4 (CD4-IgG2 and monoclonal antibody [MAb] IgG1b12), (ii) compounds that block the interaction with CCR5 (the chemokine RANTES/CCL5, the small-molecule inhibitor AD101, and the anti-CCR5 antibody PRO 140), (iii) the fusion inhibitor enfuvirtide (T-20), and (iv) neutralizing antibodies directed against gp120 (MAb 2G12) and gp41 (MAbs 2F5 and 4E10). No differences between viruses from acute and chronic infections in the susceptibility to inhibitors targeting the CD4 binding site, CCR5, or fusion or to MAb 2G12 were apparent, rendering treatment with entry inhibitors feasible across disease stages. The notable exceptions were antibodies 2F5 and 4E10, which were more potent in inhibiting viruses from acute infection (P = 0.0088 and 0.0005, respectively), although epitopes of these MAbs were equally well preserved in both groups. Activities of these MAbs correlated significantly with each other, suggesting that common features of the viral envelope modulate their potencies.     

Comparative context analysis of codon pairs on an ORFeome scale

Codon context is an important feature of gene primary structure that modulates mRNA decoding accuracy. We have developed an analytical software package and a graphical interface for comparative codon context analysis of all the open reading frames in a genome (the ORFeome). Using the complete ORFeome sequences of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Escherichia coli, we show that this methodology permits large-scale codon context comparisons and provides new insight on the rules that govern the evolution of codon-pair context.     

Evolutionary,structural and functional relationships revealed by comparative analysis of syntenic genes in Rhizobiales

Background  

Comparative genomics has provided valuable insights into the nature of gene sequence variation and chromosomal organization of closely related bacterial species. However, questions about the biological significance of gene order conservation, or synteny, remain open. Moreover, few comprehensive studies have been reported for rhizobial genomes.     

Biochemical characterization of rat intestine development using high-resolution magic-angle-spinning 1H NMR spectroscopy and multivariate data analysis

We report details of metabolic profiles for small intestinal samples obtained using high-resolution magic-angle-spinning (HRMAS) (1)H NMR spectroscopy. Intact samples of jejunum and ileum from male Long Evans rats were analyzed on a 600 MHz spectrometer using standard one and two-dimensional (1)H NMR spectroscopic pulse sequences. The metabolic profiles of ileum and jejunum predominantly comprised a number of amino acids, lipids, glycerophosphocholine (GPC), choline, creatine, and ethanol, a number of carboxylic acids including acetate and lactate, and nucleoside bases including cytosine, isocytosine, and uracil. Principal component analysis (PCA) was applied to these NMR data to characterize the biochemical differences between jejunum and ileum tissues. Compared with ileum, jejunum contained higher levels of lipids, GPC, choline, lactate and creatinine, but lower levels of amino acids and acetate. In addition, the age dependence of the biochemical composition of intestinal tissues from young rats (15, 36 days and 3-4 months old) was studied. In general, levels of lipids, lactate, taurine and creatinine were positively correlated with age while amino acids and GPC decreased in the older age group. This study will provide a metabolic reference for further studies assessing the metabolic consequences of nutrition, stress and gut microbiota on intestinal composition.