Effects of Lectins on initial attachment of cariogenic <Emphasis Type="Italic">Streptococcus mutans</Emphasis>

Oral bacteria initiate biofilm formation by attaching to tooth surfaces via an interaction of a lectin-like bacterial protein with carbohydrate chains on the pellicle. This study aimed to find naturally derived lectins that inhibit the initial attachment of a cariogenic bacterial species, Streptococcus mutans (S. mutans), to carbohydrate chains in saliva in vitro. Seventy kinds of lectins were screened for candidate motifs that inhibit the attachment of S. mutans ATCC 25175 to a saliva-coated culture plate. The inhibitory effect of the lectins on attachment of the S. mutans to the plates was quantified by crystal violet staining, and the biofilm was observed under a scanning electron microscope (SEM). Surface plasmon resonance (SPR) analysis was performed to examine the binding of S. mutans to carbohydrate chains and the binding of candidate lectins to carbohydrate chains, respectively. Moreover, binding assay between the biotinylated-lectins and the saliva components was conducted to measure the lectin binding. Lectins recognizing a salivary carbohydrate chain, Galβ1-3GalNAc, inhibited the binding of S. mutans to the plate. In particular, Agaricus bisporus agglutinin (ABA) markedly inhibited the binding. This inhibition was confirmed by SEM observation. SPR analysis indicated that S. mutans strongly binds to Galβ1-3GalNAc, and ABA binds to Galβ1-3GalNAc. Finally, the biotinylated Galβ1-3GalNAc-binding lectins including ABA demonstrated marked binding to the saliva components. These results suggest that ABA lectin inhibited the attachment of S. mutans to Galβ1-3GalNAc in saliva and ABA can be useful as a potent inhibitor for initial attachment of oral bacteria and biofilm formation.     

Dynamically engaged smiling predicts cooperation above and beyond average smiling levels

Smiling has been conceptualized as a signal of cooperative intent, yet smiles are easy to fake. We suggest that contextually appropriate, dynamically engaged smiling imposes an attentional cost, thereby making engaged smiling a plausible “honest signal” of cooperative intent. To test this hypothesis, we analyzed data from 123 pairs of same-sex strangers having “getting-to-know-you” conversations who subsequently played a one-shot prisoner's dilemma together. We calculated the strength of engagement in smiling using a cross-lagged auto-regressive model for dyadic data. We found that when an individual's partner (the signaler) tended to smile in a more responsive way, that individual (the receiver) was more likely to cooperate. Conversely, when a signaler tended to smile in a less responsive way, the receiver was less likely to cooperate. These effects were present over-and-above the effects of average levels of smiling and self-reported liking, which also predicted likelihood of cooperation. However, dynamically engaged smiling did not predict cooperation on the part of the signaler, suggesting that receivers weight the importance of engagement more highly than they should, or even that engaged smiling might be a manipulative display. These results illustrate how conversational dynamics can influence evolutionary signaling.     

Retinoic acid promotes differentiation of trophoblast stem cells to a giant cell fate.

Trophoblast stem cell (TS cell) lines have the ability to differentiate into trophoblast subtypes in vitro and contribute to the formation of placenta in chimeras. In order to investigate the possible role of retinoic acid (RA) in placentation, we analyzed the effects of exogenous RA on TS cells in vitro and the developing ectoplacental cone in vivo. TS cells expressed all subtypes of the retinoid receptor family, with the exception of RARbeta, whose expression was stimulated in response to RA. TS cells treated with RA were compromised in their ability to proliferate and exhibited properties of differentiation into trophoblast giant cells. During TS cell differentiation into trophoblast subtypes induced by withdrawal of FGF4, RA treatment further illustrated its role in the specification of cell fate by the promotion of differentiation into giant cells and the suppression of spongiotrophoblast formation. Moreover, administration of RA during pregnancy resulted in the overabundance of giant cells at the expense of spongiotrophoblast cells. RA hereby acts as an extracellular signal whose potential function can be linked to specification events mediating trophoblast cell fate. Taken together with the spatial patterns of giant-cell formation and RA synthesis in vivo, these findings implicate a function for RA in giant-cell formation during placentation.     

Biosynthesis and turnover of anandamide and other N-acylethanolamines in peritoneal macrophages.

Polyunsaturated N-acylethanolamines (NAEs), including anandamide (20:4n-6 NAE), elicit a variety of biological effects through cannabinoid receptors, whereas saturated and monounsaturated NAEs are inactive. Arachidonic acid mobilization induced by treatment of intact mouse peritoneal macrophages with Ca2+ ionophore A23187 had no effect on the production of NAE or its precursor N-acylphosphatidylethanolamine (N-acyl PE). Addition of exogenous ethanolamine resulted in enhanced NAE synthesis by its N-acylation with endogenous fatty acids, but this pathway was not selective for arachidonic acid. Incorporation of (18)O from H2 (18)O-containing media into the amide carbonyls of both NAE and N-acyl PE demonstrated a rapid, constitutive turnover of both lipids.     

Potent antagonists of the CCR2b receptor. Part 3: SAR of the (R)-3-aminopyrrolidine series

SAR studies were conducted around lead compound 1 using high-throughput parallel solution and solid phase synthesis. Our lead optimization efforts led to the identification of several CCR2b antagonists with potent activity in both binding and functional assays [Compound 71 CCR2b Binding IC(50) 3.2 nM; MCP-1-Induced Chemotaxis IC(50) 0.83 nM; Ca(2+) Flux IC(50) 7.5 nM].     

Expression of the peroxisome proliferator activated receptor γ gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes

Background  

Adipose tissues serve not only as a store for energy in the form of lipid, but also as endocrine tissues that regulates metabolic activities of the organism by secreting various kinds of hormones. Peroxisome proliferator activated receptor γ (PPARγ) is a key regulator of adipocyte differentiation that induces the expression of adipocyte-specific genes in preadipocytes and mediates their differentiation into adipocytes. Furthermore, PPARγ has an important role to maintain the physiological function of mature adipocyte by controlling expressions of various genes properly. Therefore, any reduction in amount and activity of PPARγ is linked to the pathogenesis of metabolic syndrome.     

Phosphoenolpyruvate carboxykinase is necessary for the integration of hepatic energy metabolism

We used an allelogenic Cre/loxP gene targeting strategy in mice to determine the role of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in hepatic energy metabolism. Mice that lack this enzyme die within 3 days of birth, while mice with at least a 90% global reduction of PEPCK, or a liver-specific knockout of PEPCK, are viable. Surprisingly, in both cases these animals remain euglycemic after a 24-h fast. However, mice without hepatic PEPCK develop hepatic steatosis after fasting despite up-regulation of a variety of genes encoding free fatty acid-oxidizing enzymes. Also, marked alterations in the expression of hepatic genes involved in energy metabolism occur in the absence of any changes in plasma hormone concentrations. Given that a ninefold elevation of the hepatic malate concentration occurs in the liver-specific PEPCK knockout mice, we suggest that one or more intermediary metabolites may directly regulate expression of the affected genes. Thus, hepatic PEPCK may function more as an integrator of hepatic energy metabolism than as a determinant of gluconeogenesis.