To Bet, or Not to Bet: That Is the Question of SEF Spikes

The ability of animals to monitor their own cognitive processes is called metacognition. In this issue of Neuron, Middlebrooks and Sommer (2012) show that single-unit activity of SEF neurons exhibit?a metacognitive signal while monkeys perform a postdecision wagering task.     

Kinetic analysis for the degradation of glycyl-L-leucine and L-leucyl-glycine in subcritical water

Two dipeptides, glycyl-L-leucine (G-L) and L-leucyl-glycine (L-G), the concentrations of which were 10 mmol/L, were degraded in subcritical water in order to understand fully the phenomena occurring during treatment. Treatment was administered in a stainless steel tubular reactor, which was connected to an HPLC pump and immersed in an oil bath at 200-240 °C, with residence times of 10-180 s. When G-L and L-G were treated, L-G and G-L significantly formed, respectively, and then they gradually decreased at every temperature. Irrespective of the kind of substrate, ring formation occurred, and cyclo-(glycyl-L-leucine) was one of the final products. The reaction rate constants related to degradation were estimated under the assumption that all the reactions obeyed first-order kinetics, and the simulated results corresponded well with the experimental ones in every case.     

Absorption of the indigestible disaccharide, β-1,4-mannobiose, from coconut by the rat portal vein

The intestinal absorption of β-1,4-mannobiose by rats was investigated. Mannobiose was detected in the portal vein plasma by matrix-assisted laser desorption ionization/time of flight mass spectrometry after its administration to rats. The presence of mannobiose in the rat plasma was confirmed by an experiment using β-mannosidase. These results indicate that mannobiose was directly absorbed through the intestines even without being hydrolyzed.     

Negative regulation of osteoclastogenesis by ectodomain shedding of receptor activator of NF-kappaB ligand

Receptor activator of NF-kappaB ligand (RANKL) is a transmembrane glycoprotein that has an essential role in the development of osteoclasts. The extracellular portion of RANKL is cleaved proteolytically to produce soluble RANKL, but definite RANKL sheddase(s) and the physiologic function of RANKL shedding have not yet been determined. In the present study, we found that matrix metalloproteinase (MMP) 14 and a disintegrin and metalloproteinase (ADAM) 10 have strong RANKL shedding activity. In Western blot analysis, soluble RANKL was detected as two different molecular weight products, and RNA interference of MMP14 and ADAM10 resulted in a reduction of both the lower and higher molecular weight products. Suppression of MMP14 in primary osteoblasts increased membrane-bound RANKL and promoted osteoclastogenesis in cocultures with macrophages. Soluble RANKL produced by osteoblasts from MMP14-deficient mice was markedly reduced, and their osteoclastogenic activity was promoted, consistent with the findings of increased osteoclastogenesis in vivo. RANKL shedding is an important process that down-regulates local osteoclastogenesis.     

Frictional properties of regenerated cartilage in vitro

Although tribological function is the most important mechanical property of articular cartilage, few studies have examined this function in tissue-engineered cartilage. We investigated changes in the frictional properties of cartilage regenerated from the inoculation of rabbit chondrocytes into fibroin sponge. A reciprocating friction-testing apparatus was used to measure the friction coefficient of the regenerated cartilage under a small load. The specimen was slid against a stainless steel plate in a water vessel filled with physiological saline. The applied load was 0.03 N, the stroke length was 20 mm, and the mean sliding velocity was 0.8 mm/s. The friction coefficient of the regenerated cartilage decreased with increasing cultivation time, because a hydrophilic layer of synthesized extracellular matrix was formed on the fibroin sponge surface. The friction coefficient of the regenerated cartilage was as low as that of natural cartilage in the early stages of the sliding tests, but it increased with increasing duration of sliding owing to exudation of interstitial water from the surface layer.     

Endocannabinoid, anandamide in gingival tissue regulates the periodontal inflammation through NF-kappaB pathway inhibition

Anandamide (AEA) exhibits anti-inflammatory effects. However, its role in the periodontal field remains unknown. Here, we found that gingival crevicular fluid contained a detectable level of AEA. The cannabinoid receptors CB1 and CB2 were expressed by human gingival fibroblasts (HGFs), and markedly upregulated under pathological conditions. AEA significantly reduced the production of pro-inflammatory mediators (IL-6, IL-8 and MCP-1) induced by Porphyromonas gingivalis LPS in HGFs, and this effect was attenuated by AM251 and SR144528, selective antagonists of CB1 and CB2, respectively. Moreover, AEA completely blocked LPS-triggered NF-kappaB activation, implying that AEA may regulate hyperinflammatory reactions in periodontitis.     

Mature hepatocyte growth factor/scatter factor on the surface of human granulocytes is released by a mechanism involving activated factor Xa

Serum hepatocyte growth factor (HGF) is rapidly increased in patients suffering from various tissue injuries including arterial occlusive diseases. However, the cellular sources of the HGF increase remain largely unknown. In the present study, we showed that bioactive mature HGF is constitutively present on the surface of granulocytes in human peripheral blood. Exogenously added 125I-labeled iodo-HGF efficiently bound to granulocyte surface, whereas only a scarce amount of HGF mRNA was detected in granulocytes, indicating that the mature HGF on granulocytes is likely to be derived from other cell types. Interestingly, treatment of granulocytes with human serum rapidly induced the release of the cell surface-associated HGF. In vivo, thromboplastin injection into mice increased HGF release from transplanted human granulocytes, which was inhibited by the pretreatment with DX9065a, a specific inhibitor of factor Xa. Furthermore, DX9065a also inhibited the serum-induced HGF release from human granulocytes in vitro, suggesting that the HGF-releasing factor(s) in serum is associated with factor Xa activation. Thus, human granulocytes may function as a transporter of HGF in the peripheral blood, releasing HGF at the injured sites caused by blood coagulation, where HGF may promote tissue repair.