Endothelial Insulin Resistance Exacerbates Experimental Periodontitis.

Epidemiological studies suggest that the severity of periodontitis is higher in people with diabetes than in healthy individuals. Insulin resistance might play a crucial role in the pathogenesis of multiple diabetic complications and is reportedly induced in the gingiva of rodents with type 2 diabetes; however, the molecular mechanisms underlying the pathogenesis of diabetes-related periodontitis remain unclear. Therefore, we aimed to investigate whether endothelial insulin resistance in the gingiva may contribute to the pathogenesis of periodontitis as well as elucidate its underlying molecular mechanisms. We demonstrated that insulin treatment downregulated lipopolysaccharide (LPS)-induced or tumor necrosis factor α (TNFα)-induced VCAM1 expression in endothelial cells (ECs) via the PI3K/Akt activating pathway, resulting in reduced cellular adhesion between ECs and leukocytes. Hyperglycemia-induced selective insulin resistance in ECs diminished the effect of insulin on LPS- or TNFα-stimulated VCAM1 expression. Vascular endothelial cell-specific insulin receptor knockout (VEIRKO) mice exhibited selective inhibition of the PI3K/Akt pathway in the gingiva and advanced experimental periodontitis-induced alveolar bone loss via upregulation of Vcam1, Tnfα, Mcp-1, Rankl, and neutrophil migration into the gingiva compared with that in the wild-type (WT) mice despite being free from diabetes. We also observed that insulin-mediated activation of FoxO1, a downstream target of Akt, was suppressed in the gingiva of VEIRKO and high-fat diet (HFD)-fed mice, hyperglycemia-treated ECs, and primary ECs from VEIRKO. Further analysis using ECs transfected with intact and mutated FoxO1, with mutations at 3 insulin-mediated phosphorylation sites (T24A, S256D, S316A), suggested that insulin-mediated regulation of VCAM1 expression and cellular adhesion of ECs with leukocytes was attenuated by mutated FoxO1 overexpression. These results suggest that insulin resistance in ECs may contribute to the progression of periodontitis via dysregulated VCAM1 expression and cellular adhesion with leukocytes, resulting from reduced activation of the PI3K/Akt/FoxO1 axis.

Epicatechin downregulates adipose tissue CCL19 expression and thereby ameliorates diet-induced obesity and insulin resistance.

BACKGROUND AND AIMS: Epicatechin (EC) intake has been suggested to be beneficial for the prevention of cardiovascular disorders, and it is well known that adipose tissue inflammation is one of the major risk factors for coronary heart diseases. The purpose of the present study was to determine the in vitro and in vivo effects of EC on adipose tissue inflammation and obesity. METHODS AND RESULTS: DNA microarray analysis was performed to evaluate the effects of EC on gene expression in adipocytes co-cultured with bacterial endotoxin-stimulated macrophages. To determine the in vivo effects of the catechin, C57BL/6 mice were fed either a high-fat diet (HFD) or HFD combined with EC, and metabolic changes were observed EC suppressed the expression of many inflammatory genes in the adipocytes co-cultured with endotoxin-stimulated macrophages. Specifically, EC markedly suppressed chemokine (CC motif) ligand 19 (CCL19) expression. The target cell of EC appeared to macrophages. The in vivo study indicated that mice fed the EC-supplemented HFD were protected from diet-induced obesity and insulin resistance. Accordingly, the expression levels of genes associated with inflammation in adipose tissue and in the liver were downregulated in this group of mice. CONCLUSIONS: EC exerts beneficial effects for the prevention of adipose tissue inflammation and insulin resistance. Since we previously reported that mice deficient in the CCL19 receptor were protected from diet-induced obesity and insulin resistance, it can be concluded that the beneficial effects of EC could be mediated, at least in part, by marked suppression of CCL19 expression.

Gate-Tunable Spin-Charge Conversion and the Role of Spin-Orbit Interaction in Graphene.

The small spin-orbit interaction of carbon atoms in graphene promises a long spin diffusion length and the potential to create a spin field-effect transistor. However, for this reason, graphene was largely overlooked as a possible spin-charge conversion material. We report electric gate tuning of the spin-charge conversion voltage signal in single-layer graphene. Using spin pumping from an yttrium iron garnet ferrimagnetic insulator and ionic liquid top gate, we determined that the inverse spin Hall effect is the dominant spin-charge conversion mechanism in single-layer graphene. From the gate dependence of the electromotive force we showed the dominance of the intrinsic over Rashba spin-orbit interaction, a long-standing question in graphene research.

Experimental Demonstration of Room-Temperature Spin Transport in n-Type Germanium Epilayers.

We report an experimental demonstration of room-temperature spin transport in n-type Ge epilayers grown on a Si(001) substrate. By utilizing spin pumping under ferromagnetic resonance, which inherently endows a spin battery function for semiconductors connected with a ferromagnet, a pure spin current is generated in the n-Ge at room temperature. The pure spin current is detected by using the inverse spin-Hall effect of either a Pt or Pd electrode on n-Ge. From a theoretical model that includes a geometrical contribution, the spin diffusion length in n-Ge at room temperature is estimated to be 660 nm. Moreover, the spin relaxation time decreases with increasing temperature, in agreement with a recently proposed theory of donor-driven spin relaxation in multivalley semiconductors.

Large voltage-induced magnetic anisotropy change in a few atomic layers of iron.

In the field of spintronics, researchers have manipulated magnetization using spin-polarized currents. Another option is to use a voltage-induced symmetry change in a ferromagnetic material to cause changes in magnetization or in magnetic anisotropy. However, a significant improvement in efficiency is needed before this approach can be used in memory devices with ultralow power consumption. Here, we show that a relatively small electric field (less than 100 mV nm(-1)) can cause a large change (approximately 40%) in the magnetic anisotropy of a bcc Fe(001)/MgO(001) junction. The effect is tentatively attributed to the change in the relative occupation of 3d orbitals of Fe atoms adjacent to the MgO barrier. Simulations confirm that voltage-controlled magnetization switching in magnetic tunnel junctions is possible using the anisotropy change demonstrated here, which could be of use in the development of low-power logic devices and non-volatile memory cells.

Real-space observation of current-driven domain wall motion in submicron magnetic wires.

We report direct observation of current-driven magnetic domain wall (DW) displacement by using a well-defined single DW in a microfabricated magnetic wire with submicron width. Magnetic force microscopy visualizes that a single DW introduced in a wire is displaced back and forth by positive and negative pulsed current, respectively. The direct observation gives quantitative information on the DW displacement as a function of the intensity and the duration of the pulsed current. The result is discussed in terms of the spin-transfer mechanism.

Discrete change of spin-density-wave modulation in Cr(100)/Sn multilayers as a function of Cr layer thickness.

Magnetic structures of epitaxial Cr(001)/Sn multilayers, where monatomic Sn layers are periodically embedded in a Cr(001) film, were studied using neutron diffraction and Mössbauer spectroscopy. It was found that spin-density-wave (SDW) antiferromagnetic structures with the modulation along the perpendicular direction to the film plane are stabilized at low temperatures. The wavelength of the SDW discretely changes as a function of the superlattice period. The enhanced magnetic moments of Cr at the Cr/Sn interfaces are thought to pin the antimode of the SDW modulation at the interface, resulting in the SDW with the modulation harmonic to the superlattice period.

Isolation of Pasteurella multocida during an outbreak of infectious septicemia in Japanese quail (Coturnix coturnix japonica).

In May 1994, about fifty Japanese quails out of ninety being bred for experimental purposes at Miyazaki University died of acute septicemia within a few days. At autopsy, there were no gross pathological lesions, however, severe bacteremia was observed in all cases. Bacterial examination revealed the presence of Pasteurella multocida in blood and several organs in pure culture and they were of Carter's capsular type A, Heddleston's type 3-4 and Namioka's type O-8-9. The LD50 of bacteria in quails and mice were 4.3 x 10(4) cfu and 3.9 x 10(2) cfu, respectively. All of the three chickens experimentally infected with 4 x 10(4) of the isolate died within 20 hr after the infection and several bacteria were recovered from their blood and organs. This, to our knowledge, is the first report on an outbreak of fowl cholera in Japanese quails in Japan.

Lymphoproliferative responses in pigs infected with Mycobacterium avium.

Naturally infected cases of swine mycobacteriosis were divided into two groups, localized infection (LI) and disseminated infection (DI). Lymphoproliferative response (LPR) was then examined to estimate their immunological states. Both control and LI groups showed strong response to Concanavalin A (Con A) and phytohemagglutinin (PHA) in the LPR, and lymphocytes recovered from the LI responded well to purified protein derived from M. avium (PPD). On the other hand, the DI group showed weak response to both Con A and PHA, despite their strong response to PPD stimulation. These data suggest that the low LPR to Con A and PHA observed in the DI groups was probably not due to the general unresponsiveness of T-cells.

Differentiation of Fusobacterium necrophorum subspecies from bovine pathological lesions by RAPD-PCR.

Nineteen strains from bovine abscesses identified as Fusobacterium necrophorum by the VPI method were examined by other methods. The API 20A test kit characterized all 19 strains as F. necrophorum. Seven of the strains had haemagglutinating activity and were classified as F. necrophorum subspecies necrophorum, and the remaining, 12 nonhaemagglutinating strains, were classified as F. necrophorum subspecies funduliforme. We used RAPD-PCR with a 10-mer oligonucleotide primer, W1L-2, to confirm this differentiation of the two subspecies. These results suggest that random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) with a suitable primer can be used as a new tool for the differentiation of F. necrophorum subspecies isolated from bovine pathological lesions.

[Detection of Emericella nidulans from bedding materials in horse breeding environment and its significance as a causative agent of guttural pouch mycosis in horses].

Sixty-six new and used samples of horse bedding materials: 60 rice straws, 2 wheat straws, 2 timothy hays and 2 wood chips, were collected from horse breeding stables of 33 farms in Japan and examined for the presence of Emericella nidulans (E. nidulans; anam. Aspergillus nidulans). The incidence of E. nidulans in the bedding materials was 75.8% and there was no significant difference in detection of the fungus between the new and used materials (25 out of the 33 samples, respectively). The growth of E. nidulans isolated in sterilized rice straw culture was accelerated by the addition of water up to about Aw 0.94, which as determined to be the most favorable moisture content. The addition of 0.3% urea solution onto the sterilized rice straw culture also appeared to very effectively enhance its conidial and ascocarp formation. A significant influence of urea on conidial and ascocarp formation of E. nidulans isolates was confirmed by their cultures on a synthetic medium which had urea as the sole nitrogen. These results suggest that severe contamination of E. nidulans on new bedding materials can be hazardous and its proliferation can readily occur at the stable due to the enhancing effect of urine. This analysis is meaningful to elucidate a reservoir of E. nidulans as the causative agent of guttural pouch mycosis in horses.

Reduction of magnetic moments in very thin Cr layers of Fe/Cr multilayers: evidence from 119Sn Mössbauer spectroscopy.

Fe/Cr multilayers with monatomic Sn layers embedded in the Cr layers were grown epitaxially on MgO(001) substrates, and the magnetic hyperfine field at the 119Sn nuclear sites was examined using Mössbauer spectroscopy. It was found that nonzero hyperfine field is induced at the Sn sites at room temperature and that the value reduces drastically from 10 to 2 T when the Cr layer thickness decreases from 80 to 10 A. The result indicates that the Cr layers are magnetically ordered even when the thickness is very small and that the magnetic moments of Cr become smaller as the Cr layer thickness decreases.

Magnetic vortex core observation in circular dots of permalloy

Spin structures of nanoscale magnetic dots are the subject of increasing scientific effort, as the confinement of spins imposed by the geometrical restrictions makes these structures comparable to some internal characteristic length scales of the magnet. For a vortex (a ferromagnetic dot with a curling magnetic structure), a spot of perpendicular magnetization has been theoretically predicted to exist at the center of the vortex. Experimental evidence for this magnetization spot is provided by magnetic force microscopy imaging of circular dots of permalloy (Ni(80)Fe(20)) 0.3 to 1 micrometer in diameter and 50 nanometers thick.

Endotoxin-triggered haematological interactions in Fusobacterium necrophorum infections.

The haematological mechanisms in the course of liver abscess formation were evaluated. They were examined by employing viable cells of Fusobacterium necrophorum subsp. necrophorum and Fusobacterium necrophorum subsp. funduliforme in comparison with their endotoxins. Whole cell infection with F.n. necrophorum led to neutrophilia and to a concomitant monocytosis in parallel with those responses induced by the in vivo injection of its endotoxin. Viable infection with F.n. funduliforme was characterized by a sustained endotoxin-related monocytosis against neutropenia. The stimulatory impact of endotoxin on monocytes when released from a viable F.n. funduliforme infection suggested an inherently peculiar mechanism which differed from the induction of both neutrophilia and monocytosis when F.n. funduliforme endotoxin was administered alone. The neutrophilic inducing capacity of the F.n. necrophorum endotoxin was equally illustrated by its positive chemotactic effect on polymorphonuclear neutrophils in vitro. The data presented here emphasize the virulence of F.n. necrophorum viewed in reference to changes in leucocyte trafficking and as complemented by a relatively high endotoxin content.

Propagation of a magnetic domain wall in a submicrometer magnetic wire

The motion of a magnetic domain wall in a submicrometer magnetic wire was detected by use of the giant magnetoresistance effect. Magnetization reversal in a submicrometer magnetic wire takes place by the propagation of a magnetic domain wall, which can be treated as a "particle." The propagation velocity of the magnetic domain wall was determined as a function of the applied magnetic field.

Chemical composition of endotoxins produced by Fusobacterium necrophorum subsp. necrophorum and F. necrophorum subsp. funduliforme.

The endotoxins from two recently-classified subspecies of Fusobacterium, namely F. necrophorum subsp. necrophorum and F. necrophorum subsp. funduliforme, were compared. Chemical analysis of the isolated endotoxins revealed that they were clearly different. Distinct levels of polysaccharides were demonstrated. The endotoxins isolated were devoid of heptose and 3-deoxy-D-manno-octulosonate (KDO). The endotoxins of F. n. necrophorum and F. n. funduliforme contained lipid A in a ratio of 4:1 which may account for the variations in their virulence.

The erythrocyte receptor for Fusobacterium necrophorum hemolysin: phosphatidylcholine as a possible candidate.

An attempt was made to determine the receptor for the hemolysin of Fusobacterium necrophorum using horse erythrocyte or its membranes as target. The spectrum of erythrocyte sensitivity has indicated that horse, dog and mouse erythrocytes are highly sensitive whereas cattle, sheep, goat and chicken red blood cells are insensitive to this hemolysin. A high correlation between sensitivity and phosphatidylcholine content of the erythrocyte membranes was noted. Binding of hemolysin to horse erythrocyte membranes was reduced significantly by prior treatment of membranes with phospholipase A2 but not with phospholipase C. Pretreatment of erythrocyte membranes with pronase, proteinase K, trypsin or neuraminidase did not alter binding of hemolysin to the membranes, suggesting that protein or sialyl residues are not involved as receptors. Gas liquid chromatography analysis showed that the fatty acid profile from hydrolysis of bovine liver phosphatidylcholine by hemolysin and phospholipase A2 were similar. In conclusion, this report presents evidence that phosphatidylcholine may be acting as a possible receptor for the hemolysin of F. necrophorum.

Interactions between Fusobacterium necrophorum hemolysin, erythrocytes and erythrocyte membranes.

The interactions between the hemolysin of Fusobacterium necrophorum subsp. necrophorum, erythrocytes and erythrocyte membranes were studied as an attempt to determine the initial characteristics leading to hemolysis. The spectrum of erythrocyte sensitivity indicated that horse, dog and mouse erythrocytes were highly sensitive whereas those of cattle, sheep, goat and chicken were insensitive to the hemolysin. Binding of hemolysin to horse and dog erythrocytes or their ghosts was more pronounced than to those of cattle and sheep as detected by a decrease of hemolytic activity from hemolysin preparations. The kinetics of hemolysis revealed that lysis is preceded by a prelytic phase characterized by binding of hemolysin to erythrocytes. Treatment of horse erythrocytes with hemolysin at various temperatures prior to incubation at 37 degrees C also revealed that this binding prelytic phase is temperature independent. This was followed by a temperature dependent lytic stage since erythrocytes pretreated with hemolysin and incubated at 4 degrees C showed no hemolysis. An inverse relation was found between erythrocyte concentration and hemolytic activity suggesting a multiple-hit mechanism of hemolysis.