Reconstruction of band structure induced by electronic nematicity in an FeSe superconductor.

We have performed high-resolution angle-resolved photoemission spectroscopy on an FeSe superconductor (T_{c}∼8 K), which exhibits a tetragonal-to-orthorhombic structural transition at T_{s}∼90 K. At low temperature, we found splitting of the energy bands as large as 50 meV at the M point in the Brillouin zone, likely caused by the formation of electronically driven nematic states. This band splitting persists up to T∼110 K, slightly above T_{s}, suggesting that the structural transition is triggered by the electronic nematicity. We have also revealed that at low temperature the band splitting gives rise to a van Hove singularity within 5 meV of the Fermi energy. The present result strongly suggests that this unusual electronic state is responsible for the unconventional superconductivity in FeSe.

Unconventional anisotropic s-wave superconducting gaps of the LiFeAs iron-pnictide superconductor.

We have performed high-resolution angle-resolved photoemission spectroscopy on Fe-based superconductor LiFeAs (T(c)=18 K). We reveal multiple nodeless superconducting (SC) gaps with 2Δ/k(B)T(c) ratios varying from 2.8 to 6.4, depending on the Fermi surface (FS). We also succeeded in directly observing a gap anisotropy along the FS with magnitude up to ~30%. The anisotropy is fourfold symmetric with an antiphase between the hole and electron FSs, suggesting complex anisotropic interactions for the SC pairing. The observed momentum dependence of the SC gap offers an excellent opportunity to investigate the underlying pairing mechanism.

Fermi surface nesting induced strong pairing in iron-based superconductors.

The discovery of high-temperature superconductivity in iron pnictides raised the possibility of an unconventional superconducting mechanism in multiband materials. The observation of Fermi-surface (FS)-dependent nodeless superconducting gaps suggested that inter-FS interactions may play a crucial role in superconducting pairing. In the optimally hole-doped Ba(0.6)K(0.4)Fe(2)As(2), the pairing strength is enhanced simultaneously (2Delta/T(c) approximately 7) on the nearly nested FS pockets, i.e., the inner hole-like (alpha) FS and the 2 hybridized electron-like FSs, whereas the pairing remains weak (2Delta/T(c) approximately 3.6) in the poorly nested outer hole-like (beta) FS. Here, we report that in the electron-doped BaFe(1.85)Co(0.15)As(2), the FS nesting condition switches from the alpha to the beta FS due to the opposite size changes for hole- and electron-like FSs upon electron doping. The strong pairing strength (2Delta/T(c) approximately 6) is also found to switch to the nested beta FS, indicating an intimate connection between FS nesting and superconducting pairing, and strongly supporting the inter-FS pairing mechanism in the iron-based superconductors.

Mevastatin reduces cartilage degradation in rabbit experimental osteoarthritis through inhibition of synovial inflammation.

OBJECTIVE: To examine the therapeutic efficacy of an HMG-CoA reductase inhibitor (statin) in rabbit osteoarthritis (OA) in vitro and in vivo. METHODS: In the presence or absence of mevastatin, rabbit chondrocytes and synoviocytes were incubated with Interleukin-1beta (IL-1beta), and analyzed by biochemical methods. Thirty-two mature rabbits that underwent bilateral anterior cruciate ligament transaction (ACLT) received six consecutive weekly intra-articular injections of mevastatin at three different concentrations or a control solution. All animals were sacrificed 6 weeks after ACLT, and the knee joints were assessed by morphological, histological, immunohistochemical, and biochemical methods. RESULTS: Mevastatin inhibited IL-1beta stimulation of gene expression of monocyte chemoattractant protein-1 (MCP-1) and matrix-metalloproteinases 3 (MMP-3), in synoviocytes but not chondrocytes. The levels of MCP-1 and MMP-3 productions in synoviocytes were significantly reduced by statin-treatment. In rabbit with OA, intra-articular injection of mevastatin significantly reduced cartilage degradation, as assessed by morphological and histological examinations. Synovial tissues of knees treated with mevastatin showed less severe inflammatory responses with reduced thickness of synovial cell lining and less infiltration of subsynovial CD68+monocyte lineage cells compared to untreated control knees. Relative mRNA expressions of MCP-1, IL-1beta, MMP-3, and MMP-13 were reduced in synovial tissues, but not articular cartilage, of knees treated with mevastatin compared with untreated control knees. CONCLUSION: During the development of experimental OA, intra-articular administration of HMG-CoA reductase inhibitor (statin) reduces inflammatory cell infiltration and matrix-degrading enzyme expression, thus limiting cartilage degradation.

Hochu-ekki-to inhibits rhinovirus infection in human tracheal epithelial cells.

BACKGROUND AND PURPOSE: A traditional Japanese herbal medicine, hochu-ekki-to, has been used for the symptomatic treatment of the common cold and to reduce the frequency of colds in patients with chronic obstructive pulmonary disease. However, the inhibitory effects of hochu-ekki-to on infection by rhinovirus (RV), the major cause of common colds, have not been studied. EXPERIMENTAL APPROACH: Human tracheal epithelial cells in culture were infected with a major group rhinovirus-RV14. Virus output and viral RNA were measured along with interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha), mRNA for intercellular adhesion molecule (ICAM)-1 and acidic endosomes in cells. KEY RESULTS: RV14 infection increased virus titers, the content of cytokines in supernatants and RV14 RNA in the cells. Hochu-ekki-to decreased virus output, RV14 RNA in the cells, susceptibility to RV infection and supernatant cytokine concentrations after RV14 infection. Hochu-ekki-to reduced mRNA for ICAM-1, the receptor for RV14, the concentration of the soluble form of ICAM-1 and the number and fluorescence intensity of acidic endosomes in the cells, from which RV RNA enters into the cytoplasm, at RV14 infection. Glycyrrhizin, one of the chemical constituents of hochu-ekki-to, reduced supernatant virus titers dose-dependently. CONCLUSION AND IMPLICATIONS: Hochu-ekki-to inhibited RV14 infection by decreasing ICAM-1 and by blocking entry of viral RNA into the cytoplasm from the endosomes, in airway epithelial cells. Glycyrrhizin may be partly responsible for inhibition of RV infection by hochu-ekki-to. Hochu-ekki-to could modulate airway inflammation by reducing production of cytokines in RV infections.

Inhibitory effect of green tea catechins on cysteine proteinases in Porphyromonas gingivalis.

The purpose of this study was to examine the effects of catechins and their derivatives on the activities of Arg-gingipain (Rgp) and Lys-gingipain (Kgp) in Porphyromonas gingivalis. Catechin derivatives, which included (-)-epigallocatechin gallate, (-)-epicatechin gallate, (-)-gallocatechin gallate, and (-)-catechin gallate, significantly inhibited the Rgp activity. The 50% inhibitory concentrations (IC50s) of these catechin derivatives for Rgp ranged from 3 to 5 microm. While (-)-epigallocatechin and (-)-gallocatechin moderately inhibited Rgp activity (IC50s, 20 microm), (-) -epicatechin, (+)-catechin, and gallic acid were not effective, with IC50s greater than 300 microm. Further, some of the catechin derivatives tested also inhibited the Kgp activity, though to a lesser extent than inhibition of the Rgp activity. These findings suggest that green tea catechins may have the potential to reduce periodontal breakdown resulting from the potent proteinase activity of P. gingivalis.

U box proteins as a new family of ubiquitin-protein ligases.

The U box is a domain of approximately 70 amino acids that is present in proteins from yeast to humans. The prototype U box protein, yeast Ufd2, was identified as a ubiquitin chain assembly factor that cooperates with a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin-protein ligase (E3) to catalyze ubiquitin chain formation on artificial substrates. E3 enzymes are thought to determine the substrate specificity of ubiquitination and have been classified into two families, the HECT and RING finger families. Six mammalian U box proteins have now been shown to mediate polyubiquitination in the presence of E1 and E2 and in the absence of E3. These U box proteins exhibited different specificities for E2 enzymes in this reaction. Deletion of the U box or mutation of conserved amino acids within it abolished ubiquitination activity. Some U box proteins catalyzed polyubiquitination by targeting lysine residues of ubiquitin other than lysine 48, which is utilized by HECT and RING finger E3 enzymes for polyubiquitination that serves as a signal for proteolysis by the 26 S proteasome. These data suggest that U box proteins constitute a third family of E3 enzymes and that E4 activity may reflect a specialized type of E3 activity.

Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains.

GGA (Golgi-localizing, gamma-adaptin ear homology domain, ARF-binding) proteins are potential effectors of ADP-ribosylation factors, are associated with the trans-Golgi network (TGN), and are involved in protein transport from this compartment. By yeast two-hybrid screening and subsequent two-hybrid and pull-down analyses, we have shown that GGA proteins, through their VHS (Vps27p/Hrs/STAM) domains, interact with acidic dileucine sequences found in the cytoplasmic domains of TGN-localized sorting receptors such as sortilin and mannose 6-phosphate receptor. A mutational analysis has revealed that a leucine pair and a cluster of acidic residues adjacent to the pair are mainly responsible for the interaction. A chimeric receptor with the sortilin cytoplasmic domain localizes to the TGN, whereas the chimeric receptor with a mutation at the leucine pair or the acidic cluster is mislocalized to punctate structures reminiscent of early endosomes. These results indicate that GGA proteins regulate the localization to or exit from the TGN of the sorting receptors.

Categorical perception of face identity in noise isolates configural processing.

Neuropsychological evidence suggests that face recognition based on configural (holistic) information can occur in isolation from recognition based on local feature cues. The present study shows that configural processing can be isolated experimentally in normal subjects. A phenomenon is reported that exists only for upright whole faces, namely categorical perception (CP) of face identity in noise. Three discrimination tasks (ABX, better likeness, and similarity ratings) were used to test for perceptual distortion across the category boundary predicted from binary classification of face morphs. Noise was added such that any single local region provided unreliable cues to identity. Under these conditions, CP was found for upright faces but not for inverted faces or single features, even with more than 10,000 trials. The CP-in-noise signature phenomenon was then used to show that configural processing survives image plane rotations of 45 degrees-90 degrees.

Acquisition of iron from human transferrin by Porphyromonas gingivalis: a role for Arg- and Lys-gingipain activities.

Porphyromonas gingivalis, a key causative agent of adult periodontitis, is known to produce a variety of virulence factors including proteases. The aim of this study was to evaluate the participation of Arg- and Lys-gingipain activities of P. gingivalis in the acquisition of iron from human transferrin and its subsequent utilization in growth. Iron-saturated transferrin was found to support the long-term growth of P. gingivalis. Our results indicated that P. gingivalis does not produce siderophore and does not possess ferric reductase and transferrin-binding activities. Incubating transferrin with P. gingivalis resulted in degradation of the protein, a step that may be critical for the acquisition of iron from transferrin. Spontaneous and site-directed mutants of P. gingivalis deficient in one or several proteases were used to demonstrate the key role of specific enzymes in degradation of transferrin and subsequent utilization for growth. The lack of both Arg- and Lys-gingipain activities (mutants M1 and KDP128) was associated with an absence of degradation of transferrin and the incapacity of bacteria to grow in the presence of transferrin as the sole source of iron. It was also found that the Lys-gingipain activity is more critical than the Arg-gingipain activity since the mutant KDP112 (deficient in Arg-gingipain A and B) could grow whereas the mutant KDP129 (deficient in Lys-gingipain) could not. The fact that growth of mutant KDP112 was associated with a lower final optical density and a generation time much longer compared with the parent strain suggests that the Arg-gingipain activity also participates in the acquisition of iron from transferrin. Selected inhibitors of cysteine proteases (TLCK, leupeptin and cathepsin B inhibitor II) were tested for their capacity to reduce or inhibit the growth of P. gingivalis under different iron conditions. All three inhibitors were found to completely inhibit growth of strain ATCC 33277 in a medium supplemented with transferrin as the source of iron. The inhibitors had no effects when the bacteria were grown in a medium containing hemin instead of transferrin. The ability of P. gingivalis to cleave transferrin may be an important mechanism for the acquisition of iron from this protein during periodontitis.

Protective effects of alpha-tocopherol and beta-carotene on para-nonylphenol-induced inhibition of cell growth, cellular respiration and glucose-induced proton extrusion of bacteria.

para-Nonylphenol (NP) showed a dose-dependent inhibition against the cell growth of Bacillus subtilis, Micrococcus luteus, Pseudomonas aeruginosa and Staphylococcus aureus at 5-100 microM. However, other typical plastic-derived endocrine disruptors such as bisphenol A and di-2-ethylhexyl phthalate (DEHP) did not significantly affect the cell growth of these bacteria at 5-100 microM. The NP-induced cell growth inhibition was restored when concomitantly supplemented with lipophilic antioxidants such as alpha-tocopherol and beta-carotene, but not with hydrophilic antioxidants, ascorbic acid and (-)-epigallocatechin gallate (EGCG). NP also suppressed in a dose-dependent manner cellular oxygen consumption and glucose-induced proton extrusion of these bacteria at 10-100 microM. Both effects were prevented when added with alpha-tocopherol and beta-carotene, but not with ascorbic acid and EGCG. The significance of these results is discussed from the viewpoint of environmental microbiology and a possible biochemical mechanism of the inhibitory effect of NP is suggested.

Mechanical stretch augments PDGF receptor beta expression and protein tyrosine phosphorylation in pulmonary artery tissue and smooth muscle cells.

With regard to the mechanotransduction mechanisms of vasculature involved in hypertensive diseases, we aimed to identify tyrosine-phosphorylated proteins in pulmonary artery that responded to mechanical stress. Mechanical stretch simultaneously augmented protein-tyrosine phosphorylation in p55, p95, p105, p115, p130, p165, p180 in pulmonary artery tissue and pulmonary artery-derived smooth muscle cells (PASMC), whereas p115 and p55 were preferentially phosphorylated by the stretch in endothelial cells (PAEC). A series of experiments designed to characterize these proteins indicated that p115 and p180 were focal adhesion kinase (FAK) and platelet-derived growth factor receptor beta (PDGF-Rbeta), respectively, and that stretch augmented the surface-expression of PDGF-Rbeta in PASMC but not in PAEC. Moreover, a significant increase in the steady-state mRNA level for PDGF-Rbeta was observed in the pulmonary artery of rats with monocrotaline-induced pulmonary hypertension, where the artery should be overstretched due to increasing pulmonary arterial blood pressure. These results suggest that stretch-induced overexpression of cell-surface PDGF-Rbeta as well as augmentation of yrosine phosphorylation of proteins including FAK in PASMC might be involved in the mechanotransduction of pulmonary artery.

Malignant rhabdoid tumor of the colon: report of a case.

A malignant rhabdoid tumor of the colon is very rare and only three cases have been previously described. A 76-year-old man was admitted to the hospital complaining of epigastralgia. An elastic mass was palpable in the right upper abdomen. A barium enema and endoscopic examination showed a giant gyrate tumor arising from the cecum. Abdominal ultrasonography and a computed tomography scan revealed the tumor to be located in the colon associated with multiple liver metastases and gallbladder stones. A right colectomy and cholecystectomy were thus performed. The tumor was histologically composed of sheets of large round and polygonal nuclei with vesicular chromatin, and abundant acidophilic cytoplasm, often containing hyalin-like inclusion. The cytoplasm was positive for vimentin and neuron-specific enolase, and hyaline globules of the rhabdoid tumor cells stained positive for cytokeratin in some cells. Transmission electron microscopy showed characteristic rhabdoid cells with an aggregation of intermediate filaments. A histologic diagnosis of malignant rhabdoid tumor of the colon was made. The tumor demonstrated several unusual findings for malignant rhabdoid tumors including diploidy by a flow cytometric analysis, and positive nuclear immunohistochemical staining for p53 protein and Ki-67 antigen. We report herein the third known case of a pure colonic rhabdoid tumor.

Influences of dietary omega-3 polyunsaturated fatty acids on the recovery of cardiac and renal functions after preservation in hyperlipidemic rats.

BACKGROUND: The effects of a soybean oil diet and a high-cholesterol oil (HC) diet, and an HC diet with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) supplementation, on basal and postpreservative cardiac function of the hearts and on postpreservative renal function of the kidneys from older rats were examined. METHODS: Groups 1 through 4 of 100-week-old rats were fed either soybean oil, HC, HC with EPA, or HC with DHA, respectively, for 12 weeks. Blood was collected for analysis of plasma fatty acids, and the heart and left kidney were removed from the rat. In experiment 1, the heart was perfused on a Langendorff apparatus. After evaluation of the cardiac function of each rat, the heart was stored in histidine-tryptophan-ketoglutarate solution for 8 hr at 4 degrees C. The heart was reperfused and the recovery of cardiac function was evaluated. The coronary perfusate during reperfusion was collected to measure 6-keto prostaglandin F1alpha and thromboxane B2. Coronary flow (CF) perfused with Krebs-Henseleit bicarbonate (KHB) solution containing 5-hydroxytryptamine (5-HT) and nitroglycerin were evaluated in the Langendorff mode with atrial pacing (330 beats/min). In experiment 2, the excised left kidney was immediately flushed and preserved with University of Wisconsin solution for 8 hr at 4 degrees C. The kidney was then reperfused with KHB solution and renal function was evaluated. RESULTS: The plasma and cardiac EPA levels in group 3 were significantly higher than the levels found in the other groups. The plasma and cardiac ratios of EPA to arachidonic acid were significantly higher in groups 3 and 4 than in groups 1 and 2. There were no significant differences in basal cardiac function among any of the diet-fed rats. The percentage values of the recovery of aortic flow, cardiac output (CO), and left ventricular max dp/dt in group 3 and CO in group 4 were significantly higher than in group 2. In addition, the recovery of CF in group 3 tended to be higher than in group 2 (P=0.07). The percentage values of the recovery of aortic flow, CF, CO, and left ventricular max dp/dt in group 1 were significantly lower than in the other dietary groups. CF reperfused with KHB solution containing 5-HT was significantly higher in group 3 than in groups 1 and 2. CF reperfused with KHB solution containing 5-HT was significantly higher in group 4 than in group 1. CF reperfused with KHB solution containing nitroglycerin in group 3 tended to be higher than in groups 1 and 2 (P=0.07). The thromboxame B2 concentrations in the coronary perfusate during reperfusion in groups 3 and 4 were significantly lower than in groups 1 and 2. Fractional sodium reabsorption in group 3 was significantly higher than in group 2. Inulin clearance in groups 3 and 4 was significantly higher than in group 1. The postpreservative urinary flow in group 3 was significantly higher than in groups 1 and 2. The urinary flow was significantly higher in group 4 than in group 1. CONCLUSIONS: These results suggest that EPA administration may attenuate preservation and reperfusion injury and improve the recovery of cardiac and renal functions in hyperlipidemic and older rats. DHA administration may also show beneficial effects on kidney preservation in hyperlipidemic rats.

Herbal medicine-associated lead intoxication.

A female patient visited our hospital with abdominal pain and anemia. Examination for a gastrointestinal disease gave no diagnostic information. Laboratory studies of the parameters of heme biosynthesis revealed an enzymatic inhibition by lead. The diagnosis of lead poisoning was confirmed by detection of an elevated blood lead level. Excessive lead ingestion was thought to be caused by herbal medicines and/or by an earthen teapot.

The effects of omega-3 polyunsaturated (correction of polyunsatulated) fatty acids on the recovery of cardiac function following cold preservation and reperfusion in hyperlipidemic rats.

We examined the effects of supplementation with eiosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), major components of omega-3 polyunsaturated (correction of polyunsatulated) fatty acids (PUFAs), on basal cardiac function and recovery of cardiac function of "donor hearts" from adults (30 week) rats following cold preservation and reperfusion (P/R). In groups 1, 2, 3, and 4, respectively, 30-week-old rats were fed a soybean oil diet, a high-cholesterol oil (HC) diet, an HC diet with EPA, or an HC diet with DHA for 5 weeks. After collecting blood to analyze plasma levels of fatty acids among each group, the heart was excised and perfused on a Langendorff apparatus. Following evaluation of each rat's cardiac function, each heart was stored in HTK solution for 8 hr at 4 degrees C. The heart was then reperfused and the coronary perfusate was collected to evaluate enzyme that had leaked. After cardiac functional recovery was estimated, myocardial fatty acids were measured. EPA supplementation significantly increases the plasma and cardiac levels of EPA as well as the ratio of EPA to arachidonic acid (AA). EPA supplementation also led to improved recovery of cardiac function following P/P, compared with that of rats who received soybean oil, high-cholesterol oil, and DHA. DHA supplementation significantly increased the plasma and cardiac levels of DHA as well as the ratio of DHA to AA--however, the cardiac functional recovery was almost identical to that of the rats who received high-cholesterol oil and was higher only than that of the rats who received soybean oil. There were no significant differences in enzyme that had leaked and myocardial water content among each group. These results suggest that alterations in the myocardial phospholipid composition by EPA supplementation may be profoundly responsible for attenuating myocardial I/R injuries. In contrast, DHA supplementation may not exert a cardioprotective effect following cold P/R. DHA supplementation alone may not increase the myocardial level of EPA enough to cause a protective effect against P/R injury. EPA supplementation to hyperlipidemic patients may be clinically warranted for increasing the potential number of donors.

Giant negative U waves in a patient with uncontrolled hypertension and severe hypokalemia.

A 66-year-old woman with a long history of hypertension had an electrocardiogram with giant negative U waves in left precordial leads despite hypokalemia. This seems to be the first report of giant negative U waves induced by uncontrolled hypertension with hypokalemia. The occurrence of negative U waves in the presence of profound hypokalemia is an important observation because it masks the electrocardiographic manifestation of hypokalemia.

Effects of a weak diffuse-brain-stimulation on insomniacs with vibration syndrome.

To verify the efficacy of a weak diffuse-brain-stimulation (DBS) method that was specially devised by this research team, a weak DBS was administered to seven male inpatients, who had vibration syndrome due to a prolonged use of a vibratory tool and who were simultaneously complaining of insomnia. Sleep data obtained from the polygraphic recordings on the DBS-treated night were compared with those on the pseudo DBS-treated. As the result, this DBS method proved to be effective in improving patients' sleep initiation and/or maintenance, and also their subjective ratings on the quality of actual sleep. In conclusion, the present DBS was determined to produce a decrease in the sympathetic tone which is needed at the onset of sleep.

Intracerebroventricular injection of neosurugatoxin induces a prolonged blockade of brain nicotinic acetylcholine receptors.

The intracerebroventricular injection of neosurugatoxin (2 x 3.2 micrograms) significantly reduced the specific binding of [3H]nicotine but not of [3H]cismethyldioxolane in the cerebral cortex, hippocampus and thalamus of rats 3 days after the toxin injection. Scatchard analysis of [3H]nicotine binding in the rat cerebral cortex revealed that neosurugatoxin can selectively decrease the maximal binding sites (Bmax) for [3H]nicotine by approximately 38%. A significant decrease in the Bmax value for [3H]nicotine was also observed in this brain region 7 days after the neosurugatoxin injection. Thus, the intracerebroventricular injection of neosurugatoxin can induce a prolonged blockade of brain nicotinic acetylcholine receptors.