Dual doping effects (site blockage and electronic promotion) imposed by adatoms on Pd nanocrystals for catalytic hydrogen production.

Three distinctive doping effects to modify the electronic and geometric properties of Pd nanocrystals for HCOOH decomposition to H2/CO2 are presented: Bi atoms take preferable residence on higher index sites, which leads to a reduction in HCOOH dehydration; Te atoms dwell favourably on terrace sites, which reduces the rate of dehydrogenation; Ag atoms, without site specificity, induce strong electronic effects to promote the activity on the dwindling number of surface Pd sites at high coverage.

Participation of c-FLIP in NLRP3 and AIM2 inflammasome activation.

Cellular FLICE-inhibitory protein (c-FLIP) is an inhibitor of caspase-8 and is required for macrophage survival. Recent studies have revealed a selective role of caspase-8 in noncanonical IL-1ß production that is independent of caspase-1 or inflammasome. Here we demonstrated that c-FLIP(L) is an unexpected contributor to canonical inflammasome activation for the generation of caspase-1 and active IL-1ß. Hemizygotic deletion of c-FLIP impaired ATP- and monosodium uric acid (MSU)-induced IL-1ß production in macrophages primed through Toll-like receptors (TLRs). Decreased IL-1ß expression was attributed to a reduced activation of caspase-1 in c-FLIP hemizygotic cells. In contrast, the production of TNF-α was not affected by downregulation in c-FLIP. c-FLIP(L) interacted with NLRP3 or procaspase-1. c-FLIP is required for the full NLRP3 inflammasome assembly and NLRP3 mitochondrial localization, and c-FLIP is associated with NLRP3 inflammasome. c-FLIP downregulation also reduced AIM2 inflammasome activation. In contrast, c-FLIP inhibited SMAC mimetic-, FasL-, or Dectin-1-induced IL-1ß generation that is caspase-8-mediated. Our results demonstrate a prominent role of c-FLIP(L) in the optimal activation of the NLRP3 and AIM2 inflammasomes, and suggest that c-FLIP could be a valid target for treatment of inflammatory diseases caused by over-activation of inflammasomes.

Protogenin prevents premature apoptosis of rostral cephalic neural crest cells by activating the α5ß1-integrin.

The bones and connective tissues of the murine jaws and skull are partly derived from cephalic neural crest cells (CNCCs). Here, we report that mice deficient of protogenin (Prtg) protein, an immunoglobulin domain-containing receptor expressed in the developing nervous system, have impairments of the palatine and skull. Data from lineage tracing experiments, expression patterns of neural crest cell (NCC) marker genes and detection of apoptotic cells indicate that the malformation of bones in Prtg-deficient mice is due to increased apoptosis of rostral CNCCs (R-CNCCs). Using a yeast two-hybrid screening, we found that Prtg interacts with Radil, a protein previously shown to affect the migration and survival of NCCs in zebrafish with unknown mechanism. Overexpression of Prtg induces translocation of Radil from cytoplasm to cell membrane in cultured AD293 cells. In addition, overexpression of Prtg and Radil activates α5ß1-integrins to high-affinity conformational forms, which is further enhanced by the addition of Prtg ligand ERdj3 into cultured cells. Blockage of Radil by RNA interference abolishes the effect of ERdj3 and Prtg on the α5ß1-integrin, suggesting that Radil acts downstream of Prtg. Prtg-deficient R-CNCCs display fewer activated α5ß1-integrins in embryos, and these cells show reduced migratory ability in in vitro transwell assay. These results suggest that the inside-out activation of the α5ß1-integrin mediated by ERdj3/Prtg/Radil signaling is crucial for proper functions of R-CNCCs, and the deficiency of this pathway causes premature apoptosis of a subset of R-CNCCs and malformation of craniofacial structures.

Electrically controllable spontaneous magnetism in nanoscale mixed phase multiferroics.

Magnetoelectrics and multiferroics present exciting opportunities for electric-field control of magnetism. However, there are few room-temperature ferromagnetic-ferroelectrics. Among the various types of multiferroics the bismuth ferrite system has received much attention primarily because both the ferroelectric and the antiferromagnetic orders are quite robust at room temperature. Here we demonstrate the emergence of an enhanced spontaneous magnetization in a strain-driven rhombohedral and super-tetragonal mixed phase of BiFeO3. Using X-ray magnetic circular dichroism-based photoemission electron microscopy coupled with macroscopic magnetic measurements, we find that the spontaneous magnetization of the rhombohedral phase is significantly enhanced above the canted antiferromagnetic moment in the bulk phase, as a consequence of a piezomagnetic coupling to the adjacent tetragonal-like phase and the epitaxial constraint. Reversible electric-field control and manipulation of this magnetic moment at room temperature is also shown.

Ezrin is a negative regulator of death receptor-induced apoptosis.

Ezrin links cortical actin filaments with the cell membrane, and has a critical role in many membrane-initiated events. Fas is directly associated with ezrin, but conflicting results have been reported for the involvement of ezrin in Fas-induced cell death. In this study we show that ezrin was associated with Fas in T cells before stimulation and was released shortly after Fas ligand (FasL) engagement. The knockdown of ezrin moderately increased Fas-triggered or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-triggered cell death in normal T lymphocytes and in H9 cells, but had no effect on death receptor-induced apoptosis in type II cells, such as Jurkat and CEM. Expression of a dominant-negative form of ezrin also led to an increased Fas-induced apoptosis in H9 cells. Ezrin deficiency did not affect the internalization of Fas after Fas ligation. Instead, an enhanced formation of death-inducing signaling complex (DISC) was observed in H9 cells with ezrin knockdown, leading to accelerated caspase-8 activation. Together, our results suggest that ezrin has a negative role in the recruitment of Fas into signaling complexes in type I T cells. Loss of ezrin likely removes the constraint imposed by ezrin and facilitates the assembly of death receptor complex in T cells.

Swept source optical coherence tomography for radiation-enhanced hepatocellular carcinoma cell invasion imaging.

In this study, we evaluated the effectiveness of using swept-source optical coherence tomography (SS-OCT) to monitor the enhancement of hepatocellular carcinoma (HCC) cell invasiveness by radiation. SS-OCT images were acquired and recorded to obtain three-dimensional datasets at discrete time points of 12, 24 and 48 h after irradiating HepG2 cells with 7.5 Gy. The cell migration distance in three-dimensional tissue models was quantified from images of radiation-induced and sham-irradiated cells, and this method was compared with the conventional Boyden chamber assay conducted at the same time points. SS-OCT measurements show that most cells were found near the gel surface, but a few were much deeper. Among those HCC cells with a high degree of migration capability, the mean migration distances at 24 h and 48 h were significantly greater for irradiated cells than for sham-irradiated cells (0.7 +/- 0.23 mm versus 0.65 +/- 0.26 mm at 24 h, P = 0.019 and 0.84 +/- 0.30 mm versus 0.65 +/- 0.524 mm at 48 h, P = 0.009). The results of radiation-enhanced invasion in HCC cells obtained by the non-invasive, quantitative SS-OCT method were consistent with those obtained using the traditional assay for measuring biological invasion.

Fabrication and characterization of high-T(c) YBa(2)Cu(3)O(7-x) nanoSQUIDs made by focused ion beam milling.

We have fabricated high-T(c) nanoscale superconducting quantum interference devices (nanoSQUIDs) with a hole size of 250 nm × 250 nm based on a 100 nm bridge at 77 K by focused ion beam milling and ion implantation. At 78 K, the curve of the voltage branch became roughly linear and agreed with the Josephson-like behavior. The sample exhibited strong flux flow behavior at temperatures under 76 K. The voltage flux characteristic curves, V -I(mod), of the nanoSQUID at different bias currents at 78 K were observed. Typically, critical currents of 15 µA and peak-to-peak values of the voltage flux transfer function of 3.7 µV were measured. The measured data strongly suggest that the weak link structure could be a superconducting metal with a critical temperature T(c)' smaller than that (T(c)) of other YBa(2)Cu(3)O(7-x) (YBCO) films. This fabrication method of combining a nanobridge and ion implantation can improve the yield of nanojunctions and nanoSQUIDs.

Imaging of human aortic atherosclerotic plaques by polarization-sensitive optical coherence tomography.

Optical coherence tomography (OCT) is analogous to ultrasound imaging except that it uses infrared light instead of sound. Polarization-sensitive optical coherence tomography (PS-OCT) combines the advantages of OCT and provides additional image contrast of the tested sample. We demonstrate this technique for imaging of back-reflected light, birefringence, and fast-axis orientation simultaneously in different kinds of atherosclerosis plaque. This in vitro study suggests birefringence changes in plaque are due to the prominent deposition of collagen or cholesterol by correlating PS-OCT images with histology. Thus the combination of high resolution structural imaging and birefringence detection make PS-OCT a potentially powerful tool for early assessment of atherosclerosis appearance and prediction of plaque rupture.

Effects of butorphanol and carprofen on the minimal alveolar concentration of isoflurane in dogs.

OBJECTIVE: To evaluate the effects of butorphanol and carprofen, alone and in combination, on the minimal alveolar concentration (MAC) of isoflurane in dogs. DESIGN: Randomized complete-block crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURE: Minimal alveolar concentration of isoflurane was determined following administration of carprofen alone, butorphanol alone, carprofen and butorphanol, and neither drug (control). Anesthesia was induced with isoflurane in oxygen, and MAC was determined by use of a tail clamp method. Three hours prior to induction of anesthesia, dogs were fed a small amount of canned food without any drugs (control) or with carprofen (2.2 mg/kg of body weight [1 mg/lb]). Following initial determination of MAC, butorphanol (0.4 mg/kg [0.18 mg/lb], i.v.) was administered, and MAC was determined again. Heart rate, respiratory rate, indirect arterial blood pressure, endtidal partial pressure of CO2, and saturation of hemoglobin with oxygen were recorded at the time MAC was determined. RESULTS: Mean +/- SD MAC of isoflurane following administration of butorphanol alone (1.03 +/- 0.22%) or carprofen and butorphanol (0.90 +/- 0.21%) were significantly less than the control MAC (1.28 +/- 0.14%), but MAC after administration of carprofen alone (1.20 +/- 0.13%) was not significantly different from the control value. The effects of carprofen and butorphanol on the MAC of isoflurane were additive. There were not any significant differences among treatments in regard to cardiorespiratory data. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of butorphanol alone or in combination with carprofen significantly reduces the MAC of isoflurane in dogs; however, the effects of butorphanol and carprofen are additive, not synergistic.

Comparison of anesthetic and cardiorespiratory effects of diazepam-butorphanol-ketamine, acepromazine-butorphanol-ketamine, and xylazine-butorphanol-ketamine in ferrets.

Ten ferrets were used in a crossover study to determine the sedative effects of intramuscularly administered diazepam (3 mg/kg body weight)-butorphanol (0.2 mg/kg body weight)-ketamine (15 mg/kg body weight); acepromazine (0.1 mg/kg body weight)-butorphanol (0.2 mg/kg body weight)-ketamine (15 mg/kg body weight); and xylazine (2 mg/kg body weight)-butorphanol (0.2 mg/kg body weight)-ketamine (15 mg/kg body weight). All of the ferrets became laterally recumbent following the administration of each drug combination. The xylazine-butorphanol-ketamine combination induced significantly longer (p less than 0.05) durations of tail-clamp analgesia (mean+/-standard deviation [SD], 81.0+/-19.1 min versus 20.5+/-25.4 min and 30.0+/-26.9 min), dorsal recumbency (mean+/-SD, 94.6+/-13.6 min versus 75. 6+/-34.7 min and 55.2+24.8 min), and muscle relaxation suitable for endotracheal intubation (mean+/-SD, 67.1+/-23.0 min versus 7.0+/-22.1 min and 9.5+/-15.4 min) than the diazepam-butorphanol-ketamine and acepromazine-butorphanol-ketamine combinations, respectively. The recovery time from dorsal recumbency to standing was not significantly different among the three treatment groups. The heart rate was significantly lower in the xylazine-butorphanol-ketamine group; however, systolic blood pressure was not significantly different among the treatment groups. Ventilatory function was more depressed in the diazepam-butorphanol-ketamine and xylazine-butorphanol-ketamine groups than in the acepromazine-butorphanol-ketamine group. A period (approximately 45 minutes) of hypoxia was observed in the xylazine-butorphanol-ketamine-treated ferret. Of the three combinations evaluated in ferrets, xylazine-butorphanol-ketamine was concluded to be the most effective anesthetic combination. However, hypoxemia and ventricular arrhythmias were observed in the xylazine-butorphanol-ketamine-treated ferrets, so the effectiveness of the xylazine-butorphanol-ketamine combination should be weighed against its cardiorespiratory side effects.

Evaluation of sedative and cardiorespiratory effects of diazepam-butorphanol, acepromazine-butorphanol, and xylazine-butorphanol in ferrets.

Ten ferrets were used in a crossover study to determine the sedative effects of intramuscularly (IM) administered diazepam (3 mg/kg body weight)-butorphanol (0.2 mg/kg body weight), acepromazine (0.1 mg/kg body weight)-butorphanol (0.2 mg/kg body weight), or xylazine (2.0 mg/kg body weight)-butorphanol (0.2 mg/kg body weight). All ferrets became laterally recumbent following the administration of each drug combination. The xylazine-butorphanol combination caused a significantly longer (p less than 0.05) duration of analgesia than the diazepam-butorphanol and acepromazine-butorphanol combinations. None of the ferrets could be intubated with any of the drug combinations. The time from induction to recovery was significantly shorter in the acepromazine-butorphanol-treated ferrets. A significantly lower heart rate was observed in the xylazine-butorphanol-treated ferrets; however, an acceptable systolic blood pressure was maintained. Ventilatory function was more depressed in the diazepam-butorphanol- and xylazine-butorphanol-treated ferrets than in the acepromazine-butorphanol-treated ferrets. Xylazine-butorphanol was found to be the best combination for use in ferrets.

Comparison of sedative and cardiorespiratory effects of diazepam, acepromazine, and xylazine in ferrets.

The sedative and cardiorespiratory effects of an intramuscular injection of diazepam (3 mg/kg body weight), acepromazine (0.1 mg/kg body weight), or xylazine (2 mg/kg body weight) in ferrets (n = 10, crossover design) was evaluated. Time from injection to assuming lateral recumbency was not significantly different between the three drugs. Duration of recumbency expressed as mean+/-standard deviation was significantly longer with xylazine (68.3+/-20.8 min) than with diazepam (43.2+/-8.2 min) or acepromazine (49.8+/-11.2 min). Sedation was graded to be the best in the xylazine-treated ferrets and worst in the diazepam-treated ferrets. Analgesia was judged only to be present following xylazine injection. Systolic blood pressure, oxyhemoglobin saturation, and end-expired carbon dioxide (CO2) were similar with all three drugs. It was concluded that, at the doses administered, xylazine provided better chemical restraint in the healthy ferret than either acepromazine or diazepam.

Comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-xylazine and tiletamine-zolazepam-xylazine-butorphanol in ferrets.

Nine ferrests were used in a crossover study to determine the anesthetic effects of intramuscular (i.m.) administration of a low dose of tiletamine-zolazepam (1.5 mg/kg body weight)-xylazine (1.5 mg/kg body weight); a high dose of tiletamine-zolazepam (3 mg/kg body weight)-xylazine (3 mg/kg body weight); and tiletamine-zolazepam (1.5 mg/kg body weight)-xylazine (1.5 mg/kg body weight)-butorphanol (0.2 mg/kg body weight). All ferrets became laterally recumbent within two minutes following the administration of each drug combination. The tiletamine-zolazepam-xylazine-butorphanol combination induced significantly longer (p less than 0.05) durations of tail clamp analgesia (mean +/- standard deviation [SD], 90.0 +/- 17.1 min versus 17.8 +/- 15.8 min and 41.9 +/- 26.3 min) and endotracheal intubation (mean +/- SD, 84.8 +/- 21.7 min versus 5.2 +/- 10.3 min and 26.3 +/- 29.8 min) than the low-dose tiletamine-zolazepam-xylazine and high-dose tiletamine-zolazepam-xylazine combinations, respectively. Heart rates and the times from dorsal recumbency to standing were not significantly different among the three treatment groups. However, systolic blood pressure was significantly lower in the tiletamine-zolazepam-xylazine-butorphanol group. Ventilatory function was more depressed in the tiletamine-zolazepam-xylazine-butorphanol group than in the low-dose tiletamine-zolazepam-xylazine and high-dose tiletamine-zolazepam-xylazine groups. A short period of hypoxia was observed in the tiletamine-zolazepam-xylazine-butorphanol-treated ferrets. Tiletamine-zolazepam-xylazine-butorphanol was found to be the best of the three combinations evaluated in these ferrets. The addition of butorphanol to the low-dose tiletamine-zolazepam-xylazine combination greatly enhanced the duration of analgesia, endotracheal intubation, and dorsal recumbency. However, since hypoxemia occurred during the tiletamine-zolazepam-xylazine-butorphanol anesthesia, oxygen (O2) insufflation is recommended. Doubling the dose of the low-dose tiletamine-zolazepam-xylazine increased the duration of analgesia and endotracheal intubation without prolonging the recovery when compared to the low-dose tiletamine-zolazepam-xylazine group.

Noninvasive glucose monitoring in vivo with an optical heterodyne polarimeter.

An amplitude-sensitive optical heterodyne polarimeter was set up to monitor noninvasively the aqueous glucose concentration in a rabbit's eye. A Zeeman laser in conjunction with a Glan-Thompson analyzer was used to generate an optical heterodyne signal. The amplitude of the heterodyne signal linearly related to the optical rotation angle of the aqueous glucose. The concentration of the aqueous glucose in a rabbit's eyeball was measured in vivo. There was a 30-min time delay between observations of aqueous glucose and blood glucose. The detection capability and the reproducibility of the experiment are demonstrated and discussed.

Modulation of microsomal cytochrome P450 by Scutellariae Radix and Gentianae scabrae Radix in rat liver.

The present study has determined the effects of Scutellariae Radix (Huangqin) and Gentianae scabrae Radix (Longdan) on liver microsomal cytochrome P450 (P450)-dependent mono-oxygenases using rats pretreated with crude extracts of medicinal herbs. Scutellariae Radix resulted in a 53% decrease of pentoxyresorufin O-dealkylase activity in liver microsomes. In contrast, Gentianae scabrae Radix caused a 50% increase of benzo(a)pyrene hydroxylase activity. Immunoblotting analysis of liver microsomes revealed that Scutellariae Radix induced and suppressed the levels of P450 1A and 2B proteins, respectively. Scutellariae and Gentianae scabrae Radixes had no effects on microsomal aniline hydroxylase activity and P450 2E1 protein.