Strongly correlated superconductivity in a copper-based metal-organic framework with a perfect kagome lattice.

Metal-organic frameworks (MOFs), which are self-assemblies of metal ions and organic ligands, provide a tunable platform to search a new state of matter. A two-dimensional (2D) perfect kagome lattice, whose geometrical frustration is a key to realizing quantum spin liquids, has been formed in the π - d conjugated 2D MOF [Cu3(C6S6)] n (Cu-BHT). The recent discovery of its superconductivity with a critical temperature T c of 0.25 kelvin raises fundamental questions about the nature of electron pairing. Here, we show that Cu-BHT is a strongly correlated unconventional superconductor with extremely low superfluid density. A nonexponential temperature dependence of superfluid density is observed, indicating the possible presence of superconducting gap nodes. The magnitude of superfluid density is much smaller than those in conventional superconductors and follows the Uemura's relation of strongly correlated superconductors. These results imply that the unconventional superconductivity in Cu-BHT originates from electron correlations related to spin fluctuations of kagome lattice.

Outcomes of immediate perforator flap reconstruction after skin-sparing mastectomy following neoadjuvant chemotherapy.

BACKGROUND: The impact of neoadjuvant chemotherapy (NACT) on immediate free flap breast reconstruction remains controversial. Furthermore, the oncological outcomes of immediate free flap breast reconstruction after skin-sparing mastectomy (SSM) following NACT remain unclear. This study aimed to investigate the surgical complications and oncological outcomes of immediate perforator flap reconstruction after SSM following NACT. METHODS: A total of 201 consecutive patients with indications for immediate perforator flap reconstruction after SSM were included between 2004 and 2012. Surgical and oncological outcomes were compared between patients with and without NACT. RESULTS: There were 38 patients in the NACT group and 163 in the non-NACT control group. The median age of the NACT group was 39.5 years, which was significantly younger than the control group (43.0 years; P < 0.05). Patients in the NACT group also had more advanced and aggressive disease (P < 0.05). There was no significant difference in the frequency of surgical complications between the groups, no difference in the type of complications, and no significant difference in the frequencies of major and minor complications. No patients in the NACT group had delayed adjuvant therapy. Eight patients (4%) developed recurrences, with a median follow-up time of 3.0 years. Local recurrences occurred in three control patients but no patients in the NACT group. CONCLUSION: NACT does not affect short-term or interim outcomes after immediate perforator flap reconstruction and may thus represent a safe and practical treatment option for the multidisciplinary treatment of breast cancer.

Multi-scale characterization by FIB-SEM/TEM/3DAP.

In order to improve properties of functional materials, it is important to understand the relation between the structure and the properties since the structure has large effect to the properties. This can be done by using multi-scale microstructure analysis from macro-scale to nano and atomic scale. Scanning electron microscope (SEM) equipped with focused ion beam (FIB), transmission electron microscope (TEM) and 3D atom probe (3DAP) are complementary analysis tools making it possible to know the structure and the chemistry from micron to atomic resolution. SEM gives us overall microstructural and chemical information by various kinds of detectors such as secondary electron, backscattered electron, EDS and EBSD detectors. Also, it is possible to analyze 3D structure and chemistry via FIB serial sectioning. In addition, using TEM we can focus on desired region to get more complementary information from HRTEM/STEM/Lorentz images, SAED/NBD patterns and EDS/EELS to see the detail micro or nano-structure and chemistry. Especially, combination of probe Cs corrector and split EDS detectors with large detector size enable us to analyze the atomic scale elemental distribution. Furthermore, if the specimen has a complicated 3D nanostructure, or we need to analyze light elements such as hydrogen, lithium or boron, 3DAP can be used as the only technique which can visualize and analyze distribution of all constituent atoms of our materials within a few hundreds nm area. Hence, site-specific sample preparation using FIB/SEM is necessary to get desired information from region of interest. Therefore, this complementary analysis combination works very well to understand the detail of materials.In this presentation, we will show the analysis results obtained from some of functional materials by Carl Zeiss CrossBeam 1540EsB FIB/SEM, FEI Tecnai G(2) F30, Titan G2 80-200 TEMs and locally build laser assisted 3DAP. As the one of the example, result of multi-scale characterization for ultra-fine grain Nd-Fe-B permanent magnet will be shown [1]. In order to improve the magnetic properties, especially to increase the coercivity (resistance against magnetization reversal) of the magnet, decreasing the grain size and isolating each grain by non-ferromagnetic grain boundary phase are quite important since the nucleation of magnetic reversal from grain boundary phase can be suppressed and pinning force of magnetic domain wall at the grain boundary phase can be strengthened. Therefore, micro and nano structure and chemistry analysis can shed a light do grain boundary engineering.Figure 1(a,b) shows SEM BSE images of ultrafine grain Nd-Fe-B sintered magnet and the reconstructed 3D tomography of Nd-rich phases obtained by FIB/SEM serial sectioning. This data can provide us information about the distribution of Nd-rich phase and its volume fraction. Moreover, the HRTEM image from the grain boundary phase, the 3DAP maps and the concentration depth profiles are shown in Fig. 1(c,d,e). This magnet shows high coercivity (1517kA/m), and by comparing these results with the microstructures of low coercivity specimen, importance of grain boundary formation was confirmed and it gives us hint to improve the coercivity further. We will show the detail and results from other materials.jmicro;63/suppl_1/i6/DFU046F1F1DFU046F1Fig. 1.(a) SEM BSE images of ultrafine grain Nd-Fe-B sintered magnet. (b) 3D FIB/SEM tomography of Nd-rich phases. (c) HRTEM image from the grain boundary phase. (d) 3DAP maps of Nd, Cu and Al. (e) Concentration depth profiles for Fe, Nd+Pr, B, Co, Cu and Al, determined from the selected box in (d)[1].

Hypothalamic ATF3 is involved in regulating glucose and energy metabolism in mice.

AIMS/HYPOTHESIS: The pancreas and hypothalamus are critical for maintaining nutrient and energy homeostasis, and combined disorders in these organs account for the onset of the metabolic syndrome. Activating transcription factor 3 (ATF3) is an adaptive response transcription factor. The physiological role of ATF3 in the pancreas has been controversial, and its role in the hypothalamus remains unknown. To elucidate the roles of ATF3 in these organs, we generated pancreas- and hypothalamus-specific Atf3 knockout (PHT-Atf3-KO) mice in this study. METHODS: We crossed mice bearing floxed Atf3 alleles with Pdx1-cre mice, in which cre is specifically expressed in the pancreas and hypothalamus, and analysed metabolic variables, pancreatic morphology, food intake, energy expenditure and sympathetic activity in adipose tissue. We also used a hypothalamic cell line to investigate the molecular mechanism by which ATF3 regulates transcription of the gene encoding agouti-related protein (Agrp). RESULTS: Although PHT-Atf3-KO mice displayed better glucose tolerance, neither plasma glucagon nor insulin level was altered in these mice. However, these mice exhibited higher insulin sensitivity, which was accompanied by a leaner phenotype due to decreased food intake and increased energy expenditure. We also observed decreased hypothalamic Agrp expression in PHT-Atf3-KO mice. Importantly, an increase in ATF3 levels is induced by fasting or low glucose in the hypothalamus. We also showed that ATF3 interacts with forkhead box-containing protein, O subfamily 1 (FoxO1) on the Agrp promoter and activates Agrp transcription. CONCLUSIONS/INTERPRETATION: Our results suggest that ATF3 plays an important role in the control of glucose and energy metabolism by regulating Agrp.

Surgical treatment for peritoneal carcinomatosis from gastric cancer.

This review describes the latest surgical treatments for peritoneal carcinomatosis (PC) arising from gastric cancer. Systemic chemotherapy is less effective against PC because of the existence of the blood-peritoneal barrier. Accordingly, perioperative intraperitoneal chemotherapy plus cytoreductive surgery (CRS) is a new trend of multidisciplinary therapy for PC. Intraperitoneally administered drugs penetrate directly into the peritoneal dissemination, resulting in the high loco-regional intensity of drugs. A new bidirectional chemotherapy called neoadjuvant intraperitoneal/systemic chemotherapy (NIPS) has been developed. After NIPS, the disappearance of PFCCs has been reported, and the incidence of complete cytoreduction has increased accordingly. Complete cytoreduction, a low peritoneal carcinomatosis index, and negative PFCCs are significant favorable prognostic factors. Hyperthermic intraperitoneal chemotherapy (HIPEC) after CRS is associated with improved survival with an acceptable postoperative mortality and morbidity. Early postoperative intraperitoneal chemotherapy (EPIC) has also contributed to improving survival after CRS.

Acotiamide hydrochloride (Z-338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats.

Acotiamide hydrochloride (Z-338) is a member of new class prokinetic agents currently being developed for the treatment of functional dyspepsia (FD). DNA microarray analysis showed that acotiamide altered the expressions of stress-related genes such as gamma-aminobutyric acid (GABA) receptors, GABA transporters and neuromedin U (NmU) in the medulla oblongata or hypothalamus after administration of acotiamide. Therefore, effects of acotiamide on stress-related symptoms, delayed gastric emptying and feeding inhibition, in rats were examined. Acotiamide significantly improved both delayed gastric emptying and feeding inhibition in restraint stress-induced model, but did not affect both basal gastric emptying and feeding in intact rats, indicating that acotiamide exerted effects only on gastric emptying and feeding impaired by the stress. On the other hand, mosapride showed significant acceleration of gastric emptying in intact and restraint stress-induced model, and itopride showed no effect on restraint stress-induced delayed gastric emptying. In addition, gene expression of NmU increased by restraint stress was suppressed by administration of acotiamide, while acotiamide had no effect on delayed gastric emptying induced by an intracerebroventricular administration of NmU, suggesting that the suppressive effect of acotiamide on gene expression of NmU might be important to restore delayed gastric emptying or feeding inhibition induced by restraint stress. These findings suggest that acotiamide might play an important role in regulation of stress response. As stress is considered to be a major contributing factor in the development of FD, the observed effects may be relevant for symptom improvement in FD.

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.

Neoadjuvant treatment of gastric cancer with peritoneal dissemination.

AIMS: To report our experience of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) for patients having a complete resection of the primary gastric cancer and peritoneal carcinomatosis (PC). PATIENTS AND METHODS: Patients with advanced peritoneal dissemination of primary gastric cancer had the placement of a peritoneal port system. For intraperitoneal chemotherapy, 40 mg of docetaxel and 150 mg of carboplatin were introduced in 1000 ml of saline on a weekly basis. Simultaneously, 100 mg/m2 of methotrexate and 600 mg/m2 of 5-fluorouracil were infused via a peripheral vein. A minimum of two cycles and up to six cycles of NIPS were used prior to cancer resection. At surgery a complete removal of the primary gastric cancer and the peritoneal implants by peritonectomy was attempted. RESULTS: Sixty-one patients were enrolled in the study. Thirty-nine had positive intraperitoneal cytology which reverted to negative cytology after treatment in 22. Thirty-eight showed a partial response. Thirty patients came to resection and 14 patients could be made disease-free. Median survival time of all patients was 14.4 months. Patients who received a complete resection had a median survival time of 20.4 months. Grade III/IV toxicities were not found after two courses of NIPS, but did develop in seven patients after more than three courses of NIPS. CONCLUSION: NIPS can downstage large volume peritoneal dissemination of gastric cancer. When combined with gastrectomy including peritonectomy a complete surgical resection was possible in one-quarter of the patients and resulted in a prolonged survival. This combined intraperitoneal and systemic chemotherapy for PC from gastric cancer is worthy of consideration for phase III clinical investigations.

High concentration of deoxycholic acid abrogates in vitro transformation of IEC6 intestinal cells by azoxymethane.

In this study, we designed an in vitro azoxymethane (AOM)-induced carcinogenesis model and analyzed the effect of deoxycholic acid (DCA) on growth, apoptosis, genotoxicity, and transformation of IEC6 intestinal cells. CYP2E1 production was confirmed in IEC6 cells. The growth of IEC6 cells was enhanced by DCA (100 microg/ml). However, IEC6 cells treated with DCA (200 microg/ml) were inhibited and disappeared at 48 hrs after treatment. Apoptotic cells increased 11.2 times by treatment with DCA (200 microg/ml) as compared to cells with no treatment. DNA injury detected by comet assay was found in cells treated with AOM, but not in cells treated with DCA (100 microg/ml) and AOM. The number of colony formation in soft agar increased by AOM treatment. However, the number of foci treated with DCA (100 microg/ml) plus AOM was 69% that of cells treated with AOM alone. Two out of the 6 mice subcutaneously injected with AOM-treated IEC6 cells showed tumorigenesis, whereas IEC6 cells treated with DCA (100 microg/ml) plus AOM or DCA (100 microg/ml) alone did not form any tumor. Reduced protein expression of MLH1, Bcl-2 was detected in IEC6 cells treated with DCA (100 microg/ml). Production of Bax, pJNK, TGF-beta, TGFBRI, TGFBRII, and beta-catenin were higher in IEC6 cells treated with DCA (100 microg/ml) than that in cells with no treatment. These results suggest that high-dose DCA induced apoptosis and inhibited AOM-induced in vitro transformation of IEC6 cells.

Study on optimization for current distribution in magnetic stimulation therapy for urinary incontinence.

It has been reported that magnetic stimulation effectively eliminates urinary incontinence. However, this type of therapy has not been established as a practical treatment for urinary incontinence because of its poor power conversion efficiency and the leakage of current to regions other than that of the target of stimulation. It is therefore necessary to develop magnetic stimulators that are more efficient in stimulating the sphincter muscles and the peripheral nerves, and are more convenient than those presently available. By using a large-diameter coil, the magnetic stimulation method offers a larger current distribution over a wider area of the target region than electrical stimulation method, and the placement of the coil can be relatively easily changed to obtain better therapeutic results. We attempted, with a computer simulation model of the female abdomen, to simulate the distribution of the induced current density on the basis of biological tissue conductivity. We determined which method of stimulation is the most efficient by varying the stimulator coil location and size. A genetic algorithm (GA) was used for optimization.

Rapid functional analysis of protein-protein interactions by fluorescent C-terminal labeling and single-molecule imaging.

Detection of protein-protein interactions is a fundamental step to understanding gene function. Here we report a sensitive and rapid method for assaying protein-protein interactions at the single-molecule level. Protein molecules were synthesized in a cell-free translation system in the presence of Cy5-puro, a fluorescent puromycin, using mRNA without a stop codon. The interaction of proteins thus prepared was visualized using a single-molecule imaging technique. As a demonstration of this method, a motor protein, kinesin, was labeled with Cy5-puro at an efficiency of about 90%, and the processive movement of kinesin along microtubules was observed by using total internal reflection microscopy. It took only 2 h from the synthesis of proteins to the functional analysis. This method is applicable to the functional analysis of various kinds of proteins.

Photo-oxidation of biodegraded crude oil and toxicity of the photo-oxidized products.

We investigated the physicochemical changes resulting from irradiation by sunlight of biodegraded crude oil. An Arabian light crude oil sample was first subjected to microbial degradation. n-Alkanes and aromatic compounds such as naphthalenes, fluorenes, dibenzothiophenes and phenanthrenes possessing short, alkyl side chain(s) were almost completely degraded, while the contents of the saturated and aromatic fractions were reduced by 70% and 40%, respectively. This biodegraded oil was then suspended in seawater and exposed to sunlight irradiation for several weeks. The most remarkable change caused by the irradiation was a substantial decline in the aromatic fraction with a concomitant increase in the resin and asphaltene fractions. A 13C-nuclear magnetic resonance (NMR) spectroscopic analysis showed that the aromaticity of the biodegraded oil was significantly lower in the irradiated sample. A field desorption-mass spectrometric (FD-MS) analysis showed that sunlight irradiation reduced the average molecular weight of the oil components and formed oxygenated compounds. Consistent with this observation is that the oxygen content in the oil increased as the irradiation was prolonged. The bioavailability of the biodegraded oil was increased by the photo-oxidation: the growth of seawater microbes was minimal when the non-irradiated biodegraded oil was used as the source of carbon and energy; however, growth was significant when irradiated biodegraded oil was used. The concentration of dissolved organic carbon (DOC) increased linearly during the sunlight irradiation of the biodegraded oil, and this increase was matched by an increase in ultraviolet-absorptive materials in the seawater. The photochemically formed, water-soluble fraction (WSF) showed acute toxicity against the halophilic crustacean, Artemia.

Antidepressant effects of apocynum venetum leaves in a forced swimming test.

An extract of the leaves of Apocynum venetum L. (Apocynaceae) markedly shortened the immobility time of male rats in a forced swimming test (FST) in a dose range of 30-125 mg/kg, indicating a possible antidepressant activity. This effect was comparable to that of the tricyclic antidepressant imipramine (20 mg/kg). Neither imipramine (20 mg/kg) nor the Apocynum extract in various doses (30, 60, 125 mg/kg) produced any overt behavioural change or motor dysfunction in the open field test. This result confirms the assumption that the antidepressant effect of an Apocynum extract in the FST is specific. Further, it can be speculated that this effect might be related to hyperoside and isoquercitrin which are major flavonoids in the extract.

Alkaloids and flavonoids from peanut skins.

Separation of the water-soluble fraction of peanut skins led to the isolation of 8 flavonoids and two novel indole alkaloids. Two new flavonoid glycosides have been identified as isorhamnetin 3-O-[2-O-beta-glucopyranosyl-6-O-alpha-rhamnopyranosyl]- beta-glucopyranoside and 3',5,7-trihydroxyisoflavone-4'-methoxy-3'-O-beta-glucopyranoside. Two alkaloids are 2-methoxyl-3-(3-indolyl)-propionic acid and 2-hydroxyl-3-[3-(1-N-methyl)-indolyl]-propionic acid. These isolated flavonoids were evaluated for their free radical scavenging activity and protein glycation inhibitory effects.

Acute effects of ovariectomy on wound healing of alveolar bone after maxillary molar extraction in aged rats.

Acute effects of ovariectomy on the bone wound healing processes after maxillary molar extraction in aged rats were examined by means of quantitative scanning electron microscopy (SEM), backscattered electron image (BSE) analysis and energy-dispersive X-ray (EDX) microanalysis. Six-month-old female rats underwent either sham operation or bilateral ovariectomy, and 7 days postoperatively, the maxillary first molars were extracted. On post-extraction days 7, 30 and 60, the dissected maxillary bone surfaces were examined by SEM to reveal the bone formative and resorptive areas around the extracted alveolar sockets. In addition, the resin-embedded maxillae were micromilled in the transverse direction through the extracted alveolar sockets, and the newly-formed bone mass on the buccal bone surfaces and within the extracted sockets was examined by BSE analysis. Compared with sham-operated controls, the extent of newly-formed bone mass on the buccal bone surfaces in OVX rats was significantly decreased, due to increased bone resorption. On the other hand, new bone formation within the extracted sockets was similar in the experimental groups. In EDX microanalysis of these newly-formed bone matrices, both Ca and P weight % and Ca/P molar ratio were similar in the experimental groups. Our results suggest that 1) acute estrogen deficiency induced by ovariectomy stimulates sustained bone resorption, but has less effect on bone formation, and 2) bone wound healing after maxillary molar extraction within extracted alveolar sockets is not significantly delayed by ovariectomy, but bony support by newly-formed bone mass on the maxillary bone surfaces at the buccal side of the extracted sockets is significantly decreased, due to increased bone resorption.

Langerhans cell histiocytosis limited to the pituitary-hypothalamic axis--two case reports.

Langerhans cell histiocytosis rarely presents as a solitary lesion in the pituitary-hypothalamic region, and is indistinguishable from germinoma, which occurs much more frequently, especially in Japanese. A 14-year-old girl and a 9-year-old girl presented with polydipsia and polyuria as the initial symptoms. Magnetic resonance (MR) imaging demonstrated a round mass at the pituitary stalk appearing as isointense on T1-weighted imaging and hyperintense on T2-weighted imaging. Endocrinological examination revealed mild hypopituitarism with central diabetes insipidus. Both patients underwent open craniotomy. Histological examination revealed granulomatous tissue with eosinophil infiltration and frequent Langerhans histiocyte clustering, compatible with the diagnosis of Langerhans cell histiocytosis. Low-dose local irradiation of 20 Gy was administered. First patient was followed up for 8 years, and her hypopituitarism gradually improved to a minimal level with only amenorrhea as the residual symptom. Recent MR imaging showed no residual mass at the region. Second patient was followed up for 15 months, and her diabetes insipidus is stable. MR imaging performed 5 months after the treatment showed marked reduction of the mass. These cases reemphasize the importance of histological diagnosis for lesions with similar neuroimaging appearances. Biopsy and low-dose irradiation are an effective treatment for this rare and essentially benign lesion, as opposed to attempting total removal of the mass.

Oestrogen attenuates the increases in blood pressure and platelet aggregation in ovariectomized and salt-loaded Dahl salt-sensitive rats.

OBJECTIVE: To investigate the effects of oestrogen supplementation after ovariectomy on systolic blood pressure and platelet aggregation on different sodium content diet in the female Dahl salt-sensitive rats. METHODS: At 12 weeks of age, rats were ovariectomized or sham-operated and were fed either a high NaCl (8%) or low NaCl (0.3%) diet Ovariectomized rats were treated with either 17beta-oestradiol or placebo for 8 weeks, whereas sham-operated rats received placebo alone. After 8 weeks, the systolic blood pressure and platelet aggregation were measured and analysed by two-way analysis of variance. RESULTS: The systolic blood pressure of ovariectomized rats was significantly higher than that of sham-operated rats, and this increase in systolic blood pressure was suppressed by oestrogen supplementation. Systolic blood pressure was inversely correlated with plasma 17beta-oestradiol levels (r= -0.77, P< 0.01) and with the uterus weight to body weight ratio (r = -0.47, P < 0.01). Platelet aggregation was significantly enhanced by salt loading. Salt loading and female hormonal manipulation significantly interacted on platelet aggregation. Only in Dahl salt-sensitive rats fed a low sodium diet, ovariectomy increased platelet aggregation, whereas hormone replacement did not improve it. In Dahl salt-sensitive rats fed a high sodium diet, hormone replacement reduced platelet aggregation. CONCLUSIONS: Oestrogen replacement suppresses the development of hypertension and attenuates platelet aggregatory function in the salt-loaded ovariectomized Dahl salt-sensitive rats. It has a potential to inhibit the atherosclerotic process in postmenopausal hypertension.

Individual differences in mismatch negativity measures of involuntary attention shift.

OBJECTIVE: The purpose of this study was to compare the automatic detection of deviance in introverts and extraverts. Event-related potentials were recorded to standard and deviant stimuli. These were presented either rapidly or slowly. Stimuli that are presented slowly may intrude into consciousness. METHODS: Twenty subjects were tested and divided into introverted and extraverted groups. A 500 Hz standard stimulus was presented on 85% of trials. On the remaining 15% of trials, a 750 Hz deviant was presented. In separate conditions, stimuli were presented rapidly (every 500 ms) or slowly (every 1500 ms). Subjects ignored the stimuli while reading. RESULTS: The deviant stimulus elicited a mismatch negativity (MMN) in both conditions. No inter-group differences in the MMN emerged when a rapid rate of presentation was employed. When a slower rate was employed, a late negativity was significantly larger for the extraverted than the introverted group. This was followed by a late positive wave. CONCLUSION: The late negative-positive complex is thought to reflect intrusiveness. It would therefore appear that extraverts are more distractible than introverts when stimuli are presented slowly.

Isolation and characterization of two novel phosphodiesterase PDE11A variants showing unique structure and tissue-specific expression.

cDNAs encoding a novel phosphodiesterase, phosphodiesterase 11A (PDE11A), were isolated by a combination of reverse transcriptase-polymerase chain reaction using degenerate oligonucleotide primers and rapid amplification of cDNA ends. Their catalytic domain was identical to that of PDE11A1 (490 amino acids) reported during the course of this study. However, the cDNAs we isolated had N termini distinct from PDE11A1, indicating two novel N-terminal variants of PDE11A. PDE11A3 cDNA encoded a 684-amino acid protein including one complete and one incomplete GAF domain in the N-terminal region. PDE11A4 was composed of 934 amino acids including two complete GAF domains and shared 630 C-terminal amino acids with PDE11A3 but had a distinct N terminus containing the putative phosphorylation sites for cAMP- and cGMP-dependent protein kinases. PDE11A3 transcripts were specifically expressed in testis, whereas PDE11A4 transcripts were particularly abundant in prostate. Recombinant PDE11A4 expressed in COS-7 cells hydrolyzed cAMP and cGMP with K(m) values of 3.0 and 1.4 microm, respectively, and the V(max) value with cAMP was almost twice that with cGMP. Although PDE11A3 showed the same K(m) values as PDE11A4, the relative V(max) values of PDE11A3 were approximately one-sixth of those of PDE11A4. PDE11A4, but not PDE11A3, was phosphorylated by both cAMP- and cGMP-dependent protein kinases in vitro. Thus, the PDE11A gene undergoes tissue-specific alternative splicing that generates structurally and functionally distinct gene products.