Clozapine Promotes Glycolysis And Myelin Lipid Synthesis In Cultured Oligodendrocytes.

Clozapine displays stronger systemic metabolic side effects than haloperidol and it has been hypothesized that therapeutic antipsychotic and adverse metabolic effects of these drugs are related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production. Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT) and monocarboxylate (MCT) transporters was determined after 6 and 24 h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed. Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside. Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

Hearing Preservation And Cochlear Implants According To Inner Ear Approach: Multicentric Evaluation.

Electroacoustic stimulation is an excellent option for people with residual hearing in the low frequencies, who obtain insufficient benefit with hearing aids. To be effective, the subject's residual hearing should be preserved during cochlear implant surgery. To evaluate the hearing preservation in patients that underwent implant placement and to compare the results in accordance with the approach to the inner ear. 19 subjects underwent a soft surgical technique, and the electrode MED-EL FLEX™ EAS, designed to be atraumatic, was used. We evaluated pre- and postoperative tonal audiometric tests with an average of 18.4 months after implantation, to measure the rate of hearing preservation. 17 patients had total or partial preservation of residual hearing; 5 had total hearing preservation and two individuals had no preservation of hearing. The insertion of the electrode occurred through a cochleostomy in 3 patients, and in 2 of these there was no hearing preservation; the other 16 patients experienced electrode insertion through a round window approach. All patients benefited from the cochlear implant, even those who are only using electrical stimulation. The hearing preservation occurred in 89.4% of cases. There was no significant difference between the forms of inner ear approach.

Anticariogenic Properties of ent-Pimarane Diterpenes Obtained by Microbial Transformation

In the present work, the anticariogenic activities of three pimarane-type diterpenes obtained by fungal biotransformation were investigated. Among these metabolites, ent-8(14), 15-pimaradien-19-ol was the most active compound, displaying very promising MIC values (ranging from 1.5 to 4.0 mu g mL(-1)) against the main microorganisms responsible for dental caries: Streptococcus salivarius, S. sobrinus, S. mutans, S. mitis, S. sanguinis, and Lactobacillus casei. Time kill assays performed with ent-8(14), 15-pimaradien-19-ol against the primary causative agent S. mutans revealed that this compound only avoids growth of the inoculum in the first 12 h (bacteriostatic effect). However, its bactericidal effect is clearly noted thereafter (between 12 and 24 h). The curve profile obtained by combining ent-8(14), 15-pimaradien-19-ol and chlorhexidine revealed a significant reduction in the time necessary for killing S. mutans compared with each of these two chemicals alone. However, no synergistic effect was observed using the same combination in the checkerboard assays against this microorganism. In conclusion, our results point out that ent-8(14), 15-pimaradien-19-ol is an important metabolite in the search for new effective anticariogenic agents.

Distinguishing post-AGB impostors in a sample of pre-main sequence stars

Context. A sample of 27 sources, cataloged as pre-main sequence stars by the Pico dos Dias Survey (PDS), is analyzed to investigate a possible contamination by post-AGB stars. The far-infrared excess due to dust present in the circumstellar envelope is typical of both categories: young stars and objects that have already left the main sequence and are suffering severe mass loss. Aims. The two known post-AGB stars in our sample inspired us to seek for other very likely or possible post-AGB objects among PDS sources previously suggested to be Herbig Ae/Be stars, by revisiting the observational database of this sample. Methods. In a comparative study with well known post-AGBs, several characteristics were evaluated: (i) parameters related to the circumstellar emission; (ii) spatial distribution to verify the background contribution from dark clouds; (iii) spectral features; and (iv) optical and infrared colors. Results. These characteristics suggest that seven objects of the studied sample are very likely post-AGBs, five are possible post-AGBs, eight are unlikely post-AGBs, and the nature of seven objects remains unclear.

THE GEMINI NICI PLANET-FINDING CAMPAIGN: DISCOVERY OF A CLOSE SUBSTELLAR COMPANION TO THE YOUNG DEBRIS DISK STAR PZ Tel

We report the discovery of a tight substellar companion to the young solar analog PZ Tel, a member of the beta Pic moving group observed with high-contrast adaptive optics imaging as part of the Gemini Near-Infrared Coronagraphic Imager Planet-Finding Campaign. The companion was detected at a projected separation of 16.4 +/- 1.0 AU (0.'' 33 +/- 0.'' 01) in 2009 April. Second-epoch observations in 2010 May demonstrate that the companion is physically associated and shows significant orbital motion. Monte Carlo modeling constrains the orbit of PZ Tel B to eccentricities >0.6. The near-IR colors of PZ Tel B indicate a spectral type of M7 +/- 2 and thus this object will be a new benchmark companion for studies of ultracool, low-gravity photospheres. Adopting an age of 12(-4)(+8) Myr for the system, we estimate a mass of 36 +/- 6 M(Jup) based on the Lyon/DUSTY evolutionary models. PZ Tel B is one of the few young substellar companions directly imaged at orbital separations similar to those of giant planets in our own solar system. Additionally, the primary star PZ Tel A shows a 70 mu m emission excess, evidence for a significant quantity of circumstellar dust that has not been disrupted by the orbital motion of the companion.

ANALYSIS OF THE PICO DOS DIAS SURVEY HERBIG Ae/Be CANDIDATES

A large sample of Herbig Ae/Be (HAeBe) candidates, distributed in different Galactic regions south to declination +30 degrees, were identified by the Pico dos Dias Survey (a search for young stellar objects based on IRAS colors). Most of the candidates are nearby or associated with star-forming clouds, but several others are considered isolated objects. Aiming to verify the young nature of 93 HAeBe candidates, we searched for additional information that could be useful to confirm if they are pre-main-sequence (PMS) stars or evolved objects, which coincidentally show similar IRAS colors. By adopting a spectral index that is related to the amount of infrared excess and the shape of the spectral energy distribution, we have classified the sample according to three groups, which are analyzed on the basis of (1) circumstellar luminosity; (2) spatial distribution; (3) optical polarization; (4) near-infrared colors; (5) stellar parameters (mass, age, effective temperature); and (5) intensity of emission lines. Our analysis indicates that only 76% of the studied sample, mainly the group with intermediate to low levels of circumstellar emission, can be more confidently considered PMS stars. The nature of the remaining stars, which are in the other group that contains the highest levels of infrared excess, remains to be confirmed. They share the same characteristics of evolved objects, requiring complementary studies in order to correctly classify them. At least seven objects show characteristics typical of post-asymptotic giant branch or proto-planetary nebulae.

Star formation history of Canis Major R1 I. Wide-Field X-ray study of the young stellar population

Aims. The CMa R1 star-forming region contains several compact clusters as well as many young early-B stars. It is associated with a well-known bright rimmed nebula, the nature of which is unclear (fossil HII region or supernova remnant). To help elucidate the nature of the nebula, our goal was to reconstruct the star-formation history of the CMa R1 region, including the previously unknown older, fainter low-mass stellar population, using X-rays. Methods. We analyzed images obtained with the ROSAT satellite, covering similar to 5 sq. deg. Complementary VRI photometry was performed with the Gemini South telescope. Colour-magnitude and colour-colour diagrams were used in conjunction with pre-main sequence evolutionary tracks to derive the masses and ages of the X-ray sources. Results. The ROSAT images show two distinct clusters. One is associated with the known optical clusters near Z CMa, to which similar to 40 members are added. The other, which we name the ""GU CMa"" cluster, is new, and contains similar to 60 members. The ROSAT sources are young stars with masses down to M(star) similar to 0.5 M(circle dot), and ages up to 10 Myr. The mass functions of the two clusters are similar, but the GU CMa cluster is older than the cluster around Z CMa by at least a few Myr. Also, the GU CMa cluster is away from any molecular cloud, implying that star formation must have ceased; on the contrary (as already known), star formation is very active in the Z CMa region.

Communication structure of cortical networks

Large-scale cortical networks exhibit characteristic topological properties that shape communication between brain regions and global cortical dynamics. Analysis of complex networks allows the description of connectedness, distance, clustering, and centrality that reveal different aspects of how the network's nodes communicate. Here, we focus on a novel analysis of complex walks in a series of mammalian cortical networks that model potential dynamics of information flow between individual brain regions. We introduce two new measures called absorption and driftness. Absorption is the average length of random walks between any two nodes, and takes into account all paths that may diffuse activity throughout the network. Driftness is the ratio between absorption and the corresponding shortest path length. For a given node of the network, we also define four related measurements, namely in-and out-absorption as well as in-and out-driftness, as the averages of the corresponding measures from all nodes to that node, and from that node to all nodes, respectively. We find that the cat thalamo-cortical system incorporates features of two classic network topologies, Erdos-Renyi graphs with respect to in-absorption and in-driftness, and configuration models with respect to out-absorption and out-driftness. Moreover, taken together these four measures separate the network nodes based on broad functional roles (visual, auditory, somatomotor, and frontolimbic).

Ric-8A, a G alpha protein guanine nucleotide exchange factor potentiates taste receptor signaling

Taste receptors for sweet, bitter and umami tastants are G-protein-coupled receptors (GPCRs). While much effort has been devoted to understanding G-protein-receptor interactions and identifying the components of the signalling cascade downstream of these receptors, at the level of the G-protein the modulation of receptor signal transduction remains relatively unexplored. In this regard a taste-specific regulator of G-protein signaling (RGS), RGS21, has recently been identified. To study whether guanine nucleotide exchange factors (GEFs) are involved in the transduction of the signal downstream of the taste GPCRs we investigated the expression of Ric-8A and Ric-8B in mouse taste cells and their interaction with G-protein subunits found in taste buds. Mammalian Ric-8 proteins were initially identified as potent GEFs for a range of G alpha subunits and Ric-8B has recently been shown to amplify olfactory signal transduction. We find that both Ric-8A and Ric-8B are expressed in a large portion of taste bud cells and that most of these cells contain IP3R-3 a marker for sweet, umami and bitter taste receptor cells. Ric-8A interacts with G alpha-gustducin and G alpha i2 through which it amplifies the signal transduction of hTas2R16, a receptor for bitter compounds. Overall, these findings are consistent with a role for Ric-8 in mammalian taste signal transduction.

Influence of the Solvent Evaporation Rate on the Crystalline Phases of Solution-Cast Poly(Vinylidene Fluoride) Films

The influence of the solvent-evaporation rate on the formation of of. and P crystalline phases in solution-cast poly(vinylidene fluoride) (PVDF) films was systematically investigated. Films were crystallized from PVDF/N,N-dimethylformamide solutions with concentrations of 2.5, 5.0, 10, and 20 wt % at different temperatures. During crystallization, the solvent evaporation rate was monitored in situ by means of a semianalytic balance. With this system, it was possible to determine the evaporation rate for different concentrations and temperatures of the solution under specific ambient conditions (pressure, temperature, and humidity). Fourier-Transform InfraRed spectroscopy with Attenuated Total Reflectance revealed the P-phase content in the PVDF films and its dependence on previous evaporation rates. Based on the relation between the evaporation rate and the PVDF phase composition, a consistent explanation for the different amounts of P phase observed at the upper and lower sample surfaces is achieved. Furthermore, the role of the sample thickness has also been studied. The experimental results show that not only the temperature but also the evaporation rate have to be controlled to obtain the desired crystalline phases in solution-cast PVDF films. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 116: 785-791, 2010

Ultra-thin films of alternating semi-interpenetrating layers of a conducting polymer with thermosetting phenolic resins for sensor application

In this work a new method for crosslinking ultra-thin films with potential applications in sensor systems is proposed. The films were produced by layer-by-layer (LbL) assembly using a conducting polymer, poly(o-ethoxyaniline) (POEA), alternated with a thermosetting resin, novolac-type phenolformaldehyde (PF), crosslinked by a simple thermal treatment. The PF resin served as both alternating and crosslinking agents. The films were characterized by Fourier transform infrared (FTIR) and ultraviolet-visible (UV-Vis) spectroscopy, thermogravimetry (TG), desorption, doping/dedoping cycling and electrical measurements. The results showed that film architecture and crosslinking degree can be controlled by the conditions used for film deposition (number of bilayers, polymer concentration, pH, and deposition time), and crosslinking time. Moreover, this approach offers several advantages such as fast curing time and low cost, indicating that these films can be used to produce sensors with improved stability.

Extensions of discrete triangular distributions and boundary bias in kernel estimation for discrete functions

Asymmetric discrete triangular distributions are introduced in order to extend the symmetric ones serving for discrete associated kernels in the nonparametric estimation for discrete functions. The extension from one to two orders around the mode provides a large family of discrete distributions having a finite support. Establishing a bridge between Dirac and discrete uniform distributions, some different shapes are also obtained and their properties are investigated. In particular, the mean and variance are pointed out. Applications to discrete kernel estimators are given with a solution to a boundary bias problem. (C) 2010 Elsevier B.V. All rights reserved.

SAGE transcript profiling of the juvenile cambial region of Eucalyptus grandis

Despite the importance of Eucalyptus spp. in the pulp and paper industry, functional genomic approaches have only recently been applied to understand wood formation in this genus. We attempted to establish a global view of gene expression in the juvenile cambial region of Eucalyptus grandis Hill ex Maiden. The expression profile was obtained from serial analysis of gene expression (SAGE) library data produced from 3- and 6-year-old trees. Fourteen-base expressed sequence tags (ESTs) were searched against public Eucalyptus ESTs and annotated with GenBank. Altogether 43,304 tags were generated producing 3066 unigenes with three or more copies each, 445 with a putative identity, 215 with unknown function and 2406 without an EST match. The expression profile of the juvenile cambial region revealed the presence of highly frequent transcripts related to general metabolism and energy metabolism, cellular processes, transport, structural components and information pathways. We made a quantitative analysis of a large number of genes involved in the biosynthesis of cellulose, pectin, hemicellulose and lignin. Our findings provide insight into the expression of functionally related genes involved in juvenile wood formation in young fast-growing E. grandis trees.