The Spatial Structure of Stimuli Shapes the Timescale of Correlations in Population Spiking Activity

Throughout the central nervous system, the timescale over which pairs of neural spike trains are correlated is shaped by stimulus structure and behavioral context. Such shaping is thought to underlie important changes in the neural code, but the neural circuitry responsible is largely unknown. In this study, we investigate a stimulus-induced shaping of pairwise spike train correlations in the electrosensory system of weakly electric fish. Simultaneous single unit recordings of principal electrosensory cells show that an increase in the spatial extent of stimuli increases correlations at short (~10 ms) timescales while simultaneously reducing correlations at long (~100 ms) timescales. A spiking network model of the first two stages of electrosensory processing replicates this correlation shaping, under the assumptions that spatially broad stimuli both saturate feedforward afferent input and recruit an open-loop inhibitory feedback pathway. Our model predictions are experimentally verified using both the natural heterogeneity of the electrosensory system and pharmacological blockade of descending feedback projections. For weak stimuli, linear response analysis of the spiking network shows that the reduction of long timescale correlation for spatially broad stimuli is similar to correlation cancellation mechanisms previously suggested to be operative in mammalian cortex. The mechanism for correlation shaping supports population-level filtering of irrelevant distractor stimuli, thereby enhancing the population response to relevant prey and conspecific communication inputs. © 2012 Litwin-Kumar et al

Multifunctional Magnetoelectric Materials for Device Applications

Mutiferroics are a novel class of next generation multifunctional materials, which display simultaneous magnetic spin, electric dipole, and ferroelastic ordering, and have drawn increasing interest due to their multi-functionality for a variety of device applications. Since single-phase materials exist rarely in nature with such cross-coupling properties, an intensive research activity is being pursued towards the discovery of new single-phase multiferroic materials and the design of new engineered materials with strong magneto-electric (ME) coupling. This review article summarizes the development of different kinds of multiferroic material: single-phase and composite ceramic, laminated composite, and nanostructured thin films. Thin-film nanostructures have higher magnitude direct ME coupling values and clear evidence of indirect ME coupling compared with bulk materials. Promising ME coupling coefficients have been reported in laminated composite materials in which signal to noise ratio is good for device fabrication. We describe the possible applications of these materials

Magnetic Effects on Dielectric and Polarization Behavior of Multiferroic Hetrostructures

PbZr0.52Ti0.48O3/La0.67Sr0.33MnO3(PZT/LSMO) bilayer with surface roughness ~ 1.8 nm thin films have been grown by pulsed laser deposition on LaAlO3(LAO) substrates. High remnant polarization (30-54 micro C/cm2), dielectric constant(400-1700), and well saturated magnetization were observed depending upon the deposition temperature of the ferromagnetic layer and applied frequencies. Giant frequency-dependent change in dielectric constant and loss were observed above the ferromagnetic-paramagnetic temperature. The frequency dependent dielectric anomalies are attributed to the change in metallic and magnetic nature of LSMO and also the interfacial effect across the bilayer; an enhanced magnetoelectric interaction may be due to the Parish-Littlewood mechanism of inhomogeneity near the metal-dielectric interface.Comment: 9 pages, 4 figure

Antibacterial responses of retinal Müller glia: production of antimicrobial peptides, oxidative burst and phagocytosis

BACKGROUND: We have previously shown that, in response to microbial infection, activated Müller glia secrete inflammatory cytokines/chemokines and exhibit antimicrobial properties. The aim of this study is to understand the mechanisms and the key components involved in this response. METHODS: Immortalized human retinal Müller glia (MIO-M1 cells) were challenged with Staphylococcus (S) aureus, the leading cause of severe intraocular infection followed by RT(2) profile PCR array analysis. The expression of human β-defensin 1 (HBD1), 2 (HBD2), 3 (HBD3), hepcidine and cathelicidin LL37 was checked by RT-PCR and quantified by Taqman® qPCR. The expression of AMPs was confirmed at protein level by dot-blot analysis. The production of ROS was measured by dicholoro-dihydro-fluorescein diacetate (DCFH-DA) staining by flow cytometry as well as fluorescence microscopy. The level of nitric oxide (NO) was measured by measuring a stable metabolite, nitrite using the Griess reagent. In vitro killing assay was performed by Live/Dead® BacLight™ staining as well as by dilution plating in suspension and adherent conditions following S. aureus infection. Phagocytosis was measured by CFU enumeration following infection. RESULTS: PCR array data showed that, in comparison to uninfected control cells, bacterial challenge significantly (> two-fold) induced the expression of 26 genes involved in cytokine/chemokine, antimicrobials, Toll-like receptor, apoptotic, and NF-κB signaling. RT-PCR analysis showed time-dependent increased expression of HBD1, HBD2, HBD3, LL-37, and hepcidin mRNA in bacteria-challenged Müller glia. The expression of these antimicrobial molecules was also increased at the protein level in the culture supernatant, as detected by dot-blot analysis. Additionally, the bacteria-stimulated Müller glia were found to produce reactive oxygen (ROS) and reactive nitrogen (RNS) species. In vitro, killing assays revealed that Müller glia exhibited bactericidal activity against S. aureus in both adherent and suspension cultures. Furthermore, our data demonstrated that Müller glia can phagocytize and kill the bacteria in a time-dependent manner. CONCLUSIONS: These data suggest that retinal Müller glia behave like classical innate immune cells by producing a variety of antimicrobial molecules in response to bacterial challenge, suggesting their pivotal role in retinal innate defense

BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF IBRUTINIB IN BIOLOGICAL MATRICES BY LC-MS/MS

Objective: The main aim of the research was to develop a fast and highly sensitive bioanalytical LC-MS/MS technique for the quantitation of ibrutinib in human plasma. Methods: Chromatography has achieved on a reverse phase-symmetry C18 (75 mm × 4.6 mm, 3.5 µm) column with gradient elution by acetonitrile, methanol and 0.1%v/v formic acid as the mobile phase. Chromatographic peaks were resolved with 0.7 ml/min flow rate. Drug was extracted with ethyl acetate solvent by liquid-liquid extraction method. Monitoring of transition of m/z 441.2 and 55.01 for ibrutinib and 446.5 and 60.01 for Ibrutinib-D5 were made on multiple reaction monitoring. Results: Calibration curve of ibrutinib was linear over 1-600 ng/ml concentration range with a regression coefficient (r2) value of>0.99. The % RSD values were less than 8.5% for inter-day and intra-day precision and accuracy. The method has excellent recovery and the percentage recovery values of lower quality control (LQC), median quality control (MQC) and higher quality control (HQC) samples were 101.86%, 102.8%, and 99.28% respectively. Conclusion: The drug was stable for more time at variable stability conditions and method was successfully applicable to the regular analysis of ibrutinib in biological matrices

FORMULATION AND IN VITRO EVALUATION OF ARAUCARIA BIDWILLI GUM-BASED SUSTAIN RELEASE MATRIX TABLETS OF DICLOFENAE SODIUM

A gel forming Polysaccharide gum obtained form the bark of Araucaria bidwilli was employed as a matrix sustained release tablet formulation of Diclofenac sodium (a non steroidal anti inflammatory agent). The effect of Araucaria bidwilli gum (Natural) and Synthetic polymer Hydroxypropyl methyl cellulose (HPMC K4 M) on the release of Diclofenac sodium was studied. The FT-IR spectroscopic studies of drug, gum and mixture indicated no chemical interaction. Six formulations were prepared by wet granulation method containing Araucaria bidwilli gum powder concentration 10% 20% & 30% w\w and 10% 20% &30% w\w of HPMC K4 M with sufficient volume of granulating agent Polyvinyl pyrrolene (PVP K 30), Avicel pH101 as diluents, Magnesium stearate and Aerosil is used lubricant and glidant respectively.This study was carried out to find out the difference between synthetic and natural gum and whether synthetic gum can be replaced by natural gums. Physical and technological studies of granules and tablets were compliance with Pharmacopoial standards.The drug release increased with Araucaria bidwilli gum when compared to synthetics polymer concentration .The value of release exponent were found to be almost straight line and regression coefficient value between 0.938 and 0.998.This implies that the release mechanism is diffusion. Formulation F3 ( contained 30% w\w Araucaria bidwilli gum) met the desired requirements for a sustained release dosage form