Ratiometric Detection of Glutathione Based on Disulfide Linkage Rupture between a FRET Coumarin Donor and a Rhodamine Acceptor

Abnormal levels of glutathione, a cellular antioxidant, can lead to a variety of diseases. We have constructed a near-infrared ratiometric fluorescent probe to detect glutathione concentrations in biological samples. The probe consists of a coumarin donor, which is connected through a disulfide-tethered linker to a rhodamine acceptor. Under the excitation of the coumarin donor at 405 nm, the probe shows weak visible fluorescence of the coumarin donor at 470 nm and strong near-infrared fluorescence of the rhodamine acceptor at 652 nm due to efficient Forster resonance energy transfer (FRET) from the donor to the acceptor. Glutathione breaks the disulfide bond through reduction, which results in a dramatic increase in coumarin fluorescence and a corresponding decrease in rhodamine fluorescence. The probe possesses excellent cell permeability, biocompatibility, and good ratiometric fluorescence responses to glutathione and cysteine with a self-calibration capability. The probe was utilized to ratiometrically visualize glutathione concentration alterations in HeLa cells and Drosophila melanogaster larvae.     

Differential Display of Investigative Behavior Permits Discrimination of Scent Signatures from Familiar and Unfamiliar Socially Dominant Female Marmoset Monkeys (Callithrix jacchus)

The hypothesis was tested that marmosets have differential displays of investigatory behavior towards circumgenital scent marks from socially dominant females based on degree of familiarity. In a series of two-choice behavioral discrimination bioassays, dominant males together with subordinate and dominant females were presented concurrently with scent secretions from familiar versus unfamiliar dominant females, and their investigative behaviors towards the scent were recorded. Test animals directed significantly different amounts of investigative behaviors towards familiar versus unfamiliar scents when the scent stimuli involved complete circumgenital scent marks, glandular secretion only, or urine only. When animals discriminated between the two scent samples, they did so by directing significantly increased amounts of behavior to scent from unfamiliar females. Chemical cues promoting differential displays of behavior to familiar versus unfamiliar scents appeared to be volatile in nature and were effective in the scent mark for at least one day following deposition. The reliable ability of marmosets to consistently discriminate between odors from familiar versus unfamiliar dominant females provides strong circumstantial evidence that individual female marmosets have distinct chemical signatures. The ability of marmosets to discriminate the odor from familiar versus unfamiliar dominant females may be important in the context of intergroup relations.     

Is cheating a human function? The roles of presence,state hostility,and enjoyment in an unfair video game

In sports and board games, when an opponent cheats, the other players typically greet it with disdain, anger, and disengagement. However, work has yet to fully address the role of the computer cheating in video games. In this study, participants played either a cheating or a non-cheating version of a modified open-source tower-defense game. Results indicate that when a computer competitor cheats, players perceive the opponent as being more human. Cheating also increases player aggravation and presence, but does not affect enjoyment of the experience. Additionally, players that firmly believed that their opponent was controlled by the computer exhibited significantly less state hostility compared to players that were less certain of the nature of their competitor. Game designers can integrate subtle levels of cheating into computer opponents without any real negative responses from the players. The results indicate that minor levels of cheating might also increase player engagement with video games.     

Interleukin‐4‐Clicked Surfaces Drive M2 Macrophage Polarization

Driving macrophage (M?) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin‐4 (IL‐4) promotes polarization into the M2‐M? phenotype, but its systemic use is constrained by dose‐limiting toxicity. Consequently, we developed IL‐4‐decorated surfaces aiming at sustained and localized activity. IL‐4 muteins were generated by genetic code expansion; Lys42 was replaced by unnatural amino acids (uAAs). Both muteins showed cell‐stimulation ability and binding affinity to IL4Rα similar to those of wt‐IL‐4. Copper‐catalyzed (CuAAC) and copper‐free strain‐promoted (SPAAC) 1,3‐dipolar azide–alkyne cycloadditions were used to site‐selectively anchor IL‐4 to agarose surfaces. These surfaces had sustained IL‐4 activity, as demonstrated by TF‐1 cell proliferation and M2, but not M1, polarization of M‐CSF‐generated human M?. The approach provides a blueprint for the engineering of cytokine‐activated surfaces profiled for sustained and spatially controlled activity.     

Simulation of ALTEA calibration data with PHITS,FLUKA and GEANT4

The ALTEA-Space detector has been calibrated by testing its response to several monochromatic beams. These measurements provided energy-deposition spectra in silicon of 100, 600 and 1000 MeV/nucleon ¹²C and 200 and 600 MeV/nucleon ⁴⁸Ti. The results have been compared to three Monte Carlo transport codes, namely PHITS, GEANT4 and FLUKA. Median, full width at half maximum (FWHM) and interquartile range (IQR) have been calculated for all datasets to characterize location, width and asymmetry of the energy-deposition spectra. Particular attention has been devoted to the influence of δ rays on the shape of the energy-deposition spectrum, both with the help of analytical calculations and Monte Carlo simulations. The two approaches proved that, in this range of projectile charge, projectile energy and detector size, the leakage of secondary electrons might introduce a difference between the energy-loss and energy-deposition spectrum, in particular by changing the location, width and symmetry of the distribution. The overall agreement between the Monte Carlo predictions and the measurements is fair and makes PHITS, FLUKA and GEANT4 all possible candidates for simulating ALTEA-Space experiment.     

High density hydrophilic and hydrophobic brush coatings using a polymeric primer layer

Polymer brush coatings, consisting of polymer chains covalently attached to a surface and being less than a hundred nanometer thick, allow the creation of functional surfaces without altering the inherent bulk properties or appearance of a product. Surface properties depend on the type and length of the polymer used, as well as on the grafting density of the polymer brush. By making use of a polymeric primer layer that is covalently linked to the substrate and creates a uniform and highly functionalized surface, polymer brush coatings with high grafting densities can be created. In this paper we report the preparation of hydrophilic as well as hydrophobic brush coatings on different substrates through the use of a poly(acrylic acid) primer layer. In addition, hydrophilic poly(ethylene glycol) brush coatings thus produced were shown to decrease adhesion of marine bacteria.     

The association of dental caries with blood lead in children when adjusted for IQ and neurobehavioral performance

Associations between childhood lead exposures and dental caries in children have been reported for over 30 years, with widely varying findings and conclusions, and using measures of lead exposure which ranged from food sources and water to tooth, hair or blood lead concentrations. OBJECTIVES: This study examined the relationship of lead exposure and dental caries in a population of normatively healthy children. METHODS: This cross-sectional study used a population of 507 children aged 8-12 who were participating in a clinical trial of dental materials to examine the relationship between lead and caries. Blood lead concentrations and dental caries were examined for association in both primary and permanent teeth. Because it is possible that neurobehavioral status could be associated with both lead exposure and dental caries prevalence, we also examined neurobehavioral status of the subjects. RESULTS: A gender-specific association (males only) between lead exposure and dental caries was found in primary teeth only. Neurobehavioral measures and IQ were not associated with caries status in this population. CONCLUSIONS: This study did not support neurobehavioral status as mediating any association between lead exposure and caries in a normatively healthy population. A gender-specific association between lead and caries not previously reported was found in primary teeth, and no biological explanation for this has been suggested. We conclude that this study provides only weak evidence, if any, for an association of low-level lead exposure with dental caries.     

Effects of stochasticity on the length and behaviour of ecological transients

There is a growing recognition that ecological systems can spend extended periods of time far away from an asymptotic state, and that ecological understanding will therefore require a deeper appreciation for how long ecological transients arise. Recent work has defined classes of deterministic mechanisms that can lead to long transients. Given the ubiquity of stochasticity in ecological systems, a similar systematic treatment of transients that includes the influence of stochasticity is important. Stochasticity can of course promote the appearance of transient dynamics by preventing systems from settling permanently near their asymptotic state, but stochasticity also interacts with deterministic features to create qualitatively new dynamics. As such, stochasticity may shorten, extend or fundamentally change a system’s transient dynamics. Here, we describe a general framework that is developing for understanding the range of possible outcomes when random processes impact the dynamics of ecological systems over realistic time scales. We emphasize that we can understand the ways in which stochasticity can either extend or reduce the lifetime of transients by studying the interactions between the stochastic and deterministic processes present, and we summarize both the current state of knowledge and avenues for future advances.     

Impedance Properties of Metal Electrodes for Chronic Recording from Mammalian Nerves

Over the last few years methods have been developed for recording chronically from mammalian nerves with implanted electrodes contained in silastic cuffs. The impedance of the electrodes and the changes that take place over time were studied. Platinum-iridium electrodes remain stable over long periods of time, whereas the impedance of silver wire electrodes increases and eventually the silver fractures. The impedance at low frequencies (e.g., 10 Hz) provides a measure of the capacitance of the metal electrodes, whereas the impedance at higher frequencies (1 kHz) mainly measures the resistance of the tissue filling the cuff. Increases in resistance due to growth of connective tissue around intact nerves have been studied as well as changes in resistance after cutting a nerve. Impedance measurements provide a useful way to follow the properties of electrodes and nerves in basic neuroscientific research and in future clinical applications of these chronic recording methods.