Phosphorylation of Spinophilin Modulates Its Interaction with Actin Filaments

Spinophilin is a protein phosphatase 1 (PP1)- and actin-binding protein that modulates excitatory synaptic transmission and dendritic spine morphology. We report that spinophilin is phosphorylated in vitro by protein kinase A (PKA). Phosphorylation of spinophilin was stimulated by treatment of neostriatal neurons with a dopamine D1 receptor agonist or with forskolin, consistent with spinophilin being a substrate for PKA in intact cells. Using tryptic phosphopeptide mapping, site-directed mutagenesis, and microsequencing analysis, we identified two major sites of phosphorylation, Ser-94 and Ser-177, that are located within the actin-binding domain of spinophilin. Phosphorylation of spinophilin by PKA modulated the association between spinophilin and the actin cytoskeleton. Following subcellular fractionation, unphosphorylated spinophilin was enriched in the postsynaptic density, whereas a pool of phosphorylated spinophilin was found in the cytosol. F-actin co-sedimentation and overlay analysis revealed that phosphorylation of spinophilin reduced the stoichiometry of the spinophilin-actin interaction. In contrast, the ability of spinophilin to bind to PP1 remained unchanged. Taken together, our studies suggest that phosphorylation of spinophilin by PKA modulates the anchoring of the spinophilin-PP1 complex within dendritic spines, thereby likely contributing to the efficacy and plasticity of synaptic transmission

RISK PERCEPTIONS AND MANAGEMENT RESPONSES: PRODUCER-GENERATED HYPOTHESES FOR RISK MODELING

Farm level risk analyses have used price and yield variability almost exclusively to represent risk. Results from a survey of 149 agricultural producers in 12 states indicate that producers consider a broader range of sources of variability in their operations. Significant differences exist among categories with respect to the importance of the sources of variability in crop and livestock production. Producers also used a variety of management responses to variability. There were significant difference among categories in the importance given to particular responses and their use of them. These results have implications for research, extension, and policy programs.Risk and Uncertainty,

What can a mean-field model tell us about the dynamics of the cortex?

In this chapter we examine the dynamical behavior of a spatially homogeneous two-dimensional model of the cortex that incorporates membrane potential, synaptic flux rates and long- and short-range synaptic input, in two spatial dimensions, using parameter sets broadly realistic of humans and rats. When synaptic dynamics are included, the steady states may not be stable. The bifurcation structure for the spatially symmetric case is explored, identifying the positions of saddle–node and sub- and supercritical Hopf instabilities. We go beyond consideration of small-amplitude perturbations to look at nonlinear dynamics. Spatially-symmetric (breathing mode) limit cycles are described, as well as the response to spatially-localized impulses. When close to Hopf and saddle–node bifurcations, such impulses can cause traveling waves with similarities to the slow oscillation of slow-wave sleep. Spiral waves can also be induced. We compare model dynamics with the known behavior of the cortex during natural and anesthetic-induced sleep, commenting on the physiological significance of the limit cycles and impulse responses

The central density of a neutron star is unaffected by a binary companion at linear order in μ/R\mu/R

Recent numerical work by Wilson, Mathews, and Marronetti [J. R. Wilson, G. J. Mathews and P. Marronetti, Phys. Rev. D 54, 1317 (1996)] on the coalescence of massive binary neutron stars shows a striking instability as the stars come close together: Each star's central density increases by an amount proportional to 1/(orbital radius). This overwhelms any stabilizing effects of tidal coupling [which are proportional to 1/(orbital radius)^6] and causes the stars to collapse before they merge. Since the claimed increase of density scales with the stars' mass, it should also show up in a perturbation limit where a point particle of mass $\mu$ orbits a neutron star. We prove analytically that this does not happen; the neutron star's central density is unaffected by the companion's presence to linear order in $\mu/R$. We show, further, that the density increase observed by Wilson et. al. could arise as a consequence of not faithfully maintaining boundary conditions.Comment: 3 pages, REVTeX, no figures, submitted to Phys Rev D as a Rapid Communicatio

An Apple Extract Beverage Combined with Caffeine Can Improve Alertness, Mental Fatigue, and Information Processing Speed

The psychological effects of low-dose caffeine combined with polyphenols from apples have rarely been explored scientifically yet synergistic effects are plausible. A randomized, double-blind, placebo-controlled cross-over experiment was used to test the psychological effects of apple extract beverages combined with 10, 20, 37.5, and 75 mg caffeine. Comparisons were made to both a placebo drink that was artificially sweetened and colored to mimic the test beverages and a positive control drink with 75 mg caffeine but without apple extract. Compared to placebo, it was hypothesized that dose-dependent improvements in cognitive performance, mood, and motivation would be realized after consuming the beverage with apple extract containing added caffeine. Outcomes were assessed before, 60 to 110, and 125 to 175 min post-beverage. The positive control beverage resulted in more serial seven subtractions, greater motivation to perform cognitive tasks, and reduced feelings of fatigue (all p \u3c .005). The study found that psychological effects (i) were not observed for beverages containing apple extract and 10 or 20 mg caffeine, (ii) of the apple extract beverage containing 75 mg caffeine generally mimicked the effects of the positive control drink and significantly increased serial seven processing speed, and (iii) of the apple extract beverage containing 37.5 mg improved feelings of alertness and mental fatigue. In sum, effects of apple extract combined with caffeine were not dose-dependent; the apple extract beverage containing 75 mg caffeine improved information processing speed and the apple extract beverage with 37.5 mg caffeine improved feelings of alertness and mental fatigue

Infrared Variability of Two Dusty White Dwarfs

The most heavily polluted white dwarfs often show excess infrared radiation from circumstellar dust disks, which are modeled as a result of tidal disruption of extrasolar minor planets. Interaction of dust, gas, and disintegrating objects can all contribute to the dynamical evolution of these dust disks. Here, we report on two infrared variable dusty white dwarfs, SDSS J1228+1040 and G29-38. For SDSS J1228+1040, compared to the first measurements in 2007, the IRAC [3.6] and [4.5] fluxes decreased by 20% by 2014 to a level also seen in the recent 2018 observations. For G29-38, the infrared flux of the 10 $\mu$m silicate emission feature became 10% stronger between 2004 and 2007, We explore several scenarios that could account for these changes, including tidal disruption events, perturbation from a companion, and runaway accretion. No satisfactory causes are found for the flux drop in SDSS J1228+1040 due to the limited time coverage. Continuous tidal disruption of small planetesimals could increase the mass of small grains and concurrently change the strength of the 10 $\mu$m feature of G29-38. Dust disks around white dwarfs are actively evolving and we speculate that there could be different mechanisms responsible for the temporal changes of these disks.Comment: ApJ, in pres

A case-cohort study of human herpesvirus 8 seropositivity and incident prostate cancer in Tobago

<p>Abstract</p> <p>Background</p> <p>We previously reported a cross-sectional association between the presence of human herpesvirus 8 (HHV-8) serum antibodies and screen-detected prostate cancer in men living in Tobago. In the same study population, we examined the association between HHV-8 seropositivity and incident prostate cancer discovered at later screenings.</p> <p>Methods</p> <p>In 40-81 year-old men without prostate cancer discovered at initial digital rectal examination (DRE) and prostate-specific antigen (PSA) screening, a case-cohort design measured the association between baseline HHV-8 seropositivity (modified immunofluorescence assay for antibodies against HHV-8 lytic antigens) and incident prostate cancer detected at DRE and PSA screenings three or five years later.</p> <p>Results</p> <p>Analyses included 486 unique individuals, 96 incident prostate cancer cases, and 415 randomly selected subjects representing an at-risk cohort. By design, the random sub-cohort contained 25 incident prostate cancer cases. In the sub-cohort, the frequency of HHV-8 seropositivity increased across age groupings (40-49 years: 3.5%, 50-59 years: 13.6%, and ≥ 60 years: 22.9%). HHV-8 seropositivity was higher in men with elevated (≥ 4.0 ng/mL) than men with non-elevated PSA at initial screening (30.4% <it>vs</it>. 9.9% seropositive; crude odds ratio (OR) 3.96, 95% confidence interval (CI) 1.53-10.2; age-adjusted OR 2.42, 95% CI 0.91-6.47). HHV-8 seropositivity did not increase incident prostate cancer risk (age-adjusted hazard ratio (HR) 0.88, 95% CI 0.46-1.69).</p> <p>Conclusions</p> <p>Case-cohort analysis did not identify association between HHV-8 seropositivity and incident prostate cancer. However, analyses uncovered possible association between HHV-8 and PSA (a marker of prostate inflammation). Co-occurrence of HHV-8 seropositivity and PSA elevation may explain cross-sectional association between HHV-8 and PSA screen-detected prostate cancer.</p

A Candidate Young Massive Planet in Orbit around the Classical T Tauri Star CI Tau

The ~2 Myr old classical T Tauri star CI Tau shows periodic variability in its radial velocity (RV) variations measured at infrared (IR) and optical wavelengths. We find that these observations are consistent with a massive planet in a ~9-day period orbit. These results are based on 71 IR RV measurements of this system obtained over 5 years, and on 26 optical RV measurements obtained over 9 years. CI Tau was also observed photometrically in the optical on 34 nights over ~one month in 2012. The optical RV data alone are inadequate to identify an orbital period, likely the result of star spot and activity induced noise for this relatively small dataset. The infrared RV measurements reveal significant periodicity at ~9 days. In addition, the full set of optical and IR RV measurements taken together phase coherently and with equal amplitudes to the ~9 day period. Periodic radial velocity signals can in principle be produced by cool spots, hot spots, and reflection of the stellar spectrum off the inner disk, in addition to resulting from a planetary companion. We have considered each of these and find the planet hypothesis most consistent with the data. The radial velocity amplitude yields an Msin(i) of ~8.1 M_Jup; in conjunction with a 1.3 mm continuum emission measurement of the circumstellar disk inclination from the literature, we find a planet mass of ~11.3 M_Jup, assuming alignment of the planetary orbit with the disk.Comment: 61 pages, 13 figures, accepted for publication in The Astrophysical Journa

Complexity of Fetal Movement Detection Using a Single Doppler Ultrasound Transducer

The objective of this paper is to discuss the complexity of fetal movement detection encountered during development and implementation of an automated single Doppler ultrasonic transducer based instrument. The single transducer instrument was intended to better quantify the duration, velocity, and magnitude of fetal movements. A Corometrics Model 116 fetal heart rate monitor was modified, and a fetal movement detection algorithm (Russell Algorithm) was developed to detect fetal movements on one and two (data fusion) transducers. A Hewlett-Packard (HP) M-1350-A fetal monitor and the Russell Algorithm were used to detect and record fetal movements concurrently on sixty patients between the gestation ages of31 to 41 weeks. Using a computer-controlled SVHS PC-VCR, the instrumental detection of fetal movements was time-linked with real-time video ultrasound. This allowed the fetal movements to be scored by expert examiners on a second-per-second basis. A total of 52,478 seconds of fetal movements was scored using this system. Neither system could accurately define the entire duration, velocity, or magnitude of the fetal movements as detected by real-time ultrasound. The complexity of detecting fetal movements using only one transducer has many shortcomings, such as: the amplitude of the returning Doppler signal, the small area of the fetus monitored by a single transducer, the position of the fetus, the type and variety of fetal movements, and material size and shape