Calcium-Dependent But Action Potential-Independent BCM-Like Metaplasticity in the Hippocampus

The Bienenstock, Cooper and Munro (BCM) computational model, which incorporates a metaplastic sliding threshold for LTP induction, accounts well for experience-dependent changes in synaptic plasticity in the visual cortex. BCM-like metaplasticity over a shorter timescale has also been observed in the hippocampus, thus providing a tractable experimental preparation for testing specific predictions of the model. Here, using extracellular and intracellular electrophysiological recordings from acute rat hippocampal slices, we tested the critical BCM predictions (1) that high levels of synaptic activation will induce a metaplastic state that spreads across dendritic compartments, and (2) that postsynaptic cell-firing is the critical trigger for inducing that state. In support of the first premise, high-frequency priming stimulation inhibited subsequent long-term potentiation and facilitated subsequent long-term depression at synapses quiescent during priming, including those located in a dendritic compartment different to that of the primed pathway. These effects were not dependent on changes in synaptic inhibition or NMDA/ metabotropic glutamate receptor function. However, in contrast to the BCM prediction, somatic action potentials during priming were neither necessary nor sufficient to induce the metaplasticity effect. Instead, in broad agreement with derivatives of the BCM model, calcium as released from intracellular stores and triggered byM1 muscarinic acetylcholine receptor activation was critical for altering subsequent synapticplasticity. These results indicate that synaptic plasticity in stratum radiatum of CA1 can be homeostatically regulated by the cell-wide history of synaptic activity through a calcium-dependent but action potential-independent mechanis

Predictors of Plasma Concentrations of DDE and PCBs in a Group of U.S. Women.

We evaluated predictors of plasma concentrations of dichlorodiphenyldichloroethylene (DDE), a metabolite of dichlorodiphenyltrichloroethane (DDT), and polychlorinated biphenyls (PCBs) in a group of 240 women, controls from a breast cancer case-control study nested in the Nurses' Health Study. We considered personal attributes such as age, serum cholesterol, region of residence, adiposity, lactation, and dietary intake. DDE levels increased 0.17 ppb/year of age ($p$ = 0.0003), and PCBs increased 0.08 ppb ($p$ = 0.0001). DDE and PCBs increased 0.20 ($p$ = 0.02) and 0.13 ppb ($p$ = 0.001), respectively, per 10 mg/dl serum cholesterol. Women living in the western United States had higher levels of DDE (mean = 11.0 ppb; $p$ = 0.003), and women in the Northeast and Midwest had higher levels of PCBs (mean = 5.6 ppb; $p$ = 0.0002) as compared to women from other parts of the country (mean DDE = 6.3; mean PCBs = 4. 5 ppb). Levels of DDE could not be predicted from consumption of meat, fish, poultry, dairy products, vegetables, fruits, and grains. There was a positive association between fish consumption and PCB concentrations among women in the Northeast and Midwest. Using data from the cases in the nested case-control study to assess the predictive ability of the models, we confirmed that the most reliable predictors of DDE were age and serum cholesterol, and the most important predictors of PCBs were age, serum cholesterol, and residence in the Midwest or Northeast. The null results for the majority of the food variables suggest that specific dietary factors, other than fish, are not currently a substantial contributor to human exposure to DDE and PCBs

Sparse aperture masking interferometry survey of transitional discs Search for substellar-mass companions and asymmetries in their parent discs

Context. Transitional discs are a class of circumstellar discs around young stars with extensive clearing of dusty material within their inner regions on 10s of au scales. One of the primary candidates for this kind of clearing is the formation of planet(s) within the disc that then accrete or clear their immediate area as they migrate through the disc. Aims. The goal of this survey was to search for asymmetries in the brightness distribution around a selection of transitional disc targets. We then aimed to determine whether these asymmetries trace dynamically-induced structures in the disc or the gap-opening planets themselves. Methods. Our sample included eight transitional discs. Using the Keck/NIRC2 instrument we utilised the Sparse Aperture Masking (SAM) interferometry technique to search for asymmetries indicative of ongoing planet formation. We searched for close-in companions using both model fitting and interferometric image reconstruction techniques. Using simulated data, we derived diagnostics that helped us to distinguish between point sources and extended asymmetric disc emission. In addition, we investigated the degeneracy between the contrast and separation that appear for marginally resolved companions. Results. We found FP Tau to contain a previously unseen disc wall, and DM Tau, LkHα330, and TW Hya to contain an asymmetric signal indicative of point source-like emission. We placed upper limits on the contrast of a companion in RXJ 1842.9-3532 and V2246 Oph. We ruled the asymmetry signal in RXJ 1615.3-3255 and V2062 Oph to be false positives. In the cases where our data indicated a potential companion we computed estimates for the value of McṀc and found values in the range of 10−5−10−3 M2J yr−1. Conclusions. We found significant asymmetries in four targets. Of these, three were consistent with companions. We resolved a previously unseen gap in the disc of FP Tau extending inwards from approximately 10 au

Juxtaposition of Chemical and Mutation-Induced Developmental Defects in Zebrafish Reveal a Copper-Chelating Activity for Kalihinol F

SummaryA major hurdle in using complex systems for drug screening is the difficulty of defining the mechanistic targets of small molecules. The zebrafish provides an excellent model system for juxtaposing developmental phenotypes with mechanism discovery using organism genetics. We carried out a phenotype-based screen of uncharacterized small molecules in zebrafish that produced a variety of chemically induced phenotypes with potential genetic parallels. Specifically, kalihinol F caused an undulated notochord, defects in pigment formation, hematopoiesis, and neural development. These phenotypes were strikingly similar to the zebrafish mutant, calamity, an established model of copper deficiency. Further studies into the mechanism of action of kalihinol F revealed a copper-chelating activity. Our data support this mechanism of action for kalihinol F and the utility of zebrafish as an effective system for identifying therapeutic and target pathways

Eclipsing binaries in the open cluster Ruprecht 147. II: EPIC 219568666

We report our spectroscopic monitoring of the detached, grazing, and slightly eccentric 12 day double-lined eclipsing binary EPIC 219568666 in the old nearby open cluster Ruprecht 147. This is the second eclipsing system to be analyzed in this cluster, following our earlier study of EPIC 219394517. Our analysis of the radial velocities combined with the light curve from the K2 mission yields absolute masses and radii for EPIC 219568666 of M₁ = 1.121 ± 0.013 M☉ and R₁ = 1.1779 ± 0.0070 R☉ for the F8 primary and M₂ = 0.7334 ± 0.0050 M☉ and R₂ = 0.640 ± 0.017 R☉ for the faint secondary. Comparison with current stellar evolution models calculated for the known metallicity of the cluster points to a primary star that is oversized, as is often seen in active M dwarfs, but this seems rather unlikely for a star of its mass and with a low level of activity. Instead, we suspect a subtle bias in the radius ratio inferred from the photometry, despite our best efforts to avoid it, which may be related to the presence of spots on one or both stars. The radius sum for the binary, which bypasses this possible problem, indicates an age of 2.76 ± 0.61 Gyr, which is in good agreement with a similar estimate from the binary in our earlier study

ZODIACAL EXOPLANETS IN TIME (ZEIT). III. A SHORT-PERIOD PLANET ORBITING A PRE-MAIN-SEQUENCE STAR IN THE UPPER SCORPIUS OB ASSOCIATION

We confirm and characterize a close-in (${P}_{{\rm{orb}}}$ = 5.425 days), super-Neptune sized (${5.04}_{-0.37}^{+0.34}$ ${R}_{\oplus }$) planet transiting K2-33 (2MASS J16101473-1919095), a late-type (M3) pre-main-sequence (11 Myr old) star in the Upper Scorpius subgroup of the Scorpius–Centaurus OB association. The host star has the kinematics of a member of the Upper Scorpius OB association, and its spectrum contains lithium absorption, an unambiguous sign of youth ($\lt 20$ Myr) in late-type dwarfs. We combine photometry from K2 and the ground-based MEarth project to refine the planet's properties and constrain the host star's density. We determine K2-33's bolometric flux and effective temperature from moderate-resolution spectra. By utilizing isochrones that include the effects of magnetic fields, we derive a precise radius (6%–7%) and mass (16%) for the host star, and a stellar age consistent with the established value for Upper Scorpius. Follow-up high-resolution imaging and Doppler spectroscopy confirm that the transiting object is not a stellar companion or a background eclipsing binary blended with the target. The shape of the transit, the constancy of the transit depth and periodicity over 1.5 yr, and the independence with wavelength rule out stellar variability or a dust cloud or debris disk partially occulting the star as the source of the signal; we conclude that it must instead be planetary in origin. The existence of K2-33b suggests that close-in planets can form in situ or migrate within ~10 Myr, e.g., via interactions with a disk, and that long-timescale dynamical migration such as by Lidov–Kozai or planet–planet scattering is not responsible for all short-period planets

Hip and spine bone mineral density are greater in master sprinters, but not endurance runners compared with non-athletic controls

Summary: We examined bone density in older athletes and controls. Sprinters had greater hip and spine bone density than endurance athletes and controls, whereas values were similar in the latter two groups. These results could not be explained by differences in impact, muscle size or power between sprint and endurance athletes. Purpose: We examined the relationship between prolonged participation in regular sprint or endurance running and skeletal health at key clinical sites in older age, and the factors responsible for any associations which we observed. Methods: We recruited 38 master sprint runners (28 males, 10 females, mean age 71 ± 7 years), 149 master endurance runners (111 males, 38 females, mean age 70 ± 6 years) and 59 non-athletic controls (29 males, 30 females, mean age 74 ± 5 years). Dual X-ray absorptiometry was used to assess hip and spine bone mineral density (BMD), body composition (lean and fat mass), whilst jump power was assessed with jumping mechanography. In athletes, vertical impacts were recorded over 7 days from a waist-worn accelerometer, and details of starting age, age-graded performance and training hours were recorded. Results: In ANOVA models adjusted for sex, age, height, body composition, and jump power, sprinter hip BMD was 10 and 14% greater than that of endurance runners and controls respectively. Sprinter spine BMD was also greater than that of both endurance runners and controls. There were no differences in hip or spine BMD between endurance runners and controls. Stepwise regression showed only discipline (sprint/endurance), sex, and age as predictors of athlete spine BMD, whilst these variables and starting age were predictive of hip BMD. Conclusions: Regular running is associated with greater BMD at the fracture-prone hip and spine sites in master sprinters but not endurance runners. These benefits cannot be explained by indicators of mechanical loading measured in this study including vertical impacts, body composition or muscular output

Validation of a risk prediction model for Barrett’s esophagus in an Australian population

Creative Commons License: This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Background: Esophageal adenocarcinoma is a disease that has a high mortality rate, the only known precursor being Barrett’s esophagus (BE). While screening for BE is not cost-effective at the population level, targeted screening might be beneficial. We have developed a risk prediction model to identify people with BE, and here we present the external validation of this model. Materials and methods: A cohort study was undertaken to validate a risk prediction model for BE. Individuals with endoscopy and histopathology proven BE completed a questionnaire containing variables previously identified as risk factors for this condition. Their responses were combined with data from a population sample for analysis. Risk scores were derived for each participant. Overall performance of the risk prediction model in terms of calibration and discrimination was assessed. Results: Scores from 95 individuals with BE and 636 individuals from the general population were analyzed. The Brier score was 0.118, suggesting reasonable overall performance. The area under the receiver operating characteristic was 0.83 (95% CI 0.78–0.87). The Hosmer–Lemeshow statistic was p=0.14. Minimizing false positives and false negatives, the model achieved a sensitivity of 74% and a specificity of 73%. Conclusion: This study has validated a risk prediction model for BE that has a higher sensitivity than previous models