Caged calcium in Aplysia pacemaker neurons. Characterization of calcium-activated potassium and nonspecific cation currents.

We have studied calcium-activated potassium current, IK(Ca), and calcium-activated nonspecific cation current, INS(Ca), in Aplysia bursting pacemaker neurons, using photolysis of a calcium chelator (nitr-5 or nitr-7) to release caged calcium intracellularly. A computer model of nitr photolysis, multiple buffer equilibration, and active calcium extrusion was developed to predict volume-average and front-surface calcium concentration transients. Changes in arsenazo III absorbance were used to measure calcium concentration changes caused by nitr photolysis in microcuvettes. Our model predicted the calcium increments caused by successive flashes, and their dependence on calcium loading, nitr concentration, and light intensity. Flashes also triggered the predicted calcium concentration jumps in neurons filled with nitr-arsenazo III mixtures. In physiological experiments, calcium-activated currents were recorded under voltage clamp in response to flashes of different intensity. Both IK(Ca) and INS(Ca) depended linearly without saturation upon calcium concentration jumps of 0.1-20 microM. Peak membrane currents in neurons exposed to repeated flashes first increased and then declined much like the arsenazo III absorbance changes in vitro, which also indicates a first-order calcium activation. Each flash-evoked current rose rapidly to a peak and decayed to half in 3-12 s. Our model mimicked this behavior when it included diffusion of calcium and nitr perpendicular to the surface of the neuron facing the flashlamp. Na/Ca exchange extruding about 1 pmol of calcium per square centimeter per second per micromolar free calcium appeared to speed the decline of calcium-activated membrane currents. Over a range of different membrane potentials, IK(Ca) and INS(Ca) decayed at similar rates, indicating similar calcium stoichiometries independent of voltage. IK(Ca), but not INS(Ca), relaxes exponentially to a different level when the voltage is suddenly changed. We have estimated voltage-dependent rate constants for a one-step first-order reaction scheme of the activation of IK(Ca) by calcium. After a depolarizing pulse, INS(Ca) decays at a rate that is well predicted by a model of diffusion of calcium away from the inner membrane surface after it has entered the cell, with active extrusion by surface pumps and uptake into organelles. IK(Ca) decays somewhat faster than INS(Ca) after a depolarization, because of its voltage-dependent relaxation combined with the decay of submembrane calcium. The interplay of these two currents accounts for the calcium-dependent outward-inward tail current sequence after a depolarization, and the corresponding afterpotentials after a burs

Induction of Filopodia by Direct Local Elevation of Intracellular Calcium Ion Concentration

In neuronal growth cones, cycles of filopodial protrusion and retraction are important in growth cone translocation and steering. Alteration in intracellular calcium ion concentration has been shown by several indirect methods to be critically involved in the regulation of filopodial activity. Here, we investigate whether direct elevation of [Ca2+]i, which is restricted in time and space and is isolated from earlier steps in intracellular signaling pathways, can initiate filopodial protrusion. We raised [Ca2+]i level transiently in small areas of nascent axons near growth cones in situ by localized photolysis of caged Ca2+ compounds. After photolysis, [Ca2+]i increased from ∼60 nM to ∼1 μM within the illuminated zone, and then returned to resting level in ∼10–15 s. New filopodia arose in this area within 1–5 min, and persisted for ∼15 min. Elevation of calcium concentration within a single filopodium induced new branch filopodia. In neurons coinjected with rhodamine-phalloidin, F-actin was observed in dynamic cortical patches along nascent axons; after photolysis, new filopodia often emerged from these patches. These results indicate that local transient [Ca2+]i elevation is sufficient to induce new filopodia from nascent axons or from existing filopodia

The Radcliffe Wave as the gas spine of the Orion Arm

The Radcliffe Wave is a $\sim3$ kpc long coherent gas structure containing most of the star-forming complexes near the Sun. In this Letter we aim to find a Galactic context for the Radcliffe Wave by looking into a possible relationship between the gas structure and the Orion (Local) Arm. We use catalogs of massive stars and young open clusters based on \textit{Gaia} EDR3 astrometry, in conjunction with kiloparsec-scale 3D dust maps, to investigate the Galactic \textit{XY} spatial distributions of gas and young stars. We find a quasi-parallel offset between the luminous blue stars and the Radcliffe Wave, in that massive stars and clusters are found essentially inside and downstream from the Radcliffe Wave. We examine this offset in the context of color gradients observed in the spiral arms of external galaxies, where the interplay between density wave theory, spiral shocks, and triggered star formation has been used to interpret this particular arrangement of gas/dust and OB stars, and outline other potential explanations as well. We hypothesize that the Radcliffe Wave constitutes the gas reservoir of the Orion (Local) Arm, and presents itself as a prime laboratory to study the interface between Galactic structure, the formation of molecular clouds in the Milky Way, and star formation.Comment: Published in A&A Letter

Interpolated sequences and critical LL-values of modular forms

Recently, Zagier expressed an interpolated version of the Ap\'ery numbers for $\zeta(3)$ in terms of a critical $L$-value of a modular form of weight 4. We extend this evaluation in two directions. We first prove that interpolations of Zagier's six sporadic sequences are essentially critical $L$-values of modular forms of weight 3. We then establish an infinite family of evaluations between interpolations of leading coefficients of Brown's cellular integrals and critical $L$-values of modular forms of odd weight.Comment: 23 pages, to appear in Proceedings for the KMPB conference: Elliptic Integrals, Elliptic Functions and Modular Forms in Quantum Field Theor

Really Underage Drinkers: Alcohol Use Among Elementary Students

Despite the current societal concern with underage drinking, little attention has been paid to alcohol use within the preadolescent population. This article presents the proceedings of a symposium held at the 2003 Research Society on Alcoholism meeting in Fort Lauderdale, Florida, that was organized and chaired by John E. Donovan. The intent of the symposium was to kick start research on alcohol use among elementary school children by reviewing what is known regarding drinking in childhood. Presentations included (1) The Epidemiology of Children's Alcohol Use, by John E. Donovan; (2) The Validity of Children's Self-Reports of Alcohol Use, by Sharon L. Leech; (3) Predicting Onset of Drinking From Behavior at Three Years of Age: Influence of Early Child Expectancies and Parental Alcohol Involvement Upon Early First Use, by Robert A. Zucker; and (4) Parent, Peer, and Child Risk Factors for Alcohol Use in Two Cohorts of Elementary School Children, by Carol J. Loveland-Cherry. Presentations indicated the need for better nationwide surveillance of children's experience with alcohol; suggested that children's reports of their use of alcohol tend to be reliable and valid; supported children's alcohol use schemas and parental drinking and alcoholism at child age three as independent predictors of early onset drinking; and showed that onset of drinking before fourth or fifth grade, peer pressure, and parental norms and monitoring predict elementary student alcohol use and misuse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65944/1/01.ALC.0000113922.77569.4E.pd

Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema

Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. © 2013 D'Armiento et al

Spectroscopic Confirmation of a Population of Isolated, Intermediate-Mass YSOs

Wide-field searches for young stellar objects (YSOs) can place useful constraints on the prevalence of clustered versus distributed star formation. The Spitzer/IRAC Candidate YSO (SPICY) catalog is one of the largest compilations of such objects (~120,000 candidates in the Galactic midplane). Many SPICY candidates are spatially clustered, but, perhaps surprisingly, approximately half the candidates appear spatially distributed. To better characterize this unexpected population and confirm its nature, we obtained Palomar/DBSP spectroscopy for 26 of the optically-bright (G<15 mag) "isolated" YSO candidates. We confirm the YSO classifications of all 26 sources based on their positions on the Hertzsprung-Russell diagram, H and Ca II line-emission from over half the sample, and robust detection of infrared excesses. This implies a contamination rate of <10% for SPICY stars that meet our optical selection criteria. Spectral types range from B4 to K3, with A-type stars most common. Spectral energy distributions, diffuse interstellar bands, and Galactic extinction maps indicate moderate to high extinction. Stellar masses range from ~1 to 7 $M_\odot$, and the estimated accretion rates, ranging from $3\times10^{-8}$ to $3\times10^{-7}$ $M_\odot$ yr$^{-1}$, are typical for YSOs in this mass range. The 3D spatial distribution of these stars, based on Gaia astrometry, reveals that the "isolated" YSOs are not evenly distributed in the Solar neighborhood but are concentrated in kpc-scale dusty Galactic structures that also contain the majority of the SPICY YSO clusters. Thus, the processes that produce large Galactic star-forming structures may yield nearly as many distributed as clustered YSOs.Comment: Accepted for publication in AJ. 22 pages, 9 figures, and 4 tables. Figure sets are available from https://sites.astro.caltech.edu/~mkuhn/SPICY/PaperIII

Surprising dissimilarities in a newly formed pair of 'identical twin' stars

The mass and chemical composition of a star are the primary determinants of its basic physical properties--radius, temperature, luminosity--and how those properties evolve with time. Thus, two stars born at the same time, from the same natal material, and with the same mass are 'identical twins,' and as such might be expected to possess identical physical attributes. We have discovered in the Orion Nebula a pair of stellar twins in a newborn binary star system. Each star in the binary has a mass of 0.41 +/- 0.01 solar masses, identical to within 2 percent. Here we report that these twin stars have surface temperatures that differ by ~300K (~10%), and luminosities that differ by ~50%, both at high confidence level. Preliminary results indicate that the stars' radii also differ, by 5-10%. These surprising dissimilarities suggest that one of the twins may have been delayed by several hundred thousand years in its formation relative to its sibling. Such a delay could only have been detected in a very young, definitively equal-mass binary system3 such as that reported here. Our findings reveal cosmic limits on the age synchronisation of young binary stars, often used as tests for the age calibrations of star-formation models.Comment: Published in Nature, 19 June 200

A Moderated Nonlinear Factor Model for the Development of Commensurate Measures in Integrative Data Analysis

Integrative data analysis (IDA) is a methodological framework that allows for the fitting of models to data that have been pooled across two or more independent sources. IDA offers many potential advantages including increased statistical power, greater subject heterogeneity, higher observed frequencies of low base-rate behaviors, and longer developmental periods of study. However, a core challenge is the estimation of valid and reliable psychometric scores that are based on potentially different items with different response options drawn from different studies. In Bauer and Hussong (2009) we proposed a method for obtaining scores within an IDA called moderated nonlinear factor analysis (MNLFA). Here we move significantly beyond this work in the development of a general framework for estimating MNLFA models and obtaining scale scores across a variety of settings. We propose a five step procedure and demonstrate this approach using data drawn from n=1972 individuals ranging in age from 11 to 34 years pooled across three independent studies to examine the factor structure of 17 binary items assessing depressive symptomatology. We offer substantive conclusions about the factor structure of depression, use this structure to compute individual-specific scale scores, and make recommendations for the use of these methods in practice