Carbachol and bradykinin elevate cyclic AMP and rapidly deplete ATP in cultured rat sympathetic neurons

The agonists carbachol (CCh) and bradykinin (BK) and 54 mM KCl (high K+) were among the most potent stimulants of cyclic AMP (cAMP) production in cultured rat sympathetic neurons, measured with the use of a high-fidelity assay developed for small samples. The rise in cAMP evoked by CCh (through muscarinic receptors), BK, and high K+ was inhibited in Ca2(+)-depleted medium (1.3 mM Ca2+ and 2 mM BAPTA or EGTA), which also prevented the sustained rise in [Ca2+]i evoked by each of these stimuli, showing that elevation of cAMP requires extracellular Ca2+ and, possibly, Ca2+ influx. Preliminary results obtained with the novel calmodulin inhibitor CGS 9343B, which blocked the elevation of cAMP, and with the cyclogenase inhibitor indomethacin, which partially blocked the actions of the agonists but not those of high K+, suggest that calmodulin and arachidonate metabolites may be two components of the signaling pathway. In addition to their effects on cAMP metabolism, CCh, muscarine, and BK, but not nicotine, caused a 30-40% decrease in ATP levels. This effect was much greater than that evoked by high K+ and was largely inhibited by CGS 9343B but slightly enhanced in the Ca(+)-depleted medium, showing that agonists are still active in the absence of [Ca2+]o. Thus, agonists that activate phosphoinositide metabolism can also increase cAMP production and substantially deplete cells of ATP. These novel actions may have to be taken into account when the mechanisms by which such agonists regulate cell function are being considered

A Resource Manual to Help Parents Work Effectively with At-Risk 5th Grade Students

The purpose of this project was to design and develop a resource manual to help parents work effectively with at-risk, 5th grade students, in the Clover Park School District, Lakewood, Washington. To accomplish this purpose a review of current literature regarding at-risk students and parent involvement was conducted. Additionally, various organizations were solicited for community resources including: United Way, Department of Social & Health Services, Puget Sound Educational Service District, Equal Opportunity Resource Center, and Pierce County Community Action Agency. Finally, all resource materials were compiled, organized, and assembled

Galina Ustvolskaya (1919-2006): Analytical Approach To The Pitch Content of Selected Compositions

Galina Ustvolskaya was overshadowed throughout her lifetime, both personally and professionally, by her compositional colleague, Dmitri Shostakovich. This dissertation seeks to establish Ustvolskaya’s separate identity, making her idiosyncratic compositional design the forefront of the research. A contextual transformational approach suits her compositional design built upon the element of repetition. Employing Joseph Straus’s analytical approach to the music of Ruth Crawford Seeger, this dissertation will explore a selection of Ustvolskaya’s work, demonstrating the evolution of her compositional design. The melodic foundations of Ustvolskaya’s compositional approach are based upon compact motives established at the onset of each work. The motives are then subjected to a process of development rooted in the concept of varied or developed repetition. Contextual transformations are subjected upon the motives, which are defined by their directed interval-class segments in the horizontal domain. Relationships, derivations, and associations will be revealed through the transformations, demonstrating a cohesive design. As will be demonstrated throughout the analyses, Ustvolskaya’s treatment of repetition is subjected to a process of evolution that exemplifies continual simplification over time of her compositional process. The earlier works display a less explicit use of repetition. As her style evolves, the element of repetition maintains its grasp, while at the same time infiltrating the shallower layers of the work, thus becoming more audible to the listener. As her style evolves further, the element of repetition subsumes the composition as a whole, exhibiting a fully evolved, mature design that has been stripped of superfluous elements

Ca2+ transients are not required as signals for long-term neurite outgrowth from cultured sympathetic neurons

A method for clamping cytosolic free Ca2+ ([Ca2+]i) in cultures of rat sympathetic neurons at or below resting levels for several days was devised to determine whether Ca2+ signals are required for neurite outgrowth from neurons that depend on Nerve Growth Factor (NGF) for their growth and survival. To control [Ca2+]i, normal Ca2+ influx was eliminated by titration of extracellular Ca2+ with EGTA and reinstated through voltage-sensitive Ca2+ channels. The rate of neurite outgrowth and the number of neurites thus became dependent on the extent of depolarization by KCl, and withdrawal of KCl caused an immediate cessation of growth. Neurite outgrowth was completely blocked by the L type Ca2+ channel antagonists nifedipine, nitrendipine, D600, or diltiazem at sub- or micromolar concentrations. Measurement of [Ca2+]i in cell bodies using the fluorescent Ca2+ indicator fura-2 established that optimal growth, similar to that seen in normal medium, was obtained when [Ca2+]i was clamped at resting levels. These levels of [Ca2+]i were set by serum, which elevated [Ca2+]i by integral of 30 nM, whereas the addition of NGF had no effect on [Ca2+]i. The reduction of [Ca2+]o prevented neurite fasciculation but this had no effect on the rate of neurite elongation or on the number of extending neurites. These results show that neurite outgrowth from NGF-dependent neurons occurs over long periods in the complete absence of Ca2+ signals, suggesting that Ca2+ signals are not necessary for operating the basic machinery of neurite outgrowth

Analytical Two-valued Potential Energy Functions for the Ground State Surfaces of CO2 and CS2

A potential model for two-valued triatomic surfaces is reviewed with reference to the ground state potentials O·f 02(X11;g+) and CS2(X11:g+) . A comparison is made between the observed J = O vibrational spectra and those calculated from the derived potentia1ls by a variational method. For C02 the strong Fermi-resonance in the (10"0) and (02°0) vibrational states is confirmed for the first time using a full three-dimensional potential and a complete vibrational hamiltonian

Partitioning of K, U, and Th between sulfide and silicate liquids: Implications for radioactive heating of planetary cores

The possibility of heating of planetary cores by K radioactivity has been extensively discussed, as well as the possibility that K partitioning into the terrestrial core is the reason for the difference between the terrestrial and chondritic K/U. We had previously suggested that U and Th partitioning into FeFeS liquids was more important than K. Laboratory FeFeS liquid, silicate liquid partition coefficient measurements (D) for K, U, and Th were made to test this suggestion. For a basaltic liquid at 1450°C and 1.5 GPa, D_U is 0.013 and D_K is 0.0026; thus U partitioning into FeFeS liquids is 5 times greater than K partitioning under these conditions. There are problems with 1-atm experiments in that they do not appear to equilibrate or reverse. However, measurable U and Th partitioning into sulfide was nearly always observed, but K partitioning was normally not observed (D_K ≲ 10^(−4)). A typical value for D_U from a granitic silicate liquid at one atmosphere, 1150°C, and low f0_2 is about 0.02; D_(Th) is similar. At low f0_2 and higher temperature, experiments with basaltic liquids produce strong Ca and U partitioning into the sulfide liquid with D_U > 1. D_(Th) is less strongly affected. Because of the consistently low D_K/D_U, pressure effects near the core-mantle boundary would need to increase D_U by factors of ∼10^3 with much smaller increases in DU in order to have the terrestrial K and U abundances at chondritic levels. In addition, if radioactive heating is important for planetary cores, U and Th will be more important than K unless the lower mantle has K/U greater than 10 times chondritic or large changes in partition coefficients with conditions reverse the relative importance of K versus U and Th from our measurements

Extreme Pu-U and Possible Pu-REE Fractionation in Unequilibrated Chondrites

The purpose of this study is to understand actinide chemistry in chondrites and to evaluate unequilibrated chondrites for either Pu/U or Pu/Nd chronology. Using fission track radiography for Nadiabondi (H5/(Murrell and Burnett, 1982), Dhajala (H3,4), Bremervorde (H3), Sharps (H3), and Tieschitz (H3), we find that U is primarily located in chondrule glass (50-500 ppb, average of ~ 100 ppb). Apatite from the unequilibrated chondrites contains 150-200 ppb U while whitlockite contains < 17 ppb [low compared to type-6 chondrites which have 1-6 ppm U in apatite and ~ 200 ppb in whitlockite (Pellas and Storzer, 1975)]. Nadiabondi phosphates are intermediate (Murrell and Burnett, 1982). These observations suggest that the phosphate U content increases with petrologic type (Pellas and Storzer, 1975), with U obtained from chondrule glass during metamorphism

Interplay between substrate rigidity and tissue fluidity regulates cell monolayer spreading

Coordinated and cooperative motion of cells is essential for embryonic development, tissue morphogenesis, wound healing and cancer invasion. A predictive understanding of the emergent mechanical behaviors in collective cell motion is challenging due to the complex interplay between cell-cell interactions, cell-matrix adhesions and active cell behaviors. To overcome this challenge, we develop a predictive cellular vertex model that can delineate the relative roles of substrate rigidity, tissue mechanics and active cell properties on the movement of cell collectives. We apply the model to the specific case of collective motion in cell aggregates as they spread into a two-dimensional cell monolayer adherent to a soft elastic matrix. Consistent with recent experiments, we find that substrate stiffness regulates the driving forces for the spreading of cellular monolayer, which can be pressure-driven or crawling-based depending on substrate rigidity. On soft substrates, cell monolayer spreading is driven by an active pressure due to the influx of cells coming from the aggregate, whereas on stiff substrates, cell spreading is driven primarily by active crawling forces. Our model predicts that cooperation of cell crawling and tissue pressure drives faster spreading, while the spreading rate is sensitive to the mechanical properties of the tissue. We find that solid tissues spread faster on stiff substrates, with spreading rate increasing with tissue tension. By contrast, the spreading of fluid tissues is independent of substrate stiffness and is slower than solid tissues. We compare our theoretical results with experimental results on traction force generation and spreading kinetics of cell monolayers, and provide new predictions on the role of tissue fluidity and substrate rigidity on collective cell motion