2,226 research outputs found
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
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
A National Survey of Faculty Development Evaluation Outcome Measures and Procedures
This article presents the results of a national study of 39 higher education institutions that collected information about their evaluation procedures and outcome measures for faculty development for online teaching conducted during 2011-2012. The survey results found that over 90% of institutions used measures of the faculty person’s assessment of satisfaction and usefulness of the training; student GPAs were used by only 30% of the institutions. As for how evaluations were conducted, online evaluations were used by 80% of institutions and focus groups were used by 21% of the institutions
AFM imaging reveals the assembly of a P2X receptor complex containing P2X2, P2X4 and P2X6 subunits
Seven P2X purinergic receptor subunits have been identified: P2X1-P2X7. All except P2X6 assemble as homotrimers, and six heteromeric receptors (P2X1/2, P2X1/4, P2X1/5, P2X2/3, P2X2/6 and P2X4/6) have been described. In addition, P2X4 homomers associate with P2X2 or P2X7 homomers as dimers of trimers. The various P2X receptors show individual functional properties, suggesting distinct physiological roles. The overlapping expression of P2X2, P2X4 and P2X6 subunits has been shown in different cell types, and functional analysis of P2X receptors in Leydig cells suggests that the three subunits interact
Growing Multiconfigurational Potential Energy Surfaces with Applications to X+H2 (X=C,N,O) Reactions
A previously developed method, based on a Shepard interpolation procedure to automatically construct a quantum mechanical potential energy surface (PES), is extended to the construction of multiple potential energy surfaces using multiconfigurational wave functions. These calculations are accomplished with the interface of the PES-building program, GROW, and the GAMESS suite of electronic structure programs. The efficient computation of multiconfigurational self-consistent field surfaces is illustrated with the C+H2, N+H2, and O+H2reactions
Electronic structure and the glass transition in pnictide and chalcogenide semiconductor alloys. Part I: The formation of the -network
Semiconductor glasses exhibit many unique optical and electronic anomalies.
We have put forth a semi-phenomenological scenario (J. Chem. Phys. 132, 044508
(2010)) in which several of these anomalies arise from deep midgap electronic
states residing on high-strain regions intrinsic to the activated transport
above the glass transition. Here we demonstrate at the molecular level how this
scenario is realized in an important class of semiconductor glasses, namely
chalcogen and pnictogen containing alloys. Both the glass itself and the
intrinsic electronic midgap states emerge as a result of the formation of a
network composed of -bonded atomic -orbitals that are only weakly
hybridized. Despite a large number of weak bonds, these -networks are
stable with respect to competing types of bonding, while exhibiting a high
degree of structural degeneracy. The stability is rationalized with the help of
a hereby proposed structural model, by which -networks are
symmetry-broken and distorted versions of a high symmetry structure. The latter
structure exhibits exact octahedral coordination and is fully
covalently-bonded. The present approach provides a microscopic route to a fully
consistent description of the electronic and structural excitations in vitreous
semiconductors.Comment: 22 pages, 17 figures, revised version, final version to appear in J.
Chem. Phy
State-to-State Differential and Relative Integral Cross Sections for Rotationally Inelastic Scattering of H2O by Hydrogen
State-to-state differential cross sections (DCSs) for rotationally inelastic
scattering of H2O by H2 have been measured at 71.2 meV (574 cm-1) and 44.8 meV
(361 cm-1) collision energy using crossed molecular beams combined with
velocity map imaging. A molecular beam containing variable compositions of the
(J = 0, 1, 2) rotational states of hydrogen collides with a molecular beam of
argon seeded with water vapor that is cooled by supersonic expansion to its
lowest para or ortho rotational levels (JKaKc= 000 and 101, respectively).
Angular speed distributions of fully specified rotationally excited final
states are obtained using velocity map imaging. Relative integral cross
sections are obtained by integrating the DCSs taken with the same experimental
conditions. Experimental state-specific DCSs are compared with predictions from
fully quantum scattering calculations on the most complete H2O-H2 potential
energy surface. Comparison of relative total cross sections and state-specific
DCSs show excellent agreement with theory in almost all detailsComment: 46 page
Entropy Production Rate is Maximized in Non-Contractile Actomyosin
The actin cytoskeleton is an active semi-flexible polymer network whose
non-equilibrium properties coordinate both stable and contractile behaviors to
maintain or change cell shape. While myosin motors drive the actin cytoskeleton
out-of-equilibrium, the role of myosin-driven active stresses in the
accumulation and dissipation of mechanical energy is unclear. To investigate
this, we synthesize an actomyosin material in vitro whose active stress content
can tune the network from stable to contractile. Each increment in activity
determines a characteristic spectrum of actin filament fluctuations which is
used to calculate the total mechanical work and the production of entropy in
the material. We find that the balance of work and entropy does not increase
monotonically and, surprisingly, the entropy production rate is maximized in
the non-contractile, stable state. Our study provides evidence that the origins
of system entropy production and activity-dependent dissipation arise from
disorder in the molecular interactions between actin and myosinComment: 31 pages, 5 figure
The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene.
Neuregulin-1 (NRG1) is both a candidate oncogene and a candidate tumour suppressor gene. It not only encodes the heregulins and other mitogenic ligands for the ERBB family, but also causes apoptosis in NRG1-expressing cells. We found that most breast cancer cell lines had reduced or undetectable expression of NRG1. This included cell lines that had translocation breaks in the gene. Similarly, expression in cancers was generally comparable to or less than that in various normal breast samples. Many non-expressing cell lines had extensive methylation of the CpG island at the principal transcription start site at exon 2 of NRG1. Expression was reactivated by demethylation. Many tumours also showed methylation, whereas normal mammary epithelial fragments had none. Lower NRG1 expression correlated with higher methylation. Small interfering RNA (siRNA)-mediated depletion of NRG1 increased net proliferation in a normal breast cell line and a breast cancer cell line that expressed NRG1. The short arm of chromosome 8 is frequently lost in epithelial cancers, and NRG1 is the most centromeric gene that is always affected. NRG1 may therefore be the major tumour suppressor gene postulated to be on 8p: it is in the correct location, is antiproliferative and is silenced in many breast cancers
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