Effect of calcium on phenothiazine inhibition of neutrophil degranulation

The phenothiazines are known to be potent inhibitors of calmodulin and have been used as probes for examining calmodulin‐dependent cellular functions. We report here that the characteristics of phenothiazine inhibition of exocytosis in neutrophils more closely resemble their interaction with the annexins in vitro. Ca2+‐ dependent aggregation of liposomes mediated by either annexin I or annexin II was inhibited by the phenothiazines. Inhibition of liposome aggregation was not caused by interference with the binding of annexins to phospholipids. Rather, the phenothiazines increased the concentration of Ca2+ required for aggregation. Likewise, in neutrophils pepneabilized with streptolysin O, inhibition of degranulation by phenothiazines could be overcome by increasing [Ca2+]. These results suggest that inhibition by phenothiazines of neutrophil degranulation is secondary to the ability of these compounds to inhibit membrane‐membrane contact promoted by the annexins. J. Leukoc. Biol. 58: 114–118; 1995.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141375/1/jlb0114.pd

Initial-state dependence in time-dependent density functional theory

Time-dependent density functionals in principle depend on the initial state of the system, but this is ignored in functional approximations presently in use. For one electron it is shown there is no initial-state dependence: for any density, only one initial state produces a well-behaved potential. For two non-interacting electrons with the same spin in one-dimension, an initial potential that makes an alternative initial wavefunction evolve with the same density and current as a ground state is calculated. This potential is well-behaved and can be made arbitrarily different from the original potential

Reduction of nickel oxide particles by hydrogen studied in an environmental TEM

In situ reduction of nickel oxide (NiO) particles is performed under 1.3mbar of hydrogen gas (H2) in an environmental transmission electron microscope (ETEM). Images, diffraction patterns and electron energy-loss spectra (EELS) are acquired to monitor the structural and chemical evolution of the system during reduction, whilst increasing the temperature. Ni nucleation on NiO is either observed to be epitaxial or to involve the formation of randomly oriented grains. The growth of Ni crystallites and the movement of interfaces result in the formation of pores within the NiO grains to accommodate the volume shrinkage associated with the reduction. Densification is then observed when the sample is nearly fully reduced. The reaction kinetics is obtained using EELS by monitoring changes in the shapes of the Ni L2,3 white lines. The activation energy for NiO reduction is calculated from the EELS data using both a physical model-fitting technique and a model-independent method. The results of the model-fitting procedure suggest that the reaction is described by Avrami models (whereby the growth and impingement of Ni domains control the reaction), in agreement with the ETEM observation

Identification of glyceraldehyde‐3‐phosphate dehydrogenase as a Ca2+‐dependent fusogen in human neutrophil cytosol

The membrane fusion events observed during neutrophil degranulation are important aspects of the immunoregulatory system. In an attempt to understand the regulation of granule‐plasma membrane fusion, we have begun characterizing human neutrophil cytosol for fusion activity, finding that 50% of the fusogenic activity could be attributed to members of the annexin family of proteins. The major non‐annexin fusion activity (25% of the total cytosolic activity) was enriched by ion exchange chromatography after depletion of annexins by Ca2+‐dependent phospholipid affinity chromatography. The fusion activity co‐purified with a 10,14‐kDa dimer identified as leukocyte L1 (which was non‐fusogenic), along with an approximately 36‐kDa protein. This protein was identified as glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) by amino‐terminal sequencing, and the fusion activity was verified using commercially available GAPDH. GAPDH may play an important role in degranulation because it is as potent as annexin I on a mass basis and may constitute up to 25% of the total cytosolic fusion activity of the neutrophil. J. Leukoc. Biol. 63: 331–336; 1998.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142089/1/jlb0331.pd

PLA2 promotes fusion between PMN‐specific granules and complex liposomes

Neutrophil stimulation results in the activation of a variety of phospholipases, including phospholipase A2 (PLA2), which releases arachidonic acid from the 2 position of membrane phospholipids, leaving a lysophospholipid. Because arachidonic acid is known to be a potent fusogen in vitro, we examined the effect of metabolism by PLA2 on the fusion of complex liposomes (liposomes prepared with a phospholipid composition similar to that found in neutrophil plasma membrane). We observed that PLA2 augmented the fusion of complex liposomes with each other as well as with specific granules isolated from human neutrophils, lowering the Ca2+ requirement for fusion by three orders of magnitude. Furthermore, although lysophospholipids inhibited fusion, the incorporation of arachidonic acid into liposome membranes overcame the inhibitory effects of the lysophospholipids. Thus with PLA2 and annexins we were able to obtain fusion of complex liposomes at concentations of Ca2+ that are close to physiological. Our data suggest that the activation of PLA2 and the generation of arachidonic acid may be the major fusion‐promoting event mediating neutrophil degranulation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141645/1/jlb0663.pd

Spin currents and spin dynamics in time-dependent density-functional theory

We derive and analyse the equation of motion for the spin degrees of freedom within time-dependent spin-density-functional theory (TD-SDFT). Results are (i) a prescription for obtaining many-body corrections to the single-particle spin currents from the Kohn-Sham equation of TD-SDFT, (ii) the existence of an exchange-correlation (xc) torque within TD-SDFT, (iii) a prescription for calculating, from TD-SDFT, the torque exerted by spin currents on the spin magnetization, (iv) a novel exact constraint on approximate xc functionals, and (v) the discovery of serious deficiencies of popular approximations to TD-SDFT when applied to spin dynamics.Comment: now includes discussion of OEP and GGA; to appear in Phys. Rev. Let

Exchange and Correlation Kernels at the Resonance Frequency -- Implications for Excitation Energies in Density-Functional Theory

Specific matrix elements of exchange and correlation kernels in time-dependent density-functional theory are computed. The knowledge of these matrix elements not only constraints approximate time-dependent functionals, but also allows to link different practical approaches to excited states, either based on density-functional theory, or on many-body perturbation theory, despite the approximations that have been performed to derive them.Comment: Submitted to Phys. Rev. Lett. (February 4, 1999). Other related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Diabetes Distress but Not Clinical Depression or Depressive Symptoms Is Associated With Glycemic Control in Both Cross-Sectional and Longitudinal Analyses

ObjectiveTo determine the concurrent, prospective, and time-concordant relationships among major depressive disorder (MDD), depressive symptoms, and diabetes distress with glycemic control.Research design and methodsIn a noninterventional study, we assessed 506 type 2 diabetic patients for MDD (Composite International Diagnostic Interview), for depressive symptoms (Center for Epidemiological Studies-Depression), and for diabetes distress (Diabetes Distress Scale), along with self-management, stress, demographics, and diabetes status, at baseline and 9 and 18 months later. Using multilevel modeling (MLM), we explored the cross-sectional relationships of the three affective variables with A1C, the prospective relationships of baseline variables with change in A1C over time, and the time-concordant relationships with A1C.ResultsAll three affective variables were moderately intercorrelated, although the relationship between depressive symptoms and diabetes distress was greater than the relationship of either with MDD. In the cross-sectional MLM, only diabetes distress but not MDD or depressive symptoms was significantly associated with A1C. None of the three affective variables were linked with A1C in prospective analyses. Only diabetes distress displayed significant time-concordant relationships with A1C.ConclusionsWe found no concurrent or longitudinal association between MDD or depressive symptoms with A1C, whereas both concurrent and time-concordant relationships were found between diabetes distress and A1C. What has been called "depression" among type 2 diabetic patients may really be two conditions, MDD and diabetes distress, with only the latter displaying significant associations with A1C. Ongoing evaluation of both diabetes distress and MDD may be helpful in clinical settings