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Variation of large-scale regularity in modulated structures of Ca2CoSi2O7 studied by a simulation method.

The period of two-dimensional modulation in Ca2CoSi2O7 varies with temperature (q = 0.285-1/3). The change in the modulated structure with the variation of q has been clarified by the construction of the structures using various q values and the modulation amplitudes determined at 293 K [q = 0.2913 (1), tetragonal]. The features of the modulated structures are characterized by the formation of CaO6 polyhedra and the variable distribution of bundles along the c-axis, composed of four arrays of CaO6 polyhedra and an array of CoO4 tetrahedra. The formation of octagonal arrangements of the bundles is a typical feature of the structures in the incommensurate phase. Large-scale regularities with sizes much larger than the modulation wavelength are also formed in the structures.

Journal Article↗

Modulated structure of potassium sodium strontium barium niobates (KNSBN): harmonic solution.

The structures of two specimens of the (K(1 - y)Na(y))(2F - 2)(Sr(x)Ba(1 - x))(2 - F)Nb2O6 family (KNSBN) have been solved and refined (x(I) = 0.6, y(I) = 0.45, F(I) = 1.07 and x(II) = 0.72, y(II) = 0.45, F(II) = 1.08). The KNSBN compounds appear to be incommensurately modulated, as described in a five-dimensional superspace approach with the tetragonal P4bm (pp1/2, p - p1/2) superspace group. Their modulation wavevectors are almost independent of the composition. The description of the modulation is restricted to first-order harmonics in order to limit the number of refined parameters. The modulation mainly affects the positions of the O atoms and their displacements depend on the Sr/Ba ratio. The structural models for the two compounds are not only almost identical, but also analogous to the structural model of the Sr(x)Ba(1 - x)Nb2O6 parent compound: doping with K+ and Na+ cations has no significant influence on the incommensurate modulation, contrary to the strong dependence observed for the physical properties.

Journal Article↗

Modulated structures of Cs2HgCl4: the 5a superstructure at 185 K and the 3c superstructure at 176 K.

Crystalline dicaesium mercury tetrachloride (Cs(2)HgCl(4)) is isomorphous with beta-K(2)SO(4) (space group Pnma, Z = 4) in its normal phase at room temperature. On cooling a sequence of incommensurate and commensurate superstructures occurs, below T = 221 K with modulations parallel to a*, and below 184 K with modulations along c*. The commensurately modulated structures at T = 185 K with q = (1/5)a* and at T = 176 K with q = (1/3)c* were determined using X-ray scattering with synchrotron radiation. The structure at T = 185 K has superspace group Pnma(alpha,0,0)0ss with alpha = 0.2. Lattice parameters were determined as a = 5 x 9.7729 (1), b = 7.5276 (4) and c = 13.3727 (7) Å. Structure refinements converged to R = 0.050 (R = 0.042 for 939 main reflections and R = 0.220 for 307 satellites) for the section t = 0.05 of superspace. The fivefold supercell has space group Pn2(1)a. The structure at T = 176 K has superspace group Pnma(0,0,gamma)0s0 with gamma = 1/3. Lattice parameters were determined as a = 9.789 (3), b = 7.541 (3) and c = 3 x 13.418 (4) Å. Structure refinements converged to R = 0.067 (R = 0.048 for 2130 main reflections, and R = 0.135 for 2382 satellite reflections) for the section t = 0. The threefold supercell has space group P112(1)/a. It is shown that the structures of both low-temperature phases can be characterized as different superstructures of the periodic room-temperature structure. The superstructure of the 5a-modulated phase is analysed in terms of displacements of the Cs atoms, and rotations and distortions of HgCl(4) tetrahedral groups. In the 3c-modulated phase the distortions of the tetrahedra are relaxed, but they are replaced by translations of the tetrahedral groups in addition to rotations.

Journal Article↗

Performance characteristics of a compact position-sensitive LSO detector module.

We assembled a compact detector module comprised of an array of small, individual crystals of lutetium oxyorthosilicate:Ce (LSO) coupled directly to a miniature, metal-can, position-sensitive photomultiplier tube (PSPMT). We exposed this module to sources of 511-keV annihilation radiation and beams of 30- and 140-keV photons and measured spatial linearity; spatial variations in module gain, energy resolution, and event positioning; coincidence timing; the accuracy and sensitivity of identifying the crystal-of-first-interaction at 511 keV; and the effects of intercrystal scatter and LSO background radioactivity. The results suggest that this scintillator/phototube combination should be highly effective in the coincidence mode and can be used, with some limitations, to image relatively low-energy single photon emitters. Photons that are completely absorbed on their first interaction at 511 keV are positioned by the module at the center of a crystal. Intercrystal scatter events, even those that lead to total absorption of the incident photon, are placed by the module in a regular "connect-the-dot" pattern that joins crystal centers. As a result, the accuracy of event positioning can be made to exceed 90%, though at significantly reduced sensitivity, by retaining only events that occur within small regions-of-interest around each crystal center and rejecting events that occur outside these regions in the connect-the-dot pattern.

Animals↗

Localization of the laminin alpha4 chain in the skin and identification of a heparin-dependent cell adhesion site within the laminin alpha4 chain C-terminal LG4 module.

The laminin alpha4 chain, a component of laminin-8/9, is expressed in basement membranes of endothelial cells, the peripheral nerves, and muscle fibers. The localization and functions of laminin alpha4 chain in the skin have not been elucidated. By immunostaining with specific antibodies, we demonstrate here that the alpha4 chain is located in the basement membrane zones of blood vessels and is also associated with fibroblast-like cells in the dermis. Western blot showed that cultured fibroblasts secreted a laminin trimer containing the alpha4 chain. We have also focused on the cell adhesion activities of the human laminin alpha4 LG4 module since the corresponding LG4 module of laminin alpha3 was previously identified as active for cell adhesion. Recombinant human alpha4 LG4 was active for heparin-dependent fibroblast adhesion. Screening assays with 19 synthetic peptides covering the entire alpha4 LG4 module identified three peptides (HA4G82: TLFLAHGRLVYM; HA4G83: LVYMFNVGHKKL; and HA4G90: TEATWKIKGPIYL) as active sites for heparin- and heparan sulfate-dependent cell adhesion. Serine-substituted peptides demonstrated that two basic residues, His and Arg, within HA4G82 were essential for cell adhesion activity. The cell surface heparan sulfate proteoglycans (HSPGs), syndecan-2, -4, and glypican-1, were stably expressed in 293T cells to estimate whether they function as cell adhesion receptors. 293T cells overexpressing syndecan-2 or -4 bound to recombinant alpha4 LG4 and to HA4G82, but parental or glypican-1-overexpressing 293T cells did not. Therefore, syndecan-2 and -4 could mediate cell adhesion to the laminin alpha4 LG4 module. Our study suggests that the laminin alpha4 LG4 module may play an important role in cell adhesion and/or vessel wall formation in the skin by interacting with syndecan-2 and/or -4.

Binding Sites↗

Modulation of AMPA currents by D2 dopamine receptors in striatal medium-sized spiny neurons: are dendrites necessary?

Glutamatergic afferents from the neocortex constitute the major excitatory input to striatal medium-sized spiny neurons (MSNs). Glutamate's actions on MSNs are modulated by dopamine (DA) through D1 and D2 receptor families. Although D1 modulation of glutamate responses has been well-characterized, the contribution of postsynaptic D2 receptors to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) responses has not been studied extensively. We examined DA modulation of AMPA currents using whole-cell voltage-clamp recordings of MSNs acutely dissociated and in slices. In dissociated cells, the D2 agonist quinpirole (10 micro m) produced small and inconsistent effects on AMPA currents. The magnitude of the current, as well as its modulation by quinpirole, was related to the dendritic elaboration of the dissociated cell. Thus, quinpirole altered AMPA currents only slightly when few initial dendritic segments were present. The amplitude of the current was greater and quinpirole consistently decreased this current in dissociated cells displaying at least three primary dendrites and several secondary and tertiary dendrites. Cyclothiazide, a compound that prevents AMPA receptor desensitization, greatly increased AMPA currents. In the presence of cyclothiazide, quinpirole also consistently reduced AMPA currents. Finally, in slices, AMPA current amplitude was always reduced after application of quinpirole. Sulpiride, a D2 antagonist, prevented attenuation of AMPA currents in both acutely dissociated neurons and neurons in slices. These results provide evidence that AMPA currents are attenuated by DA via activation of postsynaptic D2 receptors. In addition, they indicate that the dendrites and/or the amplitude of the current are important variables for DA modulation of AMPA currents in MSNs.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

CD3-T cell receptor modulation is selectively induced in CD8 but not CD4 lymphocytes cultured in agar.

The CD3-T cell receptor (TcR) complex is central to the immune response. Upon binding by specific ligands, internalized CD3-TcR molecules increase, and either T cell response or unresponsiveness may ensue depending on the triggering conditions. Using semi-solid agar culture, we have shown previously that quiescent CD4 but not CD8 lymphocytes generate clonal colonies under phytohaemagglutinin stimulation. Here we have demonstrated that the agar induces selective CD3-TcR modulation in the CD8 and not in the CD4 subset. CD8 lymphocytes preactivated in liquid culture and recultured in agar with exogenous recombinant interleukin-2 generate colonies with a modulated CD3-TcR surface expression. The peptides composing the CD3-TcR complex are synthesized in CD8 colonies as well as in CD4; however, the CD3 gamma chain is phosphorylated at a higher level in CD8 colonies. A component of the agar polymer, absent in agarose, appears to be the ligand that induces differential CD3-TcR modulation in the CD8 subset. In contrast to agar culture, CD8 colonies can be derived from quiescent CD8 lymphocytes in agarose. These CD8 colonies express unmodulated CD-TcR. CD3-TcR modulation with anti-CD3 monoclonal antibody prior to culturing in agarose inhibits the colony formation. We conclude that given triggering conditions can result in both CD3-TcR modulation and inhibition of the proliferative response selectively in the CD8 lymphocyte subset and not in the CD4.

Agar↗

Cytotoxic T lymphocyte antigen-4-dependent down-modulation of costimulatory molecules on dendritic cells in CD4+ CD25+ regulatory T-cell-mediated suppression.

We have previously demonstrated that CD4+ CD25+ natural regulatory T cells (Treg cells) induce down-modulation of CD80 and CD86 (B7) molecules on dendritic cells (DCs) in vitro. In this report we show that the extent of down-modulation is functionally significant because Treg-cell conditioned DCs induced poor T-cell proliferation responses. Further, we report that down-modulation was induced rapidly and was inhibited by blocking cytotoxic T lymphocyte antigen-4 (CTLA-4), which is constitutively expressed by the Treg cells. Even though Treg cells have previously been reported to kill antigen-presenting cells, the down-modulation was not due to selective killing of DCs expressing high level of the costimulatory molecules. We propose that Treg cells down-modulate B7-molecules on DCs in a CTLA-4-dependent way, thereby enhancing suppression of T-cell activity.

Animals↗

Flow cytometric analysis of CD2 modulation on human peripheral blood T lymphocytes by Dharmendra preparation of Mycobacterium leprae.

It has been reported previously that Mycobacterium leprae modulated CD2 on human peripheral blood T lymphocytes and that this modulation was accompanied by a marked reduction in the proliferative response of these cells to mitogens and antigens. In this study, we report that treatment of peripheral blood mononuclear cells from healthy individuals with Dharmendra preparation of M. leprae inhibited their ability to form rosettes with sheep red blood cells. Flow cytometric analysis of Dharmendra lepromin-treated cells showed that, in addition to CD2, CD4 and CD8 were modulated while the surface expression of CD3 was not affected. The specificity of CD2 modulation was confirmed by similar effects of Dharmendra lepromin on thymocytes and lymph node cells from human CD2 transgenic mice. The modulatory effect of Dharmendra lepromin was not observed at lower temperatures. Dharmendra lepromin treatment of activated T cells resulted in reduced binding of monoclonal antibodies to IL-2R and D66 epitope of CD2. The modulatory effects were not observed with Dharmendra preparation of BCG or other preparations of M. leprae. Our results indicate that certain M. leprae factor(s) specifically modulate(s) CD2, CD4, CD8 and IL-2R but not CD3 on T lymphocytes. The suppressive effect of Dharmendra lepromin on the T-cell proliferative response reported earlier may be explained by its modulatory effect on a number of T-cell surface molecules.

Animals↗

Epitope-specific differential modulations within the T-cell antigen receptor complex.

The feeding of cloned helper T cells by irradiated spleen cells results in the modulation of T-cell antigen receptors (TCRs) as detected by FACS. When two groups of anti-TCR antibodies--anti-idiotypic and anti-V beta--are compared, time-dependent patterns of modulation of TCR are drastically different. Whereas up to 80% of the idiotypic determinants disappear within 2 days after stimulation, almost no change is observed for the determinants recognized by V beta-specific antibodies within the same period. Sequential immunoprecipitations clearly showed that anti-idiotypic and anti-V beta antibodies recognize the same population of TCR. Moreover, surface labelling followed by immunoprecipitation of TCR did not show rapid and drastic changes in the amount of specifically precipitated material. The modulation is not significantly affected by the addition of specific antigen, but is specific for the clone's MHC restriction element. Functionally, the modulation of TCR epitopes affects the ability of anti-TCR antibody but not of the MHC/antigen complex to stimulate T cells. We conclude that the observed modulation of fluorescence intensity in the TCR complex after MHC recognition (1) is epitope specific, (2) is independent of the presence of nominal antigen and (3) does not affect the efficiency of antigen-specific stimulation.

Animals↗

The complete sequence of a 40-kDa actin-modulating protein from the earthworm Lumbricus terrestris.

The complete primary structure of a 40-kDa actin-modulating protein from the earthworm Lumbricus terrestris is presented. A muscle-specific cDNA library of the earthworm was constructed and screened with a specific DNA probe obtained by polymerase chain reaction considering information from peptide sequencing. A full-length clone with a coding region of 1098 bp was isolated. The deduced polypeptide sequence of 366 amino acids (41457 Da) reveals the segmental structure typical of both the 40-kDa and 80-kDa actin-modulating proteins. Prominent similarities to the 80-kDa protein gelsolin especially exist with respect to the first segment and to the C-terminal segment. The comparatively high nucleation efficiency of the earthworm actin modulator is probably determined by its third segment which seems to enable the earthworm actin modulator to bind a second G-actin molecule more tightly than other previously described 40-kDa modulators.

Actins↗

CaMK-II modulation of GABA(A) receptors expressed in HEK293, NG108-15 and rat cerebellar granule neurons.

The gamma-aminobutyric acid type A (GABA(A)) receptor is a pentameric ligand-gated ion channel responsible for fast synaptic inhibition in the brain. Phosphorylation of the GABA(A) receptor by serine/threonine protein kinases, at residues located in the intracellular loop between the third and fourth transmembrane domains of each subunit, can dynamically modulate receptor trafficking and function. In this study, we have assessed the effect that Ca(2+)-calmodulin-dependent protein kinase-II (CaMK-II) has on GABA(A) receptors. The intracellular application of preactivated CaMK-II failed to modulate the function of alphabeta and alphabetagamma subunit GABA(A) receptors heterologously expressed in human embryonic kidney (HEK)293 cells. However, application of similarly preactivated alpha-CaMK-II significantly potentiated the amplitudes of whole-cell GABA currents recorded from rat cultured cerebellar granule neurons and from recombinant GABA(A) receptors expressed in neuroblastoma, NG108-15, cells. The modulation by alpha-CaMK-II of current amplitude depended upon the subunit composition of GABA(A) receptors. alpha-CaMK-II potentiated GABA currents recorded from alpha1beta3 and alpha1beta3gamma2 GABA(A) receptors, but was unable to functionally modulate beta2 subunit-containing receptors. Similar results were obtained from beta2 -/- mouse cerebellar granule cell cultures and from rat granule cell cultures overexpressing recombinant alpha1beta2 or alpha1beta3 GABA(A) receptors. alpha-CaMK-II had a greater effect on the modulation of GABA responses mediated by alpha1beta3gamma2 compared with alpha1beta3 receptors, indicating a possible role for the gamma2 subunit in CaMK-II-mediated phosphorylation. In conclusion, CaMK-II can upregulate the function of GABA(A) receptors expressed in neurons or a neuronal cell line that is dependent on the beta subunit co-assembled into the receptor complex.

Animals↗

Current modulation and membrane targeting of the calcium channel alpha1C subunit are independent functions of the beta subunit.

1. The beta subunits of voltage-sensitive calcium channels facilitate the incorporation of channels into the plasma membrane and modulate calcium currents. In order to determine whether these two effects of the beta subunit are interdependent or independent of each other we studied plasma membrane incorporation of the channel subunits with green fluorescent protein and immunofluorescence labelling, and current modulation with whole-cell and single-channel patch-clamp recordings in transiently transfected human embryonic kidney tsA201 cells. 2. Coexpression of rabbit cardiac muscle alpha1C with rabbit skeletal muscle beta1a, rabbit heart/brain beta2a or rat brain beta3 subunits resulted in the colocalization of alpha1C with beta and in a marked translocation of the channel complexes into the plasma membrane. In parallel, the whole-cell current density and single-channel open probability were increased. Furthermore, the beta2a isoform specifically altered the voltage dependence of current activation and the inactivation kinetics. 3. A single amino acid substitution in the beta subunit interaction domain of alpha1C (alpha1CY467S) disrupted the colocalization and plasma membrane targeting of both subunits without affecting the beta subunit-induced modulation of whole-cell currents and single-channel properties. 4. These results show that the modulation of calcium currents by beta subunits can be explained by beta subunit-induced changes of single-channel properties, but the formation of stable alpha1C-beta complexes and their increased incorporation into the plasma membrane appear not to be necessary for functional modulation.

Animals↗

Modulation of ongoing EMG by different classes of low-threshold mechanoreceptors in the human hand.

1. We have previously demonstrated that the input from single FA I and SA II cutaneous mechanoreceptors in the glabrous skin of the human hand is sufficiently strong to modulate ongoing EMG of muscles acting on the digits. Some unresolved issues have now been addressed. 2. Single cutaneous (n = 60), joint (n = 2) and muscle spindle (n = 34) afferents were recorded via tungsten microelectrodes inserted into the median and ulnar nerves at the wrist. Spike-triggered averaging was used to investigate synaptic coupling between these afferents and muscles acting on the digits. The activity of 37 % of FA I (7/19), 20 % of FA II (1/5) and 52 % of SA II afferents (11/21) evoked a reflex response. The discharge from muscle spindles, 15 SA I and two joint afferents did not modulate EMG activity. 3. Two types of reflex responses were encountered: a single excitatory response produced by irregularly firing afferents, or a cyclic modulation evoked by regularly discharging afferents. Rhythmic stimulation of one FA I afferent generated regularly occurring bursts which corresponded to the associated cyclic EMG response. 4. Selectively triggering from the first or last spike of each burst of one FA I afferent altered the averaged EMG profile, suggesting that afferent input modulates the associated EMG and not vice versa. 5. The discharge from single FA I, FA II and SA II afferents can modify ongoing voluntary EMG in muscles of the human hand, presumably via a spinally mediated oligosynaptic pathway. Conversely, we saw no evidence of such modulation by SA I, muscle spindle or joint afferents.

Action Potentials↗

Modulation of rat erg1, erg2, erg3 and HERG K+ currents by thyrotropin-releasing hormone in anterior pituitary cells via the native signal cascade.

The mechanism of thyrotropin-releasing hormone (TRH)-induced ether-a-go-go-related gene (erg) K+ current modulation was investigated with the perforated-patch whole-cell technique in clonal somatomammotroph GH3/B6 cells. These cells express a small endogenous erg current known to be reduced by TRH. GH3/B6 cells were injected with cDNA coding for rat erg1, erg2, erg3 and HERG K+ channels. The corresponding erg currents were isolated with the help of the specific erg channel blockers E-4031 and dofetilide and their biophysical properties were determined. TRH (1 M) was able to significantly reduce the different erg currents. The voltage dependence of activation was shifted by 15 mV (erg1), 10 mV (erg2) and 6 mV (erg3) to more positive potentials without strongly affecting erg inactivation. TRH reduced the maximal available erg current amplitude by 12% (erg1), 13% (erg2) and 39% (erg3) and accelerated the time course of erg1 and erg2 channel deactivation, whereas erg3 deactivation kinetics were not significantly altered. The effects of TRH on HERG currents did not differ from those on its rat homologue erg1. In addition, coinjection of rat MiRP1 with HERG cDNA did not influence the TRH-induced modulation of HERG channels. Rat erg1 currents recorded in the cell-attached configuration were reduced by application of TRH to the extra-patch membrane in the majority of the experiments, confirming the involvement of a diffusible second messenger. Application of the phorbol ester phorbol 12-myristate 13-acetate (PMA; 1 M) shifted the voltage dependence of erg1 activation in the depolarizing direction, but it did not reduce the maximal current amplitude. The voltage shift could not be explained by a selective effect on protein kinase C (PKC) since the PKC inhibitor bisindolylmaleimide I did not block the effects of TRH and PMA on erg1. In addition, cholecystokinin, known to activate the phosphoinositol pathway similarly to TRH, did not significantly affect the erg1 current. Various agents interfering with different known TRH-elicited cellular responses were not able to completely mimic or inhibit the TRH effects on erg1. Tested substances included modulators of the cAMP-protein kinase A pathway, arachidonic acid, inhibitors of tyrosine kinase and mitogen-activated protein kinase, sodium nitroprusside and cytochalasin D. The results demonstrate that all three members of the erg channel subfamily are modulated by TRH in GH3/B6 cells. In agreement with previous studies on the TRH-induced modulation of the endogenous erg current in prolactin-secreting anterior pituitary cells, the TRH effects on overexpressed erg1 channels are not mediated by any of the tested signalling pathways.

Animals↗

Attentional modulation of startle in psychosis-prone college students.

Attentional modulation of startle eyeblink was studied in college students putatively at risk for psychosis and in normal controls. At-risk subjects had extreme scores on scales for either anhedonia or perceptual aberration-magical thinking (per-mags). Subjects were presented with to-be-attended and to-be-ignored tones; white noise startle probes were presented at lead intervals of 60, 120, 240, or 2,000 ms following the onset of attended and ignored tones and during intertone intervals. Controls showed greater inhibition of startle blink at 120 ms and greater facilitation at 2,000 ms during to-be-attended than to-be-ignored tone, demonstrating attentional modulation of prepulse inhibition and facilitation. Both at-risk groups showed normal overall levels of early inhibition and late facilitation. However, per-mags failed to show attentional modulation of either inhibition at 120 ms or facilitation at 2,000 ms; anhedonics showed no modulation of inhibition and modulation of facilitation was delayed in development. The results for the per-mags are strikingly similar to those observed in schizophrenic patients and suggest that these deficits index a trait-linked vulnerability to disorders in the schizophrenic spectrum.

Adult↗

The varying time courses of attentional and affective modulation of the startle eyeblink reflex.

In previous research on modulation of the startle eyeblink reflex, emotional effects have been demonstrated only at late probe positions, whereas attentional effects have been found at both early and late positions but only when the prepulses were affectively neutral. In Experiment 1, participants viewed emotionally valenced pictures and were instructed to attend to the duration of half of the slides. Affective modulation of the startle eyeblink occurred at long lead intervals, but attentional modulation also occurred late. In Experiment 2, participants viewed the same slides used in Experiment 1 but were instructed to attend to the duration of only the positive or the negative slides. Affective modulation occurred at both early and late probe positions, whereas attentional effects occurred only following slide offset. Early (250 ms) affective modification of startle eyeblink has not been previously reported. These results suggest that the time courses of emotional and attentional modulation of startle are variable and can occur at both early and late startle probe positions, depending on task requirements.

Adult↗

Looking for faces: Attention modulates early occipitotemporal object processing.

Looking for somebody's face in a crowd is one of the most important examples of visual search. For this goal, attention has to be directed to a well-defined perceptual category. When this categorically selective process starts is, however, still unknown. To this end, we used magnetoencephalography (MEG) recorded over right human occipitotemporal cortex to investigate the time course of attentional modulation of perceptual processes elicited by faces and by houses. The first face-distinctive MEG response was observed at 160-170 ms (M170). Nevertheless, attention did not start to modulate face processing before 190 ms. The first house-distinctive MEG activity was also found around 160-170 ms. However, house processing was not modulated by attention before 280 ms (90 ms later than face processing). Further analysis revealed that the attentional modulation of face processing is not due to later, for example, back-propagated activation of the M170 generator. Rather, subsequent stages of occipitotemporal object processing were modulated in a category-specific manner and with preferential access to face processing.

Adult↗