Uniaxial Pressure Dependence of Magnetic Order in MnSi.

We report comprehensive small angle neutron scattering measurements complemented by ac susceptibility data of the helical order, conical phase, and Skyrmion lattice phase (SLP) in MnSi under uniaxial pressures. For all crystallographic orientations uniaxial pressure favors the phase for which a spatial modulation of the magnetization is closest to the pressure axis. Uniaxial pressures as low as 1 kbar applied perpendicular to the magnetic field axis enhance the Skyrmion lattice phase substantially, whereas the Skyrmion lattice phase is suppressed for pressure parallel to the field. Taken together we present quantitative microscopic information on how strain couples to magnetic order in the chiral magnet MnSi.

Compact susceptometer for studies under transverse field geometries at very low temperatures.

We present the design of a compact AC susceptometer for studies under arbitrarily oriented static magnetic fields, in particular magnetic fields oriented transverse to the AC excitation field. The small size of the susceptometer permits versatile use in conventional cryostats with superconducting magnet systems. The design of the susceptometer minimizes parasitic signal contributions while providing excellent thermal anchoring suitable for measurements in a wide range down to very low temperatures. The performance is illustrated by means of measurements of the transverse susceptibility at the magnetic field tuned quantum phase transition of the dipolar-coupled Ising ferromagnet LiHoF4.

The effects of longitudinal chromatic aberration and a shift in the peak of the middle-wavelength sensitive cone fundamental on cone contrast.

Longitudinal chromatic aberration is a well-known imperfection of visual optics, but the consequences in natural conditions, and for the evolution of receptor spectral sensitivities are less well understood. This paper examines how chromatic aberration affects image quality in the middle-wavelength sensitive (M-) cones, viewing broad-band spectra, over a range of spatial frequencies and focal planes. We also model the effects on M-cone contrast of moving the M-cone fundamental relative to the long- and middle-wavelength (L- and M-cone) fundamentals, while the eye is accommodated at different focal planes or at a focal plane that maximizes luminance contrast. When the focal plane shifts towards longer (650 nm) or shorter wavelengths (420 nm) the effects on M-cone contrast are large: longitudinal chromatic aberration causes total loss of M-cone contrast above 10-20 c/d. In comparison, the shift of the M-cone fundamental causes smaller effects on M-cone contrast. At 10 c/d a shift in the peak of the M-cone spectrum from 560 to 460 nm decreases M-cone contrast by 30%, while a 10 nm blue-shift causes only a minor loss of contrast. However, a noticeable loss of contrast may be seen if the eye is focused at focal planes other than that which maximizes luminance contrast. The presence of separate long- and middle-wavelength sensitive cones therefore has a small, but not insignificant cost to the retinal image via longitudinal chromatic aberration. This aberration may therefore be a factor limiting evolution of visual pigments and trichromatic color vision.

Molecular profiling reveals myeloid leukemia cell lines to be faithful model systems characterized by distinct genomic aberrations.

To model and investigate different facets of leukemia pathogenesis, a widely accepted approach is to use immortalized leukemia cell lines. Although these provide powerful tools to our knowledge, few studies have addressed the question whether hematopoietic cell lines represent accurate and reliable model systems. To improve the molecular characterization of these model systems, we analyzed 17 myeloid leukemia cell lines using DNA microarray technology. By array-based comparative genomic hybridization, we identified recurrent genomic DNA gains and losses, as well as high-level amplifications. Parallel analysis of gene expression helped delineate potential candidate genes, and unsupervised analysis of gene expression data revealed cell lines to cluster in part based on underlying cytogenetic abnormalities. Comparison with clinical leukemia specimens showed that key signatures were retained, as myeloid cell lines with characteristic cytogenetic aberrations co-clustered with leukemia samples carrying the respective abnormality. Signatures were also quite robust, as expression data from cell lines correlated highly with published data. Thus, our analyses demonstrate myeloid cell lines to exhibit conserved and stable signatures reflecting the underlying primary cytogenetic aberrations. Our refined molecular characterization of myeloid cell lines supports the utility of cell lines as faithful and powerful model systems and provides additional insights into the molecular mechanisms of leukemogenesis.

Room-temperature helimagnetism in FeGe thin films.

Chiral magnets are promising materials for the realisation of high-density and low-power spintronic memory devices. For these future applications, a key requirement is the synthesis of appropriate materials in the form of thin films ordering well above room temperature. Driven by the Dzyaloshinskii-Moriya interaction, the cubic compound FeGe exhibits helimagnetism with a relatively high transition temperature of 278 K in bulk crystals. We demonstrate that this temperature can be enhanced significantly in thin films. Using x-ray scattering and ferromagnetic resonance techniques, we provide unambiguous experimental evidence for long-wavelength helimagnetic order at room temperature and magnetic properties similar to the bulk material. We obtain α intr = 0.0036 ± 0.0003 at 310 K for the intrinsic damping parameter. We probe the dynamics of the system by means of muon-spin rotation, indicating that the ground state is reached via a freezing out of slow dynamics. Our work paves the way towards the fabrication of thin films of chiral magnets that host certain spin whirls, so-called skyrmions, at room temperature and potentially offer integrability into modern electronics.

Glucose availability alters ischaemia-induced changes in intracellular pH and calcium of isolated rat spinal roots.

Peripheral nerves in diabetic patients show an enhanced liability to ischaemic lesions. Using an in vitro model, we have now analysed the possible role of intracellular proton (pHi) and calcium concentrations ([Ca2+]i) for the pathophysiology of this phenomenon. Isolated rat spinal roots were preincubated for 3 to 6 h in either 5 or 25 mM of D-glucose before transient exposure to gaseous hypoxia or cyanide. Intracellular pH and Ca2+ concentrations were measured photometrically by means of the fluorescent dyes carboxy-SNARF-1 and a combination of Calcium Green-1 and Fura Red, respectively. The following observations were made. (a) The presence of 25 mM D-glucose resulted in stronger intracellular acidification and much slower post-hypoxic recovery of pHi as compared to 5 mM D-glucose. (b) Intracellular calcium increased during hypoxia and recovered quickly on reoxygenation. There were no statistically significant differences between the Ca2+ signals in either high or normal concentrations of D-glucose, although on average less rise was seen in high glucose. (c) Inhibition of glycolysis with iodoacetate reduced the acidification but amplified the rise in [Ca2+]i seen during transient hypoxia. These data suggest that hypoxia-induced nerve acidification rather than a rise in [Ca2+]i might contribute to ischaemic lesions found in diabetic neuropathy.

Isolated short-wavelength sensitive cones can mediate a reflex accommodation response.

Both long- and middle-wavelength sensitive cones mediate the reflex accommodation signal but the contribution from the short-wavelength sensitive cones is unknown. A short-wavelength sensitive cone contribution could extend the range of the signed defocus signal from chromatic aberration. The aim was to determine whether isolated short-wavelength sensitive cones mediate reflex accommodation independently of long- and middle-wavelength sensitive cones. Accommodation was monitored continuously (eight subjects) to a sine-wave grating (3 cpd; 0.53 contrast) moving with a sum of sines motion in a Badal optometer. Two illumination conditions were used: a 'blue' condition that isolated short-wavelength sensitive cones, and a 'white' control condition that stimulated all three cone types. Of the eight subjects, two responded equally in the 'white' and 'blue' condition, four gave reduced responses in the 'blue' condition and two failed to respond in both conditions. The mean response in the 'blue' condition was reduced by 50% compared to the 'white' condition. Further analysis indicated that four of the eight subjects gave responses that were considerably greater than noise (S.D.>1.82) when short-wavelength sensitive cones were isolated. Some subjects can accommodate using only S-cones.

Thermal grill-evoked sensations of heat correlate with cold pain threshold and are enhanced by menthol and cinnamaldehyde.

BACKGROUND: Thunberg's thermal grill produces a sensation of strong heat upon skin contact with spatially interlaced innocuous warm and cool stimuli. METHODS: To examine the classes of peripheral axons that might contribute to this illusion, the effects of topical l-menthol, an activator of TRPM8, and cinnamaldehyde, a TRPA1 agonist, on the magnitude of thermal sensations were examined during grill stimulation in healthy volunteers. RESULTS: Under control conditions, cutaneous grill stimulation (interlaced 20/40 °C) evoked a sensation of heat, and for individual subjects, the magnitude of this heat sensation was positively correlated with cold pain threshold (CPT). Menthol increased the CPT and enhanced the magnitude of grill-evoked heat. Cinnamaldehyde intensified warm sensations, reduced heat pain threshold and also enhanced grill-evoked heat. CONCLUSIONS: Both TRPM8-expressing and TRPA1-expressing afferent axons can affect grill-evoked thermal sensations. The enhancement of grill-evoked sensations of temperature with menthol and cinnamaldehyde may provide an additional clinically relevant means of testing altered thermal sensitivity, which is often affected in neuropathic patient groups.

Altered miRNA and gene expression in acute myeloid leukemia with complex karyotype identify networks of prognostic relevance.

Recently, the p53-miR-34a network has been identified to have an important role in tumorigenesis. As in acute myeloid leukemia with complex karyotype (CK-AML) TP53 alterations are the most common known molecular lesion, we further analyzed the p53-miR-34a axis in a large cohort of CK-AML with known TP53 status (TP53(altered), n=57; TP53(unaltered), n=31; altered indicates loss and/or mutation of TP53). Profiling microRNA (miRNA) expression delineated TP53 alteration-associated miRNA profiles, and identified miR-34a and miR-100 as the most significantly down- and upregulated miRNA, respectively. Moreover, we found a distinct miR-34a expression-linked gene expression profile enriched for genes belonging to p53-associated pathways, and implicated in cell cycle progression or apoptosis. Clinically, low miR-34a expression and TP53 alterations predicted for chemotherapy resistance and inferior outcome. Notably, in TP53(unaltered) CK-AML, high miR-34a expression predicted for inferior overall survival (OS), whereas in TP53(biallelic altered) CK-AML, high miR-34a expression pointed to better OS. Thus, detailed molecular profiling links impaired p53 to decreased miR-34a expression, but also identifies p53-independent miR-34a induction mechanisms as shown in TP53(biallelic altered) cell lines treated with 15-deoxy-Δ(12,14)-prostaglandin. An improved understanding of this mechanism might provide novel therapeutic options to restore miR-34a function and thereby induce cell cycle arrest and apoptosis in TP53(altered) CK-AML.

Kinetics of ATP release following compression injury of a peripheral nerve trunk.

Compression and/or contusion of a peripheral nerve trunk can result in painful sensations. It is possible that release of ATP into the extracellular space may contribute to this symptom. In the present study, we used real-time measurements of ATP-induced bioluminescence together with electrophysiological recordings of compound action potentials to follow changes in the extracellular ATP concentration of isolated rat spinal roots exposed to mechanical stimuli. Nerve compression for about 8 s resulted in an immediate release of ATP into the extracellular space and in a decrease in the amplitude of compound action potentials. On average, a rise in ATP to 60 nM was observed when nerve compression blocked 50% of the myelinated axons. After the compression, the extracellular concentration of ATP returned to the resting level within a few minutes. The importance of ecto-nucleotidases for the recovery period was determined by exposure of isolated spinal roots to high concentrations of ATP and by use of inhibitors of ecto-nucleotidases. It was observed that spinal roots have a high capacity for ATP hydrolysis which is only partially blocked by betagamma-methylene ATP and ARL 67156. In conclusion, acute nerve compression produces an increase in the extracellular concentration of ATP and of its metabolites which may be sufficient for activation of purinergic P2 and/or P1 receptors on axons of nociceptive afferent neurons.

Spread of epileptiform activity in the immature rat neocortex studied with voltage-sensitive dyes and laser scanning microscopy.

1. Adult rats and rats with a postnatal age of 3-29 days (PN 3-29) were used for the preparation of in vitro slices of the frontal neocortex. Epileptiform activity was induced by bath application of the gamma-aminobutyric acid-A (GABAA) receptor antagonists bicuculline or picrotoxin. 2. The voltage-sensitive dye RH 414 and a laser scanning microscope were used for multiple-site optical recordings of membrane potential changes associated with epileptiform activity. Optical signals were compared with simultaneously measured extra-cellular field potentials. 3. Optical signals could be reliably recorded for the duration of the experiments (2-4 h). Extracellular recordings of convulsant-induced paroxysmal depolarizing shifts (PDSs) in slices stained with RH 414 were comparable with those obtained in unstained slices. Changes in dye signals in response to reductions in extracellular calcium, addition of tetrodotoxin (TTX), or application of excitatory amino acid receptor antagonists indicate that the fluorescence changes correlate well with established electrophysiological measures of epileptiform activity. 4. In slices from adult animals, dye signals were observed at all recording sites. The response with the shortest latency occurred invariably at the site of stimulation, and activity spread rapidly in both vertical and horizontal directions. Spread was significantly faster in the vertical than in the horizontal direction. 5. Epileptiform activity was absent or only weakly expressed in slices from PN 3-9 animals. Activity was detectable predominantly in upper cortical layers. 6. Dye signals were observed at all measurement points in slices from PN 10-19 animals. In this age group, peak amplitude increased with spread of activity from lower to upper cortical layers. There was no significant difference between the speed of propagation in the vertical and in the horizontal directions. Spontaneous epileptiform activity occurred at a high rate in the PN 10-19 age group, and signals associated with spontaneous epileptiform events were largest in upper layers. 7. In the PN 10-19 age group, optical signals were characterized by the repetitive occurrence of PDS discharges superimposed on a sustained response. The amplitude of the sustained response decreased with increasing distance from the site of stimulation. Analysis of the latencies revealed that the superimposed PDS-like events were generated at multiple sites within the scanning area. Amplitude and rate of rise were largest in slices from PN 10-19 animals. These values declined with ongoing development.(ABSTRACT TRUNCATED AT 400 WORDS)

Spread of excitation in chronically lesioned mouse hippocampus determined by laser scanning microscopy.

Fast optical recordings by means of laser scanning microscopy in conjunction with a voltage-sensitive dye (RH 414) were performed to monitor the spatio-temporal spread of neuronal activity in CA3/CA4-lesioned C57BL6 mouse hippocampal slices prepared approximately 3 months after intracerebroventricular kainic acid (KA) injection. The aim of our study was to assess the effects of a circumscribed neuronal loss on the propagation of electrical activity along the trisynaptic hippocampal circuit. Both in physiological bathing solution and in bicuculline (10 microM), hilar stimulation failed to activate the downstream pathway, so that, under these conditions, the chronically disinhibited CA1 region appeared to be effectively isolated from burst activity arising upstream; however, epileptiform discharges evoked in zero Mg2+ solution were reliably transmitted from the dentate gyrus to the CA1 region. That these bursts were indeed spreading across the lesion, and not along newly formed connections (e.g., between dentate gyrus and CA1), was confirmed by acute transection experiments of the Schaffer collateral/commissural pathway, which completely abolished translesional burst propagation. The fact that the surviving CA3-CA1 connections are unable to trigger epileptiform bursts after suppression of GABAergic inhibition suggests that the lesioned region might serve as a filter that shields hyperexcitable CA1 neurons from epileptic activity arising upstream, in particular from chronically disinhibited granule cells of the dentate gyrus. An impaired GABAergic inhibition will thus only have minor facilitating effects on seizure propagation in the hippocampus of CA3-lesioned animals.

Eye movement efficiency in normal and reading disabled elementary school children: effects of varying luminance and wavelength.

BACKGROUND: This investigation examines the question of whether decreasing wavelength of light and/or reducing luminance benefits oculomotor efficiency in normal and reading disabled (RD) children. METHODS: Two groups of children were identified as normal or disabled readers using standardized reading tests. After suitable practice, eye movements were objectively measured with the Visagraph II as each of the subjects silently read a series of three different selections at their independent reading level with clear (control), gray, and blue filters. Four variables were measured for each subject. Data were analyzed using a repeated measure ANOVA and post hoc tests. RESULTS: The standardized reading tests significantly differentiated average from poor readers using grade scores and percentiles. Initially, with clear filters, eye movement scores of normal readers were superior to disabled readers for fixations regressions, and rate of reading. Among the RDs--but not the normals--the three variables improved with the blue filter when compared with the clear filter, number of fixations and regressions were significantly lower, and rate was significantly higher. Gray filters yielded no significant changes. Improvement with the blue filters normalized the three variables in that there were no significant differences between normal and disabled readers. CONCLUSION: This investigation confirms a link between wavelength of light and eye movement efficiency in reading. Blue filters resulted in a significant improvement in the number of fixations and regressions and rate of reading in RD children. The outcome broadens the concept of transient system deficit established in previous research to include the effect on oculomotor efficiency. The educational implications of this study are of special interest to optometrists.

Spatial pattern of evoked synaptic excitation in the mouse neostriatum in vitro.

The spatial distribution of stimulus-evoked excitation in the mouse neostriatum was investigated in vitro by using voltage-sensitive dyes and an optical multi-site recording system (laser scanning microscopy). The scanning area (880 x 830 microns) was positioned in the center of coronal neostriatal slices and records were taken simultaneously from up to 20 detection sites. Stimulus-induced optical signals were blocked by tetrodotoxin (TTX) and disappeared following removal of Ca2+ from the extracellular medium. Furthermore, these responses were inhibited by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) indicating that the evoked signals reflected mainly glutamatergic synaptic activity. Electrical stimulation at defined positions elicited characteristic spatial patterns of activity within the neostriatum. Stimulation of the medial subcortical white matter or stimulation at the dorsomedial corner or at the midpoint of the scanning area evoked synaptic activity at all recording sites. However, the largest response amplitudes were invariably observed in the ventrolateral part of the scanning area. In contrast, stimulation at the dorsolateral, ventrolateral or at the ventromedial corner induced synaptic responses which remained restricted to a relatively small area in close vicinity to the site of stimulation. The GABAA receptor antagonist bicuculline did not influence the pattern of activity distribution. However, in the presence of bicuculline, a N-methyl-D-aspartate (NMDA) receptor-mediated delayed signal component was observed which again was most pronounced in the ventrolateral part of the scanning area. These results, obtained in an in vitro slice preparation, demonstrate that spatially defined afferent activation of neostriatal neuronal circuits leads to a characteristic pattern of activity distribution within the neostriatum. Thus, our data complement observations from morphological investigations as well as from electrophysiological studies in vivo that suggest a functional compartmentalization of this brain area.

CD95 ligand (CD95L) in normal human lymphoid tissues: a subset of plasma cells are prominent producers of CD95L.

CD95(Fas/APO-1)-ligand (CD95L) mediates apoptosis by trimerization of the CD95 receptor on the surface of sensitive cells. In vitro studies have shown CD95L expression mainly by activated T cells and suggested a role for CD95L in the regulation of immune responses. Little is known, however, about the cellular distribution of CD95L in situ in the normal human immune system. We investigated CD95L expression in tissue sections of the thymus, lymph node, spleen, tonsil, and gastrointestinal tract using in situ hybridization and two monoclonal antibodies. In all these organs, cells expressing CD95L message and protein were scarce and comprised scattered lymphocytes, rare nonlymphoid cells, and a subset of epithelioid endothelial cells. Surprisingly, a subset of plasma cells turned out to be the most prominent producers of CD95L, matching the reports on CD95L in myeloma cells. CD95L+ plasma cells were most numerous in the mucosa-associated lymphoid tissue. This also applied to acquired mucosa-associated lymphoid tissue in chronic gastritis in which CD95L+ plasma cells were found scattered in the lamina propria. Our data suggest that plasma cells as yet may be neglected modulators of immune responses.