Glutamate Excitotoxicity Inflicts Paranodal Myelin Splitting and Retraction.

Paranodal myelin damage is observed in white matter injury. However the culprit for such damage remains unknown. By coherent anti-Stokes Raman scattering imaging of myelin sheath in fresh tissues with sub-micron resolution, we observed significant paranodal myelin splitting and retraction following glutamate application both ex vivo and in vivo. Multimodal multiphoton imaging further showed that glutamate application broke axo-glial junctions and exposed juxtaparanodal K+ channels, resulting in axonal conduction deficit that was demonstrated by compound action potential measurements. The use of 4-aminopyridine, a broad-spectrum K+ channel blocker, effectively recovered both the amplitude and width of compound action potentials. Using CARS imaging as a quantitative readout of nodal length to diameter ratio, the same kind of paranodal myelin retraction was observed with applications of Ca2+ ionophore A23187. Moreover, exclusion of Ca2+ from the medium or application of calpain inhibitor abolished paranodal myelin retraction during glutamate exposure. Examinations of glutamate receptor agonists and antagonists further showed that the paranodal myelin damage was mediated by NMDA and kainate receptors. These results suggest that an increased level of glutamate in diseased white matter could impair paranodal myelin through receptor-mediated Ca2+ overloading and subsequent calpain activation

Up-regulation of p21 and TNF-α is mediated in lycorine-induced death of HL-60 cells

<p>Abstract</p> <p>Background</p> <p>Leukemia is one of the most life-threatening cancers today, and acute promyelogenous leukemia (APL) is a common type of leukemia. Many natural compounds have already been found to exhibit significant anti-tumor effects. Lycorine, a natural alkaloid extracted from Amaryllidaceae, exhibited anti-leukemia effects in vitro and in vivo. The survival rate of HL-60 cells exposed to lycorine was decreased, cell growth was slowed down, and cell regeneration potential was inhibited. HL-60 cells exhibited typical apoptotic characteristic. Lycorine can suppress leukemia growth and reduce cell survival and inducing apoptosis of tumor cells. The purpose of this work is to elucidate the mechanism by which lycorine induces APL cells.</p> <p>Results</p> <p>When HL-60 cells were treated with different concentration of lycorine, the expression of p21 and TNF-α was up-regulated in a concentration-dependent manner as shown by real-time quantitative reverse transcriptase-polymerase chain reaction and Western blotting. Lycorine also down-regulated p21-related gene expression, including Cdc2, Cyclin B, Cdk2 and Cyclin E, promoted Bid truncation, decreased IκB phosphorylation and blocked NF-κB nuclear import. Cytochrome c was released from mitochondria as observed with confocal laser microscopy.</p> <p>Conclusions</p> <p>The TNF-α signal transduction pathway and p21-mediated cell-cycle inhibition were involved in the apoptosis of HL-60 cells induced by lycorine. These results contribute to the development of new lycorine-based anti-leukemia drugs.</p

Polytypism and Unexpected Strong Interlayer Coupling of two-Dimensional Layered ReS2

The anisotropic two-dimensional (2D) van der Waals (vdW) layered materials, with both scientific interest and potential application, have one more dimension to tune the properties than the isotropic 2D materials. The interlayer vdW coupling determines the properties of 2D multi-layer materials by varying stacking orders. As an important representative anisotropic 2D materials, multilayer rhenium disulfide (ReS2) was expected to be random stacking and lack of interlayer coupling. Here, we demonstrate two stable stacking orders (aa and a-b) of N layer (NL, N>1) ReS2 from ultralow-frequency and high-frequency Raman spectroscopy, photoluminescence spectroscopy and first-principles density functional theory calculation. Two interlayer shear modes are observed in aa-stacked NL-ReS2 while only one interlayer shear mode appears in a-b-stacked NL-ReS2, suggesting anisotropic-like and isotropic-like stacking orders in aa- and a-b-stacked NL-ReS2, respectively. The frequency of the interlayer shear and breathing modes reveals unexpected strong interlayer coupling in aa- and a-b-NL-ReS2, the force constants of which are 55-90% to those of multilayer MoS2. The observation of strong interlayer coupling and polytypism in multi-layer ReS2 stimulate future studies on the structure, electronic and optical properties of other 2D anisotropic materials

Optimal coherent control of CARS: signal enhancement and background elimination

The ability to enhance resonant signals and eliminate the non-resonant background is analyzed for Coherent Anti-Stokes Raman Scattering (CARS). The analysis is done at a specific frequency as well as for broadband excitation using femtosecond pulse-shaping techniques. An appropriate objective functional is employed to balance resonant signal enhancement against non-resonant background suppression. Optimal enhancement of the signal and minimization of the background can be achieved by shaping the probe pulse alone while keeping the pump and Stokes pulses in transform-limited-form (TLF). In some cases analytical forms for the probe pulse can be found, and numerical simulations are carried out for other circumstances. It is found that a good approximate solution for the optimal pulse in the two-pulse CARS is a superposition of linear and arctangent type phases for the pump. The well-known probe delay method is shown to be a quasi-optimal scheme for background suppression. The results should provide a basis to improve the performance of CARS spectroscopy and microscopy.Comment: 11 pages,10 figures, JC