Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

Background

Junctional adhesion molecule-A (JAM-A) is an adhesive protein expressed in various cell types. JAM-A localizes to the tight junctions between contacting endothelial and epithelial cells, where it contributes to cell-cell adhesion and to the control of paracellular permeability.

Results

So far, the expression pattern of JAM-A has not been described in detail for the different cell types of the adult brain. Here we show that a subset of proliferating cells in the adult mouse brain express JAM-A. We further clarify that these cells belong to the lineage of NG2-glia cells. Although these mitotic NG2-glia cells express JAM-A, the protein never shows a polarized subcellular distribution. Also non-mitotic NG2-glia cells express JAM-A in a non-polarized pattern on their surface.

Conclusions

Our data show that JAM-A is a novel surface marker for NG2-glia cells of the adult brain.     

White versus gray matter: fMRI hemodynamic responses show similar characteristics, but differ in peak amplitude

Background

The first mammalian protein histidine phosphatase (PHP) was discovered in the late 90s of the last century. One of the known substrates of PHP is ATP-citrate lyase (ACL), which is responsible - amongst other functions - for providing acetyl-CoA for acetylcholine synthesis in neuronal tissues. It has been shown in previous studies that PHP downregulates the activity of ACL by dephosphorylation. According to this our present work focused on the influence of PHP activity on the acetylcholine level in cholinergic neurons.

Results

The amount of PHP in SN56 cholinergic neuroblastoma cells was increased after overexpression of PHP by using pIRES2-AcGFP1-PHP as a vector. We demonstrated that PHP overexpression reduced the acetylcholine level and induced cell death. The acetylcholine content of SN56 cells was measured by fast liquid chromatography-tandem mass spectrometry method. Overexpression of the inactive H53A-PHP mutant also induced cell damage, but in a significantly reduced manner. However, this overexpression of the inactive PHP mutant did not change the acetylcholine content of SN56 cells significantly. In contrast, PHP downregulation, performed by RNAi-technique, did not induce cell death, but significantly increased the acetylcholine content in SN56 cells.

Conclusions

We could show for the first time that PHP downregulation increased the acetylcholine level in SN56 cells. This might be a potential therapeutic strategy for diseases involving cholinergic deficits like Alzheimer's disease.     

Diffusional kurtosis imaging of cingulate fibers in Parkinson disease: Comparison with conventional diffusion tensor imaging

Objective

The pathological changes in Parkinson disease begin in the brainstem; reach the limbic system and ultimately spread to the cerebral cortex. In Parkinson disease (PD) patients, we evaluated the alteration of cingulate fibers, which comprise part of the limbic system, by using diffusional kurtosis imaging (DKI).

Methods

Seventeen patients with PD and 15 age-matched healthy controls underwent DKI with a 3-T MR imager. Diffusion tensor tractography images of the anterior and posterior cingulum were generated. The mean kurtosis (MK) and conventional diffusion tensor parameters measured along the images in the anterior and posterior cingulum were compared between the groups. Receiver operating characteristic (ROC) analysis was also performed to compare the diagnostic abilities of the MK and conventional diffusion tensor parameters.

Results

The MK and fractional anisotropy (FA) in the anterior cingulum were significantly lower in PD patients than in healthy controls. The area under the ROC curve was 0.912 for MK and 0.747 for FA in the anterior cingulum. MK in the anterior cingulum had the best diagnostic performance (mean cutoff, 0.967; sensitivity, 0.87; specificity, 0.94).

Conclusions

DKI can detect alterations of the anterior cingulum in PD patients more sensitively than can conventional diffusion tensor imaging. Use of DKI can be expected to improve the ability to diagnose PD.     

Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens

Background

In both schizophrenia and addiction, pathological changes in dopamine release appear to induce alterations in the circuitry of the nucleus accumbens that affect coordinated thought and motivation. Dopamine acts principally on medium-spiny GABA neurons, which comprise 95% of accumbens neurons and give rise to the majority of inhibitory synapses in the nucleus. To examine dopamine action at single medium-spiny neuron synapses, we imaged Ca²⁺ levels in their presynaptic varicosities in the acute brain slice using two-photon microscopy.

Results

Presynaptic Ca²⁺ rises were differentially modulated by dopamine. The D1/D5 selective agonist SKF81297 was exclusively facilitatory. The D2/D3 selective agonist quinpirole was predominantly inhibitory, but in some instances it was facilitatory. Studies using D2 and D3 receptor knockout mice revealed that quinpirole inhibition was either D2 or D3 receptor-mediated, while facilitation was mainly D3 receptor-mediated. Subsets of varicosities responded to both D1 and D2 agonists, showing that there was significant co-expression of these receptor families in single medium-spiny neurons. Neighboring presynaptic varicosities showed strikingly heterogeneous responses to DA agonists, suggesting that DA receptors may be differentially trafficked to individual varicosities on the same medium-spiny neuron axon.

Conclusion

Dopamine receptors are present on the presynaptic varicosities of medium-spiny neurons, where they potently control GABAergic synaptic transmission. While there is significant coexpression of D1 and D2 family dopamine receptors in individual neurons, at the subcellular level, these receptors appear to be heterogeneously distributed, potentially explaining the considerable controversy regarding dopamine action in the striatum, and in particular the degree of dopamine receptor segregation on these neurons. Assuming that post-receptor signaling is restricted to the microdomains of medium-spiny neuron varicosities, the heterogeneous distribution of dopamine receptors on individual varicosities is likely to encode patterns in striatal information processing.     

Haag Duality and the Distal Split Property for Cones in the Toric Code

We prove that Haag duality holds for cones in the toric code model. That is, for a cone ??, the algebra ${\mathcal{R}_{\Lambda}}$ of observables localized in ?? and the algebra ${\mathcal{R}_{\Lambda^c}}$ of observables localized in the complement ?? ^c generate each other??s commutant as von Neumann algebras. Moreover, we show that the distal split property holds: if ${\Lambda_1 \subset \Lambda_2}$ are two cones whose boundaries are well separated, there is a Type I factor ${\mathcal{N}}$ such that ${\mathcal{R}_{\Lambda_1} \subset \mathcal{N} \subset \mathcal{R}_{\Lambda_2}}$ . We demonstrate this by explicitly constructing ${\mathcal{N}}$ .     

Disturbed oscillatory brain dynamics in subcortical ischemic vascular dementia

Background

This study examined the effects of dietary polyunsaturated fatty acids (PUFA) as different n-6: n-3 ratios on spatial learning and gene expression of peroxisome- proliferator-activated receptors (PPARs) in the hippocampus of rats. Thirty male Sprague?CDawley rats were randomly allotted into 3 groups of ten animals each and received experimental diets with different n-6: n-3 PUFA ratios of either 65:1, 22:1 or 4.5:1. After 10?weeks, the spatial memory of the animals was assessed using the Morris Water Maze test. The expression of PPAR?? and PPAR?? genes were determined using real-time PCR.

Results

Decreasing dietary n-6: n-3 PUFA ratios improved the cognitive performance of animals in the Morris water maze test along with the upregulation of PPAR?? and PPAR?? gene expression. The animals with the lowest dietary n-6: n-3 PUFA ratio presented the highest spatial learning improvement and PPAR gene expression.

Conclusion

It can be concluded that modulation of n-6: n-3 PUFA ratios in the diet may lead to increased hippocampal PPAR gene expression and consequently improved spatial learning and memory in rats.     

Ultrasonic stimulation of the brain to enhance the release of dopamine – A potential novel treatment for Parkinson’s disease

Parkinson’s disease (PD) is characterized by the decrease of dopamine (DA) production and release in the substantia nigra and striatum regions of the brain. Transcranial ultrasound has been exploited recently for neuromodulation of the brain in a number of fields. We have stimulated DA release in PC12 cells using low-intensity continuous ultrasound (0.1 W/cm² − 0.3 W/cm², 1 MHz), 12 h after exposure at 0.2 W/cm², 40 s, the amount of DA content eventually increased 78.5% (p = 0.004). After 10-day ultrasonic treatment (0.3 W/cm², 5 min/d), the DA content in the striatum of PD mice model restored to 81.07% of the control (vs 43.42% in the untreated PD mice model). In addition to this the locomotion activity was restored to the normal level after treatment. We suggest that the low intensity ultrasound-induced DA release can be attributed to a combination of neuron regeneration and improved membrane permeability produced by the mechanical force of ultrasound. Our study indicates that the application of transcranial ultrasound applied below FDA limits, could provide a candidate for relatively safe and noninvasive PD therapy through an amplification of DA levels and the stimulation of dopaminergic neuron regeneration without contrast agents.     

Localization in the ground state of the ising model with a random transverse field

We study the zero-temperature behavior of the Ising model in the presence of a random transverse field. The Hamiltonian is given by $$H = - J\sum\limits_{\left\langle {x,y} \right\rangle } {\sigma _3 (x)\sigma _3 (y) - \sum\limits_x {h(x)\sigma _1 (x)} } $$ whereJ>0,x,y∈Z ^d, σ₁, σ₃ are the usual Pauli spin 1/2 matrices, andh={h(x),x∈Z ^d} are independent identically distributed random variables. We consider the ground state correlation function 〈σ₃(x)σ₃(y)〉 and prove:

1. Letd be arbitrary. For anym>0 andJ sufficiently small we have, for almost every choice of the random transverse fieldh and everyx∈Z ^d, that $$\left\langle {\sigma _3 (x)\sigma _3 (y)} \right\rangle \leqq C_{x,h} e^{ - m\left| {x - y} \right|} $$ for ally∈Z ^d withC _{x h} <∞.
2. Letd≧2. IfJ is sufficiently large, then, for almost every choice of the random transverse fieldh, the model exhibits long range order, i.e., $$\mathop {\overline {\lim } }\limits_{\left| y \right| \to \infty } \left\langle {\sigma _3 (x)\sigma _3 (y)} \right\rangle > 0$$ for anyx∈Z ^d.

     

Parametric study of EEG sensitivity to phase noise during face processing

Background

The zitter (zi/zi) rat, a loss-of-function mutant of the glycosylated transmembrane protein attractin (atrn), exhibits widespread age-dependent spongiform degeneration, hypomyelination, and abnormal metabolism of reactive oxygen species (ROS) in the brain. To date, the mechanisms underlying these phenotypes have remained unclear.

Results

Here, we show differentiation defects in zi/zi oligodendrocytes, accompanied by aberrant extension of cell-processes and hypomyelination. Axonal bundles were relatively preserved during postnatal development. With increasing in age, the injured oligodendrocytes in zi/zi rats become pathological, as evidenced by the accumulation of iron in their cell bodies. Immunohistochemical analysis revealed that atrn expression was absent from an oligodendrocyte lineage, including A2B5-positive progenitors and CNPase-positive differentiated cells. The number and distribution of Olig2-positive oligodendrocyte progenitors was unchanged in the zi/zi brain. Furthermore, an in vitro differentiation assay of cultured oligodendrocyte progenitors prepared from zi/zi brains revealed their normal competence for proliferation and differentiation into mature oligodendrocytes. Interestingly, we demonstrated the accelerated recruitment of ED1-positive macrophages/microglia to the developing zi/zi brain parenchyma prior to the onset of hypomyelination. Semiquantitative RT-PCR analysis revealed a significant up-regulation of CD26 and IL1-β in the zi/zi brain during this early postnatal stage.

Conclusion

We demonstrated that the onset of the impairment of oligodendrocyte differentiation occurs in a non-cell autonomous manner in zi/zi rats. Hypomyelination of oligodendrocytes was not due to a failure of the intrinsic program of oligodendrocytes, but rather, was caused by extrinsic factors that interrupt oligodendrocyte development. It is likely that macrophage/microglial activation in the zi/zi CNS leads to disturbances in oligodendrocyte differentiation via deleterious extrinsic factors, such as the cytokine IL1-β or ROS. Atrn might be involved in the activation of brain macrophages/microglia by suppressing excessive migration of monocytes into the CNS, or by accelerating the transformation of brain monocytes into resting microglia. Understanding the pathogenesis of the zi/zi rat may provide novel insights into the developmental interaction betweens macrophages/microglia and cells of an oligodendrocyte lineage.     

Non-normal tracer diffusion from stirring by swimming microorganisms

The experimentally observed non-Gaussian form of passive tracer distributions in media stirred by active swimmers (Leptos et al., Phys. Rev. Lett. 103, 198103 (2009)) are analyzed in terms of continuous time random walks. The walks are characterized by a trapping time distribution ??(??) with long time behaviour ??(??) ?? ?? ^?1??? and a step size distribution p(??x) ?? (??x)^?2??? . The experimentally observed behaviour that ??x ²?? ?? t is obtained for a one-parameter family of exponents with ?? = 2??. However, the distribution function for this case is non-Gaussian and shows exponential tails. The shape of the distributions agrees rather well with the experimental observations from Leptos et al. and allows for the determination of the exponents.      

Analysis of the 33-133-133-1final state in photon-photon collisions

The reactione ⁺ e ^- e ⁺ e ^{- 00}e ⁺ e ^- 6 has been analysed using the full data sample taken with the Crystal Ball detector at the DORIS II storage ring at DESY. The ⁰⁰ invariant mass spectrum is dominated by the ', for which we determine the radiative width (') to be (4.5±0.3±0.5)keV. Near 1.9 GeV/c² we observe a second enhancement in the ⁰⁰ mass distribution. Assuming that these events are created by the production and subsequent decay of a wide resonanceX(1900), we have investigated the decay modes, the invariant mass distributions of the ⁰ and ⁰⁰ subsystems and the angular distributions of the final state mesons. We find that the data is best described byJ ^PC=2. For thisJ ^P assignment the resonance parameters are (X) BR(X)=(0.95±0.27±0.20) keV _tot (X)=(221±92±44)MeV, andM(X)=(1881±32±40) MeV/c².Deceased     

N-benzoate-N′ salicylaldehyde ethynelediamine: A new fluorescent sensor for Zn2+ ion by “off-on” mode

Imbalance of zinc ion (Zn²⁺) in human body causes diseases like Alzheimer’s and Parkinson’s and therefore Zn²⁺ estimation in biological fluids has diagnostic values. Fluorescence “off-on” sensors have advantages of high sensitivity and in situ application over other sensors. A new fluorescent “off-on” Zn²⁺ sensor, N-benzoate-N′ salicylaldehyde ethynelediamine (L), has been synthesisied. In 1:1(v/v) CH₃OH:PBS (PBS?=?phosphate buffer solution), L shows ca. 20 times enhancement in fluorescence intensity on interaction with Zn²⁺, due to snapping of photoinduced electron transfer (PET) process, which is selective over metal ions - Na⁺, K⁺, Ca²⁺, Ni²⁺, Cu²⁺, Cd²⁺, Hg²⁺ and Pb²⁺. These metal ions either individually or all together does not interfere the sensing ability of L towards Zn²⁺. A 1:1 interaction between L and Zn²⁺ ion with binding constant 10^4.25 has been established from spectroscopic data.     

Calibration of absolute jet energy scale in CMS detector using W → q \bar q process in pp-Collisions at \sqrt s = 7 TeV

Calibration of absolute jet energy scale in CMS experiment at $\sqrt s = 7$ TeV using the W-mass constraint in t $\bar t$ -events with W ?? q $\bar t$ decay is made. Data sample with an integrated luminosity of 3 fb^?1 is used. Calibration procedure is made for calorimetric jets, ??Jet-Plus-Track?? jets, and ??Particle-Flow?? jets. Statistical errors of calibration as well as systematical uncertainties of the method are up to 3%. The results are abstracted from degree thesis.     

Quantum deformation of compactified Minkowski space

The quantum GrassmanianG(2|0; ? _q ^4|0 ) of “quantum 2-planes ? _q ^2|0 in the quantum 4-plane ? _q ^4|0 ”, which provides aq-deformation of compactified complexified Minkowski space, is proposed. A quantum analogue of classical Plücker embedding of the usual GrassmanianG(2; ?²) into a non-degenerate quadric in ??⁵ is found.     

A Rhodamine-Based Off�COn Fluorescent Chemosensor for Selectively Sensing Cu(II) in Aqueous Solution

A novel chromogenic and fluorogenic chemosensor RhB-pMOSal comprising a rhodamine fluorophore and a salicylaldehyde receptor being connected by an iminohydrazine link was synthesized and fully characterized. Its sensing behavior toward various metal ions in neutral aqueous solution was investigated by absorption and fluorescence spectroscopy. RhB-pMOSal exhibited a reversible and sensitive ??turn-on?? response of absorption and fluorescence toward Cu²⁺ in aqueous acetonitrile solution. Approximate 65 and 6-fold enhancement in the absorbance at 556 nm and fluorescence intensity at 573 nm were estimated when equivalent Cu²⁺ was added to the RhB-pMOSal solution. Under the same conditions, RhB-pMOSal displayed more sensitive than a reported analogue RhB-Sal to Cu²⁺ ion. The competition experiments for Cu²⁺ mixed with common metal ions exhibited no obvious change in absorption and emission except Cr³⁺ ion that can induce the fluorescence quenching of RhB-pMOSal to some extent.     

Theoretical prediction of cosmological constant Λ in Veneziano ghost theory of QCD

Based on the Veneziano ghost theory of QCD, we predict the cosmological constant ??, which is related to energy density of cosmological vacuum by $ \Lambda = \frac{{8\pi G}} {3}\rho _\Lambda $ . In the Veneziano ghost theory, the vacuum energy density ?? _?? is expressed by absolute value of the product of quark vacuum condensate and quark current mass: $ \rho _\Lambda = \frac{{2N_f H}} {{m_{\eta '} }}c|m_q < 0|:\bar qq:|0 > | $ . We calculate the quark local vacuum condensates ??0|: $ \bar q $ q: |0?? by solving Dyson-Schwinger Equations for a fully dressed confining quark propagator S _f (p) with an effective gluon propagator G _???? ^ab (q). The quark current mass m _q is predicted by use of chiral perturbation theory. Our theoretical result of ??, with the resulting ??0|: 471-4 q: |0?? = ?(235 MeV)³ and light quark current mass m _q ? 3.29?C6.15 MeV, is in a good agreement with the observable of the ?? ?? 10^?52 m^?2 used widely in a great amount of literatures.     

The effect of air impurities on pure neon luminescence

The luminescence decay curves of the 2p ₁ level of the NeI atom (the transition 3p??[1/2]₀?3s??[1/2] ₁ ^° , ?? = 585.2 nm) and the B ²?? _u ⁺ level of the N ₂ ⁺ molecule (the transition B ²?? _u ⁺ (?? = 0)?X ²?? _g ⁺ (??? = 0), ?? = 391.4 nm) in pure and air-containing neon are measured. The gas was excited by electron beam pulses (E _e = 150 keV, ?? = 5 ns, I _max = 500 A). It is shown that the molecular gases contained in air strongly quench the long-lived component of neon luminescence exciting due to dissociative recombination of Ne ₂ ⁺ molecular ions. The relative light yield at a wavelength of 585.2 nm as a function of the partial pressure of air in neon is determined to be ?? = (1+ 2??p)^?1, where p is the air pressure in Torr.     

A Schiff-Based Colorimetric Fluorescent Sensor with the Potential for Detection of Fluoride Ions

A simple Schiff-based colorimetric fluorescent receptor 1 was prepared. It exhibits a “turn-on-type” mode with high sensitivity in the presence of F^?. The change in color is very easily observed by the naked eye in the presence of F^?, whereas other anions do not induce such a change. Job plot indicated a 1:2 complexation stoichiometry between receptor 1 and F^?. The association constant for 1-F^? in CH₃CN was determined as 1.32*10⁵ M^?2 by a Hill plot.

Neutron-rich hypernuclei in the chiral soliton model

The binding energies of neutron-rich strangeness S = ?1 hypernuclei are estimated in the chiral soliton approach using the bound state rigid oscillator version of the SU(3) quantization model. Additional binding of strange hypernuclei in comparison with nonstrange neutron-rich nuclei takes place at not large values of atomic (baryon) numbers, A = B ?? ??10. This effect becomes stronger with increasing isospin of nuclides, and for the ??nuclear variant?? of the model with rescaled Skyrme constant e. Binding energies of _?? ⁸ He and recently discovered _?? ⁶ H satisfactorily agree with data. Hypernuclei _?? ⁷ H, _?? ⁹ He are predicted to be bound stronger in comparison with their nonstrange analogues ⁷H, ⁹He; hypernuclei _?? ¹⁰ Li, _?? ¹¹ LI, _?? ¹² Be, _?? ¹³ Be, etc. are bound stronger in the nuclear variant of the model.     

Mass spectrometer studies of the ion composition in the pink afterglow

The time dependences of the ion number densities in the pink afterglow of nitrogen, as represented by the ion wall currents, have been measured. The ions were extracted through an orifice from a flow system and analysed by a quadrupol mass spectrometer. It has been found thatN ₂ ⁺ ions are dominating in the early afterglow. With the beginning of the ionization processN ₃ ⁺ and at pressure >6 TorrN ₄ ⁺ become the majority ions. The ratio of the number densities(N ₃ ⁺ )/(N ₂ ⁺ ) reaches a maximum during the increase of the ionization processes before the maximum is reached. This behaviour suggestsN ₃ ⁺ ions to be the primary ions created by the ionization processes. The time dependences of the ion number densities (N ₂ ⁺ ), (N ₃ ⁺ ) and(N ₄ ⁺ ) are found to vary similar, showing that the ions are strongly coupled by conversion processes. The conversion processes are discussed. In the maximum of ionization at a total pressure of 4.4 Torr the ratios of the number densities of the afterglow ions (N ₂ ⁺ )∶(N ₃ ⁺ )∶(N ₄ ⁺) are 1∶1.9∶0.64.