Calcium signals in the nucleus accumbens: Activation of astrocytes by ATP and succinate

Background

Late cerebral ischemia carries high morbidity and mortality after subarachnoid hemorrhage (SAH) due to reduced cerebral blood flow (CBF) and the subsequent cerebral ischemia which is associated with upregulation of contractile receptors in the vascular smooth muscle cells (SMC) via activation of mitogen-activated protein kinase (MAPK) of the extracellular signal-regulated kinase (ERK)1/2 signal pathway. We hypothesize that SAH initiates cerebrovascular ERK1/2 activation, resulting in receptor upregulation. The raf inhibitor will inhibit the molecular events upstream ERK1/2 and may provide a therapeutic window for treatment of cerebral ischemia after SAH.

Results

Here we demonstrate that SAH increases the phosphorylation level of ERK1/2 in cerebral vessels and reduces the neurology score in rats in additional with the CBF measured by an autoradiographic method. The intracisternal administration of SB-386023-b, a specific inhibitor of raf, given 6 h after SAH, aborts the receptor changes and protects the brain from the development of late cerebral ischemia at 48 h. This is accompanied by reduced phosphorylation of ERK1/2 in cerebrovascular SMC. SAH per se enhances contractile responses to endothelin-1 (ET-1), 5-carboxamidotryptamine (5-CT) and angiotensin II (Ang II), upregulates ET_B, 5-HT_1B and AT₁ receptor mRNA and protein levels. Treatment with SB-386023-b given as late as at 6 h but not at 12 h after the SAH significantly decreased the receptor upregulation, the reduction in CBF and the neurology score.

Conclusion

These results provide evidence for a role of the ERK1/2 pathway in regulation of expression of cerebrovascular SMC receptors. It is suggested that raf inhibition may reduce late cerebral ischemia after SAH and provides a realistic time window for therapy.     

Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

Background

Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting.

Results

Here, we demonstrate that minocycline attenuates both in vitro (oxygen glucose deprivation) and in vivo (middle cerebral artery occlusion) experimentally induced ischemic deficits by direct inhibition of apoptotic-like neuronal cell death involving the anti-apoptotic Bcl-2/cytochrome c pathway. Such anti-apoptotic effect of minocycline is seen in neurons, but not apparent in astrocytes. Our data further indicate that the neuroprotection is dose-dependent, in that only low dose minocycline inhibits neuronal cell death cascades at the acute stroke phase, whereas the high dose exacerbates the ischemic injury.

Conclusion

The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.     

Microcanonical Analysis of the Curie–Weiss Anisotropic Quantum Heisenberg Model in a Magnetic Field

The anisotropic quantum Heisenberg model with Curie-Weiss-type interactions is studied analytically in several variants of the microcanonical ensemble. (Non)equivalence of microcanonical and canonical ensembles is investigated by studying the concavity properties of entropies. The microcanonical entropy \(s(e,\varvec{m})\) is obtained as a function of the energy \(e\) and the magnetization vector \({\varvec{m}}\) in the thermodynamic limit. Since, for this model, \(e\) is uniquely determined by \({\varvec{m}}\) , the same information can be encoded either in \(s(\varvec{m})\) or \(s(e,m_1,m_2)\) . Although these two entropies correspond to the same physical setting of fixed \(e\) and \({\varvec{m}}\) , their concavity properties differ. The entropy \(s_{{\varvec{h}}}(u)\) , describing the model at fixed total energy \(u\) and in a homogeneous external magnetic field \({\varvec{h}}\) of arbitrary direction, is obtained by reduction from the nonconcave entropy \(s(e,m_1,m_2)\) . In doing so, concavity, and therefore equivalence of ensembles, is restored. \(s_{{\varvec{h}}}(u)\) has nonanalyticities on surfaces of co-dimension 1 in the \((u,\varvec{h})\) -space. Projecting these surfaces into lower-dimensional phase diagrams, we observe that the resulting phase transition lines are situated in the positive-temperature region for some parameter values, and in the negative-temperature region for others. In the canonical setting of a system coupled to a heat bath of positive temperatures, the nonanalyticities in the microcanonical negative-temperature region cannot be observed, and this leads to a situation of effective nonequivalence even when formal equivalence holds.     

PKCε phosphorylation regulates the mitochondrial translocation of ATF2 in ischemia-induced neurodegeneration

Background

Global cerebral ischemia triggers neurodegeneration in the hippocampal CA1 region, but the mechanism of neuronal death remains elusive. The epsilon isoform of protein kinase C (PKCε) has recently been identified as a master switch that controls the nucleocytoplasmic trafficking of ATF2 and the survival of melanoma cells. It is of interest to assess the role of PKCε–ATF2 signaling in neurodegeneration.

Results

Phosphorylation of ATF2 at Thr-52 was reduced in the hippocampus of PKCε null mice, suggesting that ATF2 is a phosphorylation substrate of PKCε. PKCε protein concentrations were significantly reduced 4, 24, 48 and 72 h after transient global cerebral ischemia, resulting in translocation of nuclear ATF2 to the mitochondria. Degenerating neurons staining positively with Fluoro-Jade C exhibited cytoplasmic ATF2.

Conclusions

Our results support the hypothesis that PKCε regulates phosphorylation and nuclear sequestration of ATF2 in hippocampal neurons during ischemia-induced neurodegeneration.

     

Canonical Basis for Quantum {\mathfrak{osp}(1|2)}

We introduce a modified quantum enveloping algebra as well as a (modified) covering quantum algebra for the ortho-symplectic Lie superalgebra ${\mathfrak{osp}(1|2)}$ . Then we formulate and compute the corresponding canonical bases, and relate them to the counterpart for ${\mathfrak{sl}(2)}$ . This provides a first example of canonical basis for quantum superalgebras.     

Relating the Quantum Mechanics of Discrete Systems to Standard Canonical Quantum Mechanics

Standard canonical quantum mechanics makes much use of operators whose spectra cover the set of real numbers, such as the coordinates of space, or the values of the momenta. Discrete quantum mechanics uses only strictly discrete operators. We show how one can transform systems with pairs of integer-valued, commuting operators $P_i$ and $Q_i$ , to systems with real-valued canonical coordinates $q_i$ and their associated momentum operators $p_i$ . The discrete system could be entirely deterministic while the corresponding (p, q) system could still be typically quantum mechanical.     

Changes in corticospinal excitability and the direction of evoked movements during motor preparation: A TMS study

Background

Huntington's disease (HD) is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line), expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit.

Results

We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks), with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC) in HD mice, nor the overall decrease in brain weight, measured at 9 months of age. At this age, the density of ubiquitinated protein aggregates in the striatum and ACC is also not significantly ameliorated by environmental enrichment or wheel running.

Conclusion

These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment. However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment. Comparison of different environmental manipulations, performed in specific time windows, can identify critical periods for the induction of neuroprotective 'brain reserve' in animal models of HD and related neurodegenerative diseases.     

Real-time monitoring of ischemic and contralateral brain pO2 during stroke by variable length multisite resonators

Purpose

Electron paramagnetic resonance (EPR) oximetry using variable length multi-probe implantable resonator (IR), was used to investigate the temporal changes in the ischemic and contralateral brain pO₂ during stroke in rats.

Material and methods

The EPR signal to noise ratio (S/N) of the IR with four sensor loops at a depth of up to 11 mm were compared with direct implantation of lithium phthalocyanine (LiPc, oximetry probe) deposits in vitro. These IRs were used to follow the temporal changes in pO₂ at two sites in each hemisphere during ischemia induced by left middle cerebral artery occlusion (MCAO) in rats breathing 30% O₂ or 100% O₂.

Results

The S/N ratios of the IRs were significantly greater than the LiPc deposits. A similar pO₂ at two sites in each hemisphere prior to the onset of ischemia was observed in rats breathing 30% O₂. However, a significant decline in the pO₂ of the left cortex and striatum occurred during ischemia, but no change in the pO₂ of the contralateral brain was observed. A significant increase in the pO₂ of only the contralateral non-ischemic brain was observed in the rats breathing 100% O₂. No significant difference in the infarct volume was evident between the animals breathing 30% O₂ or 100% O₂ during ischemia.

Conclusions

EPR oximetry with IRs can repeatedly assess temporal changes in the brain pO₂ at four sites simultaneously during stroke. This oximetry approach can be used to test and develop interventions to rescue ischemic tissue by modulating cerebral pO₂ during stroke.     

Topological Invariants of Eigenvalue Intersections and Decrease of Wannier Functions in Graphene

We investigate the asymptotic decrease of the Wannier functions for the valence and conduction band of graphene, both in the monolayer and the multilayer case. Since the decrease of the Wannier functions is characterised by the structure of the Bloch eigenspaces around the Dirac points, we introduce a geometric invariant of the family of eigenspaces, baptised eigenspace vorticity. We compare it with the pseudospin winding number. For every value $n \in \mathbb {Z}$ of the eigenspace vorticity, we exhibit a canonical model for the local topology of the eigenspaces. With the help of these canonical models, we show that the single band Wannier function $w$ satisfies $|w(x)| \le {\mathrm {const}} \cdot |x|^{-2}$ as $|x| \rightarrow \infty $ , both in monolayer and bilayer graphene.     

General quantum mechanical canonical point transformations

Problems related to the operator form of the generalized canonical momenta in quantum mechanics are resolved by use of the general quantum mechanical canonical point transformation method. This method can be applied to any general canonical point transformation irrespective of the relationship between the domains of the original and transformed variables. The differential representation of the original canonical momenta p_i in the original coordinate space is ?i \(\begin{array}{*{20}c} / \\ h \\ \end{array}\) ?/?x _i and of the transformed canonical momentap _i ′ in the transformed coordinate space is ?i \(\begin{array}{*{20}c} / \\ h \\ \end{array}\) ?/?x _i ′. Relationships are derived between the eigenvalues of the original and transformed momenta in either space. The ordering problem for general point transformations is discussed and is shown to be solved. As an example of the generality of the method, it is demonstrated on the point transformation in three dimensions from Cartesian rectilinear to spherical rectilinear coordinates.     

Generation of sub wavelength super long dark channel using azimuthally polarized annular multi-Gaussian beam

We investigate the interesting focal properties of phase modulation azimuthally polarized annular multi Gaussian beam employing a high numerical aperture (NA) lens on the basis of vector diffraction theory. We observe that our proposed system generates a sub wavelength focal hole of \(0.43 \uplambda \) having large uniform focal depth of \(84 \uplambda \) . This kind of nondiffracting focal hole is called dark channel, which may have applications in atom optical experiments, such as with atomic lenses, atom traps, and atom switches.     

Thermodynamics of a class of non-asymptotically flat black holes in Einstein–Maxwell–Dilaton theory

We analyse in detail the thermodynamics in the canonical and grand canonical ensembles of a class of non-asymptotically flat black holes of the Einstein-(anti) Maxwell-(anti) Dilaton theory in 4D with spherical symmetry. We present the first law of thermodynamics, the thermodynamic analysis of the system through the geometrothermodynamics methods, Weinhold, Ruppeiner, Liu–Lu–Luo–Shao and the most common, that made by the specific heat. The geometric methods show a curvature scalar identically zero, which is incompatible with the results of the analysis made by the non null specific heat, which shows that the system is thermodynamically interacting, does not possess extreme case nor phase transition. We also analyse the local and global stability of the thermodynamic system, and obtain a local and global stability for the normal case for $0<\gamma <1$ and for other values of $\gamma $ , an unstable system. The solution where $\gamma =0$ separates the class of locally and globally stable solutions from the unstable ones.     

Design of spectral crosstalk suppressing structure in two-color HgCdTe infrared focal plane arrays detector

Spectral crosstalk suppressing design of two-color HgCdTe medium-wave/long-wave (MW/LW) \(\hbox {n}^{+}\) – \(\hbox {p}_{1}\) – \(\hbox {P}_{2}\) – \(\hbox {P}_{3}\) – \(\hbox {N}^{+}\) infrared focal plane arrays (IRFPAs) detector functioning in simultaneous mode is carried out in this study, using Crosslight Technology Computer Aided Design (TCAD) software. A compositional barrier of \(\hbox {P}_{2}\) -region sandwiched between LW absorption layer of \(\hbox {p}_{1}\) -region and MW absorption layer of \(\hbox {P}_{3}\) -region is designed to suppress spectral crosstalk. MW-to-LW crosstalk can be significantly suppressed to 2.1 % while LW-to-MW crosstalk can be maintained less than 1 % by integrating an optimized compositional barrier.     

On resonant classical Hamiltonians with two equal frequencies

This paper contains a detailed study of the flow that the classical Hamiltonian $$H = \tfrac{1}{2}(x_1^2 + y_1^2 ) - \tfrac{1}{2}(x_2^2 + y_2^2 ) + \mathcal{O}_3 $$ induces near the origin of its phase spaceR ⁴. Here the perturbation term \(\mathcal{O}_3 \) represents a convergent power series. In particular, criteria for the existence and stability of periodic orbits are developed and expressed in terms of canonical invariants that are extracted from the perturbation term.     

Second quantization of classical nonlinear relativistic field theory

The construction of a relativistic interacting local quantum field is given in two steps: first the classical nonlinear relativistic field theory is written down in terms of Poisson brackets, with initial conditions as canonical variables: next a representation of Poisson bracket Lie algebra by means of linear operators in the topological vector space is given and an explicit form of a local interacting relativistic quantum field \(\hat \Phi \) is obtained. The construction of asymptotic local relativistic fields \(\hat \Phi _{in} \) and \(\hat \Phi _{out} \) associated with \(\hat \Phi \) is also given.     

Courant–Dorfman Algebras and their Cohomology

We introduce a new type of algebra, the Courant–Dorfman algebra. These are to Courant algebroids what Lie–Rinehart algebras are to Lie algebroids, or Poisson algebras to Poisson manifolds. We work with arbitrary rings and modules, without any regularity, finiteness or non-degeneracy assumptions. To each Courant–Dorfman algebra ${(\mathcal{R}, \mathcal{E})}$ we associate a differential graded algebra ${\mathcal{C}(\mathcal{E}, \mathcal{R})}$ in a functorial way by means of explicit formulas. We describe two canonical filtrations on ${\mathcal{C}(\mathcal{E}, \mathcal{R})}$ , and derive an analogue of the Cartan relations for derivations of ${\mathcal{C}(\mathcal{E}, \mathcal{R})}$ ; we classify central extensions of ${\mathcal{E}}$ in terms of ${H^2(\mathcal{E}, \mathcal{R})}$ and study the canonical cocycle ${\Theta \in \mathcal{C}^3(\mathcal{E}, \mathcal{R})}$ whose class ${[\Theta]}$ obstructs re-scalings of the Courant–Dorfman structure. In the nondegenerate case, we also explicitly describe the Poisson bracket on ${\mathcal{C}(\mathcal{E}, \mathcal{R})}$ ; for Courant–Dorfman algebras associated to Courant algebroids over finite-dimensional smooth manifolds, we prove that the Poisson dg algebra ${\mathcal{C}(\mathcal{E}, \mathcal{R})}$ is isomorphic to the one constructed in Roytenberg (On the structure of graded symplectic supermanifolds and Courant algebroids. American Mathematical Society, Providence, 2002) using graded manifolds.     

Serum anticholinergic activity and cerebral cholinergic dysfunction: An EEG study in frail elderly with and without delirium

Background

Delirium increases morbidity, mortality and healthcare costs especially in the elderly. Serum anticholinergic activity (SAA) is a suggested biomarker for anticholinergic burden and delirium risk, but the association with cerebral cholinergic function remains unclear. To clarify this relationship, we prospectively assessed the correlation of SAA with quantitative electroencephalography (qEEG) power, delirium occurrence, functional and cognitive measures in a cross-sectional sample of acutely hospitalized elderly (> 80 y) with high dementia and delirium prevalence.

Methods

61 consecutively admitted patients over 80 years underwent an extensive clinical and neuropsychological evaluation. SAA was determined by using radio receptor assay as developed by Tune, and standard as well as quantitative EEGs were obtained.

Results

15 patients had dementia with additional delirium (DD) according to expert consensus using DSM-IV criteria, 31 suffered from dementia without delirium (D), 15 were cognitively unimpaired (CU). SAA was clearly detectable in all patients but one (mean 10.9 ± 7.1 pmol/ml), but was not associated with expert-panel approved delirium diagnosis or cognitive functions. Delirium-associated EEG abnormalities included occipital slowing, peak power and alpha decrease, delta and theta power increase and slow wave ratio increase during active delirious states. EEG measures correlated significantly with cognitive performance and delirium severity, but not with SAA levels.

Conclusion

In elderly with acute disease, EEG parameters reliable indicate delirium, but SAA does not seem to reflect cerebral cholinergic function as measured by EEG and is not related to delirium diagnosis.     

Design,synthesis, and biological activities of novel azole-bonded \upbeta -hydroxypropyl oxime O-ethers

The synthesis and biological effects of 15 novel azole-bonded \(\upbeta \) -hydroxypropyl oxime \(O\) -ethers have been described. In this synthesis, the oximation of aromatic ketones followed by an \(O\) -alkylation reaction with epichlorohydrin and/or epibromohydrin led to the corresponding \(O\) -oxime ether adducts. Subsequently, the attained \(O\) -oxime ether adducts were used to synthesize the target molecules after treating them with the appropriate azole derivatives. The in vitro antifungal and antibacterial activities of title compounds were obtained against several pathogenic fungi, Gram-positive and/or Gram-negative bacteria. Benzophenone \(O\) -2-hydroxy-3-(2-phenyl-1 \(H\) -imidazol-1-yl) propyl oxime and 9 \(H\) -fluoren-9-one \(O\) -2-hydroxy-3-(2-phenyl-1 \(H\) -imidazol-1-yl)propyl oxime proved to have considerable antifungal activity against Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum. These two compounds demonstrated comparable antifungal activity to clotrimazole and fluconazole (standard drugs). All compounds were also tested against Escherichia coli and Staphylococcus aureus as Gram-negative and Gram-positive bacteria, respectively, and their activities were compared to gentamycin and ampicillin (reference drugs). In general, marginal antibacterial activity against tested bacteria was observed for the title compounds. A molecular docking study is also discussed for the two most potent compounds against fungi. The docking study reveals a considerable interaction between the two most potent compounds and the active site of Mycobacterium P450DM. Moreover, these two compounds are much strongly bound to the active site of Mycobacterium P450DM compared to fluconazole.     

Heavy Meson Decay in Three-Mesons and FSI

The final state interaction contribution to charged D decay into \({K \pi \pi}\) is computed within a light-front framework, considering S-wave \({K\pi}\) interactions in 1/2 and 3/2 isospin states. The convergence of the rescattering series is checked computing terms up to the third perturbative order. The role of the resonances above \({K^*_0(1430)}\) , and the contribution of the \({K\pi 3/2}\) isospin channel to charged three-body D decays, are studied against the available phase-shift analysis.     

Deformed spinor networks for loop gravity: towards hyperbolic twisted geometries

In the context of a canonical quantization of general relativity, one can deform the loop gravity phase space on a graph by replacing the \(T^*\mathrm{SU}(2)\) phase space attached to each edge by \(\mathrm{SL}(2,{\mathbb C})\) seen as a phase space. This deformation is supposed to encode the presence of a non-zero cosmological constant.Here we show how to parametrize this phase space in terms of spinor variables, thus obtaining deformed spinor networks for loop gravity, with a deformed action of the gauge group \(\mathrm{SU}(2)\) at the vertices. These are to be formally interpreted as the generalization of loop gravity twisted geometries to a hyperbolic curvature.