A non-circadian role for clock-genes in sleep homeostasis:a strain comparison

Background  

We have previously reported that the expression of circadian clock-genes increases in the cerebral cortex after sleep deprivation (SD) and that the sleep rebound following SD is attenuated in mice deficient for one or more clock-genes. We hypothesized that besides generating circadian rhythms, clock-genes also play a role in the homeostatic regulation of sleep. Here we follow the time course of the forebrain changes in the expression of the clock-genes period (per)-1, per2, and of the clock-controlled gene albumin D-binding protein (dbp) during a 6 h SD and subsequent recovery sleep in three inbred strains of mice for which the homeostatic sleep rebound following SD differs. We reasoned that if clock genes are functionally implicated in sleep homeostasis then the SD-induced changes in gene expression should vary according to the genotypic differences in the sleep rebound.     

Regulation of prokineticin 2 expression by light and the circadian clock

Background  

The suprachiasmatic nucleus (SCN) contains the master circadian clock that regulates daily rhythms of many physiological and behavioural processes in mammals. Previously we have shown that prokineticin 2 (PK2) is a clock-controlled gene that may function as a critical SCN output molecule responsible for circadian locomotor rhythms. As light is the principal zeitgeber that entrains the circadian oscillator, and PK2 expression is responsive to nocturnal light pulses, we further investigated the effects of light on the molecular rhythm of PK2 in the SCN. In particular, we examined how PK2 responds to shifts of light/dark cycles and changes in photoperiod. We also investigated which photoreceptors are responsible for the light-induced PK2 expression in the SCN. To determine whether light requires an intact functional circadian pacemaker to regulate PK2, we examined PK2 expression in cryptochrome1,2-deficient (Cry1-/-Cry2-/-) mice that lack functional circadian clock under normal light/dark cycles and constant darkness.     

Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain

Background  

The mammalian suprachiasmatic nucleus (SCN), located in the ventral hypothalamus, is a major regulator of circadian rhythms in mammals and birds. However, the role of the SCN in lower vertebrates remains poorly understood. Zebrafish cyclops (cyc) mutants lack ventral brain, including the region that gives rise to the SCN. We have used cyc embryos to define the function of the zebrafish SCN in regulating circadian rhythms in the developing pineal organ. The pineal organ is the major source of the circadian hormone melatonin, which regulates rhythms such as daily rest/activity cycles. Mammalian pineal rhythms are controlled almost exclusively by the SCN. In zebrafish and many other lower vertebrates, the pineal has an endogenous clock that is responsible in part for cyclic melatonin biosynthesis and gene expression.     

Myelination in the absence of UDP-galactose:ceramide galactosyl-transferase and fatty acid 2 -hydroxylase

Background  

The sphingolipids galactosylceramide (GalCer) and sulfatide are major myelin components and are thought to play important roles in myelin function. The importance of GalCer and sulfatide has been validated using UDP-galactose:ceramide galactosyltransferase-deficient (Cgt ^-/-) mice, which are impaired in myelin maintenance. These mice, however, are still able to form compact myelin. Loss of GalCer and sulfatide in these mice is accompanied by up-regulation of 2-hydroxylated fatty acid containing (HFA)-glucosylceramide in myelin. This was interpreted as a partial compensation of the loss of HFA-GalCer, which may prevent a more severe myelin phenotype. In order to test this hypothesis, we have generated Cgt ^-/- mice with an additional deletion of the fatty acid 2-hydroxylase (Fa2h) gene.     

Combined constraints on modified Chaplygin gas model from cosmological observed data: Markov Chain Monte Carlo approach

We use the Markov Chain Monte Carlo method to investigate a global constraints on the modified Chaplygin gas (MCG) model as the unification of dark matter and dark energy from the latest observational data: the Union2 dataset of type supernovae Ia (SNIa), the observational Hubble data (OHD), the cluster X-ray gas mass fraction, the baryon acoustic oscillation (BAO), and the cosmic microwave background (CMB) data. In a flat universe, the constraint results for MCG model are, W_bh² = 0.02263^+0.00184_-0.00162 (1s)^+0.00213_-0.00195 (2s){\Omega_{b}h^{2}\,{=}\,0.02263^{+0.00184}_{-0.00162} (1\sigma)^{+0.00213}_{-0.00195} (2\sigma)}, B_s = 0.7788^+0.0736_-0.0723(1s)^+0.0918_-0.0904 (2s){B_{s}\,{=}\,0.7788^{+0.0736}_{-0.0723}(1\sigma)^{+0.0918}_{-0.0904} (2\sigma)}, a = 0.1079^+0.3397_-0.2539 (1s)^+0.4678_-0.2911 (2s){\alpha\,{=}\,0.1079^{+0.3397}_{-0.2539} (1\sigma)^{+0.4678}_{-0.2911} (2\sigma)}, B = 0.00189^+0.00583_-0.00756(1s)^+0.00660_-0.00915 (2s){B\,{=}\,0.00189^{+0.00583}_{-0.00756}(1\sigma)^{+0.00660}_{-0.00915} (2\sigma)}, and H₀=70.711^+4.188_-3.142 (1s)^+5.281_-4.149(2s){H_{0}=70.711^{+4.188}_{-3.142} (1\sigma)^{+5.281}_{-4.149}(2\sigma)}.     

Advanced analysis of a cryptochrome mutation's effects on the robustness and phase of molecular cycles in isolated peripheral tissues of Drosophila

Background  

Previously, we reported effects of the cry ^b mutation on circadian rhythms in period and timeless gene expression within isolated peripheral Drosophila tissues. We relied on luciferase activity driven by the respective regulatory genomic elements to provide real-time reporting of cycling gene expression. Subsequently, we developed a tool kit for the analysis of behavioral and molecular cycles. Here, we use these tools to analyze our earlier results as well as additional data obtained using the same experimental designs.     

Errorless and errorful learning modulated by transcranial direct current stimulation

Background

Caspase-3 is one of the most downstream enzymes activated in the apoptotic pathway. In caspase-3 deficient mice, loss of cochlear hair cells and spiral ganglion cells coincide closely with hearing loss. In contrast with the auditory system, details of the vestibular phenotype have not been characterized. Here we report the vestibular phenotype and inner ear anatomy in the caspase-3 deficient (Casp3 ^-/- ) mouse strain.

Results

Average ABR thresholds of Casp3 ^-/- mice were significantly elevated (P < 0.05) compared to Casp3 ^+/- mice and Casp3 ^+/+ mice at 3 months of age. In DPOAE testing, distortion product 2F1-F2 was significantly decreased (P < 0.05) in Casp3 ^-/- mice, whereas Casp3 ^+/- and Casp3 ^+/+ mice showed normal and comparable values to each other. Casp3 ^-/- mice were hyperactive and exhibited circling behavior when excited. In lateral canal VOR testing, Casp3 ^-/- mice had minimal response to any of the stimuli tested, whereas Casp3 ^+/- mice had an intermediate response compared to Casp3 ^+/+ mice. Inner ear anatomical and histological analysis revealed gross hypomorphism of the vestibular organs, in which the main site was the anterior semicircular canal. Hair cell numbers in the anterior- and lateral crista, and utricle were significantly smaller in Casp3 ^-/- mice whereas the Casp3 ^+/- and Casp3 ^+/+ mice had normal hair cell numbers.

Conclusions

These results indicate that caspase-3 is essential for correct functioning of the cochlea as well as normal development and function of the vestibule.     

Critical Hardy–Lieb–Thirring Inequalities for Fourth-Order Operators in Low Dimensions

This paper considers Hardy–Lieb–Thirring inequalities for higher order differential operators. A result for general fourth-order operators on the half-line is developed, and the trace inequality

Synthesis of cyano-2,3-dihydropyrrolo[1,2-<Emphasis Type="Italic">f</Emphasis>]phenanthridine derivatives via a domino-Knoevenagel-cyclization

Abstract  

In a new multicomponent reaction phenanthridine reacts with isocyanides and malonitrile in the presence of benzaldehyde derivatives to produce 2-aryl-3-(alkyl- or arylimino)-2,3-dihydropyrrolo[1,2-f]phenanthridine-1,1(12b H)-dicarbonitrile in a simple, mild, and efficient protocol in excellent yields.     

Nuclear Magnetic Resonance Spectroscopy Study of a Disaccharidic Crown Ether.

Abstract

The disaccharidic anhydro derivative 6-O-(5,6-anhydro-3-deoxy-1,2-O-isopropylidene α-D-glucofuranos-3-yl)-1,2-O-isopropylidene-3-O-n-dodecyl-α-D-glucofuranose (1) led to the disaccharidic crown ether 2 in 40% yield when treated at low concentration with 2.5 eq. of KOH in toluene-Me₂SO. Compound 2 structure was proved through a detailed NMR analysis (¹H, ¹³C, ¹H-¹H and ¹³C-¹H 2D correlations). This structural elucidation indicated that compound 2 resulted from the intramolecular attack of the C-5-O^?alkoxide group, generated in the basic medium, on the C-6′ carbon of the 5′,6′-anhydro group.     

One-pot microwave-assisted protocol for the synthesis of substituted 2-amino-1<Emphasis Type="Italic">H</Emphasis>-imidazoles

Abstract  

An efficient microwave-assisted one-pot two-step protocol was developed for the construction of disubstituted 2-amino-1H-imidazoles. This process involves the sequential formation of 2,3-dihydro-2-hydroxyimidazo[1,2-a]pyrimidinium salts from readily available 2-aminopyrimidines and α-bromoketones, followed by cleavage of the pyrimidine ring with hydrazine.     

Synthesis of novel 4H-pyrimido[1,6-a]pyrimidines via a one-pot three-component condensation

Abstract  

Highly substituted novel 4H-pyrimido[1,6-a] pyrimidines were prepared by a trifluoromethanesulfonic acid catalyzed one-pot three-component condensation of 4-aminopyrimidines, aldehydes, and β-ketoesters. A preliminary feasibility study was undertaken on these compounds, to assess the potential production of a library of further diversified compounds by nucleophilic replacement of Cl (R¹) or by reaction of electrophiles with the NH₂ (R²) group.     

Effective Action and Phase Transitions in Yang-Mills Theory on Spheres

We study the covariantly constant Savvidy-type chromomagnetic vacuum in finite-temperature Yang-Mills theory on the four-dimensional curved spacetime. Motivated by the fact that a positive spatial curvature acts as an effective gluon mass we consider the compact Euclidean spacetime S ¹ × S ¹ × S ², with the radius of the first circle determined by the temperature a ₁ = (2π T)⁻¹. We show that covariantly constant Yang-Mills fields on S ² cannot be arbitrary but are rather a collection of monopole-antimonopole pairs. We compute the heat kernels of all relevant operators exactly and show that the gluon operator on such a background has negative modes for any compact semi-simple gauge group. We compute the infrared regularized effective action and apply the result for the computation of the entropy and the heat capacity of the quark-gluon gas. We compute the heat capacity for the gauge group SU(2N) for a field configuration of N monopole-antimonopole pairs. We show that in the high-temperature limit the heat capacity per unit volume is well defined in the infrared limit and exhibits a typical behavior of second-order phase transition ~ (T-T_c)^-3/2{\sim(T-T_c)^{-3/2}} with the critical temperature T _c  = (2π a)⁻¹, where a is the radius of the 2-sphere S ².     

General Dynamical Equations for Dingle’s Space-Times Filled with a Charged Non-perfect Fluid

In this paper we have assumed charged non-perfect fluid as the material content of the space-time. The expression for the “mass function-M(r,y,z,t)” is obtained for the general situation and the contributions from the Ricci tensor in the form of material energy density ρ, pressure anisotropy [\fracp₂+p₃2-p₁][\frac{p_{2}+p_{3}}{2}-p_{1}] , electromagnetic field energy ℰ and the conformal Weyl tensor, viz. energy density of the free gravitational field ε (=\frac-3Y₂4p)(=\frac{-3\Psi_{2}}{4\pi}) are made explicit. This work is an extension of the work obtained earlier by Rao and Hasmani (Math. Today XIIA:71, 1993; New Directions in Relativity and Cosmology, Hadronic Press, Nonantum, 1997) for deriving general dynamical equations for Dingle’s space-times described by this most general orthogonal metric,

Low Temperature Properties for Correlation Functions in Classical N-Vector Spin Models

We obtain convergent multi-scale expansions for the one-and two-point correlation functions of the low temperature lattice classical N - vector spin model in d S 3 dimensions, N S 2. The Gibbs factor is taken as exp[-b(1/2 ||?f||² +l/8 || |f|² - 1 ||² + v/2||f- h||²)], \exp [-\beta (1/2 ||\partial \phi||^2 +\lambda/8 ||\, |\phi|^2 - 1 ||^2 + v/2||\phi - h||^2)], where f(x), h ? R^N\phi(x), h \in R^N, x ? Z^dx \in Z^d, |h|=1, b < ￥|h|=1, \beta < \infty, l 3 ￥\lambda \geq \infty are large and 0 < v h 1. In the thermodynamic and v ˉ 0v \downarrow 0 limits, with h = e₁, and j L ‘^½ ‘, the expansion gives áf₁(x)? = 1+0(1/b^1/2)\langle \phi_1(x)\rangle = 1+0(1/\beta^{1/2}) (spontaneous magnetization), áf₁(x)f_i(y)? = 0\langle \phi_1(x)\phi_i(y)\rangle=0, áf_i (x)f_i (y)? = c₀ D^-1(x,y)+R(x,y)\langle \phi_i (x)\phi_i (y)\rangle = c_0 \Delta^{-1}(x,y)+R(x,y) (Goldstone Bosons), i = 2, 3, ?, Ni= 2, 3,\,\ldots, N, and áf₁(x)f₁(y)?^T=R￠(x,y)\langle \phi_1(x)\phi_1(y)\rangle^T=R'(x,y), where |R(x,y)||R(x,y)|, |R￠(x,y)| < 0(1)(1+|x-y|)^d-2+r|R'(x,y)|< 0(1)(1+|x-y|)^{d-2+\rho} for some „ > 0, and c₀ is aprecisely determined constant.     

Organic synthesis in water: a green protocol for the synthesis of 2-(cyclohexylamino)-3- aryl- indeno[1,2-b]furan-4-ones

Aldehydes, 1,3-indandione and cyclohexylisocyanide undergo smooth coupling-cyclization in water to produce the corresponding 2-(cyclohexylamino)-3-aryl- indeno [1,2-b] furan-4-ones in good yields. Water was used as a solvent to avoid the use of other highly toxic and environmentally unfavorable solvents for this synthesis.

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Graphical Abstract  A simple and efficient synthesis of 2-(cyclohexylamino)-3-aryl- indeno[1,2-b]furan-4-ones was achieved via a one-pot three-component reaction of cyclohexylisocyanide, aldehydes, and 1,3-indandione in water for 5 h in good yields. zFX

     

Elevated intracellular chloride level in albino visual cortex neurons is mediated by Na-K-Cl co-transporter

Background  

During development the switch from a depolarizing to a hyperpolarizing action of GABA is a consequence of a decrease of the Na⁺-K⁺-2Cl^- co-transporter (NKCC1, Cl^--uptake) and increase of the K⁺-Cl^- co-transporter (KCC2, Cl^--extrusion) expression. However albino visual cortex neurons don't show a corresponding decrease in intracellular chloride concentration during development of the visual system as compared to pigmented animals.     

Tyrosine phosphatases such as SHP-2 act in a balance with Src-family kinases in stabilization of postsynaptic clusters of acetylcholine receptors

Background  

Development of neural networks requires that synapses are formed, eliminated and stabilized. At the neuromuscular junction (NMJ), agrin/MuSK signaling, by triggering downstream pathways, causes clustering and phosphorylation of postsynaptic acetylcholine receptors (AChRs). Postnatally, AChR aggregates are stabilized by molecular pathways that are poorly characterized. Gain or loss of function of Src-family kinases (SFKs) disassembles AChR clusters at adult NMJs in vivo, whereas AChR aggregates disperse rapidly upon withdrawal of agrin from cultured src ^-/-;fyn ^-/- myotubes. This suggests that a balance between protein tyrosine phosphatases (PTPs) and protein tyrosine kinases (PTKs) such as those of the Src-family may be essential in stabilizing clusters of AChRs.