Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model

Background

Proteoglycan (PG) in the extracellular matrix (ECM) of the central nervous system (CNS) may act as a barrier for neurite elongation in a growth tract, and regulate other characteristics collectively defined as structural neural plasticity. Proteolytic cleavage of PGs appears to alter the environment to one favoring plasticity and growth. Brevican belongs to the lectican family of aggregating, chondroitin sulfate (CS)-bearing PGs, and it modulates neurite outgrowth and synaptogenesis. Several ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) are glutamyl-endopeptidases that proteolytically cleave brevican. The purpose of this study was to localize regions of adult CNS that contain a proteolytic-derived fragment of brevican which bears the ADAMTS-cleaved neoepitope sequence. These regions were compared to areas of Wisteria floribunda agglutin (WFA) reactivity, a common reagent used to detect "perineuronal nets" (PNNs) of intact matrix and a marker which is thought to label regions of relative neural stability.

Results

WFA reactivity was found primarily as PNNs, whereas brevican and the ADAMTS-cleaved fragment of brevican were more broadly distributed in neuropil, and in particular regions localized to PNNs. One example is hippocampus where the ADAMTS-cleaved brevican fragment is found surrounding pyramidal neurons, in neuropil of stratum oriens/radiatum and the lacunosum moleculare. The fragment was less abundant in the molecular layer of the dentate gyrus. Mostly PNNs of scattered interneurons along the pyramidal layer were identified by WFA. In lateral thalamus, the reticular thalamic nucleus stained abundantly with WFA whereas ventral posterior nuclei were markedly immunopositive for ADAMTS-cleaved brevican. Using Western blotting techniques, no common species were reactive for brevican and WFA.

Conclusion

In general, a marked discordance was observed in the regional localization between WFA and brevican or the ADAMTS-derived N-terminal fragment of brevican. Functionally, this difference may correspond to regions with varied prevalence for neural stability/plasticity.     

NMR Studies of Agricultural Compounds. Applications of Achiral and Chiral Lanthanide Shift Reagents to the Herbicide,Fenoxaprop-Ethyl

The 200 MHz H NMR spectra of the herbicide, fenoxaprop-ethyl, 1, have been studied in CDCl₃ solution at ambient temperatures as the racemic ester free base with the added chiral lanthanide shift reagent (LSR), tris [3 - (heptafluoropropylhydroxymethylene) - (+) - camphorato]europium(III), Eu(HFC)₃, 2, with some additional runs using the achiral LSR, tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) europium(III), Eu(FOD)₃, 3, for supplemental spectral simplification. With 2, definite enantiomeric shift differences (ΔΔδ) were observed only for the CH₃CH₂O resonance. Although increased spectral complexity for the CH₂O signal was seen with added 2, this could have resulted from anisochrony of the diastereotopic protons, H_a and H_b, of this methylene group rather than true ΔΔδ, since the achiral 3 led to near-baseline separation between the CH_aH_bO signals. Lanthanide-induced shift (LIS) magnitudes were interpreted as consistent with predominant LSR binding at the ester carbonyl.     

Chondroitin sulfate proteoglycans regulate the growth, differentiation and migration of multipotent neural precursor cells through the integrin signaling pathway

Background  

Neural precursor cells (NPCs) are defined by their ability to proliferate, self-renew, and retain the potential to differentiate into neurons and glia. Deciphering the factors that regulate their behaviors will greatly aid in their use as potential therapeutic agents or targets. Chondroitin sulfate proteoglycans (CSPGs) are prominent components of the extracellular matrix (ECM) in the central nervous system (CNS) and are assumed to play important roles in controlling neuronal differentiation and development.     

Chronic fluoxetine treatment in middle-aged rats induces changes in the expression of plasticity-related molecules and in neurogenesis

Background  

Antidepressants promote neuronal structural plasticity in young-adult rodents, but little is known of their effects on older animals. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) may mediate these structural changes through its anti-adhesive properties. PSA-NCAM is expressed in immature neurons and in a subpopulation of mature interneurons and its expression is modulated by antidepressants in the telencephalon of young-adult rodents.     

Conformational Studies of 1-(2′-Hydroxythiobenzoyl)piperidine and 4-(2′-Hydroxythiobenzoyl)morpholine by High Resolution N.M.R. Spectroscopy

Abstract

The 220 MHz ¹H nmr spectra of the title compounds (1a) and (2a), respectively, at low temperature in CDCl₃ solution are interpreted in terms of two interconverting chair forms with unequal populations (K_e = 1.17, δG° ～70 cals/mole for 1a and K_e = 1.8, δG° ～0.2 kcal/mole for 2a at ?30°C). A strong intramolecular OH…S hydrogen bond in both compounds reduces the number of degrees of freedom of the bulky N-thiobenzoyl substituent, which nearly eclipses the equatorial α-CH₂ hydrogen atoms in both comformations. Steric interactions between the 6′ phenyl proton and the hetero-ring α-CH₂ protons trans to the thiocarbonyl group are different in the two conformations of la and 2a.     

Hippocampal CA1/subiculum-prefrontal cortical pathways induce plastic changes of nociceptive responses in cingulate and prelimbic areas

Background  

Projections from hippocampal CA1-subiculum (CA1/SB) areas to the prefrontal cortex (PFC), which are involved in memory and learning processes, produce long term synaptic plasticity in PFC neurons. We examined modifying effects of these projections on nociceptive responses recorded in the prelimbic and cingulate areas of the PFC.     

Bi-directional modulation of AMPA receptor unitary conductance by synaptic activity

Background  

Knowledge of how synapses alter their efficiency of communication is central to the understanding of learning and memory. The most extensively studied forms of synaptic plasticity are long-term potentiation (LTP) and its counterpart long-term depression (LTD) of AMPA receptor-mediated synaptic transmission. In the CA1 region of the hippocampus, it has been shown that LTP often involves a rapid increase in the unitary conductance of AMPA receptor channels. However, LTP can also occur in the absence of any alteration in AMPA receptor unitary conductance. In the present study we have used whole-cell dendritic recording, failures analysis and non-stationary fluctuation analysis to investigate the mechanism of depotentiation of LTP.     

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.     

Synthesis and Characterization of 2,2-Biimidazole Complexes of Oxocations of Molybdenum (VI,V) and Uranium(VI)

Abstract

2,2′-Biimidazole complexes of MoO₂ ⁺², MoO₂ ⁺ and UO₂ ⁺² have been prepared and characterized by elemental analysis, conductance; and ¹H NMR, IR and electronic spectra. Two types of complexes have been identified. Those obtained from slightly acidic solutions have the formulae MoO₂ (H₂bim)Cl₂.2H₂O 1, UO₂(H₂bim) (Ac)₂ 2 and UO₂(H₂bim)Cl₂.2H₂O 3; whereas those from alkaline solutions have the formulae Mo₂O₄(Hbim)₂.2H₂O 4, and MO₂(Hbim)₂ (M = Mo(VI) 5, U(VI) 6). The infrared spectra of these complexes show characteristic biimidazole frequencies in the 3200–2500, 1550–1000 and 750 cm^?1 regions as well as metal oxygen double bonds in the 900 cm^?1 region. The stoichiometries of the acetate complex has been confirmed from ¹H NMR signal ratios of bimidazole to acetate protons at 7.3 and 2.3 ppm, respectively. The electronic spectrum of molybdenum(V) complex showed d-d transition band at ?13,500 cm^?1 in accord with that reported for copper (d⁹) imidazole complexes; as well as peaks due to charge transfer bands at 30,000–26,000 cm^?1 Peaks assignable to BIM → U(VI) were located at ?26,600 cm^?1. The most probable structures of these complexes have been suggested.     

Normal Coordinate Analysis of M-CH3-Moieties in Transition Metal Complexes and Comparison to Results Obtained for Methylhalides

In order to examine the influence of the transition metal on the metal-methyl fragment M-CH₃ polarized Raman spectra of the complexes Cp(CO)₂Fe-CH₃ (I), Cp(CO)₃W-CH₃ (2), Cp(CO)₂(PMe₃)W-CH₃ (3) and O₃Re-CH₃ have been recorded. The spectral data were interpreted on the basis of a normal coordinate analysis of the M-CH₃-core and the derived force constants and potential energy distributions were compared to results obtained for analogous halogen derivatives in the series X-CH₃ [X = Br (5), I (6)].     

NMR Studies of Agricultural Products. Applications of Achiral and Chiral Lanthanide Shift Reagents to the Fungicide,Triadimefon.

Abstract

The 60 MHz ¹H NMR spectra of the systemic agricultural fungicide, triadimefon, 1, have been studied in CDCl₃ at 28±1° (as the racemic free base) with the added achiral lanthanide shift reagent (LSR), tris(6, 6, 7, 7, 8, 8, 8-heptafluoro-2, 2-dimethyl-3, 5-octanedionato) europium(III), Eu(FOD)₃, 2, for spectral simplification, and with the chiral LSR, tris [3-(heptafluoropropylhydroxymethylene)-(+) -camphorato)europium(III), Eu(HFC)₃, 3, to induce enantiomeric shift differences (ΔΔδ) for several nuclei. Significant ΔΔδ values were seen for the two protons of the heterocyclic ring, the OCH methine, and aryl H-2′, 6′ of the chlorophenoxy ring. For each of these nuclei exhibiting ΔΔδ with added 3, the ΔΔδ magnitudes reached maximum values with 3: 1 molar ratios ca. 0. 18–0. 29, and decreased with higher levels of 3. To confirm analytical utility of 3 for % e. e. determinations of 1, a nonracemic (“spiked”) sample of racemic 1, with added R-(?) triadimefon, was examined with 3. At low 3: 1 ratios, both triazole H-3 and H-5, as well as the OCH and aryl H-2′, 6′ protons of (?)-1 showed a downfield sense of magnetic nonequivalence with (+) -3. With 3: 1 ratios ca. 0. 8, triazole proton H-3 reversed its sense of magnetic noneguivalence. The H-3 and H-5 signals were useful for % e. e determinations at this higher 3: 1 ratio.     

Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity

Background  

The involvement of different NMDA receptor (NMDAR) subunits has been implicated in several forms of synaptic plasticity. However, it is still controversial to what extent the involvement is specific, and little is known about the role of NMDAR subunits in certain "non-conventional" forms of plasticity. In this study we used subunit-specific blockers to test the roles of NR2A- and NR2B-containing NMDARs in a type of chemical long-term depression (LTD) induced by brief bath application of the NMDAR agonist NMDA to hippocampal slices from 12–18 days old rats. For comparison, we also examined other forms of plasticity, including a "slow LTD" induced by 0.1 Hz stimulation under low Mg²⁺ conditions as well as long-term potentiation (LTP).     

High-efficient Schottky-junction silicon solar cell using silver nanowires covering nitrogen-doped amorphous carbon

Synthesized graphene (Gr) on metal substrates that requires additional surface-to-surface transfer procedure to form Gr-on-silicon (Gr-Si) Schottky-junction configuration, which in turn results in the photovoltaic degradation caused by both mechanical damages and chemical contaminations during several wet chemical steps. This current issue has motivated us to develop alternative Schottky-junction configuration using silver nanowires (AgNWs) covering nitrogen (N)-doped amorphous carbon (a-C) films annealed in the temperature range 750–900 °C. Compared to the Schottky-junction Si solar cell based on 900 °C annealed N-doped a-C films (C_N-900-Si) with only Ag grid, all of AgNWs-C_N-900-Si solar cells exhibit the significant enhancement of photovoltaic characteristics. Consequently, the remarkable power conversion efficiency (PCE) of 6.17% is achieved on 0.2 wt% AgNWs-C_N-900-Si solar cell, which is far superior to that of the C_N-900-Si solar cell with only Ag grid (~0.13%). Furthermore, the 0.2 wt% AgNWs-C_N-900-SiNWs solar cell shows the highest short-circuit current density (J_SC) of 23.42 mA/cm² and PCE of 7.67%, which is a PCE enhancement of ~24% when compared to the 0.2 wt% AgNWs-C_N-900-Si solar cell. This study demonstrates that AgNWs network can accelerate the charge carrier extraction from Schottky-contact between C_N-900 and n-Si substrate, leading to greatly reduced series resistance that results in significantly enhanced photovoltaic characteristics.     

NMR Studies of Drugs. 5-Methyl-5-phenylhydantoin. Applications of Lanthanide Shift Reagents in Polar Solvents to a Non-Chelating Substrate

The 200.1 MHz ¹H NMR spectra of 5-methyl-5-phenylhydantoin, 1, have been studied in CD₃CN solution at ambient temperatures with the achiral shift reagent, tris (6, 6, 7, 7, 8, 8, 8-heptafluoro-2,2-dimethyl-3,5-octanedionato) europium (III), 2, and the chiral reagent, tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato] europium (III), 3. Although 1 cannot chelate the LSRs, use of sufficiently high LSR:1 molar ratios served to compensate for competitive binding of LSR by the polar solvent, and permitted substantial lanthanide-induced shifts to be observed with 2 or 3. With 3, significant enantiomeric shift differences were produced for the ortho aryl protons and for the CH₃ signals. The ortho proton signal appears to offer excellent potential for direct determination of enantiomeric excess of 1. These results demonstrate the utility of LSRs 2 or 3 even in a polar solvent with a nonchelating substrate.     

Expression of Cre recombinase in dopaminoceptive neurons

Background  

Dopamine-activated signaling regulates locomotor and emotional responses and alterations in dopamine-signaling are responsible of several psychomotor disorders. In order to identify specific functions of these pathways, the Cre/loxP system has been used. Here, we describe the generation and the characterization of a transgenic mouse line expressing the Cre recombinase in dopaminoceptive neurons. To this purpose, we used as expression vector a 140 kb yeast artificial chromosome (YAC) containing the dopamine D1 receptor gene (Drd1a).     

Extinction, scattering, and absorption of anomalous radar-reflected emission in a cloud and atmosphere

For the anomalous radar reflection from the oversized water drops originating in water-ice phase transition observable in the submillimeter band transparency window of ice [1] we consider the process of extinction, scattering, and absorption in a cloud and atmosphere. Our calculations, which are based on experimental results, show that in the situation when the convective cloud is illuminated from nadir by a narrow-beam submillimeter radar (carried on board an airplane or a satellite), the total extinction and absorption in the cloud and atmosphere is nearby 20dB in the long-wave transparency window of atmosphere. In the central part of submillimeter band these losses may be as high as 40dB.However,the level of losses has no effect on a difference between the radar reflection coefficients for overcooled water and ice existing due to phase transition, and this difference may be over 20dB in the 0.3 to 0.8mm ice transparency window.     

On the structure of non-superconducting YBa2Cu3O6+ɛ

The crystal structure of non-superconducting, tetragonal YBa₂Cu₃O₆₊ ( close to 0) (s.g.P4/mmm) was studied at room temperature by means of single crystal X-ray diffraction, electron microscopy and electron diffraction. Crystals may easily be obtained by heating YBa₂Cu₃O₇ samples under vacuum. For 0, the tetragonal single crystals are chemically and crystallographically homogeneous — without any twin domains. The only defects immediately apparent are stacking faults alongc. The structure is very closely related to that of the high-T _c superconductor YBa₂Cu₃O₇. The most important difference is, that the oxygen on theb-axis (O(1)), which together with Cu(1) forms Cu–O–Cu–O-chains alongb in YBa₂Cu₃O₇, is vacant in YBa₂Cu₃O₆. Some crystals show a superstructure with superstructure reflections which are sharp in thea ^*–a ^*-plane but form diffuse streaks alongc ^*. We propose a model which relates these superstructure reflections to a 2-dimensional ordering of residual oxygen atoms on the O(1) site (corresponding to >0 in the chemical formula YBa₂Cu₃O₆₊).     

Dynamin-dependent NMDAR endocytosis during LTD and its dependence on synaptic state

Background  

The N-methyl-D-aspartate (NMDA)-type glutamate receptor expressed at excitatory glutamatergic synapses is required for learning and memory and is critical for normal brain function. At a cellular level, this receptor plays a pivotal role in triggering and controlling synaptic plasticity. While it has been long recognized that this receptor plays a regulatory role, it was considered by many to be itself immune to synaptic activity-induced plasticity. More recently, we and others have shown that NMDA receptor-mediated synaptic responses can be subject to activity-dependent depression.