Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment.

The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals.

Radical-Enhanced Intersystem Crossing in a Bay-Substituted Perylene Bisimide-TEMPO Dyad and the Electron Spin Polarization Dynamics upon Photoexcitation*.

A 4-amino-2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) radical was attached to the bay position of perylene-3,4 : 9,10-bis(dicarboximide) (perylenebisimide, PBI) to study the radical-enhanced intersystem crossing (REISC) and electron spin dynamics of the photo-induced high-spin states. The dyads give strong visible light absorption (ϵ=27000 M  cm at 607 nm). Attaching a TEMPO radical to the PBI unit transforms the otherwise non-radiative decay of S state (fluorescence quantum yield: Φ =2.

Design of Novel 4-Aminobenzofuroxans and Evaluation of Their Antimicrobial and Anticancer Activity.

A series of novel 4-aminobenzofuroxan derivatives containing aromatic/aliphatic amines fragments was achieved via aromatic nucleophilic substitution reaction of 4,6-dichloro-5-nitrobenzofuroxan. The quantum chemistry calculations were performed to identify the factors affecting the regioselectivity of the reaction. The formation of 4-substituted isomer is favored both by its greater stability and the lower activation barrier.

On the Nucleophilic Reactivity of 4,6-Dichloro-5-nitrobenzofuroxan with Some Aliphatic and Aromatic Amines: Selective Nucleophilic Substitution.

The reaction rates for the nucleophilic aromatic substitution of 4,6-dichloro-5-nitrobenzofuroxan with eight aliphatic amines (characterized by very different basicities/nucleophilicities) and three anilines have been measured in both methanol and toluene. The obtained rates have been related to the basicity (p in water and in benzene) or nucleophilicity ( Mayr constants) of the tested amines. The whole of the obtained kinetic data has furnished useful information on the high nucleophilic reactivity of benzofuroxan derivatives, which has been related essentially to two factors: the high electron-drawing ability/power of the condensed furoxan ring and the low aromatic character of the benzofuroxan system.

Unusually large hyperfine structure of the electron spin levels in an endohedral dimetallofullerene and its spin coherent properties.

We report the synthesis, ESR spectroscopic and spin coherent properties of the dimetallofullerene Sc2@C80(CH2Ph). The single-electron metal-metal bond of the Sc2 dimer inside the fullerene's cage is stabilized with the electron spin density being fully localized at the metal bond. This results in an extraordinary strong hyperfine interaction of the electron spin with the 45Sc nuclear spins with a coupling constant a = 18.

Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat.

Currently, the main fundamental and clinical interest for stroke therapy is focused on developing a neuroprotective treatment of a penumbra region within the therapeutic window. The development of treatments for ischemic stroke in at-risk patients is of particular interest. Preventive gene therapy may significantly reduce the negative consequences of ischemia-induced brain injury.

Intriguing enigma of nitrobenzofuroxan's 'Sphinx': Boulton-Katritzky rearrangement or unusual evidence of the -1/-3-oxide rearrangement?

The SAr/SAr reaction between 7-chloro-4,6-dinitrobenzofuroxan (ClDNBF) and 2-morpholinyl-, 2-piperidinyl-, or 2-pyrrolidinylthiazole afforded unexpectedly two isomeric products, bearing the benzofuroxanyl moiety bound to the C-5 carbon atom of the thiazole ring. The relative ratio for the two isomers was dependent on temperature and solvent, suggesting the occurrence of an equilibrium between the two novel species. In order to investigate their structure and to design a plausible mechanistic pathway, a series of synthetic and spectroscopic experiments was planned.

Plant Soft Rot Development and Regulation from the Viewpoint of Transcriptomic Profiling.

Soft rot caused by species is a devastating plant disease poorly characterized in terms of host plant responses. In this study, changes in the transcriptome of tobacco plants after infection with () were analyzed using RNA-Seq. To draw a comprehensive and nontrivially itemized picture of physiological events in -infected plants and to reveal novel potential molecular "players" in plant- interactions, an original functional gene classification was performed.

[(MeCN)Ni(CF)] and [Ni(CF)]: Foundations toward the Development of Trifluoromethylations at Unsupported Nickel.

Nickel anions [(MeCN)Ni(CF)] and [Ni(CF)] were prepared by the formal addition of 3 and 4 equiv, respectively, of AgCF to [(dme)NiBr] in the presence of the [PPh] counterion. Detailed insights into the electronic properties of these new compounds were obtained through the use of density functional theory (DFT) calculations, spectroscopy-oriented configuration interaction (SORCI) calculations, X-ray absorption spectroscopy, and cyclic voltammetry. The data collectively show that trifluoromethyl complexes of nickel, even in the most common oxidation state of nickel(II), are highly covalent systems whereby a hole is distributed on the trifluoromethyl ligands, surprisingly rendering the metal to a physically more reduced state.

Mapping Stem Rust ( f. sp. ) Resistance in Self-Fertile Winter Rye Populations.

Rye stem rust caused by f. sp. can be found in all European rye growing regions.

Bis(α-hydroxycycloalkyl)phosphine Oxides Obtained from White Phosphorus via Phosphine Oxide H PO: Synthesis, Molecular Structure, Coordination Properties and Biological Activity.

Reaction of the electrochemically in situ from elemental white phosphorus generated phosphine oxide H PO in a single electrochemical cell, supplied with lead cathode and aluminium anode, with cyclic ketones (cyclopentanone and cyclohexanone) results in formation of secondary phosphine oxides (bis(α-hydroxycyclopentyl)phosphine oxide 2 a, isolated yield 15 %, and bis(α-hydroxycyclohexyl)phosphine oxide 2 b, isolated yield 12 %) with two α-hydroxycycloalkyl substituents at the phosphorus atom. Bis(α-hydroxycyclopentyl)phosphine oxide reacts with [PdCl (COD)] (COD=1,5-cyclooctadiene) to give a new palladium complex trans-[PdCl {P(OH)(cyclo-C H -1-OH) } ] (3 a, isolated yield 11 %) bearing phosphinous acid as a ligand formed via tautomerization of the phosphine oxide. Finally, the cytotoxicity of the synthesized secondary phosphine oxides on tumor and healthy human cell lines was studied.

Synthesis, structure-activity relationship and biological evaluation of tetracationic gemini Dabco-surfactants for transdermal liposomal formulations.

In this study, we report the relationship between structure, self-assembly behavior and antimicrobial activity of multicationic gemini surfactants and their successful use as stabilizers of a new liposomal formulation for transdermal drug delivery. New surfactants containing natural moiety 1,4-diazabicyclo[2.2.

Ytterbium increases transmembrane water transport in Zea mays roots via aquaporin modulation.

In our study, the rare earth element ytterbium (Yb) was demonstrated to affect water exchange in roots of Zea mays seedlings. Herewith, the overall membrane permeability (P) increased. The P increase was determined by aquaporin activity but not the membrane lipid component since the closure of aquaporin channels due to low intracellular pH abolished the positive effect of Yb on P.

Delivery nanosystems based on sterically hindered phenol derivatives containing a quaternary ammonium moiety: Synthesis, cholinesterase inhibition and antioxidant activity.

Multitarget ligands (MTL) based on sterically hindered phenol and containing a quaternary ammonium moiety (SHP-n-Q) were synthesized. These compounds are inhibitors of cholinesterases with antioxidant properties. The inhibitory selectivity is 10-fold potent for BChE than for AChE.

Components of the GABAergic signaling in the peripheral cholinergic synapses of vertebrates: a review.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system. Since the 1970s, many studies have focused on the role of GABA in the mammalian peripheral nervous system, and particularly in the cholinergic synapses. In this review, we present current findings for the cholinergic neurons of vegetative ganglia as well as for the neurons innervating smooth and striated muscles.

Epoxyalcohol Synthase RjEAS (CYP74A88) from the Japanese Buttercup (Ranunculus japonicus): Cloning and Characterization of Catalytic Properties.

Cytochromes P450 of the CYP74 family play a key role in the lipoxygenase cascade generating oxylipins (products of polyunsaturated fatty acid oxidation). The CYP74 family includes allene oxide synthases, hydroperoxide lyases, divinyl ether synthases, and epoxyalcohol synthases. In this work, we cloned the CYP74A88 gene from the Japanese buttercup (Ranunculus japonicus) and studied the properties of the encoded recombinant protein.

Enhancement of mouse diaphragm contractility in the presence of antagonists of GABA and GABA receptors.

New Findings: What is the central question of this study? Do GABA receptors play any role at the neuromuscular junction? What is the main finding and its importance? In the presence of either ionotropic or metabotropic GABA receptor antagonists, diaphragm muscle force production elicited by stimulating the motor nerve at ≥50 Hz was increased. Our data indicate the presence of GABAergic signalling at the neuromuscular junction.

Abstract: Despite the signalling role of GABA in the brain and spinal cord, the role of this molecule in the peripheral nervous system and, in particular, at the neuromuscular junction remains practically unexplored.

Multi-targeted approach by 2-benzimidazolylquinoxalines-loaded cationic arginine liposomes against сervical cancer cells in vitro.

Multi-targeted approaches for inhibition of сervical cancer cells in vitro were developed by implementing two different strategies and drug combination for creation of new therapeutic target agents and for nanotechnological-enhancement of intracellular delivery. New 2-benzimidazolylquinoxalines derivatives were synthesized and characterized by combining two different pharmacophores - benzimidazole and quinoxaline rings directly bonded in their structures. Spectrophotometric technique for determination of content of compounds in various media was developed to evaluate their solubility in water and micellar solutions of surfactants.

Polyelectrolyte-coated ultra-small nanoparticles with Tb(III)-centered luminescence as cell labels with unusual charge effect on their cell internalization.

The present work reports ultra-small polyelectrolyte-coated water insoluble Tb(III) complex species with bright Tb(III)-centered luminescence resulted from efficient ligand-to-metal energy transfer as efficient labels for Hep-2 cells. The flow cytometry data revealed the enhanced cellular uptake of negatively charged nanoparticles coated by the polystyrenesulfonate (PSS)-monolayer versus the positively charged nanoparticles. The latter are obtained by layer-by-layer deposition of polyethyleneimine (PEI) onto PSS-coated ones.

Protealysin is not Secreted Constitutively.

Background: Protealysin, a zinc metalloprotease of Serratia proteamaculans, is the prototype of a new group within the peptidase family M4. Protealysin-like proteases (PLPs) are widely spread in bacteria but are also found in fungi and archaea. The biological functions of PLPs have not been well studied, but published data showed the involvement of enzymes of this group in the interaction of bacteria with higher organisms, and most likely in the pathogenesis.

Synthesis of 3-Hydroxy-4-arylquinolin-2-ones Including Viridicatol via a Darzens Condensation/Friedel-Crafts Alkylation Strategy.

The new efficient synthesis of biologically important 3-hydroxy-4-arylquinolin-2-ones through the Darzens condensation (epoxidation) of dichloroacetanilides with aromatic aldehydes followed by one-pot dechlorative epoxide-arene cyclization is described. This methodology has been utilized for the synthesis of naturally occurring viridicatol, a fungal metabolite isolated from the penicillium species.

Autoregulation of Acetylcholine Release and Micro-Pharmacodynamic Mechanisms at Neuromuscular Junction: Selective Acetylcholinesterase Inhibitors for Therapy of Myasthenic Syndromes.

Neuromuscular junctions (NMJs) are directly involved into such indispensable to life processes as respiration and locomotion. However, motor nerve forms only one synaptic contact at each muscle fiber. This unique configuration requires specific properties and constrains to be effective.

Adamantyl thioureas as soluble epoxide hydrolase inhibitors.

A series of inhibitors of the soluble epoxide hydrolase (sEH) containing one or two thiourea groups has been developed. Inhibition potency of the described compounds ranges from 50 μM to 7.2 nM.