Uncoupling neurotrophic function from nociception of nerve growth factor: what can be learned from a rare human disease?

Nerve growth factor (NGF) is a powerful trophic factor that provides essential support for the survival and differentiation of sympathetic and sensory neurons during development. However, NGF also activates nociceptors contributing significantly to inflammatory pain and neuropathic pain after tissue injury. As such anti-NGF based therapies represent a promising strategy for pain management. Because of dose-dependent serious side effects such as back pain, injection site hyperalgesia, clinical trials of using NGF to treat various disorders such as diabetic neuropathies, chemotherapy-induced and human immunodeficiency virus-associated peripheral neuropathies were all discontinued. Thus far, worldwide clinical applications of NGF in treating patients are very limited except in China. Hereditary sensory autonomic neuropathy type V (HSAN V) is an extremely rare disease. Genetic analyses have revealed that HSAN V is associated with autosomal recessive mutations in NGF. One of the mutations occurred at the 100th position of mature NGF resulting in a change of residue from arginine to tryptophan (R100W). Although those HSAN V patients associated with the NGFR100W mutation suffer from severe loss of deep pain, bone fractures and joint destruction, interestingly patients with the NGFR100W mutation do not show apparent cognitive deficits, suggesting important trophic support function is preserved. We believe that NGFR100W provides an ideal tool to uncouple the two important functions of NGF: trophic versus nociceptive. Studies from investigators including ourselves have indeed confirmed in animal testing that the NGFR100W no longer induced pain. More importantly, the trophic function seemed to be largely preserved in NGF harboring the R100W mutation. On the mechanistic level, we found that the NGFR100W mutation was capable of binding to and signaling through the tyrosine receptor kinase A receptor. But its ability to bind to and activate the 75 kDa neurotrophic factor was significantly diminished. The significance of these findings is at least two folds: 1) the NGFR100W mutation can be used as an alternative to the wildtype NGF to treat human conditions without eliciting pain; and 2) the 75 kDa neurotrophic factor may serve as a novel target for pain management. We will discuss all the details in this mini-review

Living β-selective cyclopolymerization using Ru dithiolate catalysts

Cyclopolymerization (CP) of 1,6-heptadiyne derivatives is a powerful method for synthesizing conjugated polyenes containing five- or six-membered rings via α- or β-addition, respectively. Fifteen years of studies on CP have revealed that user-friendly Ru-based catalysts promoted only α-addition; however, we recently achieved β-selective regiocontrol to produce polyenes containing six-membered-rings, using a dithiolate-chelated Ru-based catalyst. Unfortunately, slow initiation and relatively low catalyst stability inevitably led to uncontrolled polymerization. Nevertheless, this investigation gave us some clues to how successful living polymerization could be achieved. Herein, we report living β-selective CP by rational engineering of the steric factor on monomer or catalyst structures. As a result, the molecular weight of the conjugated polymers from various monomers could be controlled with narrow dispersities, according to the catalyst loading. A mechanistic investigation by in situ kinetic studies using ^1H NMR spectroscopy revealed that with appropriate pyridine additives, imposing a steric demand on either the monomer or the catalyst significantly improved the stability of the propagating carbene as well as the relative rates of initiation over propagation, thereby achieving living polymerization. Furthermore, we successfully prepared diblock and even triblock copolymers with a broad monomer scope

Photocatalytic Ohmic layered nanocomposite for efficient utilization of visible light photons

The WO3/W/PbBi2Nb1.9Ti0.1O9 photocatalyst was fabricated by depositing the tungsten clusters over the p-type perovskite base material with the chemical vapor deposition method, and later partly oxidizing the surfaces of these clusters to obtain n-type WO3 overlayers and W metal layer as an Ohmic junction. This NCPC showed unprecedented high activity for the photocatalytic oxidation of water, photocurrent generation, and acetaldehyde decomposition under visible light irradiation (lambda >= 420 nm). (c) 2006 American Institute of Physicsclose313

Investigations on association schemes with elementary abelian thin residue

In this paper, we give a new class of association schemes whose thin residues are isomorphic to an elementary abelian p role= presentation \u3e-group of order p2 role= presentation \u3e. We then study the automorphism groups of these schemes and determine whether these schemes are schurian

Solution-Based Synthesis of a CdS Nanoparticle/ZnO Nanowire Heterostructure Array

CdS nanoparticle (NP)/ZnO nanowire (NW) heterostructure arrays were fabricated by a two-step chemical solution deposition method. First, vertically aligned ZnO nanowire arrays were grown on a substrate from Zn(NO(3))(2) (10 mM) and an aqueous ammonia (pH similar to 11) solution at 95 degrees C for 6 h. Then, CdS nanoparticles were deposited on the ZnO nanowire array in a chemical bath containing CdSO(4), thiourea, and an aqueous ammonia solution (molar ratio of 1:5:500) at 60 degrees C. The effects of deposition reaction conditions, such as solution concentrations and deposition time, were investigated. Synthesized US NP/ZnO NW heterostructures were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and transmission electron microscopy (TEM), and their optical absorption property was measured by light absorbance spectrometry. As the solution concentrations and deposition time increased, the sizes and density of CdS nanoparticles on the surfaces of ZnO nanowires increased and the visible-light absorption capability was improved. The CdS NP/ZnO NW heterostructure arrays presented here offer promising applications in solar-energy converting devices. The photoelectrochemical cells using CdS NP/ZnO NW heterostructure arrays as photoelectrodes showed enhanced photocurrent characteristics compared with the photoelectrode cell of a bare ZnO nanowire arrayclose909

Highly Efficient and Stable Cadmium Chalcogenide Quantum Dot/ZnO Nanowires for Photoelectrochemical Hydrogen Generation

Although cadmium chalcogenide quantum dot-sensitized photoanode can utilize the whole visible region of the solar spectrum, its poor photochemical stability owing to hole-induced anodic corrosion remains a major problem for the application in photoelectrochemical hydrogen generation systems. Here, modification with IrOx center dot nH(2)O, a well-known water-oxidation catalyst substantially improves the photochemical stability of the quantum dot-sensitized photoanode. Moreover, it induces an increased photocurrent and a cathodic shift of the onset potential. This is the first example that an oxygen-evolution catalyst is employed on a quantum dot-sensitized electrode system, and it shows 13.9 mA cm(-2) (at 0.6 V) and -0.277 V vs the reversible hydrogen electrode (RHE), which are the highest photocurrent density and the lowest onset potential attained with a ZnO-based electrode, respectively. An average hydrogen evolution rate of 240 mu mol h(-1) cm(-2) at 0.6 V vs RHE has been achieved on a IrOx center dot nH(2)O efficiency. modified electrode, with almost 100% of faradaiclos