Michael Gozin

Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis

Axonal degeneration is an important determinant of progressive neurological disability in multiple sclerosis (MS). Thus, therapeutic approaches promoting neuroprotection could aid the treatment of progressive MS. Here, we used what we believe is a novel water-soluble fullerene derivative (ABS-75) attached to an NMDA receptor antagonist, which combines antioxidant and anti-excitotoxic properties, to block axonal damage and reduce disease progression in a chronic progressive EAE model. Fullerene ABS-75 treatment initiated after disease onset reduced the clinical progression of chronic EAE in NOD mice immunized with myelin-oligodendrocyte glycoprotein (MOG). Reduced disease progression in ABS-75-treated mice was associated with reduced axonal loss and demyelination in the spinal cord. Fullerene ABS-75 halted oxidative injury, CD11b+ infiltration, and CCL2 expression in the spinal cord of mice without interfering with antigen-specific T cell responses. In vitro, fullerene ABS-75 protected neurons from oxidative and glutamate-induced injury and restored glutamine synthetase and glutamate transporter expression in astrocytes under inflammatory insult. Glutamine synthetase expression was also increased in the white matter of fullerene ABS-75-treated animals. Our data demonstrate the neuroprotective effect of treatment with a fullerene compound combined with a NMDA receptor antagonist, which may be useful in the treatment of progressive MS and other neurodegenerative diseases.

Formation of a Soluble Stable Complex between Pristine C60‐Fullerene and a Native Blood Protein

Concern is growing about the potential impact of human exposure to carbonaceous nanomaterials (such as fullerenes) in the environment. A valid biological study of how native biomolecules interact with nanomaterials at the molecular level in physiological conditions requires the preservation of their physicochemical properties, yet most investigations rely on the use of modified fullerene conjugates or aggregates. We report the formation of a stable, water‐soluble, well‐defined complex between a single molecule of pristine C60‐fullerene and a native protein, bovine serum albumin protein (BSA), with the normal three‐dimensional structure of BSA preserved. The ability to produce a pristine C60‐fullerene–BSA hybrid at a physiological pH range lays a solid foundation for studying carbonaceous materials, biodelivery systems, and transport mechanisms and for characterizing the potential effects of nanomaterials on wildlife and human health, both in vitro and in vivo.

In vitro synthesis of uniform poly(dG)–poly(dC) by Klenow exo− fragment of polymerase I

In this paper, we describe a production procedure of the one-to-one double helical complex of poly(dG)–poly(dC), characterized by a well-defined length (up to 10 kb) and narrow size distribution of molecules. Direct evidence of strands slippage during poly(dG)–poly(dC) synthesis by Klenow exo− fragment of polymerase I is obtained by fluorescence resonance energy transfer (FRET). We show that the polymer extension results in an increase in the separation distance between fluorescent dyes attached to 5′ ends of the strands in time and, as a result, losing communication between the dyes via FRET. Analysis of the products of the early steps of the synthesis by high-performance liquid chromatography and mass spectroscopy suggest that only one nucleotide is added to each of the strand composing poly(dG)–poly(dC) in the elementary step of the polymer extension. We show that proper pairing of a base at the 3′ end of the primer strand with a base in sequence of the template strand is required for initiation of the synthesis. If the 3′ end nucleotide in either poly(dG) or poly(dC) strand is substituted for A, the polymer does not grow. Introduction of the T-nucleotide into the complementary strand to permit pairing with A-nucleotide results in the restoration of the synthesis. The data reported here correspond with a slippage model of replication, which includes the formation of loops on the 3′ ends of both strands composing poly(dG)–poly(dC) and their migration over long-molecular distances (μm) to 5′ ends of the strands.

Efficient Separation of Dyes by Mucin: Toward Bioinspired White‐Luminescent Devices

The production of organic white-light-emitting devices is one of the main technological and scientifi c challenges in the fi eld of optoelectronics [ 1–4 ] because the formation of such a broad emission spectrum with the use of a single dye is diffi cult to accomplish. [ 5 , 6 ] In practice, the emission of white light is achieved by the use of a mixture of the three primary dyes, which emit red (R), green (G), and blue (B) light. [ 7 ] However, as a result of nonradiative interactions between very close color elements, such as Förster resonance energy transfer (FRET), an undesirable shift in the emission spectrum is often observed, which prevents the achievement of white-light emission. [ 8 ]

Mucin complexes of nanomaterials: first biochemical encounter.

In recent years, the exposure of biological systems to various nanomaterials has become an issue of great public concern. Although living organisms have arrays of biological defense mechanisms against exposure to exogenous compounds, the biochemical mechanisms allowing various nanomaterials to enter the body are not well understood. A unique example of a typical mucosal glycoprotein capable of binding and solubilizing nanomaterials in physiological solution is provided, suggesting a possible route for entry into biological systems.

Tuning the Critical Temperature of Cuprate Superconductor Films with Self‐Assembled Organic Layers

Control over the T(c) value of high-T(c) superconductors by self-assembled monolayers is demonstrated (T(c) = critical temperature). Molecular control was achieved by adsorption of polar molecules on the superconductor surface (see scheme) that change its carrier concentration through charge transport or light-induced polarization.

Enhanced bioavailability of polyaromatic hydrocarbons in the form of mucin complexes.

Increasing exposure of biological systems to large amounts of polycyclic aromatic hydrocarbons is of great public concern. Organisms have an array of biological defense mechanisms, and it is believed that mucosal gel (which covers the respiratory system, the gastrointestinal tract, etc.) provides an effective chemical shield against a range of toxic materials. However, in this work, we demonstrate, for the first time, that, upon complexation of polyaromatic hydrocarbons with mucins, enhanced bioavailability and, therefore, toxicity are obtained. This work was aimed to demonstrate how complexation of various highly hydrophobic polycyclic aromatic hydrocarbons with representative mucin glycoprotein could lead to the formation of previously undescribed materials, which exhibit increased toxicity versus pristine polycyclic aromatic hydrocarbons. In the present work, we show that a representative mucin glycoprotein, bovine submaxillary mucin, has impressive and unprecedented capabilities of binding and solubilizing water-insoluble materials in physiological solution. The complexes formed between the mucin and a series of polycyclic aromatic hydrocarbons were comprehensively characterized, and their toxicity was evaluated by both in vivo and in vitro assays. In addition, the bioavailability and membrane-penetration capabilities were tested using an internalization assay. Our results provide, for the first time, evidence of an unknown route by which hydrophobic materials may achieve higher bioavailability, penetrating some of the biological defense systems, in the form of water-soluble complexes with mucosal proteins.

Highly insensitive and thermostable energetic coordination nanomaterials based on functionalized graphene oxides

In this research, a group of new energetic coordination nanomaterials (CNMs) based on functionalized graphene oxide sheets (FGS) have been designed and characterized. GO was first functionalized with N-rich energetic ligands such as triaminoguanidine (TAG), and then the resulting FGS was coordinated with metal ions to prepare energetic CNMs with high thermostability and insensitivity to mechanical stimuli. The density of GO–TAG–Cu(II)/Cu(I) is as high as 3.14 g cm−3, while it has a Tp of 495 °C and VoD of 7723 m s−1 by using 40 wt% ammonium perchlorate as the oxidant. These insensitive (Im > 81 J) and highly thermostable energetic CNMs in combination with oxidizers are good candidate ingredients of low-vulnerability solid propellants and charges of deep-well perforating guns.

Diameter-selective dispersion of carbon nanotubes by β-lactoglobulin whey protein

The β-lactoglobulin (β-LG) protein was discovered to be an efficient and selective dispersant for carbon nanotubes (CTNs) with certain diameters. A dispersion process of CTNs by the β-LG was studied, focusing on the relationships between the surface curvature of the CNT and the β-LGs efficiency in dispersing them, using cryogenic-transmission electron microscopy (cryo-TEM) and optical spectroscopy. Plausible binding sites of the β-LG, responsible for the interaction of the protein with CNTs of various diameters (surface curvatures) were also investigated and were found to be in good agreement with corresponding docking calculations.

Toward Development of Targeted Nonsteroidal Antiandrogen-1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid−Gadolinium Complex for Prostate Cancer Diagnostics

Androgen receptors are present in most advanced prostate cancer specimens, having a critical role in development of this type of cancer. For correct prognosis of patient conditions and treatment monitoring, noninvasive imaging techniques have great advantages over surgical procedures. We developed synthetic methodologies for preparation of novel androgen receptor-targeting agents in an attempt to build a versatile platform for prostate cancer imaging and treatment. The structure of these compounds comprises of a lanthanoid metal ion, gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd-DOTA)-based binding fragment and, connected to it by a flexible linker, bicalutamide-derived nonsteroidal antiandrogen moiety. A representative gadolinium complex 15 was evaluated as a magnetic resonance imaging (MRI) agent in C57/bl6 male mouse bearing orthotopic TRAMP C2 prostate tumor.