Cyclic voltammetry modeling, geometries, and electronic properties for metallofullerene complexes with mu3-eta2:eta2:eta2-C60 bonding mode

Reduction potential (E(red)) values have been calculated and compared with available cyclic voltammetry (CV) data for 10 metallofullerene complexes with the mu(3)-eta(2):eta(2):eta(2)-C(60) (M(3)-C(6)[C(60)]) bonding mode. Consideration of bulk solvent effects is essential for the calculation of the E(red) values. Scaling factors for the electrostatic terms of the solvation energies have been introduced to fully describe the experimental cyclic voltammograms with a small mean deviation of 0.07 V. Multiple electron reductions induce movement of the metal cluster moieties on the C(60) surface, which is accompanied with the changes in some M-C[C(60)] bonds from pi-type to sigma-type mode. However, the changes in M(3)-C(60) distances, as well as the geometric changes of M(3) and C(60), are small for the reductions, which is in harmony with the high chemical and electrochemical stability of the metallofullerenes. Our population analyses reveal that the added electrons are not localized at the C(60) moieties, and electron population in the metal clusters is significant, more than 20% (av. 37%), for all the reductions. Furthermore, we demonstrated that the two close one-electron redox waves in CV diagrams are strongly correlated with significant electron delocalization, about 40-80%, to the metal-cluster moieties in these metallofullerene complexes.     

Sesterterpenoids

The literature concerning sesterterpenoids is reviewed. They are a group of pentaprenyl terpenoids with diverse biological properties, attractive targets for both biomedical and synthetic purposes.     

Synthesis,X-ray crystal structure,and electrochemistry of trans-bis(ferrocenecarboxylato)(tetraphenylporphyrinato)tin(IV)

trans-Bis(ferrocenecarboxylato)(5,10,15,20-tetraphenylporphyrinato)tin(IV) complex Sn(TPP)(FcCOO)₂ has been synthesized and fully characterized. The X-ray structural analysis of Sn(TPP)(FcCOO)₂ reveals that the tin(IV) center is octahedrally coordinated by the porphyrin occupying the square base and axial coordination of two ferrocenecarboxylato ligands in an anti orientation with respect to each other. The Fe(II) center of the ferrocenecarboxylato ligand lies 5.7 Å from the tin(IV) center of the porphyrin ring. The cyclic voltammogram of Sn(TPP)(FcCOO)₂ exhibits three distinctive redox couples consisting of one oxidative wave and two reductive waves due to the ferrocenecarboxylato ligands and the porphyrin ring, respectively.     

A fluorescence-based synthetic LPS sensor

For the detection of bioanalytes, there is an ongoing search for synthetic sensors to replace enzyme-based assays which are sensitive to contaminants or suboptimal storage conditions. Lipopolysaccharide (LPS), a bacteria-borne endotoxin that may lead to life-threatening conditions such as septic shock, is one such case. Fluorescently labeled analogues of two peptide variants derived from the putative ligand-binding domain of the LPS-binding protein CD14 were developed that detect and discriminate LPS and lipids down to the submicromolar concentration range. Peptides are terminally labeled with carboxyfluorescein and tetramethylrhodamine. For one given peptide, sensitivity and specificity for the detection of LPS and discrimination from other lipids are achieved by spectral signatures that combine changes in the fluorescence resonance energy transfer (FRET) between both dyes and the total emission of tetramethylrhodamine. Alternatively, specificity is obtained by combining the FRET efficiencies of both peptide variants. In comparison to published synthetic LPS sensors, the CD14-derived sensors yield an increase in sensitivity by about 3 orders of magnitude and exhibit specificity for analytes for which the design of synthetic recognition elements is a challenging task. Moreover, one of the sensors enabled the detection of LPS in the presence of up to 50% fetal calf serum, thereby demonstrating the feasibility of this peptide-based approach for clinically relevant samples.     

Thermally cross-linked superparamagnetic iron oxide nanoparticles: synthesis and application as a dual imaging probe for cancer in vivo

We report the fabrication and characterization of thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) and their application to the dual imaging of cancer in vivo. Unlike dextran-coated cross-linked iron oxide nanoparticles, which are prepared by a chemical cross-linking method, TCL-SPION are prepared by a simple, thermal cross-linking method using a Si-OH-containing copolymer. The copolymer, poly(3-(trimethoxysilyl)propyl methacrylate-r-PEG methyl ether methacrylate-r-N-acryloxysuccinimide), was synthesized by radical polymerization and used as a coating material for as-synthesized magnetite (Fe3O4) SPION. The polymer-coated SPION was further heated at 80 degrees C to induce cross-linking between the -Si(OH)3 groups in the polymer chains, which finally generated TCL-SPION bearing a carboxyl group as a surface functional group. The particle size, surface charge, presence of polymer-coating layers, and the extent of thermal cross-linking were characterized and confirmed by various measurements, including dynamic light scattering, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The carboxyl TCL-SPION was converted to amine-modified TCL-SPION and then finally to Cy5.5 dye-conjugated TCL-SPION for use in dual (magnetic resonance/optical) in vivo cancer imaging. When the Cy5.5 TCL-SPION was administered to Lewis lung carcinoma tumor allograft mice by intravenous injection, the tumor was unambiguously detected in T2-weighted magnetic resonance images as a 68% signal drop as well as in optical fluorescence images within 4 h, indicating a high level of accumulation of the nanomagnets within the tumor site. In addition, ex vivo fluorescence images of the harvested tumor and other major organs further confirmed the highest accumulation of the Cy5.5 TCL-SPION within the tumor. It is noteworthy that, despite the fact that TCL-SPION does not bear any targeting ligands on its surface, it was highly effective for tumor detection in vivo by dual imaging.     

Two phase transitions for the contact process on small worlds

In our version of Watts and Strogatz’s small world model, space is a d$d$-dimensional torus in which each individual has in addition exactly one long-range neighbor chosen at random from the grid. This modification is natural if one thinks of a town where an individual’s interactions at school, at work, or in social situations introduce long-range connections. However, this change dramatically alters the behavior of the contact process, producing two phase transitions. We establish this by relating the small world to an infinite “big world” graph where the contact process behavior is similar to the contact process on a tree. We then consider the contact process on a slightly modified small world model in order to show that its behavior is decidedly different from that of the contact process on a tree.     

A class of small molecules that inhibit TNFalpha-induced survival and death pathways via prevention of interactions between TNFalphaRI, TRADD, and RIP1

Small-molecule library screening to find compounds that inhibit TNFalpha-induced, but not interleukin 1beta (IL-1beta)-induced, intercellular adhesion molecule 1 (ICAM-1) expression in lung epithelial cells identified a class of triazoloquinoxalines. These compounds not only inhibited the TNFalpha-induced nuclear factor kappaB (NFkappaB) survival pathway but also blocked death-pathway activation. Such dual activity makes them unique against other known NFkappaB-pathway inhibitors that inhibit only a subset of TNFalpha signals leading to increased TNFalpha-induced cytotoxicity. Interestingly, these compounds inhibited association of TNFalpha receptor (TNFalphaR) I with TNFalphaR-associated death domain protein (TRADD) and receptor interacting protein 1 (RIP1), the initial intracellular signaling event following TNFalpha stimulation. Further study showed that they blocked ligand-dependent internalization of the TNFalpha-TNFalphaR complex, thereby inhibiting most of the TNFalpha-induced cellular responses. Thus, compounds with a triazoloquinoxaline scaffold could be a valuable tool to investigate small molecule-based anti-TNFalpha therapies.     

The centrosomal localization of KM-HN-1 (MGC33607) depends on the leucine zipper motif and the C-terminal coiled-coil domain

KM-HN-1 is a C-terminal coiled-coil domain containing protein previously referred to as image clone MGC33607. This protein has been previously identified as a cancer/testis antigen and reported as nuclear and chromatin localizing protein. We raised polyclonal antisera with the GST fusion protein and identified them as a 105 kDa protein. Motif analysis showed that this protein harbors the leucine zipper motif in internal 1/3 region and the coiled-coil domain in the C-terminal region. Using the full length and various deletion mutants, we determined the motif that governs the subcellular localization of KM-HN-1. Immunofluorescence staining of the endogenous KM-HN-1 and various kinds of GFP-tagged KM-HN-1 revealed that KM-HN-1 localizes to the centrosomes as well as nucleus. The centrosomal localization-determining region of this protein is C-terminal coiled-coil domain in which the leucine zipper motif and the nuclear export signal (NES) harbor.     

Isolation of neural precursor cells from skeletal muscle tissues and their differentiation into neuron-like cells

Skeletal muscle contains several precursor cells that generate muscle, bone, cartilage and blood cells. Although there are reports that skeletal muscle-derived cells can trans-differentiate into neural-lineage cells, methods for isolating precursor cells, and procedures for successful neural induction have not been fully established. Here, we show that the preplate cell isolation method, which separates cells based on their adhesion characteristics, permits separation of cells possessing neural precursor characteristics from other cells of skeletal muscle tissues. We term these isolated cells skeletal muscle-derived neural precursor cells (SMNPs). The isolated SMNPs constitutively expressed neural stem cell markers. In addition, we describe effective neural induction materials permitting the neuron-like cell differentiation of SMNPs. Treatment with retinoic acid or forskolin facilitated morphological changes in SMNPs; they differentiated into neuron-like cells that possessed specific neuronal markers. These results suggest that the preplate isolation method, and treatment with retinoic acid or forskolin, may provide vital assistance in the use of SMNPs in cell-based therapy of neuronal disease.