Using spectral moments of spiral networks based on PSA/mass spectra outcomes to derive quantitative proteome-disease relationships (QPDRs) and predicting prostate cancer

In prostate cancer (PCa), prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic, and biomolecular levels. Blood contains a treasure of previously unstudied biomarkers that could reflect the ongoing physiological state of all tissue. The serum prostate-specific antigen (PSA) measurement is a very good biomarker for PCa, but the percentage of bad classification is somewhat high. The blood proteome mass spectra (MS) represent a potential tool for detection of diseases; however the identification of a single biomarker from the complex output from MS is often difficult. In this paper, we propose a general strategy, based on computational chemistry techniques, which should improve the predictive power of PSA. Our group adapted the square-spiral graph to represent human serum-plasma-proteome MS for healthy and PCa patients. These graphs were previously applied to DNA and/or protein sequences. In this work, we calculated different classes of connectivity indices (CIs), and created various models based on the spectral moments. The best QPDRs model found showed accuracy values ranging from 71.7% to 97.2%, and 70.4% to 99.2% of specificity. This methodology might be useful for several applications in computational chemistry.     

Essential role of BMPs in FGF-induced secondary lens fiber differentiation

It is widely accepted that vitreous humor-derived FGFs are required for the differentiation of anterior lens epithelial cells into crystallin-rich fibers. We show that BMP2, 4, and 7 can induce the expression of markers of fiber differentiation in primary lens cell cultures to an extent equivalent to FGF or medium conditioned by intact vitreous bodies (VBCM). Abolishing BMP2/4/7 signaling with noggin inhibited VBCM from upregulating fiber marker expression. Remarkably, noggin and anti-BMP antibodies also prevented purified FGF (but not unrelated stimuli) from upregulating the same fiber-specific proteins. This effect is attributable to inhibition of BMPs produced by the lens cells themselves. Although BMP signaling is required for FGF to enhance fiber differentiation, the converse is not true. Expression of noggin in the lenses of transgenic mice resulted in a postnatal block of epithelial-to-secondary fiber differentiation, with extension of the epithelial monolayer to the posterior pole of the organ. These results reveal the central importance of BMP in secondary fiber formation and show that although FGF may be necessary for this process, it is not sufficient. Differentiation of fiber cells, and thus proper vision, is dependent on cross-talk between the FGF and BMP signaling pathways.     

Structure of Co2(CO)6(dppm) and Co2(CO)5(CHCO2Et)(dppm) (dppm = Ph2PCH2PPh2) and exchange reaction with CO: An experimental and computational study

Crystal structures of Co₂(CO)₆(dppm) (1) and Co₂(CO)₅(CHCO₂Et)(dppm) (2) (dppm = Ph₂PCH₂PPh₂) show asymmetry with respect to the orientation of the phenyl groups in 1 and owing to the bridging ethoxycarbonylcarbene ligand in 2. The effect of this asymmetry was recognized in the solid-state ³¹P NMR spectra of 1 and 2 and in the solid-state and solution ¹³C NMR spectra of 2 as well, but not in the solid-state and solution ¹³C NMR spectra of 1. In CH₂Cl₂ solution under an atmosphere of ¹³CO, the CO ligands of both complexes exchange with ¹³CO. The overall rate of ¹³CO exchange at 10 °C was found to be k_obs = 0.107 × 10⁻³ s⁻¹ for 1 and k_obs = 0.243 × 10⁻³ s⁻¹ for 2. Two-layered ONIOM(B3LYP/6-31G(d):LSDA/LANL2MB) studies revealed fluxional behavior of 1 with rather small barriers of activation of the rearrangements. Four possible isomers have been computed for 2, close to each other energetically.     

Theoretical studies on the absorption spectra of heteroleptic ruthenium polypyridyl dyes for nanocrystalline TiO2 solar cells: Revisited with transition-component analysis

The absorption spectra of Ru complexes of the type cis-[Ru(H₂dcbpy)(L)(NCS)₂], where H₂dcbpy = 4,4′-dicarboxy-2,2′-bipyridine and L = 1,10-phenanthroline (phen) (1) or dipyrido[3,2-a:2′,3′-c]phenazine (dppz) (2), in water were calculated by means of the time-dependent density functional theory, and the calculated spectra were subjected to transition-component analysis. Comparison of the calculated spectra of protonated, partially and fully deprotonated, and electrostatically non-compensated and fully compensated forms of 1 and 2 in water with the corresponding experimental absorption spectra in 0.01 M aqueous NaOH indicated that the predominant molecular structures are fully deprotonated anionic structures that are fully compensated with counter cations. The shapes of the calculated absorption spectra well reproduce the shapes of the corresponding experimental spectra in detail over the entire visible region. The calculated results indicated that the difference between the performances of 1- and 2-sensitized solar cells is due to differences in the contributions of the various electronic excitations that make up the absorption spectra. Transition-component analysis provided a detailed, quantitative explanation of the components of the absorption spectra of 1 and 2 and may be useful for the design and synthesis of improved sensitizers for high-performance dye-sensitized solar cells.     

Is o-carborane photoluminescent?

At 77 K in the solid state and in ethanol glasses, o-carborane (1,2-C₂B₁₀H₁₂) shows a relatively intense (? ∼ 10⁻³ at λ_exc = 260 nm) structured photoluminescence (λ_max = 441 nm).In agreement with the rather slow decay of this emission (τ ∼ 4 s) it is suggested to be a phosphorescence. While it appears to be a genuine property of o-carborane an unknown impurity as origin of this luminescence is not completely excluded.     

Oxidation of [Ir(η-C5Me5)(C3S5)] [C3S5 = 4,5-disulfanyl-1,3-dithiole-2-thionate(2−)] and X-ray crystal structure of [IrBr(η-C5Me5)(μ-C2S4)IrBr(η-C5Me5)]

[Ir(η⁵-C₅Me₅)(C₃S₅)] [C₃S₅²⁻ = 4,5-disulfanyl-1,3-dithiole-2-thionate(2−)] was prepared by a reaction of [NMe₄]₂[C₃S₅] with [Ir(η⁵- C₅Me₅)Cl₂]₂ in ethanol. It was reacted with bromine to afford a paramagnetic species [IrBr(η⁵-C₅Me₅)(C₃S₅)] with the Ir-Br bond and in the one-electron-oxidized state, and a diamagnetic dinuclear species [IrBr(η⁵-C₅Me₅)(μ-C₂S₄)IrBr(η⁵-C₅Me₅)]. ESR spectra for the one-electron-oxidized species in solution are discussed. The X-ray crystal structural analysis for the latter complex revealed the geometry consisting of dinuclear IrBr(η⁵-C₅Me₅) moieties bridged by the C₂S₄²⁻ ligand.     

Role of Histidine-152 in cofactor orientation in the PLP-dependent O-acetylserine sulfhydrylase reaction

O-Acetylserine sulfhydrylase catalyzes the final step of the biosynthesis of l-cysteine, the replacement of the β-acetoxy group of O-acetyl-l-serine (OAS) by a thiol. The 5′-phosphate of the PLP cofactor is very tightly bound to the enzyme; it accepts 8 hydrogen bonds from enzyme side chains and a pair of water molecules, and is in close proximity to a helix dipole. Histidine-152 (H152) is one of the residues that, via a water molecule, is responsible for positioning the 5′-phosphate. Mutation of H152 to alanine was predicted to increase the freedom of the 5′-phosphate, and as a result the cofactor, giving a decrease in the overall rate of the reaction. The H152A mutant enzyme was thus prepared and characterized by UV-visible absorbance, fluorescence, visible CD, and ³¹P NMR spectral studies, as well as steady state and pre-steady state kinetic studies. UV-visible absorbance and visible CD spectra are consistent with a shift in the ketoeneamine to enolimine tautomeric equilibrium toward the neutral enolimine in the internal Schiff base of the free enzyme (ISB), the amino acid external Schiff base (ESB), and the α-aminoacrylate intermediate (AA). ³¹P NMR spectra clearly indicate the presence of two conformers (presumably open and closed forms of the enzyme) that interconvert slowly on the NMR time scale in the ISB and ESB. Kinetic data suggest the decreased rate of the enzyme likely reflects a decrease in the amount of active enzyme as a result of an increased flexibility of the cofactor which results in substantial nonproductive binding of OAS in its external Schiff base, and a stabilization of the external Schiff bases of OAS and S-carboxynitrophenyl-l-cysteine. The nonproductive binding and stabilization of the external Schiff bases are thus linked to the shift in the tautomeric equilibrium and increase in the rate of interconversion of the open and closed forms of the enzyme. The location of the 5′-phosphate in the cofactor-binding site determines additional interactions between the cofactor and enzyme in the closed (ESB) form of the enzyme, consistent with an increased rate of interconversion of the open and closed forms of the enzyme upon increasing the rate of flexibility of the cofactor.     

Seasonal changes of excitation energy transfer and thylakoid stacking in the evergreen tree Taxus cuspidata: How does it divert excess energy from photosynthetic reaction center?

Photosystems must efficiently dissipate absorbed light energy under freezing conditions. To clarify the energy dissipation mechanisms, we examined energy transfer and dissipation dynamics in needles of the evergreen plant Taxus cuspidata by time-resolved fluorescence spectroscopy. In summer and autumn, the energy transfer processes were similar to those reported in other higher plants. However, in winter needles, fluorescence lifetimes became shorter not only in PSII but also in PSI, indicating energy dissipation in winter needles. In addition, almost the same fluorescence spectra were obtained with different excitation wavelengths. In contrast, the fluorescence spectrum showed a large difference due to excitation wavelength in spring needles. The fluorescence spectrum of spring needles in 550-nm excitation showed similar spectra to that of winter needles, however, red-chlorophyll fluorescence was not observed in chlorophyll excitation. These observations suggest that some complexes with some kind of red-shifted carotenoid and red-chlorophyll unlink from the core complex in spring. Seasonal changes of excitation energy dynamics are also discussed in relation to changes in thylakoid stacking.     

Interactions of fluorinated surfactants with diphtheria toxin T-domain: testing new media for studies of membrane proteins

The principal difficulty in experimental exploration of the folding and stability of membrane proteins (MPs) is their aggregation outside of the native environment of the lipid bilayer. To circumvent this problem, we recently applied fluorinated nondetergent surfactants that act as chemical chaperones. The ideal chaperone surfactant would 1), maintain the MP in solution; 2), minimally perturb the MP's structure; 3), dissociate from the MP during membrane insertion; and 4), not partition into the lipid bilayer. Here, we compare how surfactants with hemifluorinated (HFTAC) and completely fluorinated (FTAC) hydrophobic chains of different length compare to this ideal. Using fluorescence correlation spectroscopy of dye-labeled FTAC and HFTAC, we demonstrate that neither type of surfactant will bind lipid vesicles. Thus, unlike detergents, fluorinated surfactants do not compromise vesicle integrity even at concentrations far in excess of their critical micelle concentration. We examined the interaction of surfactants with a model MP, DTT, using a variety of spectroscopic techniques. Site-selective labeling of DTT with fluorescent dyes indicates that the surfactants do not interact with DTT uniformly, instead concentrating in the most hydrophobic patches. Circular dichroism measurements suggest that the presence of surfactants does not alter the structure of DTT. However, the cooperativity of the thermal unfolding transition is reduced by the presence of surfactants, especially above the critical micelle concentration (a feature of regular detergents, too). The linear dependence of DTT's enthalpy of unfolding on the surfactant concentration is encouraging for future application of (H)FTACs to determine the stability of the membrane-competent conformations of other MPs. The observed reduction in the efficiency of Förster resonance energy transfer between donor-labeled (H)FTACs and acceptor-labeled DTT upon addition of lipid vesicles indicates that the protein sheds the layer of surfactant during its bilayer insertion. We discuss the advantages of fluorinated surfactants over other types of solubilizing agents, with a specific emphasis on their possible applications in thermodynamic measurements.