Origin of the Second-Order Proton Catalysis of Ferriin Reduction in Belousov-Zhabotinsky Reactions: Density Functional Studies of Ferroin and Ferriin Aggregates with Outer Sphere Ligands Sulfate, Bisulfate, and Sulfuric Acid

The detailed mechanisms of Belousov-Zhabotinsky oscillating reactions continue to present grand challenges, even after half a century of study. The origin of the pH dependence of the oscillation pattern had never been rigorously identified. In our recent kinetic study of one of the key Belousov-Zhabotinsky reactions, the iron-catalyzed bromate oxidation of malonic acid, compelling agreement between experiments and kinetic simulations was achieved only with the inclusion of second-order proton catalysis of the reduction of the [Fe(phen)3]3+ species. After exhausting all other avenues in search of an explanation of this proton catalysis, we considered the possibility that the parent iron-phenanthroline complexes could aggregate with neutral and anionic outer sphere ligands (OSLs) in the highly concentrated sulfuric acid solution, and we hypothesized that OSL protonation would increase the capacity of the aggregated complex to oxidize the organic fuel. We performed potential energy surface analyses at the SMD(APFD/6-311G*) level of complexes of the types [Fe(phen)3(SO42-)m(HSO4-)n(H2SO4)o](c-2m-n)+ for ferriin (c = 3) and ferroin (c = 2) aggregated with m sulfate, n bisulfate, and o sulfuric acid OSLs. We present structures of the OSL aggregates, develop a nomenclature for their description, and characterize their electronic structure. The structural chemistry provides the foundation to discuss the ferroin/ferriin redox couple with emphasis on the relationship between the vertical electron affinities of ferriin aggregates and their OSL protonation states. For proton catalysis to manifest itself, double-protonation paths that are slightly endergonic should be present, and proton affinities of aggregated OSLs allow the identification of such double-protonation chains. As a first test of our mechanistic proposal for the second-order proton catalysis of the Belousov-Zhabotinsky reaction, the results presented here provide compelling evidence in support of the importance of outer sphere ligation of the iron catalyst

Meta-Inflammation and Metabolic Reprogramming of Macrophages in Diabetes and Obesity:The Importance of Metabolites

Diabetes mellitus type II and obesity are two important causes of death in modern society. They are characterized by low-grade chronic inflammation and metabolic dysfunction (meta-inflammation), which is observed in all tissues involved in energy homeostasis. A substantial body of evidence has established an important role for macrophages in these tissues during the development of diabetes mellitus type II and obesity. Macrophages can activate into specialized subsets by cues from their microenvironment to handle a variety of tasks. Many different subsets have been described and in diabetes/obesity literature two main classifications are widely used that are also defined by differential metabolic reprogramming taking place to fuel their main functions. Classically activated, pro-inflammatory macrophages (often referred to as M1) favor glycolysis, produce lactate instead of metabolizing pyruvate to acetyl-CoA, and have a tricarboxylic acid cycle that is interrupted at two points. Alternatively activated macrophages (often referred to as M2) mainly use beta-oxidation of fatty acids and oxidative phosphorylation to create energy-rich molecules such as ATP and are involved in tissue repair and downregulation of inflammation. Since diabetes type II and obesity are characterized by metabolic alterations at the organism level, these alterations may also induce changes in macrophage metabolism resulting in unique macrophage activation patterns in diabetes and obesity. This review describes the interactions between metabolic reprogramming of macrophages and conditions of metabolic dysfunction like diabetes and obesity. We also focus on different possibilities of measuring a range of metabolites intra-and extracellularly in a precise and comprehensive manner to better identify the subsets of polarized macrophages that are unique to diabetes and obesity. Advantages and disadvantages of the currently most widely used metabolite analysis approaches are highlighted. We further describe how their combined use may serve to provide a comprehensive overview of the metabolic changes that take place intracellularly during macrophage activation in conditions like diabetes and obesity

An Upper Limit on the Albedo of HD 209458b: Direct Imaging Photometry with the MOST Satellite

We present space-based photometry of the transiting exoplanetary system HD 209458 obtained with the MOST (Microvariablity and Oscillations of STars) satellite, spanning 14 days and covering 4 transits and 4 secondary eclipses. The HD 209458 photometry was obtained in MOST's lower-precision Direct Imaging mode, which is used for targets in the brightness range $6.5 < V < 13$. We describe the photometric reduction techniques for this mode of observing, in particular the corrections for stray Earthshine. We do not detect the secondary eclipse in the MOST data, to a limit in depth of 0.053 mmag (1 \sigma). We set a 1 \sigma upper limit on the planet-star flux ratio of 4.88 x 10^-5 corresponding to a geometric albedo upper limit in the MOST bandpass (400 to 700 nm) of 0.25. The corresponding numbers at the 3 \sigma level are 1.34 x 10^-4 and 0.68 respectively. HD 209458b is half as bright as Jupiter in the MOST bandpass. This low geometric albedo value is an important constraint for theoretical models of the HD209458b atmosphere, in particular ruling out the presence of reflective clouds. A second MOST campaign on HD 209458 is expected to be sensitive to an exoplanet albedo as low as 0.13 (1 sigma), if the star does not become more intrinsically variable in the meantime.Comment: 29 pages, 9 figures. Accepted for publication in the Astrophysical Journal (July 2006, v645n1

Assessment of sample preparation bias in mass spectrometry-based proteomics

For mass spectrometry-based proteomics, the selected sample preparation strategy is a key determinant for information that will be obtained. However, the corresponding selection is often not based on a fit-for-purpose evaluation. Here we report a comparison of in-gel (IGD), in-solution (ISD), on-filter (OFD), and on-pellet digestion (OPD) workflows on the basis of targeted (QconCAT-multiple reaction monitoring (MRM) method for mitochondrial proteins) and discovery proteomics (data dependent acquisition, DDA) analyses using three different human head and neck tissues (i.e. nasal polyps, parotid gland, and palatine tonsils). Our study reveals differences between the sample preparation methods, for example with respect to protein and peptide losses, quantification variability, protocol-induced methionine oxidation and asparagine/glutamine deamidation as well as identification of cysteine containing peptides. However, none of the methods performed best for all types of tissues, which argues against the existence of a universal sample preparation method for proteome analysis

Scattered Light from Close-in Extrasolar Planets: Prospects of Detection with the MOST Satellite

The ultra-precise photometric space satellite MOST (Microvariability and Oscillations of STars) will provide the first opportunity to measure the albedos and scattered light curves from known short-period extrasolar planets. Due to the changing phases of an extrasolar planet as it orbits its parent star, the combined light of the planet-star system will vary on the order of tens of micromagnitudes. The amplitude and shape of the resulting light curve is sensitive to the planet's radius and orbital inclination, as well as the composition and size distribution of the scattering particles in the planet's atmosphere. To predict the capabilities of MOST and other planned space missions, we have constructed a series of models of such light curves, improving upon earlier work by incorporating more realistic details such as: limb darkening of the star, intrinsic granulation noise in the star itself, tidal distortion and back-heating, higher angular resolution of the light scattering from the planet, and exploration of the significance of the angular size of the star as seen from the planet. We use photometric performance simulations of the MOST satellite, with the light curve models as inputs, for one of the mission's primary targets, $\tau$ Bo\"otis. These simulations demonstrate that, even adopting a very conservative signal detection limit of 4.2 $\mu$mag in amplitude (not power), we will be able to either detect the $\tau$ Bo\"otis planet light curve or put severe constraints on possible extrasolar planet atmospheric models.Comment: Accepted to ApJ, 24 pages, 8 figure

Physicochemical parameters affecting the electrospray ionization efficiency of amino acids after acylation

Electrospray ionization (ESI) is widely used in liquid chromatography coupled to mass spectrometry (LC–MS) for the analysis of biomolecules. However, the ESI process is still not completely understood, and it is often a matter of trial and error to enhance ESI efficiency and, hence, the response of a given set of compounds. In this work we performed a systematic study of the ESI response of 14 amino acids that were acylated with organic acid anhydrides of increasing chain length and with poly­(ethylene glycol) (PEG) changing certain physicochemical properties in a predictable manner. By comparing the ESI response of 70 derivatives, we found that there was a strong correlation between the calculated molecular volume and the ESI response, while correlation with hydrophobicity (log <i>P</i> values), p<i>K</i>_a, and the inverse calculated surface tension was significantly lower although still present, especially for individual derivatized amino acids with increasing acyl chain lengths. Acylation with PEG containing five ethylene glycol units led to the largest gain in ESI response. This response was maximal independent of the calculated physicochemical properties or the type of amino acid. Since no actual physicochemical data is available for most derivatized compounds, the responses were also used as input for a quantitative structure–property relationship (QSPR) model to find the best physicochemical descriptors relating to the ESI response from molecular structures using the amino acids and their derivatives as a reference set. A topological descriptor related to molecular size (SPAN) was isolated next to a descriptor related to the atomic composition and structural groups (BIC0). The validity of the model was checked with a test set of 43 additional compounds that were unrelated to amino acids. While prediction was generally good (<i>R</i>² > 0.9), compounds containing halogen atoms or nitro groups gave a lower predicted ESI response