Mechanistic investigations reveal that dibromobimane extrudes sulfur from biological sulfhydryl sources other than hydrogen sulfide

Hydrogen sulfide (H₂S) has emerged as an important biological signaling molecule in the last decade. During the growth of this field, significant controversy has arisen centered on the physiological concentrations of H₂S. Recently, a monobromobimane (mBB) method has been developed for the quantification of different biologically-relevant sulfide pools. Based on the prevalence of the mBB method for sulfide quantification, we expand on this method to report the use of dibromobimane (dBB) for sulfide quantification. Reaction of H₂S with dBB results in formation of highly-fluorescent bimane thioether (BTE), which is readily quantifiable by HPLC. Additionally, the reaction of sulfide with dBB to form BTE is significantly faster than the reaction of sulfide with mBB to form sulfide dibimane. Using the dBB method, BTE levels as low as 0.6 pM can be detected. Upon use of the dBB method in wild-type and CSE^–/– mice, however, dBB reports significantly higher sulfide levels than those measured using mBB. Further investigation revealed that dBB is able to extract sulfur from other sulfhydryl sources including thiols. Based on mechanistic studies, we demonstrate that dBB extracts sulfur from thiols with α- or β-hydrogens, thus leading to higher BTE formation than from sulfide alone. Taken together, the dBB method is a highly sensitive method for H₂S but is not compatible for use in studies in which other thiols are present.     

B-MWW Zeolite: The Case Against Single-Site Catalysis

Boron-containing materials have recently been identified as highly selective catalysts for the oxidative dehydrogenation (ODH) of alkanes to olefins. It has previously been demonstrated by several spectroscopic characterization techniques that the surface of these boron-containing ODH catalysts oxidize and hydrolyze under reaction conditions, forming an amorphous B₂(OH)_xO_(3−x/2) (x=0–6) layer. Yet, the precise nature of the active site(s) remains elusive. In this Communication, we provide a detailed characterization of zeolite MCM-22 isomorphously substituted with boron (B-MWW). Using ¹¹B solid-state NMR spectroscopy, we show that the majority of boron species in B-MWW exist as isolated BO₃ units, fully incorporated into the zeolite framework. However, this material shows no catalytic activity for ODH of propane to propene. The catalytic inactivity of B-MWW for ODH of propane falsifies the hypothesis that site-isolated BO₃ units are the active site in boron-based catalysts. This observation is at odds with other traditionally studied catalysts like vanadium-based catalysts and provides an important piece of the mechanistic puzzle.     

B‐MWW Zeolite: The Case Against Single‐Site Catalysis

Boron‐containing materials have recently been identified as highly selective catalysts for the oxidative dehydrogenation (ODH) of alkanes to olefins. It has previously been demonstrated by several spectroscopic characterization techniques that the surface of these boron‐containing ODH catalysts oxidize and hydrolyze under reaction conditions, forming an amorphous B₂(OH)_xO_(3?x/2) (x=0–6) layer. Yet, the precise nature of the active site(s) remains elusive. In this Communication, we provide a detailed characterization of zeolite MCM‐22 isomorphously substituted with boron (B‐MWW). Using ¹¹B solid‐state NMR spectroscopy, we show that the majority of boron species in B‐MWW exist as isolated BO₃ units, fully incorporated into the zeolite framework. However, this material shows no catalytic activity for ODH of propane to propene. The catalytic inactivity of B‐MWW for ODH of propane falsifies the hypothesis that site‐isolated BO₃ units are the active site in boron‐based catalysts. This observation is at odds with other traditionally studied catalysts like vanadium‐based catalysts and provides an important piece of the mechanistic puzzle.     

Why Boron Nitride is such a Selective Catalyst for the Oxidative Dehydrogenation of Propane

Boron‐containing materials, and in particular boron nitride, have recently been identified as highly selective catalysts for the oxidative dehydrogenation of alkanes such as propane. To date, no mechanism exists that can explain both the unprecedented selectivity, the observed surface oxyfunctionalization, and the peculiar kinetic features of this reaction. We combine catalytic activity measurements with quantum chemical calculations to put forward a bold new hypothesis. We argue that the remarkable product distribution can be rationalized by a combination of surface‐mediated formation of radicals over metastable sites, and their sequential propagation in the gas phase. Based on known radical propagation steps, we quantitatively describe the oxygen pressure‐dependent relative formation of the main product propylene and by‐product ethylene. Free radical intermediates most likely differentiate this catalytic system from less selective vanadium‐based catalysts.     

Influence of acute hyperglycemia on otoacoustic emissions and the medial olivocochlear reflex

Stimulus-frequency (SF) otoacoustic emission (OAE) amplitude and the amplitude of medial olivocochlear (MOC) inhibition of SF OAEs for ipsilateral, contralateral and bilateral MOC reflex elicitors were recorded in six subjects with type 2 diabetes during a glucose tolerance test (GTT). Five of the six subjects were tested twice for a total of 11 trials and three subjects were tested in a control experiment. During the GTT experiment, the subjects' blood glucose was elevated from a euglycemic level below 150 mg/dL to a hyperglycemic level above 160 mg/dL following the consumption of a bolus of 80 g of sugar. A subset of three subjects were tested in a control experiment during which SF OAE and MOC reflex measurements were made while blood sugar levels remained constant within the euglycemic region. Mean SF OAE amplitudes were elevated following glucose consumption. A statistically significant increase in MOC inhibition amplitude was observed during elevated sugar levels for the 11 GTT trials. Maximum inhibition occurred about an hour after glucose consumption when blood glucose levels peaked. Results indicate that acute hyperglycemia influences efferent control of the cochlea in people with type 2 diabetes.     

Three-dimensional magnetic resonance spectroscopic imaging of histologically confirmed brain tumors

The goal of this study was to determine whether presurgical metabolite levels measured by 3D MR Spectroscopic Imaging (MRSI) can accurately detect viable cancer within human brain tumor masses. A total of 31 patients (33 exams, 39 pathology correlations) with brain tumors were studied prior to surgical biopsy and/or resection. The 3D MRSI was obtained with a spatial resolution of 0.2 to 1 cc throughout the majority of the mass and adjacent brain tissue using PRESS-CSI localization. Levels of choline, creatine and NAA were estimated from the locations of the resected tissue and normalized to normal appearing brain tissue. The data were correlated with subsequent histologic analysis of the biopsy tissue samples. Although there were large variations in the metabolite ratios, all regions of confirmed cancer demonstrated significant choline levels and a mean choline/NAA ratio of 5.84 + 2.58 with the lowest value being 1.3. This lowest value is greater than 4 standard deviations above the mean (0.52 +/- 0.13) found in 8 normal volunteers. The choline signal intensities in confirmed cancers were significantly elevated compared to normal appearing brain tissue with a mean ratio of 1.71 +/- 0.69. Spectra with no significant metabolite levels were observed in the non-enhancing necrotic core of the tumor masses. The results of this study indicate that 3D MRSI of brain tumors can detect abnormal metabolite levels in regions of viable cancer and grades and can differentiate cancer from necrosis and/or normal brain tissue.     

Diffusion within a near-critical nanopore fluid

Results are presented for grand canonical Monte Carlo (GCMC) and both equilibrium and non-equilibrium molecular dynamics simulations (EMD and NEMD) conducted over a range of densities and temperatures that span the two-phase coexistence and supercritical regions for a pure fluid adsorbed within a model crystalline nanopore. The GCMC simulations provided the low temperature coexistence points for the open pore fluid and were used to locate the capillary critical temperature for the system. The equilibrium configurational states obtained from these simulations were then used as input data for the EMD simulations in which the self-diffusion coefficients were computed using the Einstein equation. NEMD colour diffusion simulations were also conducted to validate the use of a system averaged Einstein analysis for this inhomogeneous fluid. In all cases excellent agreement was observed between the equilibrium (linear response theory) predictions for the diffusivities and non-equilibrium colour diffusivities. The simulation results are also compared with a recently published quasi-hydrodynamic theory of Pozhar and Gubbins (Pozhar, L. A., and Gubbins, K. E., 1993, J. Chem. Phys., 99, 8970; 1997, Phys. Rev. E, 56, 5367.). The model fluid and the nature of the fluid wall interactions employed conform to the decomposition of the particle–particle interaction potential explicitly used by Pozhar and Gubbins. The local self-diffusivity was calculated from the local fluid–fluid and fluid wall hard core collision frequencies. While this theory provides reasonable results at moderate pore fluid densities, poor agreement is observed in the low density limit.     

Closeness of worlds

An objection is presented to Lewis’s analysis of counterfactual conditionals in terms of relative closeness of possible worlds. The objection depends on no special assumptions about the ‘closer-than’ relation. The argument also casts doubt on Lewis’s claim that Antecedent Strengthening fails for counterfactuals.     

Bile UPLC-MS fingerprinting and bile acid fluxes during human liver transplantation

Bile flow restoration is a crucial step in the recovery process post transplantation of the liver. Here, metabolic trajectories based on changes in bile secretion - a known marker of functionality - have been utilised as an approach for discovering bile fluxes during transplantation. A total of ten liver transplants were monitored and from these 68 bile samples from both donors and recipients were collected and analysed using ultra-performance LC-MS in combination with multivariate statistical analysis. Based on the principal component scores constructed from the total bile fingerprint, differentiation of the bile acid concentrations before and after transplantation was detected. A trend was also observed, by constructing metabolic trajectories, whereby the post-transplant profiles approached the position of pre-transplant profiles within 30-60?min of the restoration of bile secretion function. The ten major conjugated bile acid salts were measured and a significant increase in concentrations of taurocholic acid and taurochenodeoxycholic acid were seen after transplantation. In addition, the ratios of secondary bile acids detected in gall bladder and hepatic bile were measured before and after transplantation. This study suggests that bile acid ratios in the donor liver at the pre-transplant and post-transplant stage may be important and that profiling of secreted bile after transplantation may aid clinical assessment and progress post-transplantation.