Multiscale Modeling of the Active Site of [Fe] Hydrogenase: The H2 Binding Site in Open and Closed Protein Conformations

A series of QM/MM optimizations of the full protein of [Fe] hydrogenase were performed. The FeGP cofactor has been optimized in the water‐bound resting state ( 1 ), with a side‐on bound dihydrogen ( 2 ), or as a hydride intermediate ( 3 ). For inclusion of H₄ MPT in the closed structure, advanced multiscale modeling appears to be necessary, especially to obtain reliable distances between CH‐H₄MPT⁺ and the dihydrogen (H₂) or hydride (H^?) ligand in the FeGP cofactor. Inclusion of the full protein is further important for the relative energies of the two intermediates 2 and 3 . We finally find that hydride transfer from 3 has a significantly higher barrier than found in previous studies neglecting the full protein environment.     

A new ent-clerodane diterpenoid from Crassocephalum bauchiense Huch. (Asteraceae)

A phytochemical investigation of the whole plant of Crassocephalum bauchiense Huch. resulted in the isolation of a new clerodane diterpenoid, ent-2β,18,19-trihydroxycleroda-3,13-dien-16,15-olide (1), together with two known flavonoids 3′,5-dihydroxy-4′,5′,6,7,8-pentamethoxyflavone (2) and 4′,5-dihydroxy-3′,5′,6,7,8-pentamethoxyflavone (3). The compounds were tested against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Compound 2 showed weak activity (IC₅₀ = 10.1 g/mL) whilst compounds 1 and 3 were inactive. The structures of the compounds were elucidated by using detailed spectral analyses, especially ¹H and ¹³C NMR, ¹H–¹H COSY, NOESY, HMBC and HR-ESI-MS.     

Action of generalized symmetric groups on symmetric and exterior powers of their natural representations

We establish upper and lower bounds on the dimension of the space spanned by the symmetric powers of the natural character of generalized symmetric groups. We adapt the methods of Savitt and Stanley from [4 Savitt, D., Stanley, R. P. (2000). A note on the symmetric powers of the standard representation of S_n. Electron. J. Combin. 7:R6. [Google Scholar]] to obtain bounds both over the complex numbers and in prime characteristic.     

A REVIEW OF POLAR STRATOSPHERIC CLOUD FORMATION

Liquid and solid particles in polar stratospheric clouds （PSCs） have been known to play a crucial role in the chemical loss of stratospheric ozone over the Antarctic and Arctic regions in late winter and early spring. The stratospheric aerosol and cloud particles provide the sites where fast heterogeneous chemical reactions convert inactive halogen reservoir species into potential ozone destroying radicals. The sedimentation of nitric acid-containing PSC particles irreversibly removes HNO3 gas （denitrification） from the lower stratosphere, which slows the return of chlorine to its inactive forms, resulting in more severe stratospheric ozone destruction. Although these clouds have been investigated extensively during the past decade using in situ field observation, laboratory experiment and modeling studies, the detailed microphysics processes under cold stratospheric conditions are still uncertain. This paper reviews the recent advances in our understanding of PSCs.     

Teachers Describe Epistemologies of Science Instruction Through Q Methodology

Creating scientifically literate students is a common goal among educational stakeholders. An understanding of nature of science is an important component of scientific literacy in K‐12 science education. Q methodology was used to investigate the opinions of preservice and in‐service teachers on how they intend to teach or currently teach science. Q methodology is a measurement tool designed to capture personal beliefs. Participants included 40 preservice and in‐service elementary and secondary science teachers who sorted 40 self‐referential statements regarding science instruction. The results identified three epistemologies toward teaching science: A Changing World, My Beliefs, and Tried and True. Participants with the A Changing World epistemology believe evidence is reliable, scientific knowledge is generated in multiple ways, and science changes in light of new evidence. The My Beliefs epistemology reflects that scientific knowledge is subject to change due to embedded bias, science is affected by culture and religion, and evolution should not be taught in the classroom. The Tried and True epistemology views a scientific method as an exact method to prove science, believes experiments are crucial for scientific discoveries, absolute truth exists in scientific knowledge, and society and cultural factors can be eliminated from investigations. Implications for preservice teacher education programs and in‐service teacher professional development are addressed.     

Parameterization of Org27569: An allosteric modulator of the cannabinoid CB1 G protein‐coupled receptor

The cannabinoid CB₁ receptor is a class A G protein‐coupled receptor (GPCR) that is the most widely expressed GPCR in the brain. Many GPCRs contain allosteric binding sites for endogenous and/or synthetic ligands, which are topographically distinct from the agonist‐binding site that is known as the orthosteric site. While both endogenous and synthetic ligands that act at the CB₁ orthosteric site have been known for some time, compounds that act at a CB₁ allosteric site have only recently been discovered. The most studied of these is 5‐chloro‐3‐ethyl‐1H‐indole‐2‐carboxylic acid [2‐(4‐piperidin‐1‐ylphenyl)ethyl]amide (Org27569). Because allosteric ligands are thought to act through conformational changes in the receptor that are transmitted from the allosteric to the orthosteric site, computational studies of the structural and dynamic interactions of Org27569 with the CB₁ receptor are crucial to achieve a molecular level understanding of the basis of action of this important new class of compounds. To date, such computational studies have not been possible due to the lack of a complete set of molecular mechanics force field parameters for Org27569. Here, we present the development of missing CHARMM force field parameters for Org27569 using previously published methods and the validation and application of these new parameters using normal mode analysis and molecular dynamics simulations combined with experimental infrared measurements. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

Determination of seven arsenic species in seafood by ion exchange chromatography coupled to inductively coupled plasma-mass spectrometry following microwave assisted extraction: method validation and occurrence data

The determination of seven arsenic species in seafood was performed using ion exchange chromatography on an IonPac AS7 column with inductively coupled plasma mass spectrometry detection after microwave assisted extraction. The effect of five parameters on arsenic extraction recoveries was evaluated in certified reference materials. The recoveries of total arsenic and of arsenic species with the two best extraction media (100% H₂O and 80% aqueous MeOH) were generally similar in the five seafood certified reference materials considered. However, because MeOH co-elutes with arsenite, which would result in a positively biased arsenite concentration, the 100% H₂O extraction conditions were selected for validation of the method. Figures of merit (linearity, LOQs (0.019-0.075 mg As kg⁻¹), specificity, trueness (with recoveries between 82% (As(III)) and 104% (As(V) based on spikes or certified concentrations), repeatability (3-14%), and intermediate precision reproducibility (9-16%) of the proposed method were satisfactory for the determination of arsenite, monomethylarsonic acid, dimethylarsinic acid, arsenate, arsenobetaine and arsenocholine in fish and shellfish. The performance criteria for trimethylarsine oxide, however, were less satisfactory. The method was then applied to 65 different seafood samples. Arsenobetaine was the main species in all samples. The percentage of inorganic arsenic varied between 0.4-15.8% in shellfish and 0.5-1.9% at the utmost in fish. The main advantage of this method that uses only H₂O as an extractant and nitric acid as gradient eluent is its great compatibility with the long-term stability of both IEC separation and ICP-MS detection.     

Near-complete suppression of surface recombination in solar photoelectrolysis by "Co-Pi" catalyst-modified W:BiVO4

The influence of an earth-abundant water oxidation electrocatalyst (Co-Pi) on solar water oxidation by W:BiVO(4) has been studied using photoelectrochemical (PEC) techniques. Modification of W:BiVO(4) photoanode surfaces with Co-Pi has yielded a very large (～440 mV) cathodic shift in the onset potential for sustained PEC water oxidation at pH 8. PEC experiments with H(2)O(2) as a surrogate substrate have revealed that interfacing Co-Pi with these W:BiVO(4) photoanodes almost completely eliminates losses due to surface electron-hole recombination. The results obtained for W:BiVO(4) are compared with those reported recently for Co-Pi/α-Fe(2)O(3) photoanodes. The low absolute onset potential of ～310 mV vs RHE achieved with the Co-Pi/W:BiVO(4) combination is promising for overall solar water splitting in low-cost tandem PEC cells, and is encouraging for application of this surface modification strategy to other candidate photoanodes.     

Disruption of Wnt planar cell polarity signaling by aberrant accumulation of the MetAP-2 substrate Rab37

Identification of methionine aminopeptidase-2 (MetAP-2) as the molecular target of the antiangiogenic compound TNP-470 has sparked interest in N-terminal Met excision's (NME) role in endothelial cell biology. In this regard, we recently demonstrated that MetAP-2 inhibition suppresses Wnt planar cell polarity (PCP) signaling and that endothelial cells depend on this pathway for normal function. Despite this advance, the substrate(s) whose activity is altered upon MetAP-2 inhibition, resulting in loss of Wnt PCP signaling, is not known. Here we identify the small G protein Rab37 as a MetAP-2-specific substrate that accumulates in the presence of TNP-470. A functional role for aberrant Rab37 accumulation in TNP-470's mode of action is demonstrated using a Rab37 point mutant that is resistant to NME, because expression of this mutant phenocopies the effects of MetAP-2 inhibition on Wnt PCP signaling-dependent processes.