Diffusive gradients in thin films predicts crop response better than calcium-acetate-lactate extraction

Nutrient Cycling in Agroecosystems - Soil P testing has been widely used to predict crop yields, P uptake, and fertilizer demands in agriculture. Diffusive gradients in thin films (DGT) provides a...     

Non-heme Fe(IV)-oxo intermediates

High-valent non-heme iron-oxo intermediates have been proposed for decades as the key intermediates in numerous biological oxidation reactions. In the past three years, the first direct characterization of such intermediates has been provided by studies of several alphaKG-dependent oxygenases that catalyze either hydroxylation or halogenation of their substrates. In each case, the Fe(IV)-oxo intermediate is implicated in cleavage of the aliphatic C-H bond to initiate hydroxylation or halogenation. The observation of non-heme Fe(IV)-oxo intermediates and Fe(II)-containing product(s) complexes with almost identical spectroscopic parameters in the reactions of two distantly related alphaKG-dependent hydroxylases suggests that members of this subfamily follow a conserved mechanism for substrate hydroxylation. In contrast, for the alphaKG-dependent non-heme iron halogenase, CytC3, two distinct Fe(IV) complexes form and decay together, suggesting that they are in rapid equilibrium. The existence of two distinct conformers of the Fe site may be the key factor accounting for the divergence of the halogenase reaction from the more usual hydroxylation pathway after C-H bond cleavage. Distinct transformations catalyzed by other mononuclear non-heme enzymes are likely also to involve initial C-H bond cleavage by Fe(IV)-oxo complexes, followed by diverging reactivities of the resulting Fe(III)-hydroxo/substrate radical intermediates.     

Structure‐Based Mechanism of Oleate Hydratase from Elizabethkingia meningoseptica

Hydratases provide access to secondary and tertiary alcohols by regio‐ and/or stereospecifically adding water to carbon‐carbon double bonds. Thereby, hydroxy groups are introduced without the need for costly cofactor recycling, and that makes this approach highly interesting on an industrial scale. Here we present the first crystal structure of a recombinant oleate hydratase originating from Elizabethkingia meningoseptica in the presence of flavin adenine dinucleotide (FAD). A structure‐based mutagenesis study targeting active site residues identified E122 and Y241 as crucial for the activation of a water molecule and for protonation of the double bond, respectively. Moreover, we also observed that two‐electron reduction of FAD results in a sevenfold increase in the substrate hydration rate. We propose the first reaction mechanism for this enzyme class that explains the requirement for the flavin cofactor and the involvement of conserved amino acid residues in this regio‐ and stereoselective hydration.     

Current Trends in Pretreatment and Fractionation of Lignocellulose as Reflected in Industrial Patent Activities

The pretreatment process to disintegrate lignocellulose and to fractionate its three main components hemicellulose, cellulose, and lignin, is a crucial step to enable sustainable and economic value chains based on biomass feedstock. This review provides an overview of the recent patenting activities on pretreatment. Most of these activities focus on optimization of different known processes to improve economics, such as increased catalyst efficiency, effluents recirculation, or lignin valorization. However, also a number of patents and demonstration activities based on emerging concepts for pretreatments are observed.     

Potent,Metabolically Stable 2‐Alkyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐adenines as Adenosine A2A Receptor Ligands

Inhibition of adenosine A_2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson’s disease (PD). We previously identified the triazolo‐9H‐purine, ST1535, as a potent A_2AR antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω‐1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω‐1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A_2AR was determined. Two compounds, (2‐(3,3‐dimethylbutyl)‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐6‐amine ( 3 b ) and 4‐(6‐amino‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐2‐yl)‐2‐methylbutan‐2‐ol ( 3 c ), exhibited good affinity against A_2AR (K_i=0.4 nM and 2 nM , respectively) and high in vitro metabolic stability (89.5 % and 95.3 % recovery, respectively, after incubation with HLM for two hours).     

Selective synthesis of alcohols from syngas and hydroformylation of ethylene over supported cluster-derived cobalt catalysts

Hydroformylation of ethylene and CO hydrogenation were studied over cobalt-based catalysts derived from reaction of Co₂(CO)₈ with ZnO, MgO and La₂O₃ supports. At 433 K a similar activity sequence was reached for both reactions: Co/ ZnO > Co/La₂O₃ > Co/MgO. This confirms the deep analogy between hydroformylation and CO hydrogenation into alcohols. In the CO hydrogenation the selectivity towards alcohol mixture (C₁-C₃) was found to be near 100% at 433 K for a conversion of 6% over the Co/ZnO catalyst; this catalyst showed oxo selectivity higher than 98% in the hydroformylation of ethylene. Magnetic experiments showed that no metallic cobalt particles were formed at 433 K. It is suggested that the active site for the step that is common to both reactions is related to the surface homonuclear Co²⁺/[Co(CO)₄]^– ion-pairing species.     

Dual,Site‐Specific Modification of Antibodies by Using Solid‐Phase Immobilized Microbial Transglutaminase

Microbial transglutaminase (MTG) was stably solid‐phase immobilized on glass microbeads by using a second‐generation dendronized polymer. Immobilized MTG enabled the efficient generation of site‐specifically conjugated proteins, including antibody fragments, as well as whole antibodies through distinct glutamines and, unprecedentedly, also through lysines with various bifunctional substrates with defined stoichiometries. With this method, we generated dual, site‐specifically modified antibodies comprising a fluorescent probe and a metal chelator for radiolabeling—a strategy anticipated to design antibodies for imaging and simultaneous therapy. Furthermore, we provide evidence that immobilized MTG features higher siteselectivity than soluble MTG.     

Consistent Monitoring of Cointegrating Relationships: The US Housing Market and the Subprime Crisis

We propose a consistent monitoring procedure for structural change in a cointegrating relationship. The procedure is inspired by Chu et al. (1996) by being based on parameter estimation on a prebreak ‘calibration’ period. We use three modified least squares estimators to obtain nuisance parameter‐free limiting distributions. We study the asymptotic and finite sample properties of the procedures and finally apply the approach to monitor two‐fundamentals‐driven US housing prices cointegrating relationships over the period 1976:Q1–2010:Q4 using the data of Anundsen (2015). Depending on the relationship considered and the estimation method used, a break point is detected as early as 2003:Q2, that is, well before US housing prices started to fall in 2007.     

Experimental and calculated liquid-liquid interfacial tension in demixing metal alloys

Liquid-liquid interracial tension in binary and temary Al-based monotectic systems has been determined experimentally with a tensiometric method in a wide temperature interval. The temperature dependence of the interfacial tension is well described by a power law function of the type σαβ - （1 - T/Tc）δ with the critical exponent δ= 1.3 and a critical temperature Tc. Theoretical models describing the liquid-liquid interface in monotectic alloys and their applicability for calculation of the interfacial tension and its temperature dependence in binary systems are considered.     

REPLACE: a strategy for iterative design of cyclin-binding groove inhibitors

We describe a drug-design strategy termed REPLACE (REplacement with Partial Ligand Alternatives through Computational Enrichment) in which nonpeptidic surrogates for specific determinants of known peptide ligands are identified in silico by using a core peptide-bound protein structure as a design anchor. In the REPLACE application example, we present the effective replacement of two critical binding motifs in a lead protein-protein interaction inhibitor pentapeptide with more druglike phenyltriazole and diphenyl ether groups. These were identified through docking of fragment libraries into the volume of the cyclin-binding groove of CDK2/cyclin A vacated through truncation of the inhibitor peptide-binding determinants. Proof of concept for this strategy was obtained through the generation of potent peptide-small-molecule hybrids and by the confirmation of inhibitor-binding modes in X-ray crystal structures. This method therefore allows nonpeptide fragments to be identified without the requirement for a high-sensitivity binding assay and should be generally applicable in replacing amino acids as individual residues or groups in peptide inhibitors to generate pharmaceutically acceptable lead molecules.