Aromatic dioxygenases: Molecular biocatalysis and applications

Aromatic dioxygenases have been found to catalyse single and tandem oxidation reactions of conjugated polyenes. Rational selection and design of dioxygenases, allied to substrate shape, size and substitution pattern, has been used to control regiochemistry and stereochemistry during the oxygenation process. The resulting enantiopure bioproducts have been increasingly utilised as precursors for new and alternative routes in chiral synthesis.

Hull fouling on commercial ships as a vector of macroalgal introduction

Hull fouling is thought to have been the vector of introduction for many algal species. We studied ships arriving at a Mediterranean harbour to clarify the present role of commercial cargo shipping in algal introductions. A total of 31 macroalgal taxa were identified from 22 sampled hulls. The majority of records (58%) were of species with a known cosmopolitan geographical distribution. Due to a prevalence of cosmopolitan species and a high turnover of fouling communities, species composition of assemblages did not appear to be influenced by the area of origin, length of ship or age of coating. In the light of the present results, hull fouling on standard trading commercial vessels does not seem to pose a significant risk for new macroalgal species introductions. However, a high proportion of non-cosmopolitan species found on a ship with non-toxic coating may modify this assessment, especially in the light of the increasing use of such coatings and the potential future changes in shipping routes.

Hydrogenation/hydrogenolysis of disulfides using sulfided Ni/Mo catalysts

The mechanism of the hydrogenation/hydrogenolysis of dinitrodiphenyldisulfides using sulfided NiMo/ gamma Al2O3 catalysts has been examined in detail. Although two routes are possible, the major pathway involves an initial S-S bond cleavage followed by reduction of the nitro group. Importantly, the disulfide hydrogenolysis occurs in the absence of the catalyst with the role of the catalyst thought to be to activate the hydrogen and trap the cleaved intermediate as well as facilitate the reduction of the nitro group. Monitoring the mass balance throughout the reaction demonstrates the difficulty in measuring intrinsic kinetics for gas-liquid-solid reactions. Although the mass balance is restored at the end of the reaction, up to 45% of the substrate/products is found to be adsorbed on the catalyst during the reaction. (c) 2008 Elsevier B.V. All rights reserved.

The catalytic role of water in CO oxidation

Water, one of the most popular species in our planet, can play a catalytic role in many reactions, including reactions in heterogeneous catalysis. In a recent experimental work, Bergeld, Kasemo, and Chakarov demonstrated that water is able to promote CO oxidation under low temperatures (similar to200 K). In this study, we choose CO oxidation on Pt(111) in the presence of water as a model system to address the catalytic role of water for surface reactions in general using density functional theory. Many elementary steps possibly involved in the CO oxidation on Pt(111) at low temperatures have been investigated. We find the following. First, in the presence of water, the CO oxidation barrier is reduced to 0.33 eV (without water the barrier is 0.80 eV). This barrier reduction is mainly due to the H-bonding between the H in the H2O and the O at the transition state (TS), which stabilizes the TS. Second, CO can readily react with OH with a barrier of 0.44 eV, while COOH dissociation to produce CO2 is not easy (the barrier is 1.02 eV). Third, in the H2O+OH mixed phase, CO can be easily converted into CO2. It occurs through two steps: CO reacts with OH, forming COOH; and COOH transfers the H to a nearby H2O and, at the same time, an H in the H2O transfers to a OH, leading to CO2 formation. The reaction barrier of this process is 0.60 eV under CO coverage of 1/6 ML and 0.33 eV under CO coverage of 1/3 ML. The mechanism of CO oxidation at low temperatures is discussed. On the basis of our calculations, we propose that the water promotion effect can in general be divided into two classes: (i) By H-bonding between the H of H2O and an electron negative species such as the O in the reaction of CO+O+H2O-->CO2+H2O, H2O can stabilize the TS of the reaction and hence reduce the barrier. (ii) H2O first dissociates into H and OH and then OH or H participates directly in the reaction to induce new reaction mechanism with more favorable routes, in which OH or H can act as an intermediate. (C) 2003 American Institute of Physics.

Enzymatic and chemoenzymatic synthesis of arene trans-dihydrodiols

Several potential approaches to the enzyme-catalysed synthesis of arene trans-diols have been examined including epoxidation/hydrolysis, bis-benzylic hydroxylation, cis-dihydroxylation/alcohol dehydrogenation/ketone reduction, cisdihydroxylation/cis-trans isomerisation. and multi-enzyme synthesis of trans-dihydrodiol secondary metabolites from primary metabolites. The lack of general applicability of these enzymatic methods has led to the development of several chemoenzymatic routes for the synthesis of a series of trans-dihydrodiols from the readily available cis-dihydrodiol precursors. Partial hydrogenation of cis-dihydrodiol metabolites to yield the corresponding cis-tetrahydrodiols followed by a regioselective Mitsunobu inversion process gave trans-tetrahydrodiols that were in turn converted to trans-dihydrodiols. The formation of anti-benzene dioxides or iron tricarbonyl complexes from the corresponding cis-dihydrodiol precursors provided shorter and more convenient chemoenzymatic routes to trans-dihydrodiols. The application of cis-dihydrodiol metabolites of polycyclic azaarenes in the synthesis of the corresponding arene oxides followed by chemical hydrolysis provides a convenient route to trans-dihydrodiols. (C) 2002 Elsevier Science B.V. All rights reserved.

Utilization of analgesics, sedatives, and pain scores in infants with a prolonged hospitlaization: A prospective descriptive cohort study

Aim
Describe the utilization of analgesic and sedative medications and documentation of pain scores in a cohort of critically ill infants in a neonatal intensive care unit.

Method
A prospective, longitudinal, cohort study of infants with a predicted length of stay =28 days. Dosages and routes of administration of analgesic and sedative medications and documentation of pain scores were collected on a daily basis.

Results
55 infants were enrolled into the study. Oral sucrose was administered to all 55 infants, 51 infants (93%) were administered enteral acetaminophen and 50 (91%) infants were administered morphine during their hospitalization. Sedatives were administered to 42 infants (76%); 36 (65%) were administered chloral hydrate and 32 (58%) were administered intravenous midazolam. With the exception of the first week of admission, when there was highest utilization of opioids and lower use of sucrose, acetaminophen and sedatives, the pattern of administration of analgesic and sedative agents remained relatively constant throughout the hospitalization. Pain scores were documented for 36 (65%) infants during their hospitalisation, however for these 36 infants, pain scores were infrequently recorded.

Conclusion
There was substantial and varied analgesic and sedative use in this cohort of infants, yet infrequent documentation of pain assessment scores. These practices highlight important clinical implications for sick infants requiring careful consideration of pain and distress management.

Friedel-Crafts Benzoylation of Anisole in Ionic Liquids: Catalysis, Separation, and Recycle Studies

The comparison of three ionic liquid-mediated catalytic processes for the benzoylation of anisole with benzoic anhydride is presented. A detailed understanding of the mechanism by which the zeolite and metal triflate reactions in bis{trifluoromethanesulfonyl}imide-based ionic liquids has been reported previously, and these routes are considered together with an indium chloride-based ionic liquid system. Solvent extraction and vacuum/steam distillation have been assessed as possible workup procedures, and an overall preliminary economic evaluation of each overall process is reported. Although the predominant activity is associated with the in situ formation of a homogeneous acid catalyst, the low cost and facile separation of the zeolite-catalysed process leads to this route being the most economically viable overall option. The results of a continuous flow miniplant based on the zeolite catalyst are also presented and compared with the reaction using a small plug How reactor.

Ionic liquids: Improved syntheses and new products

We report here the improved syntheses of 1-alkyl-3-methylimidazolium ionic liquids. Microwave irradiation drastically reduces the preparation time of 1-alkyl-3-methylimidazolium and N-alkylpyridinium halide salts and, in addition, three halide-free routes to ionic liquids have been developed. New, chiral, imidazolium-based ionic liquids were prepared using both conventional and halide-free procedures. Chirality was introduced in the new compounds at either the cation or the anion, or both.

Selective synthesis of chlorophosphoramidites using ionic liquids

A range of chlorophosphoramidites have been prepared in ionic liquids and compared with material synthesised in molecular solvents. Through the use of ionic liquids as reaction media the moisture sensitivity and impurity issues hampering existing traditional synthetic routes have been eased. Not only can stock chemicals be used without purification, but the reactions may be conducted at room temperature and at high concentrations. Furthermore, reaction times are reduced and rapid addition of reagents is possible whilst retaining tight control over product selectivity. Beyond their role as reaction media, ionic liquids also present a unique storage medium for these highly moisture sensitive chlorophosphoramidites.

Reterritorialising Canada: Arctic ice’s liquid modernity and the imagining of a Canadian archipelago

Studying mobile actor networks of moving people, objects, images, and discourses, in conjunction with changing time-spaces, offers a unique opportunity to understand important, and yet relatively neglected, “relational material” dynamics of mobility. A key example of this phenomenon is the recontinentalization of Canada amidst dramatically changing articulations of the meanings and boundaries of the Canadian land-ice- ocean mass. A notable reason why Canada is being re-articulated in current times is the extensiveness of Arctic thawing. The reconfiguration of space and “motility” options in the Arctic constitutes an example of how “materiality and sociality produce themselves together.” In this paper we examine the possibilities and risks connected to this recontinentalization of Canada’s North. In exploring the past, present, and immediate future of this setting, we advance the paradigmatic view that Canada’s changing Arctic is the key element in a process of transformation of Canada into a peninsular body encompassed within a larger archipelagic entity: a place more intimately attuned to its immense (and growing) coastal and insular routes.

The Deubiquitinating Enzyme USP17 Blocks N-Ras Membrane Trafficking and Activation but Leaves K-Ras Unaffected

The proto-oncogenic Ras isoforms (H, N, and K) have a C-terminal CAAX motif and undergo the same post-translational processing steps, although they traffic to the plasma membrane through different routes. Previously, we have shown that overexpression of the deubiquitinating enzyme USP17 inhibits H-Ras localization to the plasma membrane. Now we report that whereas H-Ras and N-Ras were unable to localize to the plasma membrane in the presence of USP17, K-Ras4b localization was unaffected. EGF stimulation was unable to induce N-Ras membrane localization in USP17-expressing cells. In addition, N-Ras activity and downstream signaling through the MAPK MEK/ERK and PI3K/JNK pathways were blunted. However, we still detected abundant N-Ras localization at the ER and Golgi in USP17-expressing cells. Collectively, our data showed that the deubiquitinating enzyme USP17 blocks EGF-induced N-Ras membrane trafficking and activation, but left K-Ras unaffected.

Evaluating signatures of glacial refugia for North Atlantic benthic marine taxa

A goal of phylogeography is to relate patterns of genetic differentiation to potential historical geographic isolating events. Quaternary glaciations, particularly the one culminating in the Last Glacial Maximum ~21 ka (thousands of years ago), greatly affected the distributions and population sizes of temperate marine species as their ranges retreated southward to escape ice sheets. Traditional genetic models of glacial refugia and routes of recolonization include these predictions: low genetic diversity in formerly glaciated areas, with a small number of alleles/haplotypes dominating disproportionately large areas, and high diversity including "private" alleles in glacial refugia. In the Northern Hemisphere, low diversity in the north and high diversity in the south are expected. This simple model does not account for the possibility of populations surviving in relatively small northern periglacial refugia. If these periglacial populations experienced extreme bottlenecks, they could have the low genetic diversity expected in recolonized areas with no refugia, but should have more endemic diversity (private alleles) than recently recolonized areas. This review examines evidence of putative glacial refugia for eight benthic marine taxa in the temperate North Atlantic. All data sets were reanalyzed to allow direct comparisons between geographic patterns of genetic diversity and distribution of particular clades and haplotypes including private alleles. We contend that for marine organisms the genetic signatures of northern periglacial and southern refugia can be distinguished from one another. There is evidence for several periglacial refugia in northern latitudes, giving credence to recent climatic reconstructions with less extensive glaciation.

Recent Advances in Antidiabetic Drug Therapies Targeting the Enteroinsular Axis

The enteroinsular axis (EIA) constitutes a physiological signalling system whereby intestinal endocrine cells secrete incretin hormones following feeding that potentiate insulin secretion and contribute to the regulation of blood glucose homeostasis. The two key hormones responsible are named glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Recent years have witnessed sustained development of antidiabetic therapies that exploit the EIA. Current clinical compounds divide neatly into two classes. One concerns analogues or mimetics of GLP-1, such as exenatide (Byetta) or liraglutide (NN2211). The other group comprises the gliptins (e. g. sitagliptin and vildagliptin) which boost endogenous incretin activity by inhibiting the enzyme dipeptidyl peptidase 4 (DPP 4) that degrades both GLP-1 and GIP. Ongoing research indicates that further incretin and gliptin compounds will become available for clinical use in the near future, offering comparable or improved efficacy. For incretin analogues there is the prospect of prolonged duration of action and alternative routes of administration. This review focuses on recent advances in pre-clinical research and their translation into clinical studies to provide future therapies for type 2 diabetes targeting the EIA.