Chemomimetic Biocatalysis: Exploiting the Synthetic Potential of Cofactor-Dependent Enzymes To Create New Catalysts

Despite the astonishing breadth of enzymes in nature, no enzymes are known for many of the valuable catalytic transformations discovered by chemists. Recent work in enzyme design and evolution, however, gives us good reason to think that this will change. We describe a chemomimetic biocatalysis approach that draws from small-molecule catalysis and synthetic chemistry, enzymology, and molecular evolution to discover or create enzymes with non-natural reactivities. We illustrate how cofactor-dependent enzymes can be exploited to promote reactions first established with related chemical catalysts. The cofactors can be biological, or they can be non-biological to further expand catalytic possibilities. The ability of enzymes to amplify and precisely control the reactivity of their cofactors together with the ability to optimize non-natural reactivity by directed evolution promises to yield exceptional catalysts for challenging transformations that have no biological counterparts

Comportement agronomique de 7 variétés de tomate cultivées sous abri pleine terre à Mayotte. Saison des pluies 2004/2005 : compte rendu d'essai

Pendant la saison des pluies, la production de légumes est rendue difficile à cause des fortes pluies (sols détrempés et inondés), des températures et hygrométries élevées (perturbation de la nouaison) et des maladies qui peuvent limiter considérablement le rendement. Pendant cette saison, le choix de variétés adaptées aux contraintes biotiques et abiotiques vise à obtenir une production satisfaisante. Ainsi, 7 variétés de tomate ont été évaluées pendant la saison des pluies 2004/2005 pour apprécier leur résistance à la chaleur et leur tolérance vis à vis de Ralstonia solanacearum, agent causal du flétrissement bactérien des Solanacées. Certaines de ces variétés ont déjà été testées en 2004 (Huat et al., 2004), telles que Mongal, Titao et Sumo. (Résumé d'auteur

Allocation of patients with liver cirrhosis and organ failure to intensive care:Systematic review and a proposal for clinical practice

AIM: To propose an allocation system of patients with liver cirrhosis to intensive care unit (ICU), and developed a decision tool for clinical practice. METHODS: A systematic review of the literature was performed in PubMed, MEDLINE and EMBASE databases. The search includes studies on hospitalized patients with cirrhosis and organ failure, or acute on chronic liver failure and/or intensive care therapy. RESULTS: The initial search identified 660 potentially relevant articles. Ultimately, five articles were selected; two cohort studies and three reviews were found eligible. The literature on this topic is scarce and no studies specifically address allocation of patients with liver cirrhosis to ICU. Throughout the literature, there is consensus that selection criteria for ICU admission should be developed and validated for this group of patients and multidisciplinary approach is mandatory. Based on current available data we developed an algorithm, to determine if a patient is candidate to intensive care if needed, based on three scoring systems: premorbid Child-Pugh Score, Model of End stage Liver Disease score and the liver specific Sequential Organ Failure Assessment score. CONCLUSION: There are no established systems for allocation of patients with liver cirrhosis to the ICU and no evidence-based recommendations can be made

Transcriptional Enhancers in the Regulation of T Cell Differentiation

The changes in phenotype and function that characterise the differentiation of naïve T cells to effector and memory states are underscored by large-scale, coordinated, and stable changes in gene expression. In turn, these changes are choreographed by the interplay between transcription factors and epigenetic regulators that act to restructure the genome, ultimately ensuring lineage-appropriate gene expression. Here, we focus on the mechanisms that control T cell differentiation, with a particular focus on the role of regulatory elements encoded within the genome, known as transcriptional enhancers. We discuss the central role of transcriptional enhancers in regulating T cell differentiation, both in health and disease

Accelerated gas-liquid visible light photoredox catalysis with continuous-flow photochemical microreactors

In this protocol, we describe the construction and use of an operationally simple photochemical microreactor for gas-liquid photoredox catalysis using visible light. The general procedure includes details on how to set up the microreactor appropriately with inlets for gaseous reagents and organic starting materials, and it includes examples of how to use it to achieve continuous-flow preparation of disulfides or trifluoromethylated heterocycles and thiols. The reported photomicroreactors are modular, inexpensive and can be prepared rapidly from commercially available parts within 1 h even by nonspecialists. Interestingly, typical reaction times of gas-liquid visible light photocatalytic reactions performed in microflow are lower (in the minute range) than comparable reactions performed as a batch process (in the hour range). This can be attributed to the improved irradiation efficiency of the reaction mixture and the enhanced gas-liquid mass transfer in the segmented gas-liquid flow regime

Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein

Chiral 1,2‐amino alcohols are widely represented in biologically active compounds from neurotransmitters to antivirals. While many synthetic methods have been developed for accessing amino alcohols, the direct aminohydroxylation of alkenes to unprotected, enantioenriched amino alcohols remains a challenge. Using directed evolution, we have engineered a hemoprotein biocatalyst based on a thermostable cytochrome c that directly transforms alkenes to amino alcohols with high enantioselectivity (up to 2500 TTN and 90 % ee) under anaerobic conditions with O‐pivaloylhydroxylamine as an aminating reagent. The reaction is proposed to proceed via a reactive iron‐nitrogen species generated in the enzyme active site, enabling tuning of the catalyst's activity and selectivity by protein engineering

How do bacteraemic patients present to the emergency department and what is the diagnostic validity of the clinical parameters; temperature, C-reactive protein and systemic inflammatory response syndrome?

OBJECTIVE: Although blood cultures are often ordered based on the presence of fever, it is a clinical challenge to identify patients eligible for blood cultures. Our aim was to evaluate the diagnostic value of temperature, C-reactive-protein (CRP), and Systemic Inflammatory Response Syndrome (SIRS) to identify bacteraemic patients in the Medical Emergency Department (MED). METHODS: A population-based cohort study including all adult patients at the MED at Odense University Hospital between August 1st 2009 - August 31st 2011. RESULTS: 11,988 patients were admitted to the MED within the study period. Blood cultures were performed on 5,499 (45.9%) patients within 2 days of arrival, of which 418 (7.6%) patients were diagnosed with bacteraemia. This corresponded to 3.5% of all patients. 34.1% of the bacteraemic patients had a normal rectal temperature (36.0°–38.0°C) recorded at arrival, 32.6% had a CRP < 100 mg/L and 28.0% did not fulfil the SIRS criteria. For a temperature cut-point of >38.0°C sensitivity was 0.64 (95% CI 0.59–0.69) and specificity was 0.81 (0.80–0.82) to identify bacteraemic patients. CONCLUSION: One third of the acute medical bacteraemic patients had a normal temperature at arrival to the MED. A normal temperature combined with a CRP < 100 mg/L and no SIRS criteria, ruled out bacteraemia

The Inverse Domination Number Problem, DI-Pathological Graphs, and Fractional Analogues

The conjecture that $\alpha(G) \geq \gamma'(G)$ is unproven where $\alpha(G)$ is the vertex independence number and $\gamma'(G)$ is the inverse domination number of a simple graph G. We have found the conjecture to be true for all graphs with domination number less than 5 and for many other infinite classes of graphs. We examine related questions involving DI-pathological graphs which are graphs such that every maximal independent set intersects with every minimum dominating set. Finally, we use two central results in linear programming to characterize minimum fractional total dominating functions as well as maximum fractional open neighborhood packings for certain graphs