Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L⁻¹). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.     

Chromium evaporation and oxidation characteristics of alumina-forming austenitic stainless steels for balance of plant applications in solid oxide fuel cells

The chromium (Cr) evaporation behavior of several different types of iron (Fe)-based AFA alloys and benchmark Cr₂O₃-forming Fe-based 310 and Ni-based 625 alloys was investigated for 500 h exposures at 800 °C to 900 °C in air with 10% H₂O. The Cr evaporation rates from alumina-forming austenitic (AFA) alloys were ~5 to 35 times lower than that of the Cr₂O₃-forming alloys depending on alloy and temperature. The Cr evaporation behavior was correlated with extensive characterization of the chemistry and microstructure of the oxide scales, which also revealed a degree of quartz tube Si contamination during the test. Long-term oxidation kinetics were also assessed at 800 to 1000 °C for up to 10,000 h in air with 10% H₂O to provide further guidance for SOFC BOP component alloy selection.     

Effect of processing on the microbiological quality and safety of chicken carcasses at slaughterhouse

Microbiological contamination of chicken meat depends on the conditions under which the animals are reared, slaughtered and processed. The aim of this study was to determine the influence of farm origin and processing stages at slaughterhouse on the microbial safety and quality of chicken. Samples of chicken carcasses from three different farms were taken from a slaughterhouse. Mesophiles, Escherichia coli, coagulase positive Staphylococcci counts, presence of Listeria monocytogenes,Campylobacter and Salmonella were determined at five sampling points: after defeathering, after evisceration, after washing, after chilling and after cutting. Chilling reduced log numbers of mesophiles, coagulase positive Staphylococci and E. coli by 0.85, 1.52 and 2.2 log units, respectively. Salmonella was not detected after chilling. High prevalence of Campylobacter spp was observed at all the stages ranging between 84% and 100%. L. monocytogenes was not detected in chicken carcasses after defeathering. However, it was detected after evisceration and after washing and chilling. The most critical stage for L. monocytogenes contamination was the portioning operation, the prevalence in breast and legs being 88% and 84%, respectively.     

The generalized discrete ‐centroid problem

The ‐centroid problem or leader–follower problem is generalized considering different customer choice rules where a customer may use facilities belonging to different firms, if the difference in travel distance (or time) is small enough. Assuming essential goods, some particular customer choice rules are analyzed. Linear programming formulations for the generalized ‐medianoid and ‐centroid problems are presented and an exact solution approach is applied. Some computational examples are included.     

Skeletal Muscle Health and Cognitive Function: A Narrative Review

Sarcopenia is the loss of skeletal muscle mass and function with advancing age. It involves both complex genetic and modifiable risk factors, such as lack of exercise, malnutrition and reduced neurological drive. Cognitive decline refers to diminished or impaired mental and/or intellectual functioning. Contracting skeletal muscle is a major source of neurotrophic factors, including brain-derived neurotrophic factor, which regulate synapses in the brain. Furthermore, skeletal muscle activity has important immune and redox effects that modify brain function and reduce muscle catabolism. The identification of common risk factors and underlying mechanisms for sarcopenia and cognition may allow the development of targeted interventions that slow or reverse sarcopenia and also certain forms of cognitive decline. However, the links between cognition and skeletal muscle have not been elucidated fully. This review provides a critical appraisal of the literature on the relationship between skeletal muscle health and cognition. The literature suggests that sarcopenia and cognitive decline share pathophysiological pathways. Ageing plays a role in both skeletal muscle deterioration and cognitive decline. Furthermore, lifestyle risk factors, such as physical inactivity, poor diet and smoking, are common to both disorders, so their potential role in the muscle–brain relationship warrants investigation.     

Assessing students' conceptual understanding using an online three‐tier diagnostic test

When solving a mathematical problem, students who do not have sufficient conceptual understanding may perform poorly and exhibit misconceptions. This study was aimed to examine students' conceptual understanding and significant misconceptions when solving number sense‐related problems. An online three‐tier diagnostic test was administered to 125 fifth‐grade students with varied socio‐economic backgrounds in Hong Kong. Only 14.40% of the students exhibited high performance with high confidence, indicating that these students had a profound conceptual understanding of number sense. In addition, the majority of the students (66.40%) did not demonstrate number sense; these students exhibited several significant misconceptions and could solve the questions only by using a rule‐based method or guessing. Accordingly, most students performed unsatisfactorily on number sense‐related problems. This study is imperative in identifying early predictors and provides information for further compatible interventions in the teaching and learning of number sense in Hong Kong in particular and worldwide in general.     

2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.     

Controlled Secure Direct Communication Protocol via the Three-Qubit Partially Entangled Set of States

In this paper, we first re-examine the previous protocol of controlled quantum secure direct communication of Zhang et al.’s scheme, which was found insecure under two kinds of attacks, fake entangled particles attack and disentanglement attack. Then, by changing the party of the preparation of cluster states and using unitary operations, we present an improved protocol which can avoid these two kinds of attacks. Moreover, the protocol is proposed using the three-qubit partially entangled set of states. It is more efficient by only using three particles rather than four or even more to transmit one bit secret information. Given our using state is much easier to prepare for multiqubit states and our protocol needs less measurement resource, it makes this protocol more convenient from an applied point of view.     

Biocatalytic Alkylation Cascades: Recent Advances and Future Opportunities for Late-Stage Functionalization

This Concept article describes the latest developments in the emerging area of late-stage biocatalytic alkylation. Central to these developments is the ability to efficiently prepare S-adenosyl methionine (SAM) cofactor analogues and couple this with enzymatic alkyl transfer. Recent developments in the enzymatic synthesis of SAM cofactor analogues are summarized first, followed by their application as alkyl transfer agents catalyzed by methyltransferases (MTases). Second, innovative methods to regenerate SAM cofactors by enzymatic cascades is reported. Finally, future opportunities towards establishing a generalized platform for late-stage alkylation are described.