Uncoupling Protein 1 Does Not Produce Heat without Activation

Mitochondrial uncoupling protein 1 (UCP1) is the crucial mechanistic component of heat production in classical brown fat and the newly identified beige or brite fat. Thermogenesis inevitably comes at a high energetic cost and brown fat, ultimately, is an energy-wasting organ. A constrained strategy that minimizes brown fat activity unless obligate will have been favored during natural selection to safeguard metabolic thriftiness. Accordingly, UCP1 is constitutively inhibited and is inherently not leaky without activation. It follows that increasing brown adipocyte number or UCP1 abundance genetically or pharmacologically does not lead to an automatic increase in thermogenesis or subsequent metabolic consequences in the absence of a plausible route of concomitant activation. Despite its apparent obviousness, this tenet is frequently ignored. Consequently, incorrect conclusions are often drawn from increased BAT or brite/beige depot mass, e.g., predicting or causally linking beneficial metabolic effects. Here, we highlight the inherently inactive nature of UCP1, with a particular emphasis on the molecular brakes and releases of UCP1 activation under physiological conditions. These controls of UCP1 activity represent potential targets of therapeutic interventions to unlock constraints and efficiently harness the energy-expending potential of brown fat to prevent and treat obesity and associated metabolic disorders.     

Cost-benefit analysis for disruption prevention in low-volume assembly

Manufacturing companies face rising pressure due to increased competition. Traditionally, companies have merely concentrated on offering impeccable, cost-efficient products. Today, however, flexibility and on-time delivery are additional requirements to satisfy the customers. At the same time, disruptions in production, especially in low-volume assembly, still frequently occur, leading to economic losses and delayed customer deliveries. The approach proposed in this paper strives for improving the disruption situation in low-volume assemblies. A detailed disruption management methodology has been developed, aiming at realizing an efficient reduction of disruptions, while at the same time considering the specific characteristics of low-volume assembly. The methodology is supported by a catalog of pre-emptive measures. These measures are known to reduce the disruptions’ occurrence or to diminish their consequences. In general, the approach pursues the basic idea to implement particularly those measures, which have the best cost-benefit-ratio. Based on the analysis of the cost-benefit-ratio of each measure, the developed methodology aims at improving the disruption situation in assembly and thus providing a high on-time delivery rate. The usability of the methodology for the low-volume assembly context has been confirmed by assembly experts on the basis of an application of the methodology in an exemplary case study.     

Chemoenzymatic Total Synthesis of Sorbicatechol Structural Analogues and Evaluation of Their Antiviral Potential

Sorbicillinoids are fungal polyketides characterized by highly complex and diverse molecular structures, with considerable stereochemical intricacy combined with a high degree of oxygenation. Many sorbicillinoids possess promising biological activities. An interesting member of this natural product family is sorbicatechol A, which is reported to have antiviral activity, particularly against influenza A virus (H1N1). Through a straightforward, one-pot chemoenzymatic approach with recently developed oxidoreductase SorbC, the characteristic bicyclo[2.2.2]octane core of sorbicatechol is structurally diversified by variation of its natural 2-methoxyphenol substituent. This facilitates the preparation of a focused library of structural analogues bearing substituted aromatic systems, alkanes, heterocycles, and ethers. Fast access to this structural diversity provides an opportunity to explore the antiviral potential of the sorbicatechol family.     

N-methyl-2-hydroxyethylammonium oleate ionic liquid performance as corrosion inhibitor for mild steel in hydrochloric acid medium

The aim of the present study is to evaluate the performance of N-methyl-2-hydroxyethylammonium oleate ([m-2HEA][Ol]) as a corrosion inhibitor for mild steel in a 0.1-mol/L hydrochloric acid solution and also investigate the role of chloride in the inhibition mechanism. This protic ionic liquid (PIL) has formerly shown a high efficiency as a corrosion inhibitor in a neutral chloride medium. Electrochemical and weight loss measurements, surface contact angle determination, scanning electron microscopy, and Raman spectroscopy were used to understand the factors that influence the response of the studied inhibitor. Results revealed that [m-2HEA][Ol] behaves as a mixed-type adsorption inhibitor, by blocking cathodic sites and by modifying the activation energy of the anodic reaction, and it can reach up to 94–97% of inhibition efficiency. PIL adsorption was enhanced by the excess of positive charge of the mild steel. The effect of inhibitor molecule has been discussed to propose a mechanism that explains the inhibitory action of the corrosion inhibitor, pointing out the role of chloride in the inhibition mechanism.     

Purification and characterization of an endopeptidase from Lactobacillus delbrueckii subsp. bulgaricus B14

An intracellular endopeptidase was purified from cell-free extracts of Lactobacillus delbrueckii subsp. bulgaricus B14 by anion exchange chromatography on DEAE-Sepharose, hydroxyapatite chromatography, second anion exchange chromatography on Mono-Q, and metal-chelating affinity chromatography. The endopeptidase was a monomer with a molecular mass of approximately 70 kDa determined by SDS-PAGE and gel filtration. Various oligopeptides (e.g. Met-enkephalin, bradykinin) were hydrolysed by the endopeptidase. Exopeptidase activity and cleavage of dipeptides or tripeptides was not observed. The K_M value for the cleavage of Metenkephalin was 1.2 mM. Temperature and pH optima were 47 °C and pH 7.7, respectively. The endopeptidase was inhibited by the classical agents for metal-dependent (EDTA) and serine (DFP) enzymes. Activity was increased by Co²⁺ and Mg²⁺, no effect was observed with Ca²⁺. After inhibition with EDTA, enzyme activity could be restored fully by Co²⁺. Activity was inhibited by Zn²⁺, Mn²⁺, Fe²⁺, Cu²⁺, Cd²⁺ and Hg²⁺. The N-terminal sequence of the endopeptidase was determined as: H₂N-Val-Arg-Gly-Gly-Ser-Gly-Asp-Thr-Thr-Val-0H.     

Quantifying unfrozen water in frozen soil by high-field 2H NMR

To understand wintertime controls of biogeochemical processes in high latitude soils it is essential to distinguish between direct temperature effects and the effects of changes in water availability mediated by freezing. Efforts to separate these controls are hampered by a lack of adequate methods to determine the proportion of unfrozen water. In this study we present a high-field 2H2O NMR method for quantifying unfrozen water content in frozen soil. The experimental material consisted of the humic layer of a boreal spruce forest soil mixed with varying proportions of quartz sand and humidified with deuterium-enriched water. The relative standard deviation of unfrozen water content (measured as NMR signal integral) was less than 2% for repeated measurements on a given sample and 3.5% among all samples, based on a total of 16 measurements. As compared to 1H NMR, this 2H NMR method was found to be superior for several reasons: it is less sensitive to field inhomogeneity and paramagnetic impurities, it gives a bigger line shape difference between the ice and liquid signal, it shows a sharper response to water fusion, and it excludes the possibility of hydrogen in the organic material interfering with the measurement.     

Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

Glycerolysis of Fatty Acid Methyl Esters: 1. Investigations in a Batch Reactor

The present work focused on the glycerolysis of fatty acid methyl esters. The aim was to develop and test a kinetic model that could be used to reliably simulate different process alternatives for this reaction. A prerequisite was the identification and characterization of the factors that affect the reaction kinetics. Experiments were carried out in a batch reactor with and without forced removal of methanol, which is one of the reaction products. Concentrations of all components in the two-phase system were measured. It was found that the methanol concentration has a strong effect on the reaction rate and equilibrium conversion. Near-complete conversions were obtained by stripping methanol with an inert gas. The glycerol concentration in the ester phase was found to increase as the reaction proceeds, which also accelerates the reaction. Effects of mass transfer on the reaction rate were not found to control the reaction rate under well-agitated conditions. A semi-empirical model was used to simulate the reaction. The results from the semi-empirical model show good agreement with experimental results.