The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.     

Epinephrine doses delivered from auto-injectors stored at excessively high temperatures

Context: Prompt injection of epinephrine (adrenaline) from epinephrine auto-injectors (EAIs) is the primary treatment for anaphylaxis in out-of-hospital settings. Storage of EAIs at room temperature (25?°C) is advised; however, storage at excessively high temperatures sometimes occurs. To our knowledge, there are no previous publications on the doses of epinephrine ejected from EAIs after storage at such temperatures.

Objective: We examined the epinephrine doses delivered from activated EAIs stored constantly or cyclically at 70?°C.

Methods: Twenty-five in-date EAIs were stored constantly or cyclically at 70?°C (excessive heat) or 25?°C (controls) for 5?d or 10?d. EAIs were activated and the epinephrine doses in the ejected solutions were measured using HPLC-UV. The enantiomeric purity of epinephrine was also measured by HPLC-UV.

Results: Control EAIs ejected a volume of 0.300?±?0.006?mL containing 103.7?±?3.3% of labeled dose (LD). After 5?d or 10?d of constant storage at 70?°C and activation at 70?°C, EAIs ejected a volume of 0.367?±?0.008?mL containing 96.8?±?3.8% LD and 0.373?±?0.007?mL containing 77.7?±?3.3% LD, respectively. After 5?d of cyclic storage at 70?°C and cooling to 25?°C before activation, EAIs ejected a volume of 0.311?±?0.008?mL containing 87.2?±?1.9% LD. Under the experimental conditions of this study, the resultant chromatographic peaks of epinephrine solutions from all EAIs represented only the pure l-enantiomer of epinephrine.

Conclusion: EAIs should be stored under recommended conditions of the manufacturer. EAIs stored at excessively high temperatures cannot be used to treat humans while still hot, and when cooled, cannot be relied on to deliver the labeled epinephrine dose in anaphylaxis.     

Stereoisomers composition of 4-[(1′-methylpropyl)-oxycarbonyl]-2-oxetanone and related compounds,as precursors of fuctional polyesters,determined by chiral gas chromatography

Summary The configurational analysis of racemic and optically active stereoisomers of 4-[(1-methylpropyl)oxycarbonyl]-2-oxetanone has been carried out by using chiral gas chromatography. This technique has been successful in the stereoisomers composition determination of these -substituted -lactones prepared by two different routes and used as monomers in the preparation of malic acid stereocopolymers. Result are in good agreement with those obtained from high resolution ¹H NMR, in the presence of an Europium salt, as chiral shift reagent. This method has been extended to 3-methyl-4-[(1,2,2-trimethyl propyl)oxycarbonyl]-2-oxetanone. The exact knowledge of precursors configurational structure is very important in regard to the obtention of the corresponding polystereoisomers with a strictly controlled enantiomeric or diastereoisomeric composition and consequently with predictable properties.     

Combining a new data classification technique and regression analysis to predict the Cost-To-Serve new customers

Identifying the Cost-To-Serve (CTS) of customers is one of the most challenging problems in Supply Chain Management because of the diversity in their business activities. For the particular case of the industrial gas business, we are interested in predicting the cost to deliver bulk (liquefied) gas to new customers using a multifactor linear regression model. Developing a single model, i.e. analyzing the observations all at once, produces poor prediction results. Therefore prior to the regression analysis, a new supervised learning technique is used to group customers who are similar in some sense. Classes of customers are represented by hyper-boxes and a linear regression model is subsequently built within each class. The combination of data classification and regression is proven to increase the accuracy of the prediction.Two Mixed-Integer-Linear Programming (MILP) models are developed for data classification purposes. Although we are dealing with a supervised learning method, classes are not predefined in our case. Rather, we input a continuous “classification” attribute that is optimally discretized by the MILP’s in order to minimize the number of misclassifications. Therefore our data classification model offers a broader range of applications. A number of illustrative examples are used to prove the effectiveness of the proposed approach.     

Deforestation and foreign transfers: a Stackelberg differential game approach

In this paper, our concern is with deforestation as a global environmental issue. Foreign transfers from developed or Northern countries to developing or Southern countries have been proposed to deal with that issue. We use a Stackelberg differential game approach where the two players are: a donor community (the leader) and a recipient country (the follower). We study the impact of different specifications for the transfer function, related to the different information structures the players can consider when playing the Stackelberg game. The different scenarios are compared both from the environmental and economic points of view.     

The highest form of art

Abstract

If anyone still believes that Alfred Stieglitz's vaunted Photo-Secession sprang up, full-grown, like Pallas Athena from the forehead of Zeus, armed and ready to do battle for the recognition of photography as a fine art, much recent scholarship considerably revises that flattering view. The predecessors of the American Photo-Secession were strongly developed European societies and movements, among them the earnestly aesthetic Linked Ring Brotherhood, founded in May 1892 by a talented group of English pictorialists which included A. Horsky Hinton, George Davison, H. H. H. Cameron, and—rather unexpectedly—the manipulator of tableaux, Henry Peach Robinson.     

The Effect of Age and Intrinsic Aerobic Exercise Capacity on the Expression of Inflammation and Remodeling Markers in Rat Achilles Tendons

Old age, adiposity, and metabolic disorders are known as risk factors for chronic tendinopathy, which is a common problem in both athletes and the general population. However, the importance of these influencing factors has not yet been well understood. This study investigated alterations in gene expression and histology of Achilles tendons of young (10 weeks) and old (100 weeks) rats bred for low (low capacity runners, LCR) and high (high capacity runners, HCR) intrinsic aerobic exercise capacity. In this rat model, LCR displayed a phenotype of reduced exercise capacity, higher body weight, and metabolic dysfunctions compared to HCR. We hypothesized that the risk factors for tendinopathy in old LCR could lead to more pronounced impairments in Achilles tendon tissue. In quantitative real-time PCR (qPCR), age-related downregulation of tenocyte markers e.g., tenomodulin, genes related to matrix modeling and remodeling (e.g., collagens, elastin, biglycan, fibronectin, tenascin C) as well as transforming growth factor beta 3 (Tgfb3) have been detected. Inflammation marker cyclooxygenase 2 (Cox2) was downregulated in old rats, while microsomal prostaglandin E synthase 2 (Ptges2) was upregulated in old HCR and old LCR. In all groups, interleukin 6 (Il6), interleukin 1 beta (Il1b), and tumor necrosis factor alpha (Tnfa) showed no significant alteration. In histological evaluation, tendons of old rats had fewer and more elongated tenocyte nuclei than young rats. Even though a higher content of glycosaminoglycans, a sign of degeneration, was found in old HCR and LCR, no further signs of tendinopathy were detectable in tendons of old rats by histological evaluation. Low intrinsic aerobic exercise capacity and the associated phenotype did not show significant effects on gene expression and tendon histology. These findings indicate that aging seems to play a prominent role in molecular and structural alterations of Achilles tendon tissue and suggests that other risk factors associated with intrinsic aerobic exercise capacity are less influential in this rat model.     

Evaluation and comparison of five matrix excipients for the controlled release of acrivastine and pseudoephedrine

For treatment of allergic rhinitis, acrivastine with pseudoephedrine in Semprex®-D conventional capsules requires dosing every 6-8 hours. This study was designed to develop a controlled release matrix tablet of acrivastine and pseudoephedrine and evaluate 5 different matrix excipients for their in vitro controlled-release profiles. Compritol® 888ATO, Eudragit® RS, Methocel® K100M, Polyox® WSR301 and Precirol® ATO5 were used alone or in varying combinations for the formulation of controlled release matrix tablets. In vitro drug dissolution and mathematical modeling were used to characterize drug release rate and extent. All tablet formulations yielded quality matrix preparations with satisfactory tableting properties. Due to the aqueous solubility of pseudoephedrine and the size of the dose, none of the matrix excipients used alone prolonged drug release significantly to meet the desired twice-daily administration frequency. The use of two excipients in combination, however, significantly decreased the dissolution rate of both active ingredients. A combined lipid-based Compritol® and hydrophilic Methocel® produced optimal controlled drug release for longer than 8 hours for both acrivastine and pseudoephedrine.     

A New Sidelobe Correction Algorithm for Microwave Radiometers: Application to the Envisat Instrument

The antenna temperature measured by a microwave radiometer is converted in brightness temperature (TB) by removing the different contributions that do not come from the main lobe of the antenna. Among them, the Earth contribution in the sidelobes may be significant as for the Environmental Satellite mission due to the antenna position on the platform. In such a case, simple corrections commonly applied on previous altimetry missions are inadequate, and a more accurate correction should be determined. We propose in this paper a new method based on global seasonal tables of contamination. This allows application of an accurate sidelobe correction in space and time in the retrieved TB computation