Site-Specific PEGylation of Therapeutic Proteins

The use of proteins as therapeutics has a long history and is becoming ever more common in modern medicine. While the number of protein-based drugs is growing every year, significant problems still remain with their use. Among these problems are rapid degradation and excretion from patients, thus requiring frequent dosing, which in turn increases the chances for an immunological response as well as increasing the cost of therapy. One of the main strategies to alleviate these problems is to link a polyethylene glycol (PEG) group to the protein of interest. This process, called PEGylation, has grown dramatically in recent years resulting in several approved drugs. Installing a single PEG chain at a defined site in a protein is challenging. Recently, there is has been considerable research into various methods for the site-specific PEGylation of proteins. This review seeks to summarize that work and provide background and context for how site-specific PEGylation is performed. After introducing the topic of site-specific PEGylation, recent developments using chemical methods are described. That is followed by a more extensive discussion of bioorthogonal reactions and enzymatic labeling.     

Experimental investigation of unconfined spherical and cylindrical flame propagation in hydrogen-air mixtures

This paper presents results of experimental investigations on spherical and cylindrical flame propagation in pre-mixed H₂/air-mixtures in unconfined and semi-confined geometries. The experiments were performed in a facility consisting of two transparent solid walls with 1 m² area and four weak side walls made from thin plastic film. The gap size between the solid walls was varied stepwise from thin layer geometry (6 mm) to cube geometry (1 m). A wide range of H₂/air-mixtures with volumetric hydrogen concentrations from 10% to 45% H₂ was ignited between the transparent solid walls. The propagating flame front and its structure was observed with a large scale high speed shadow system. Results of spherical and cylindrical flame propagation up to a radius of 0.5 m were analyzed. The presented spherical burning velocity model is used to discuss the self-acceleration phenomena in unconfined and unobstructed pre-mixed H₂/air flames.     

Escherichia coli,Salmonella spp., and Staphylococcus aureus susceptibility to antimicrobials of human and veterinary importance in poultry sector of India

In India, little attention has been paid on antimicrobial resistance (AMR) in the context of developing “One Health” approach. Hence, utilizing multi-disciplinary approach, we assess the AMR level and dynamics/pattern of multi-drug resistance (MDR) in Escherichia coli, Salmonella spp., and Staphylococcus aureus circulating over the different stages of poultry in India. A total of 342 isolates including E. coli (n = 143), Salmonella spp. (n = 104), and S. aureus (n = 95) were recovered from fecal (n = 80) and cecal (n = 80) samples of chicken, collected across the different poultry-retail shops and poultry-farms located at urban and rural areas of Rajasthan, India, respectively. High rates of AMR to drugs that are critically/highly important both in human and veterinary medicine were observed among all the isolates. Upward trends in AMR prevalence was observed in poultry-retail shops than in poultry-farms. Notably, >90% of all the isolates were MDR, of particular, pattern/prevalence of MDR was substantially varied across the poultry-farms vs. poultry-retail shops. Our results indicate AMR including MDR to be common in E. coli, Salmonella spp., and S. aureus distributed frequently in poultry. The study encourages the formulation of national policy, programmes and further research with a “One Health” approach that can benefits to the human/animal and the environment.