![]() To date, the antibiotic market remains stocked with classical antibacterial drugs with slight chemical variations on existing antibiotic classes. 5 With limited revenues from antibiotic investment, many big pharmaceutical firms have redirected their antimicrobial research programs to more profitable fields such as anticancer drugs. 4 A recent economic model for evaluating the global cost of a newly developed active antibiotic with FDA approval was estimated at US$1.58 billion, excluding the marketing and surveillance after approval. ![]() 3 The ongoing COVID-19 pandemic is further constricting the pipeline of antimicrobials to handle bacterial infections and highlights the critical need for novel treatments by antibacterial agents. 1,2 The O'Neill report estimates deaths caused by AMR will exceed 10 million by 2050. Introduction Since the discovery of penicillin and subsequent antibiotics, the increasing global consumption of such wonder drugs has played a critical role in driving antimicrobial resistance (AMR) at an alarming rate in the last two decades as assessed by the World Health Organization (WHO). These findings highlight the advantages of use of such bifunctional tethers to produce first-in-class, potent PrAMP dimers against MDR/XDR bacterial infections. Molecular dynamics simulations of adsorption and permeation mechanisms of the PrAMP on a mixed lipid membrane bilayer showed that a rigid, planar tethered dimer orientation, together with the presence of fluorine atoms that provide increased bacterial membrane interaction, is critical for enhanced dimer activity. Additionally, 6 and 7 possess potent immunomodulatory activity and neutralise inflammation via nitric oxide production in macrophages. Mode of action studies indicated these lead PrAMPs can interact with both outer and inner bacterial membranes to affect the membrane potential and stress response. Greatest advantage was conferred using perfluoroaromatic linkers (tetrafluorobenzene and octofluorobiphenyl) with the resulting dimeric peptides 6 and 7 exhibiting potent action against Gram-negative bacteria, especially the World Health Organization's critical priority-listed multidrug-resistant (MDR)/extensively drug-resistant (XDR) Acinetobacter baumannii as well as preformed biofilms. ![]() Antibacterial assays confirmed that dimerization per se significantly enhances Chex1-Arg20 hydrazide action. Our current studies examined dimerization of the de novo designed proline-rich AMP (PrAMP), Chex1-Arg20 hydrazide, via C-terminal thiol addition to a series of bifunctional benzene or phenyl tethers to determine the effect of orientation of the peptides and linker length on antimicrobial activity. They are attractive lead molecules for rational development to improve their therapeutic index. The findings of the study indicate that the Arabic subtitles produced by the satellite Arabic TV channel reflect a higher level of politeness where euphemism, as a politeness strategy, was clearly applied by the subtitler to avoid rude and embarrassing terms.Antimicrobial peptides (AMPs) are host defense peptides, and unlike conventional antibiotics, they possess potent broad spectrum activities and, induce little or no antimicrobial resistance. The study draws on the euphemistic strategies suggested by Williams (1975) and Warren (1992) and further developed by Al-Adwan (2015) to analyze the Arabic subtitles produced by each media outlet. The first translation was produced by the Arabic TV channel MBC4 and the second by the subscription-based video streaming service Netflix. ![]() ![]() To achieve this goal, the study compares two different Arabic subtitles of the taboo terms used in the American sitcom How I Met Your Mother. The assumption the study makes is that Arabic satellite TV channels, unlike video streaming services, receive interference from religious, political, and social authorities to maintain a “clean” content and censored language of the shows they air. The study sets out to examine if different subtitling policy is adopted in each media outlet to deal with taboo words based on the social and religious limitations expected to be found in the Arab society. This paper explores the different sets of strategies applied by two different media outlets in subtitling taboo terms from English into Arabic. ![]()
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