Temporin L and aurein 2.5 have identical conformations but subtly distinct membrane and antibacterial activities

Frogs such as Rana temporaria and Litoria aurea secrete numerous closely related antimicrobial peptides (AMPs) as an effective chemical dermal defence. Damage or penetration of the bacterial plasma membrane is considered essential for AMP activity and such properties are commonly ascribed to their ability to form secondary amphipathic, α-helix conformations in membrane mimicking milieu. Nevertheless, despite the high similarity in physical properties and preference for adopting such conformations, the spectrum of activity and potency of AMPs often varies considerably. Hence distinguishing apparently similar AMPs according to their behaviour in, and effects on, model membranes will inform understanding of primary-sequence-specific antimicrobial mechanisms. Here we use a combination of molecular dynamics simulations, circular dichroism and patch-clamp to investigate the basis for differing anti-bacterial activities in representative AMPs from each species; temporin L and aurein 2.5. Despite adopting near identical, α-helix conformations in the steady-state in a variety of membrane models, these two AMPs can be distinguished both in vitro and in silico based on their dynamic interactions with model membranes, notably their differing conformational flexibility at the N-terminus, ability to form higher order aggregates and the characteristics of induced ion conductance. Taken together, these differences provide an explanation of the greater potency and broader antibacterial spectrum of activity of temporin L over aurein 2.5. Consequently, while the secondary amphipathic, α-helix conformation is a key determinant of the ability of a cationic AMP to penetrate and disrupt the bacterial plasma membrane, the exact mechanism, potency and spectrum of activity is determined by precise structural and dynamic contributions from specific residues in each AMP sequence

O fardo holandês: escravidão, África e imigrantes nos livros de história da escola primária na Holanda

Há muito, os holandeses se orgulham de sua identidade de povo tolerante, "terra prometida" para imigrantes perseguidos e generosa com fundos de "desenvolvimento" direcionados a outras nações. Esquivam-se, contudo, do papel que desempenharam historicamente no imperialismo, na escravatura e no genocídio colonialistas e consideram os não brancos, tanto na Holanda quanto fora dela, ingratos para com a ajuda de seu país. Esse artigo sintetiza pesquisas anteriores1 sobre as representações de escravidão, imigração e da África em todos os livros didáticos de história para ensino fundamental na Holanda publicados a partir de 1980, argumentando que estes apresentam metanarrativas eurocêntricas de europeização racial no contexto único da sociedade holandesa. Esses livros perpetuam o esquecimento social, pelos holandeses, da escravidão e do colonialismo científico, justificam intervenções históricas e contemporâneas na África, essencializam e problematizam os imigrantes e suas culturas, destacam a superioridade holandesa e facilitam a ideia de um "fardo holandês", que encontra a Holanda auxiliando, com relutância, minorias dentro e fora de suas fronteiras. Essas descobertas têm implicações importantes para o país e para todas as nações com uma população crescente de imigrantes, pois os discursos e conhecimentos apresentados nos livros didáticos têm afetado gerações sucessivas de estudantes, que formulam políticas locais e nacionais a respeito das minorias, identidades e ideologias raciais

Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients

Background: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied. Methods: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2: 1). Results: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days). Conclusion: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding