MaRS

In the original publication [...].

ABSTRACT Protein-DNA interactions can be manipulated in vitro by changing buffer conditions. Here, we develop a methodology to map the cleavage preferences of chimeric gene editors that are fusions of the I-TevI nuclease domain to CRIPSR nucleases by manipulating in vitro salt concentrations. We found that DNA cleavage by the I-TevI (Tev) nuclease domain at CNNNG sites was de-coupled from the gRNA-targeted site in low salt buffers. For TevCas12a, this non-targeted cleavage activity was enriched at Tev CNNNG cleavage motifs optimally positioned within a 30-bp window upstream of a Cas12a TTTV PAM site. Non-targeted cleavage did not require Cas12a nuclease activity or specific Cas12a gRNA targeting. Similar non-targeted products were observed in low salt buffer conditions for TevSaCas9, Tev-meganuclease and Tev-zinc finger editors. Cas12a and SaCas9 activity at gRNA-directed sites and sites with multiple mismatches were also sensitive to buffer salt concentration. Oxford Nanopore sequencing revealed a remarkably similar Tev CNNNG cleavage preference at different salt concentrations and in different fusion contexts, emphasizing the robustness and specificity of Tev activity. More generally, our work highlights the sensitivity of gene editors to in vitro reaction conditions and how these conditions can be leveraged to functionally dissect the activity of individual domains of chimeric gene editors.

Plastic pollution in the world’s oceans threatens ecosystems and biodiversity. The connected nature of the marine environment suggests that coordinated actions by countries sharing an ocean border may provide more effective pollution control than unilateral actions by any one country. However, countries often fail to cooperate, even when joint economic benefits would be higher under cooperation. Here we present a modelling framework to determine the potential economic benefits of cooperative marine plastic pollution management. The framework integrates an estimated plastic transfer matrix from a particle tracking model with game theory to derive the economic benefits of international cooperation for 16 countries bordering the North Atlantic Ocean. Subject to modelling uncertainties, a fully cooperative agreement yields aggregate annual net benefits of around $36 billion and a 64% reduction in emissions. The net benefits of cooperation persist over alternative scenarios and considering the impact of uncertainties but vary in magnitude and distribution.

This study aims to identify and categorize nonmedical barriers encountered by recipients, donors, and health care providers in the context of living donor liver transplantation (LDLT). Liver transplantation is vital for individuals with liver failure, yet high mortality rates on the transplant waitlist persist. LDLT was introduced to address deceased donor organ shortages; however, its adoption varies widely across regions, prompting the need to explore barriers hindering its implementation. The scoping review employed inclusion and exclusion criteria to identify studies focusing on nonmedical barriers to LDLT in both adult and pediatric populations. Qualitative, quantitative, and mixed-method studies were considered, covering the period from January 2005 to February 2023. The review's search strategy was conducted in the Ovid MEDLINE and Ovid EMBASE databases. Studies meeting the criteria were assessed for their characteristics and findings, which were synthesized into recipient, donor, and provider-level barriers. Among 2394 initially screened articles, 17 studies were eligible for inclusion. Recipient-level barriers encompassed systemic disparities in access, limited social support, immigration status, and inadequate awareness of LDLT. Donor-level barriers involved surgery-related risks, recovery time concerns, financial burdens, and religious beliefs. Provider-level barriers highlighted institutional support inadequacies and specialized surgeon shortages. The scoping review underscores nonmedical barriers to LDLT across recipient, donor, and provider levels. These barriers include socioeconomic disparities, information gaps, and inadequate institutional support. The findings underscore the need for comprehensive national efforts to raise awareness about LDLT and provide essential financial support.

Ce rapport présente une recension des travaux récents sur l’incidence fiscale de l’imposition des entreprises. Après une discussion des effets théoriques d’une hausse de la taxation des entreprises sur les actionnaires, les travailleurs et les consommateurs, les études empiriques sur le sujet sont discutées suivant quatre dimensions : (i) l’incidence de l’imposition des revenus des sociétés (en ce compris les dividendes), (ii) l’incidence de la taxation de la masse salariale, (iii) l’évitement de la taxation par les choix de localisation des unités de production, (iv) l’évitement de la taxation par les choix de localisation des profits d’un point de vue comptable. L’analyse permet de tirer 9 enseignements utiles pour penser la mise en place des politiques fiscales et leurs implications.

Examine the factors that promote vaccine hesitancy or acceptance during pandemics, major epidemics and global outbreaks. A systematic review and thematic analysis of 28 studies on the Influenza A/H1N1 pandemic and the global spread of Ebola Virus Disease. We found seven major factors that promote vaccine hesitancy or acceptance: demographic factors influencing vaccination (ethnicity, age, sex, pregnancy, education, and employment), accessibility and cost, personal responsibility and risk perceptions, precautionary measures taken based on the decision to vaccinate, trust in health authorities and vaccines, the safety and efficacy of a new vaccine, and lack of information or vaccine misinformation. An understanding of participant experiences and perspectives toward vaccines from previous pandemics will greatly inform the development of strategies to address the present situation with the COVID-19 pandemic. We discuss the impact vaccine hesitancy might have for the introduction and effectiveness of a potential COVID-19 vaccine. In particular, we believe that skepticism toward vaccines can still exist when there are no vaccines available, which is contrary to contemporary conceptualizations of vaccine hesitancy. We recommend conducting further research assessing the relationship between the accessibility and cost of vaccines, and vaccine hesitancy.