Oligonucleotide delivery with cell surface binding and cell penetrating peptide amphiphile nanospheres

Cataloged from PDF version of article.A drug delivery system designed specifically for oligonucleotide therapeutics can ameliorate the problems associated with the in vivo delivery of these molecules. The internalization of free oligonudeotides is challenging, and cytotoxicity is the main obstacle for current transfection vehicles. To develop nontoxic delivery vehicles for efficient transfection of oligonudeotides, we designed a self-assembling peptide amphiphile (PA) nanosphere delivery system decorated with cell penetrating peptides (CPPs) containing multiple arginine residues (R-4 and R-8), and a cell surface binding peptide (KRSR), and report the efficiency of this system in delivering G-3129, a Bcl-2 antisense oligonucleotide (AON). PA/AON (peptide amphiphile/antisense oligonucleotide) complexes were characterized with regards to their size and secondary structure, and their cellular internalization efficiencies were evaluated. The effect of the number of arginine residues on the cellular internalization was investigated by both flow cytometry and confocal imaging, and the results revealed that uptake efficiency improved as the number of arginines in the sequence increased. The combined effect of cell penetration and surface binding property on the cellular internalization and its uptake mechanism was also evaluated by mixing R-8-PA and KRSR-PA. R-8 and R-8/KRSR decorated PAs were found to drastically increase the internalization of AONs compared to nonbioactive PA control. Overall, the KRSR-decorated self-assembled PA nanospheres were demonstrated to be noncytotoxic delivery vectors with high transfection rates and may serve as a promising delivery system for AONs

Noncovalent funstionalization of mesoporous silica nanoparticles with amphiphilic peptides

Cataloged from PDF version of article.The surface of mesoporous silica nanoparticles (MSNs) has been modified for enhancing their cellular uptake, cell targeting, bioimaging, and controlled drug release. For this purpose, covalent anchorage on the silica surface was predominantly exploited with a wide range of bioactive molecules. Here, we describe a facile self-assembly method to prepare a hybrid peptide silica system composed of octyl-modified mesoporous silica nanoparticles (MSNs) and peptide amphiphiles (PAs). The hydrophobic organosilane surface of mesoporous silica was coated with amphiphilic peptide molecules. The peptide functionalized particles exhibited good cyto-compatibility with vascular smooth muscle and vascular endothelial cells. The peptide coating also improved the cellular uptake of particles up to 6.3 fold, which is promising for the development of highly efficient MSN based theranostic agents. © 2014 the Partner Organisations

Navigating ‘taxation’ on the Congo River: the interplay of legitimation and ‘officialisation’

Based on comprehensive research among boat operators and navy personnel working on the Congo River (DRC), this article explores how assessments of ‘taxation’ are shaped by the interplay of legitimation and ‘officialisation’. As such, it draws upon and contributes to scholarly debates on taxpayers’ attitudes towards taxation. While boat operators resent having to pay a plethora of authorities, including the navy, along the Congo River, the article demonstrates how they locate these ‘taxes’ on a spectrum from more to less legitimate. These assessments are shaped by various factors: authorities’ legitimacy as ‘measured’ by their official mandate and importance; public and non-official service provision; and the deployment of symbols of ‘stateness’. In interaction, these factors legitimise and ‘officialise’ ‘taxes’ by the navy that are prohibited in legislation. These findings caution against the a priori use of the labels ‘official’ and ‘non-official’, emphasising the need to better grasp these notions’ emic understandings

Norms, Networks, Power, and Control: Understanding Informal Payments and Brokerage in Cross-Border Trade in Sierra Leone

Recent research has cast light on the variety of informal payments and practices that govern the day-to-day interactions between traders and customs agents at border posts in low-income countries. Building on this literature, this paper draws on survey and qualitative evidence in an effort to explore which groups are most advantaged and disadvantaged by the largely informal processes and norms governing cross-border trade. We find that understanding variation in strategies and outcomes across traders can only be effectively understood with reference to the importance of norms, networks, power, and the logic of control.Department for International DevelopmentBill and Melinda Gates Foundatio

Integrating institutional and behavioural measures of bribery

Bribery involves individuals exchanging material benefits for a service of a public institution. To understand the process of bribery we need to integrate measures of individual behaviour and institutional attributes rather than rely exclusively on surveys of individual perceptions and experience or macro-level corruption indexes national institutions. This paper integrates institutional and behavioural measures to show that where you live and who you are have independent influence on whether a person pays a bribe. The analysis of 76 nationwide Global Corruption Barometer surveys from six continents provides a date set in which both institutional and individual differences vary greatly. Multi-level multivariate logit analysis is used to test hypotheses about the influence of institutional context and individual contact with public services, socio-economic inequalities and roles, and conflicting behavioural and ethical norms. It finds that path-determined histories of early bureaucratization or colonialism have a major impact after controlling for individual differences. At the individual level, people who frequently make use of public services and perceive government as corrupt are more likely to pay bribes, while socio-economic inequality has no significant influence. While institutional history cannot be changed, changing the design of public services offers is something that contemporary governors could do to reduce the vulnerability of their citizens to bribery

Determinants of Refusal of A/H1N1 Pandemic Vaccination in a High Risk Population: A Qualitative Approach

International audienceBackground: Our study analyses the main determinants of refusal or acceptance of the 2009 A/H1N1 vaccine in patients with cystic fibrosis, a high-risk population for severe flu infection, usually very compliant for seasonal flu vaccine.Methodology/Principal Findings: We conducted a qualitative study based on semi-structured interviews in 3 cystic fibrosis referral centres in Paris, France. The study included 42 patients with cystic fibrosis: 24 who refused the vaccine and 18 who were vaccinated. The two groups differed quite substantially in their perceptions of vaccine- and disease-related risks. Those who refused the vaccine were motivated mainly by the fears it aroused and did not explicitly consider the 2009 A/H1N1 flu a potentially severe disease. People who were vaccinated explained their choice, first and foremost, as intended to prevent the flu’s potential consequences on respiratory cystic fibrosis disease. Moreover, they considered vaccination to be an indirect collective prevention tool. Patients who refused the vaccine mentioned multiple, contradictory information sources and did not appear to consider the recommendation of their local health care provider as predominant. On the contrary, those who were vaccinated stated that they had based their decision solely on the clear and unequivocal advice of their health care provider.Conclusions/Significance: These results of our survey led us to formulate three main recommendations for improving adhesion to new pandemic vaccines. (1) it appears necessary to reinforce patient education about the disease and its specific risks, but also general population information about community immunity. (2) it is essential to disseminate a clear and effective message about the safety of novel vaccines. (3) this message should be conveyed by local health care providers, who should be involved in implementing immunization

Action to protect the independence and integrity of global health research

Storeng KT, Abimbola S, Balabanova D, et al. Action to protect the independence and integrity of global health research. BMJ GLOBAL HEALTH. 2019;4(3): e001746