The Role of Host Cell Glycans on Virus Infectivity: The SARS-CoV-2 Case.

Glycans are ubiquitously expressed sugars, coating the cell and protein surfaces. They are found on many proteins as either short and branched chains or long chains sticking out from special membrane proteins, known as proteoglycans. This sugar cushion, the glycocalyx, modulates specific interactions and protects the cell. Here it is shown that both the expression of proteoglycans and the glycans expressed on the surface of both the host and virus proteins have a critical role in modulating viral attachment to the cell. A mathematical model using SARS-Cov-2 as an archetypical virus to study the glycan role during infection is proposed. It is shown that this occurs via a tug-of-war of forces. On one side, the multivalent molecular recognition that viral proteins have toward specific host glycans and receptors. On the other side, the glycan steric repulsion that a virus must overcome to approach such specific receptors. By balancing both interactions, viral tropism can be predicted. In other words, the authors can map out the cells susceptible to virus infection in terms of receptors and proteoglycans compositions.

Identification of Novel Molecular Regulators Modulating Ethylene Biosynthesis Using EMS-Based Genetic Screening.

The gaseous hormone ethylene regulates a diverse range of plant development and stress responses. Ethylene biosynthesis is tightly regulated by the transcriptional and posttranscriptional regulation of ethylene biosynthetic enzymes. ACC synthase (ACS) is the rate-limiting enzyme that controls the speed of ethylene biosynthesis in plant tissues, thus serving as a primary target for biotic and abiotic stresses to modulate ethylene production. Despite the critical role of ACS in ethylene biosynthesis, only a few regulatory components regulating ACS stability or ACS transcript levels have been identified and characterized. Here we show a genetic approach for identifying novel regulatory components in ethylene biosynthesis by screening EMS-mutagenized Arabidopsis seeds.

Development of Natural-Based Bone Cement for a Controlled Doxorubicin-Drug Release.

Osteosarcoma (OS) accounts for 60% of all global bone cancer diagnoses. Intravenous administration of Doxorubicin Hydrochloride (DOXO) is the current form of OS treatment, however, systemic delivery has been linked to the onset of DOXO induced cardiomyopathy. Biomaterials including calcium phosphate cements (CPCs) and nanoparticles (NPs) have been tested as localized drug delivery scaffolds for OS cells. However, the tumor microenvironment is critical in cancer progression, with mesenchymal stem cells (MSCs) thought to promote OS metastasis and drug resistance. The extent of MSC assisted survival of OS cells in response to DOXO delivered by CPCs is unknown. In this study, we aimed at investigating the effect of DOXO release from a new formulation of calcium phosphate-based bone cement on the viability of OS cells cocultured with hMSC in vitro. NPs made of PLGA were loaded with DOXO and incorporated in the formulated bone cement to achieve local drug release. The inclusion of PLGA-DOXO NPs into CPCs was also proven to increase the levels of cytotoxicity of U2OS cells in mono- and coculture after 24 and 72 h. Our results demonstrate that a more effective localized DOXO delivery can be achieved via the use of CPCs loaded with PLGA-DOXO NPs compared to CPCs loaded with DOXO, by an observed reduction in metabolic activity of U2OS cells in indirect coculture with hMSCs. The presence of hMSCs offer a degree of DOXO resistance in U2OS cells cultured on PLGA-DOXO NP bone cements. The consideration of the tumor microenvironment via the indirect inclusion of hMSCs in this study can act as a starting point for future direct coculture and in vivo investigations.

How do patients feel about taking part in clinical trials in emergency care?

BACKGROUND: There is little in-depth research into how patients feel about emergency medical trials, and what influences these feelings. OBJECTIVES: To investigate patients' feelings on taking part in emergency medical research, particularly trials conducted without prospective consent. METHODS: Seventeen inpatients, all recently admitted with a medical emergency, were interviewed. Questions focused on feelings on taking part in hypothetical trials, particularly trials conducted with deferred consent. RESULTS: Five main themes were identified. Level of trust in the medical profession-high levels of trust tended to correlate with willingness to participate in trials. Previous bad healthcare experiences tended to diminish trust. Concerns for personal well-being-patients identified a conflict between aversion to unknown side effects and desire for access to newer and potentially better treatments. Some would be less inclined to participate in research if they were severely unwell, some more so. Altruism-many cited the importance of helping to advance medical knowledge and of 'giving back to the health service'. Concerns over autonomy-some felt that deferred consent was a violation of personal autonomy. Uncertainty-many patients seemed to struggle to understand the more complex concepts discussed. CONCLUSIONS: Patients are broadly trusting, and open to participating in emergency medical trials, but want to be kept as informed as possible throughout the process. Willingness may be improved by providing more complete explanations, although this may be limited by the complexity of relevant concepts. Good communication and improved public understanding of clinical trials would likely increase acceptance of emergency care research.