Clinically relevant mutations in the ABCG2 transporter uncovered by genetic analysis linked to erythrocyte membrane protein expression

The ABCG2 membrane protein is a key xeno- and endobiotic transporter, modulating the absorption and metabolism of pharmacological agents and causing multidrug resistance in cancer. ABCG2 is also involved in uric acid elimination and its impaired function is causative in gout. Analysis of ABCG2 expression in the erythrocyte membranes of healthy volunteers and gout patients showed an enrichment of lower expression levels in the patients. By genetic screening based on protein expression, we found a relatively frequent, novel ABCG2 mutation (ABCG2-M71V), which, according to cellular expression studies, causes reduced protein expression, although with preserved transporter capability. Molecular dynamics simulations indicated a stumbled dynamics of the mutant protein, while ABCG2-M71V expression in vitro could be corrected by therapeutically relevant small molecules. These results suggest that personalized medicine should consider this newly discovered ABCG2 mutation, and genetic analysis linked to protein expression provides a new tool to uncover clinically important mutations in membrane proteins. © 2018 The Author(s)

Determination, occurrence, and treatment of saccharin in water: A review

Saccharin (SAC) is an emerging contaminant, widely detected in the environment, with potential ecotoxicity risks to aqueous organisms and human beings. Wastewater treatment plants (WWTPs) are key sources and sinks of SAC, and play a vital role in eliminating SAC entering the environment. An overview is provided of the potential ecotoxicity of SAC, its occurrence in the aqueous environment, and its degradation performance in WWTPs. SAC treatments, including physical, chemical (mainly advanced oxidation processes AOPs), biological, and hybrid processes, and possible degradation mechanisms are also considered. Of the various SAC removal processes, we find that adsorption-based physical methods exhibit relatively poor performance in terms of SAC removal, whereas chemical methods, especially hydroxy radical-mediated oxidation processes, possess excellent capacities for SAC elimination. Although biological degradation can be efficient at removing SAC, its efficiency depends on oxygen supply and the presence of other co-existing pollutants. Hybrid aerobic biodegradation processes combined with other treatments including AOPs could achieve complete SAC reduction. Furthermore, novel adsorbents, sustainable chemical methods, and bioaugmentation technologies, informed by in-depth studies of degradation mechanisms and the metabolic toxicity of intermediates, are expected further to enhance SAC removal efficiency and enable comprehensive control of SAC potential risks

A View from the Past Into our Collective Future: The Oncofertility Consortium Vision Statement

Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future