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Tuning sterol extraction kinetics yields a renal-sparing polyene antifungal

Decades of previous efforts to develop renal-sparing polyene antifungals were misguided by the classic membrane permeabilization model1. Recently, the clinically vital but also highly renal-toxic small-molecule natural product amphotericin B was instead found to kill fungi primarily by forming extramembraneous sponge-like aggregates that extract ergosterol from lipid bilayers2–6. Here we show that rapid and selective extraction of fungal ergosterol can yield potent and renal-sparing polyene antifungals. Cholesterol extraction was found to drive the toxicity of amphotericin B to human renal cells. Our examination of high-resolution structures of amphotericin B sponges in sterol-free and sterol-bound states guided us to a promising structural derivative that does not bind cholesterol and is thus renal sparing. This derivative was also less potent because it extracts ergosterol more slowly. Selective acceleration of ergosterol extraction with a second structural modification y ....

South Korea , Fungal Priority Pathogens List To Guide Research , Mcgraw Hill , Laboratory Standards Institute , Public Health Action World Organization , Clinical Pharmacology , Priority Pathogens List , Guide Research , Public Health Action , World Health Organization , Growth Design , Comprehensive Organic Synthesis , Drug Monit , Broth Dilution Antifungal Susceptibility Testing , Filamentous Fungi , Antifungal Susceptibility Testing ,

Migrant flocks arrive early, shift to sandy beaches

Migrant flocks arrive early, shift to sandy beaches
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Chaliyam Pulimuttu , Photo Credit , Western Coast , Global Ecology ,

Special issue of Journal of Safety Research highlights injury research symposium

The Journal of Safety Research is offering free access – through February – to a special issue featuring select papers from the National Occupational Injury Research Symposium. ....

National Safety Council , Journal Of Safety Research , National Occupational Injury Research Symposium , Safety Research , National Occupational Injury Research , Workplace Injuries , Changing World ,

Research assessment 'fails to encourage impact' | Times Higher Education (THE)

Sector leaders quizzed in Elsevier survey back shift to more holistic methods of evaluating scholarship ....

United Kingdom , New Zealand , James Wilsdon , Nick Fowler , Research Excellence Framework , Times Higher Education Innovation , Impact Summit ,

Unveiling The Patient Engagement Solutions Market 2032

Unveiling The Patient Engagement Solutions Market 2032
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United States , Asia Pacific , Understanding Patient Engagement Solutions , Financial Health Management , Patient Engagement Solutions , Getwellnetwork Inc , Orion Health , Cerner Corporation , Mckesson Corporation , Home Health Management , Oneview Ltd , Menafn Alliance News Market Overview , Health Management , Market Overview , Free Sample , Chronic Conditions , Government Policies , Market Growth , Behavioral Management , Financial Health , Report Ocean , Michigan Ave ,