Publications by authors named "K Locher"

ABCG2 is a multidrug transporter that protects tissues from xenobiotics, affects drug pharmacokinetics, and contributes to multidrug resistance of cancer cells. Here, we present tetracyclic fumitremorgin C analog Ko143 derivatives, evaluate their modulation of purified ABCG2, and report four high-resolution cryo-EM structures and computational analyses to elucidate their interactions with ABCG2. We found that Ko143 derivatives that are based on a ring-opened scaffold no longer inhibit ABCG2-mediated transport activity.

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Article Synopsis
  • False positive norovirus results were suspected after using the BioFire® FilmArray® Gastrointestinal panel at six labs in British Columbia, prompting further investigation.
  • The study involved additional molecular testing and whole genome sequencing (WGS) to confirm results from BF-GIP, with 215 out of 784 results initially suspecting false positives.
  • Ultimately, it was found that BF-GIP does produce false positives for norovirus, and these cannot be reliably predicted through a review of melting curves.
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Background: Current molecular diagnostics are limited in the number and type of detectable pathogens. Metagenomic next-generation sequencing (mNGS) is an emerging, and increasingly feasible, pathogen-agnostic diagnostic approach. Translational barriers prohibit the widespread adoption of this technology in clinical laboratories.

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Cellular entry of the hepatitis B and D viruses (HBV/HDV) requires binding of the viral surface polypeptide preS1 to the hepatobiliary transporter Na-taurocholate co-transporting polypeptide (NTCP). This interaction can be blocked by bulevirtide (BLV, formerly Myrcludex B), a preS1 derivative and approved drug for treating HDV infection. Here, to elucidate the basis of this inhibitory function, we determined a cryo-EM structure of BLV-bound human NTCP.

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