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| http://dx.doi.org/10.1186/1753-6561-5-S8-P33 | DOI Listing |
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Investigating the effects of formulation variables on the disintegration of spray dried amorphous solid dispersion tablets.
J Pharm Sci
January 2025
Synthetic Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address:
Amorphous solid dispersion (ASD) tablets based on hydrophilic polymer carriers may encounter disintegration challenges. In this work, the effect of different formulation composition variables on the ASD tablet disintegration performance was systematically studied. GDC-0334: copovidone (PVPVA) 60: 40 ASD prepared by spray drying was selected as the model ASD system.
View Article and Find Full Text PDFSingle-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans.
Nat Microbiol
November 2024
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA.
Genomic copy number changes are associated with antifungal drug resistance and virulence across diverse fungal pathogens, but the rate and dynamics of these genomic changes in the presence of antifungal drugs are unknown. Here we optimized a dual-fluorescent reporter system in the diploid pathogen Candida albicans to quantify haplotype-specific copy number variation (CNV) and loss of heterozygosity (LOH) at the single-cell level with flow cytometry. We followed the frequency and dynamics of CNV and LOH at two distinct genomic locations in the presence and absence of antifungal drugs in vitro and in a murine model of candidiasis.
View Article and Find Full Text PDFStep-wise evolution of azole resistance through copy number variation followed by KSR1 loss of heterozygosity in Candida albicans.
PLoS Pathog
August 2024
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, United States of America.
Antimicrobial drug resistance poses a global health threat, requiring a deeper understanding of the evolutionary processes that lead to its emergence in pathogens. Complex evolutionary dynamics involve multiple mutations that can result in cooperative or competitive (clonal interference) effects. Candida albicans, a major fungal pathogen, displays high rates of copy number variation (CNV) and loss of heterozygosity (LOH).
View Article and Find Full Text PDFA Brg1-Rme1 circuit in hyphal gene regulation.
mBio
September 2024
Department of Microbiology, University of Georgia, Athens, Georgia, USA.
Major virulence traits include its ability to make hyphae, to produce a biofilm, and to damage host cells. These traits depend upon expression of hypha-associated genes. A gene expression comparison among clinical isolates suggested that transcription factor Rme1 established by previous studies to be a positive regulator of chlamydospore formation, may also be a negative regulator of hypha-associated genes.
View Article and Find Full Text PDFPEI-Mediated Transient Gene Expression in CHO Cells.
Methods Mol Biol
June 2024
Denali Therapeutics, South San Francisco, CA, USA.
We describe a method for polyethyleneimine (PEI)-mediated transient transfection of suspension-adapted Chinese hamster ovary (CHO-DG44) cells for protein expression applicable at scales from 2 mL to 2 L. The method involves transfection at a high cell density (5 × 10 cells/mL) by direct addition of plasmid DNA (pDNA) and PEI to the culture and subsequent incubation at 31 °C with agitation by orbital shaking. This method requires 0.
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