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Insights into Heterocycle Biosynthesis in the Cytotoxic Polyketide Alkaloid Janustatin A from a Plant-Associated Bacterium.
Biochemistry
January 2025
Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
Janustatin A is a potently cytotoxic polyketide alkaloid produced at trace amounts by the marine bacterial plant symbiont . Its biosynthetic terminus features an unusual pyridine-containing bicyclic system of unclear origin, in which polyketide and amino acid extension units appear reversed compared to the order of enzymatic modules in the polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) assembly line. To elucidate unknown steps in heterocycle formation, we first established robust genome engineering tools in .
View Article and Find Full Text PDFMolecular and cellular dynamics of the developing human neocortex.
Nature
January 2025
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
The development of the human neocortex is highly dynamic, involving complex cellular trajectories controlled by gene regulation. Here we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and the primary visual cortex. These samples span five main developmental stages, ranging from the first trimester to adolescence.
View Article and Find Full Text PDFThe Metabolic Treatabolome and Inborn Errors of Metabolism Knowledgebase therapy tool: Do not miss the opportunity to treat!
J Inherit Metab Dis
January 2025
Department of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.
Inborn errors of metabolism (IEMs) are rare genetic conditions with significant morbidity and mortality. Technological advances have increased therapeutic options, making it challenging to remain up to date. A centralized therapy knowledgebase is needed for early diagnosis and targeted treatment.
View Article and Find Full Text PDFOxidative Phosphorylation is a Metabolic Vulnerability of Endocrine Therapy-Tolerant Persister Cells in ER+ Breast Cancer.
Cancer Res
January 2025
Medical College of Wisconsin, Milwaukee, WI, United States.
Despite adjuvant treatment with endocrine therapies, estrogen receptor-positive (ER+) breast cancers recur in a significant proportion of patients. Recurrences are attributable to clinically undetectable endocrine-tolerant persister cancer cells that retain tumor-forming potential. Therefore, strategies targeting such persister cells may prevent recurrent disease.
View Article and Find Full Text PDFCharacterization of an Invisible HIV-1 Circulating Recombinant Form (CRF149_01B) in China.
AIDS Res Hum Retroviruses
January 2025
Yunnan Provincial Key Laboratory of Public Health and Biosafety & Institute for AIDS/STD Control and Prevention, Yunnan Center for Disease Control and Prevention, Kunming, China.
In this study, by analyzing the available near full-length genome (NFLG) sequences of CRF55_01B, it was found that two of the NFLG sequences could not be clustered with other NFLG sequences. Recombination analysis and phylogenetic analysis suggested that these two NFLG sequences arose by recombination with subtype B based on CRF55_01B, rather than by recombination directly derived from CRF01_AE and subtype B. In addition, two other HIV-1 partial gene fragments found in the database shared the same characteristics as these two NFLG sequences in the key recombination region.
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