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An understanding of the link between genotype and phenotype is essential for biology students. A 3-wk laboratory project aimed at demonstrating this link and introducing early year students to some aspects of the research process is described. Students investigate the properties of wild type and mutant variants of alkaline phosphatase using the techniques of both biochemistry and molecular biology. Changes in enzyme activity are correlated with the changes in DNA sequence that introduce restriction enzyme sites. Mutants are also used to analyze the regulation of phoA gene expression. The application of different techniques to the same experimental system helps students to integrate information from different parts of the course.
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http://dx.doi.org/10.1002/bmb.91 | DOI Listing |
FEBS Lett
September 2025
Laboratory of Molecular Diagnostics and Biotechnology, Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, Minsk, Belarus.
Genetic variants of various cytochrome P450 (CYP) enzymes significantly impact pharmacokinetics. The highly polymorphic hepatic CYP2C9 metabolizes ~ 15% of clinically used drugs. This study aimed to characterize the ligand-binding properties of the understudied CYP2C9.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
September 2025
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.
Organic molecular glasses are attractive matrices to disperse active ingredients in pharmaceuticals or electronic devices. Typically, they i) have lower glass transition temperatures than inorganic or polymeric glasses, making them easier to process, and ii) are less prone to phase segregation from other organic active materials. However, there is a dearth of functional groups that are known to induce glass formation in preference to crystallization.
View Article and Find Full Text PDFNat Commun
September 2025
Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China.
ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome is a rare genetic disease caused by variants in alpha-kinase 1 (ALPK1) resulting in downstream pro-inflammatory signaling mediated by the TIFA/TRAF6/NF-κB pathway. Here, we report the design of an ALPK1 inhibitor, DF-003, with pharmacokinetic properties suitable for daily oral dosing. In biochemical assays, DF-003 potently inhibits human ALPK1 (IC = 1.
View Article and Find Full Text PDFCancer Lett
September 2025
State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Department of Radiology, Department of Clinical Research and Translational Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou,
The tumor microenvironment (TME) plays a pivotal role in cancer progression, though the molecular regulators governing its immunosuppressive properties remain incompletely characterized. In this study, we identify Makorin-2 (MKRN2) as a novel modulator of TME remodeling through integrated analyses of genetically engineered mouse models and human clinical data. Utilizing MKRN2 knockout mice, we observed significantly accelerated tumor growth compared to wild-type control, which was associated with profound alterations in immune cell composition, especially M2 macrophages.
View Article and Find Full Text PDFJ Med Chem
September 2025
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
Three generations of EGFR tyrosine kinase inhibitors (EGFR-TKIs) have shown clinical efficacy in nonsmall cell lung cancer (NSCLC), but acquired resistance mutations─especially the -EGFR─remain a major challenge. Here, we report the identification of a series of pyrrolo[2,3-]pyrimidine derivatives that inhibit C797S-mediated EGFR triple mutants. Among them, compound shows subnanomolar IC values against Ba/F3 EGFR and Ba/F3 EGFR, while sparing wild-type EGFR.
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