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Impact of pathogenic mutations of the GLUT1 glucose transporter on solute carrier dynamics using ComDYN enhanced sampling.
F1000Res
January 2025
Dept. Computer Science, Integrative Bioinformatics, Vrije Universiteit, Amsterdam, The Netherlands.
The solute carrier (SLC) family of membrane proteins is a large class of transporters for many small molecules that are vital for cellular function. Several pathogenic mutations are reported in the glucose transporter subfamily SLC2, causing Glut1-deficiency syndrome (GLUT1DS1, GLUT1DS2), epilepsy (EIG2) and cryohydrocytosis with neurological defects (Dystonia-9). Understanding the link between these mutations and transporter dynamics is crucial to elucidate their role in the dysfunction of the underlying transport mechanism, which we investigate using molecular dynamics simulations.
View Article and Find Full Text PDFPharmacological ascorbate combined with rucosopasem selectively radio-chemo-sensitizes NSCLC via generation of HO.
Redox Biol
January 2025
Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa College of Medicine, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, 52242, USA.
Differences in cancer and normal cell oxidative metabolism provide a unique therapeutic opportunity for developing combined modality approaches with redox-active small molecules as radio-chemosensitizers that are well-tolerated by normal tissues. Pentaazamacrocyclic Mn (II)-containing (MnPAM) superoxide dismutase (SOD) mimetics and pharmacological ascorbate given IV to achieve [mM] plasma levels (pharmacological ascorbate: P-AscH‾) have been shown to act individually as cancer cell radio- and chemosensitizers via the generation of HOin vivo. The current study shows that the combination of newly developed MnPAM dismutase mimetic, rucosopasem manganese (RUC) with P-AscH‾ radio-sensitizes non-small cell lung cancer cells (NSCLC) and increases steady state levels of intracellular HO with no additional toxicity to normal human bronchial epithelial cells (HBECs).
View Article and Find Full Text PDFSynthesis, antimicrobial evaluation, ADMET prediction, molecular docking and dynamics studies of pyridine and thiophene moiety-containing chalcones.
R Soc Open Sci
January 2025
Department of Chemistry, Jagannath University, Dhaka 1100, Bangladesh.
In this study, three pyridine- and four thiophene-containing chalcone derivatives were synthesized via Claisen-Schmidt condensation reaction, where five derivatives were new. Different spectral analyses (IR, H NMR, HRMS) clarified the structures and these proposed compounds were screened for antimicrobial activity by the agar disc diffusion technique. Compound was conspicuously active against most of the bacterial and fungal strains.
View Article and Find Full Text PDFEvaluation of undergraduate forensic medicine education in Nepal: a critical analysis using Schwab's five commonplaces and Schubert's curriculum images.
BMC Med Educ
January 2025
Department of Forensic Medicine, Karnali Academy of Health Sciences, Chandannath, Jumla, 21200, Nepal.
Following the establishment of Nepal's first medical college in 1972, forensic medicine was introduced in 1978. To date, 25 medical colleges in the country have included forensic medicine as a compulsory subject in the undergraduate medical curriculum. Although this subject has been introduced into the medical curriculum, the outcome is unsatisfactory, as reflected by the poor medico-legal reports prepared by newly graduated medical students.
View Article and Find Full Text PDFSister chromatid cohesion through the lens of biochemical experiments.
Curr Opin Cell Biol
January 2025
Department of Chromosome Science, National Institute of Genetics, Mishima, 411-8540, Japan; Department of Genetics, Graduate University for Advanced Studies (SOKENDAI), Mishima, 411-8540, Japan. Electronic address:
Faithful chromosome segregation in eukaryotes relies on physical cohesion between newly duplicated sister chromatids. Cohesin is a ring-shaped ATPase assembly that mediates sister chromatid cohesion through its ability to topologically entrap DNA. Cohesin, assisted by several regulatory proteins, binds to DNA prior to DNA replication and then holds two sister DNAs together when it encounters the replication machinery.
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